1 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 P R O C E E D I N G S 10:05:09 3 (Trial proceedings reconvened 10:05:09 4 9:00 a.m., May 22, 2001.) 10:05:09 8 MR. VICKERY: We call Dr. David Healy. 10:18:50 9 (Witness sworn.) 10:19:20 10 MR. PREUSS: Your Honor, before we 10:19:20 11 commence I would like to state for the record an objection 10:19:21 12 based upon the grounds stated in our Daubert motion, are 10:19:23 13 cognizant of the ruling and I would like to reserve my 10:19:28 14 right to examine as part of my normal cross. 10:19:31 15 THE COURT: Very well. Thank you. 10:19:34 16 You may proceed. 10:19:37 17 THE CLERK: Please state your name and 10:19:39 18 spell it for the record. 10:19:39 19 Q. (BY MR. VICKERY) State your name, please, sir. 10:19:44 20 A. My name is David Healy, D A V I D, H E A L Y. 10:19:46 21 Q. Okay, sir. When I called you, I said Dr. Healy. 10:19:56 22 Are you in fact a doctor of some sort? 10:19:59 23 A. I am, yes, Mr. Vickery. I'm a medical doctor. 10:20:02 24 I'm also a consultant psychiatrist and a doctor doctor in 10:20:04 25 the sense of I've got a postgraduate hire degree in this 10:20:11 4 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 area. 10:20:18 3 Q. Is that sort of like a Ph.D. in this country? 10:20:19 4 A. Yes, it is. 10:20:23 5 Q. We can all tell from your accent you're not from 10:20:24 6 here, are you? 10:20:27 7 A. No, I'm Irish, Mr. Vickery and I hope -- well, 10:20:27 8 my accent may cause some problems to the court. I realize 10:20:31 9 the jury can't intervene if my accent is a problem, but I 10:20:35 10 would hope Judge Beaman and perhaps the court reporter 10:20:41 11 would, if anything I say seems unclear, please help me. 10:20:44 12 Q. I think if you keep your voice up like you're 10:20:52 13 doing now, you'll do just fine. 10:20:54 14 Dr. Healy, how old a gentleman are you? 10:20:57 15 A. I'm 47, Mr. Vickery. 10:20:59 16 Q. Where were you born and raised? 10:21:01 17 A. I was born in Ireland, the north side of Dublin. 10:21:03 18 I was raised there before going to university there. I 10:21:07 19 then went over to the university of Galway to do research 10:21:11 20 and left Galway for England for the University of 10:21:15 21 Cambridge around 1986 and have been in the UK since then. 10:21:20 22 Q. Did you do your medical degree first or your 10:21:23 23 Ph.D. equivalent first? 10:21:25 24 A. Well, where people here have an M.D., we do an 10:21:28 25 MB in Europe, usually, and I did my MB first and after 10:21:31 5 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 that did the Ph.D. work. 10:21:36 3 Q. Did you then pursue a residency in psychiatry? 10:21:39 4 A. Yes, I did. 10:21:43 5 Q. And did you do that after the Ph.D. kind of work 10:21:44 6 or -- 10:21:49 7 A. Yes. After I had done my research and actually 10:21:49 8 during the course of the research, I did the early part of 10:21:53 9 my psychiatric training in Ireland and the later part of 10:21:55 10 the training at the University of Cambridge. 10:21:59 11 Q. When you were doing the Ph.D. equivalent work, 10:22:02 12 did you have a particular field of interest or study? 10:22:05 13 A. Yes, I did. My Ph.D. is based largely on the 10:22:08 14 serotonin reuptake mechanism, the mechanism on which drugs 10:22:14 15 like paroxetine work. I also looked at various different 10:22:17 16 serotonin receptors like the serotonin 2 receptor, which 10:22:23 17 is of interest, I think, in terms of the problems that 10:22:30 18 drugs like Paxil can cause. 10:22:35 19 Q. Let's break it down a minute there. 10:22:42 20 Serotonin -- I know the jury has heard the opening 10:22:44 21 statements and a little bit of testimony from Mr. Haase 10:22:46 22 yesterday about it. 10:22:50 23 But would you just explain for them what 10:22:51 24 serotonin is and how important it is or how it functions 10:22:53 25 in the brain. 10:22:55 6 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 A. Serotonin is one of many brain 10:22:57 3 neurotransmitters. There may be up to 100 of these. It 10:23:01 4 is one of the ones that we learned about first. We 10:23:07 5 learned about it first largely because a drug which you 10:23:11 6 will all know well, LSD, acts on this system. 10:23:15 7 It is a system that later in the -- in the early 10:23:20 8 1970s became of interest to people working in the field of 10:23:24 9 mood disorders. They thought it may be useful to create 10:23:30 10 drugs which acted on this brain system to see would these 10:23:34 11 be useful drugs to treat nervous problems. 10:23:38 12 Q. When you say neurotransmitter, can you just 10:23:41 13 explain that process? Is that some kind of communication 10:23:45 14 process between cells in the brain? 10:23:48 15 A. Yes. I mean, that's the easiest way to put it. 10:23:51 16 Q. And did I understand you to say there may be up 10:23:56 17 to a hundred different chemical neurotransmitters? 10:23:59 18 A. There may well be, yes. 10:24:03 19 Q. You mentioned receptors. Would you just explain 10:24:04 20 in real plain terms what a receptor is. 10:24:07 21 A. Yes, if you think of serotonin as the key, there 10:24:10 22 are a bunch of locks on the other nerve cells, and 10:24:14 23 serotonin can fit into a number of different locks. Now, 10:24:18 24 it will only fit into what are called serotonin locks and 10:24:22 25 there's serotonin 1, serotonin 2, serotonin 3 locks. And 10:24:26 7 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 there are more, but they're the ones, I think, of interest 10:24:32 3 to us. 10:24:35 4 Q. You mentioned the 1, 2 and 3. Is serotonin 10:24:38 5 typically writing in scientific literature as 5HT? 10:24:44 6 A. Yes, Mr. Vickery, that's the way it was really 10:24:48 7 written first of all. The word "serotonin" has largely 10:24:50 8 gained currency thanks to SmithKline Beecham. If 10:24:54 9 SmithKline Beecham hadn't coined the acronym SSRI probably 10:24:58 10 we wouldn't be using the word now today. 10:25:04 11 Q. Now, I have written here on this sheet of paper 10:25:07 12 5HT1 and then down below 5HT2. I still can't do that 10:25:09 13 thing right. 10:25:19 14 Is that the way that one writes when they're 10:25:20 15 describing the serotonin 1 or 2 receptor? 10:25:24 16 A. Yes, it is. 10:25:28 17 Q. Has anything good in the history of mankind ever 10:25:28 18 happened as a result of some drug impacting the 5HT2 10:25:33 19 receptor? 10:25:39 20 A. No. The drug company and probably the 10:25:40 21 researcher who has looked at this particular receptor the 10:25:43 22 most is a man called Paul Janssen. And you've just 10:25:46 23 slightly paraphrased his quote, which that there's nothing 10:25:51 24 good known to man that comes from serotonin acting on this 10:25:54 25 particular receptor. 10:25:58 8 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 LSD, for instance, acts on this receptor. 10:26:00 3 Paroxetine makes a large amount of serotonin, excess 10:26:08 4 serotonin, available to this receptor. 10:26:08 5 Q. And we really kind of got diverted. We were 10:26:13 6 talking about your background and your education. 10:26:16 7 Has any of your research either before you got 10:26:19 8 the Ph.D. equivalent or after, any of your research on the 10:26:22 9 serotonin system in the body been funded by SmithKline 10:26:27 10 Beecham? 10:26:29 11 A. Yes, a great deal of the research that I 10:26:30 12 did during the 1980s was funded by Beecham as it was then. 10:26:33 13 I was looking at serotonin reuptake and the drug 10:26:40 14 that they had at the time was a drug called miaserin which 10:26:43 15 was a nonserotonin reuptake inhibitor that we have in 10:26:48 16 Europe that you have never had over here and what I was 10:26:53 17 doing was giving this drug and another drug which was a 10:26:56 18 serotonin reuptake inhibitor to a group of people who were 10:26:59 19 depressed and looking at what changes in the serotonin 10:27:03 20 reuptake system as people get well. 10:27:05 21 Q. And was that research funded by SmithKline 10:27:10 22 Beecham? 10:27:12 23 A. Yes, it was. 10:27:12 24 Q. And you were a clinical investigator for it? 10:27:13 25 A. Not a clinical investigator, no. I was doing -- 10:27:16 9 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 what I was doing was we were looking at people going 10:27:19 3 through the psychiatric unit where I trained and any of 10:27:22 4 the people who were actually very severely depressed were 10:27:29 5 the ones we actually recruited to the trial where we gave 10:27:33 6 miaserin, Beecham's drug, and the other drug we were 10:27:39 7 looking at. I have been a clinical trialist for 10:27:41 8 SmithKline Beecham since after I moved to the UK. 10:27:44 9 MR. VICKERY: Let me ask counsel 10:27:50 10 something. 10:27:53 11 Q. (BY MR. VICKERY) How many different trials have 10:27:58 12 you conducted for SmithKline Beecham or at least where 10:27:59 13 they funded it? 10:28:05 14 A. Yes. I've been involved in three different 10:28:06 15 clinical trials. In one of these, it was a clinical trial 10:28:08 16 looking at SmithKline Beecham's drug paroxetine which is 10:28:14 17 the one of interest to us. And we were looking to compare 10:28:19 18 it with another drug called lofepramine which you don't 10:28:23 19 have over here, but the interesting thing with this drug 10:28:30 20 is that it has no actions on the serotonin system at all. 10:28:33 21 We were looking at the two drugs in an elderly 10:28:36 22 group of people who were depressed and we were looking to 10:28:40 23 see which of the two drugs was actually the one that was 10:28:42 24 probably -- perhaps the best drug to use for older people 10:28:45 25 who were depressed. 10:28:50 10 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Q. All right. Of the -- did you say three total? 10:28:51 3 A. Yes, that's only one. The other one we did then 10:28:55 4 was -- SB as we usually refer to them over in the UK -- 10:28:58 5 Q. They're headquartered over there; is that right? 10:29:02 6 A. Yes. 10:29:05 7 Q. And you're over there? 10:29:05 8 A. Yes, I am. They had a drug which acts on the 10:29:06 9 serotonin 3 receptor and they had hoped that a drug that 10:29:10 10 would block this brain receptor would be an anxiolytic 10:29:15 11 drug so they ran a clinical trial. 10:29:21 12 Q. That's a ten penny word. Don't want any ten 10:29:25 13 penny words. What does anxiolytic mean? 10:29:27 14 A. It means would make people who are anxious less 10:29:29 15 anxious. 10:29:32 16 Q. Continue telling us about this study. 10:29:33 17 A. Again, this was a clinical trial that I was 10:29:35 18 involved in for them and it was being used to look at 10:29:38 19 people who were anxious. 10:29:46 20 Q. And then what was the third trial? 10:29:49 21 A. The third trial was later on, again, this was 10:29:51 22 probably about 1993, '94, where they were looking to 10:29:57 23 compare paroxetine, Paxil, with a drug called clomipramine 10:30:01 24 to treat people who had OCD which is obsessive-compulsive 10:30:08 25 disorder. 10:30:14 11 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 And again, we were actually involved as one of 10:30:16 3 the clinical trial centers which recruited people for this 10:30:22 4 particular study. 10:30:26 5 Q. All right. Dr. Healy, were all of those studies 10:30:27 6 completed? Did you complete all of those studies? 10:30:31 7 A. Yes, we did. 10:30:36 8 Q. And did you turn over all of the data that was 10:30:36 9 generated from them to SmithKline Beecham? 10:30:38 10 A. Yes, we did. 10:30:40 11 Q. And was all of that data made publicly 10:30:43 12 available? 10:30:45 13 A. No, it wasn't. Two of the trials were sealed 10:30:46 14 and have never seen the light of day as far as I know. 10:30:48 15 Q. Okay, sir. 10:30:53 16 Now, you've told us already you're a 10:30:54 17 psychiatrist. Are you also a neuropsychopharmacologist? 10:30:57 18 A. Yes, I am, Mr. Vickery. During the early 1990s 10:31:01 19 I was the secretary for the British association for 10:31:07 20 psychopharmacology. During the course of this trial 10:31:10 21 you've heard people refer to the ACNP, an article actually 10:31:14 22 brought out by the ACNP authored by J. John Mann. ACNP 10:31:18 23 stands for the American college of 10:31:24 24 neuropsychopharmacology. In the UK the BAP, which is what 10:31:27 25 I was the secretary of, is the UK version of ACNP here. 10:31:33 12 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Q. Okay, sir. Now, tell me this: In addition to 10:31:41 3 being a psychiatrist and a neuropsychopharmacologist, are 10:31:49 4 you also a historian? 10:31:55 5 A. Yes, I have been interested in 10:31:56 6 the history of the field for some considerable period now, 10:32:00 7 perhaps since I actually began the research in this area 10:32:06 8 looking at serotonin reuptake and recently, as you will 10:32:08 9 know, authored the only book on the history of the 10:32:14 10 antidepressants which was published by Harvard University 10:32:17 11 Press. 10:32:22 12 I have a further book due out later this year 10:32:22 13 from Harvard University Press called the Creation of 10:32:25 14 Psychopharmacology. 10:32:28 15 Q. In addition to those do you have a series of 10:32:30 16 three volumes of interviews with the major players in the 10:32:32 17 field of psychopharmacology? 10:32:35 18 A. Yes. Since about 1993 or thereabouts I've made 10:32:37 19 it my business for research purposes to go around with a 10:32:42 20 tape-recorder to approximately 100 of the leading people 10:32:49 21 in the field, both the people who have made the drugs, the 10:32:55 22 people who have worked with them clinically, the people 10:32:58 23 who have devised the marketing campaigns, people who have 10:33:01 24 won Nobel prizes, the lot and I've interviewed at least 10:33:06 25 100 of these people. 10:33:09 13 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 The interviews have been brought out so far in 10:33:11 3 three volumes. There's over a million and a half words 10:33:13 4 and something like 2,000 pages. 10:33:17 5 Q. Back to a moment to your contacts with 10:33:23 6 SmithKline Beecham. 10:33:25 7 Have you ever been asked by them to speak 10:33:26 8 publicly on behalf of Paxil? 10:33:28 9 A. I have been asked on a number of occasions. 10:33:31 10 When the clinical trial for paroxetine in OCD was done, 10:33:36 11 there was a launch meeting that was held in Nice I guess 10:33:41 12 around '95, '96. 10:33:46 13 Q. Is that in France? 10:33:49 14 A. Nice in France, the south of France where they 10:33:50 15 brought clinical people from all over Europe, speakers 10:33:53 16 from the U S to this meeting, and they also brought me to 10:33:56 17 speak on the podium about the issues to do with the 10:33:59 18 treatment of people who had OCD. 10:34:03 19 There's been a further time actually. 10:34:09 20 Q. I was going to say when is the last time that 10:34:11 21 you spoke at the instance of SmithKline Beecham? 10:34:12 22 A. I have spoken rather regularly, been asked 10:34:19 23 fairly often over the course of the last nine or so odd 10:34:22 24 years and prior to that during the 1980s in forums in 10:34:27 25 Wales where I work and in forums in the north of England 10:34:32 14 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 to consultant psychiatrists, G Ps and others on the 10:34:35 3 treatment of people who were depressed with either the 10:34:40 4 SSRIs or other drugs. 10:34:43 5 Q. And, Dr. Healy, how long have you been writing 10:34:51 6 about and speaking publicly in scientific settings about 10:34:53 7 the problem of SSRI-induced suicide or violence? 10:34:56 8 A. I have been speaking on this issue publicly 10:35:01 9 since about 1991. The most recent lecture I gave was five 10:35:04 10 weeks ago at the university of Toronto. Roughly a year 10:35:12 11 ago I was asked to speak on the issue of antidepressants 10:35:18 12 and suicide by SmithKline Beecham in north Wales, and the 10:35:21 13 interesting thing about this particular lecture was it was 10:35:25 14 made clear to me by the representative from SmithKline 10:35:28 15 Beecham afterwards that they would not be asking me to 10:35:30 16 talk again. 10:35:32 17 Q. Did you express the opinions in that lecture 10:35:39 18 that you intend today to express in this courtroom? 10:35:41 19 A. Yes, I did. 10:35:43 20 Q. Did you use in connection with that lecture some 10:35:44 21 of the slides you have prepared to illustrate your 10:35:46 22 testimony here? 10:35:49 23 A. Yes, I did. 10:35:49 24 Q. Are all of the slides you prepared to illustrate 10:35:51 25 your testimony here slides that you have used in numerous 10:35:52 15 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 professional lectures? 10:35:55 3 A. Yes, absolutely, to audiences of 1 or 200 or 10:35:56 4 more on regular occasions during the last two or three 10:36:00 5 years. What you will have when we later show these slides 10:36:04 6 are the ones I've been using for roughly the last two 10:36:08 7 years. 10:36:12 8 Q. You mentioned a minute ago something about 10:36:12 9 SmithKline Beecham coining the term "SSRI"? 10:36:15 10 A. Yes. It is an interesting little story, I 10:36:20 11 guess. Having got very close contacts with SmithKline 10:36:24 12 Beecham in the early 1980s, I was aware that they had a 10:36:29 13 drug called paroxetine. You have heard only of the story 10:36:33 14 that this emerges in 1988. In actual fact, it was a drug 10:36:37 15 they got from a company called Ferrosan in 1978. Ferrosan 10:36:42 16 at this stage had two drugs which were SSRIs. 10:36:48 17 SmithKline Beecham purchased from Ferrosan the 10:36:52 18 drug that was thought to be the weaker of the two 10:36:56 19 clinically but commercially more interesting in that you 10:36:59 20 only had to give one pill per day. 10:37:02 21 Q. Let me stop you and make sure we're 10:37:04 22 communicating. This company Ferrosan had two drugs? 10:37:07 23 A. This company Ferrosan had two SSRIs. 10:37:10 24 Q. Two SSRIs. And one of them was better 10:37:13 25 clinically? 10:37:16 16 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 A. Well, one of them had been made first which was 10:37:16 3 another drug made in 1975. 1978 they make paroxetine. 10:37:19 4 Q. Are these synthetic drugs. They you say made, 10:37:29 5 is this something they make up in the lab? 10:37:30 6 A. Yes, they were the ones who actually went 10:37:32 7 through the process of working at what you had to do to a 10:37:34 8 molecule to make it do this thing which was to inhibit 10:37:38 9 serotonin reuptake. 10:37:42 10 Q. And in what way was the other drug better than 10:37:43 11 paroxetine? 10:37:46 12 A. The clinical results, the early clinical work 10:37:47 13 they had suggested that it was probably more potent. 10:37:50 14 Q. When you say clinical work, are you talking 10:37:54 15 about trials with patients? 10:37:56 16 A. Early clinical trials with patients. 10:37:58 17 Q. All right. And can you tell us, then, why they 10:38:00 18 chose the one that was less potent? 10:38:06 19 A. I can't particularly tell you. 10:38:08 20 MR. PREUSS: Objection, foundation, Your 10:38:10 21 Honor. 10:38:11 22 THE COURT: Sustained. 10:38:11 23 Q. (BY MR. VICKERY) Can you kind of skip forward 10:38:13 24 in the story and tell us when and why they coined the term 10:38:17 25 "SSRI"? 10:38:24 17 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 A. Yes, I think -- it is quite clear. It is a 10:38:25 3 clear matter of the record that they came to the market 10:38:28 4 after a number of the other drugs which are now called 10:38:30 5 SSRIs, and the marketing department within SmithKline 10:38:33 6 thought that a snappy acronym -- 10:38:39 7 MR. PREUSS: Objection, no foundation, 10:38:42 8 Your Honor. 10:38:44 9 MR. VICKERY: Let me lay the foundation, 10:38:44 10 if I may. 10:38:45 11 THE COURT: Very well. 10:38:46 12 Q. (BY MR. VICKERY) Did you personally have 10:38:47 13 contact with SmithKline Beecham people at the point of 10:38:48 14 time of these events you're about to relate to us? 10:38:51 15 A. Yes, I did. The whole way through the 1980s, 10:38:54 16 the early 1990s, I was in very, very close contact with a 10:38:58 17 range of different people from the company. 10:39:02 18 Q. And is your source of information what you were 10:39:04 19 told by SmithKline Beecham people? 10:39:06 20 A. Yes, it is. 10:39:07 21 Q. Okay. Then tell us, if you would, please why it 10:39:08 22 is that they coined the SSRI term. 10:39:11 23 A. Well, having come to the market after drugs like 10:39:13 24 Prozac, which had a very large market share to begin with, 10:39:16 25 you have got to work out some marketing angle that will 10:39:20 18 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 help your drug to sell. 10:39:24 3 One of the obvious marketing angles at this 10:39:26 4 point in time was the idea that our drug is cleaner and 10:39:29 5 more selective than drugs like Prozac, and the early adverts 10:39:32 6 here in the US and in the UK also heavily stressed 10:39:43 7 just this point, which was paroxetine was more selective 10:39:48 8 than Prozac and other drugs which are now called SSRIs. 10:39:51 9 Because of this, SmithKline Beecham began 10:39:56 10 saying, "We are the selective serotonin reuptake 10:39:58 11 inhibitor. The others are serotonin reuptake inhibitors. 10:40:02 12 We are the selective one. We are the SSRI." 10:40:06 13 But the acronym was just so good that all of the 10:40:10 14 other companies said, "Oh, that's a good name. We will 10:40:15 15 have it too. We're all SSRIs. And the interesting irony 10:40:19 16 in this is part of the argument put forth by SmithKline 10:40:25 17 Beecham's experts in this particular case is, "What do you 10:40:29 18 know. We're not selective after all. We're a drug that 10:40:31 19 has actions on other brain systems," like the 10:40:34 20 noradrenergic system. Drugs like Prozac, the hint 10:40:41 21 is causes problems, we don't cause the problems because 10:40:45 22 we're not selective," which is an extraordinary irony. 10:40:48 23 THE COURT: Mr. Vickery, let's take our 10:40:53 24 morning recess at this time. We will stand in recess for 10:40:55 25 15 minutes. 10:40:58 19 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 (Recess taken 10:35 a.m. until 10:50 a.m.) 10:41:01 3 THE COURT: Dr. Healy, I'm sure you 10:56:54 4 understand you're still under oath? 10:56:56 5 THE WITNESS: Yes, Judge Beaman. 10:56:58 6 MR. VICKERY: May I proceed, Your Honor. 10:57:01 7 THE COURT: Yes. 10:57:02 8 Q. (BY MR. VICKERY) I want to finish up briefly 10:57:03 9 with your background and credentials and then move into 10:57:04 10 your opinions in this case. 10:57:07 11 Are you a practicing psychiatrist and by that I 10:57:08 12 mean do you see patients? 10:57:12 13 A. Yes, Mr. Vickery, I look after the area of 10:57:15 14 25,000 people, would be half the size of Cheyenne, for 10:57:18 15 instance, and I look after all of those psychiatric needs 10:57:22 16 in that area. I spend half my week doing clinical work 10:57:25 17 and the other half doing research or university work. 10:57:29 18 Q. Do you prescribe Paxil or the other SSRI drugs? 10:57:32 19 A. Yes, I do, Mr. Vickery. I am a supporter of the 10:57:37 20 SSRI group of drugs. I use them regularly in my clinical 10:57:44 21 practice. 10:57:47 22 Q. Do you have one you use more than others or how 10:57:55 23 does it divide out? 10:57:58 24 A. For a number of reasons -- let it put it like 10:57:59 25 this to you. I sit on the hospital formulary group where 10:58:02 20 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 I'm the person who actually advises on what drugs are used 10:58:06 3 actually within psychiatry and I've picked two of the 10:58:11 4 SSRIs. The ones I've picked for the formulary committee 10:58:14 5 are Zoloft and Celexa. We didn't pick Prozac because 10:58:17 6 in a hospital group of people. This drug interacts 10:58:26 7 with all sorts of other drugs that you could be on and 10:58:27 8 lasts for a very long period of time in the body, so it 10:58:30 9 didn't seem to be a good drug to 10:58:34 10 give to people who are ill for other reasons and on a 10:58:38 11 range of other drugs. 10:58:41 12 Paroxetine we didn't pick because in the UK 10:58:43 13 there are great concerns about physical dependence on this 10:58:48 14 SSRI. And the other drug we've got is Luvox which is just 10:58:53 15 the one that is really used least widely. 10:59:00 16 Q. Okay. Now, are you also a teacher? Do you 10:59:05 17 teach or supervise other doctors, either in the clinical 10:59:10 18 end or in a more academic end? 10:59:16 19 A. Yes, I am, Mr. Vickery. I teach both students, 10:59:19 20 I teach people who have been qualified for some years and 10:59:23 21 who have gone on to do training in psychiatry, and I also 10:59:26 22 lecture on what are the primary professional training 10:59:31 23 courses for people who are actually going on to be 10:59:37 24 psychiatrists. 10:59:42 25 When they want psychopharmacology covered, 10:59:43 21 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 places from the university of Cambridge to the university 10:59:47 3 of Liverpool, a wide range of universities ask me to come 10:59:49 4 in and lecture. 10:59:54 5 I also lecture to nursing staff, social workers 10:59:55 6 and a range of other mental health workers. 10:59:58 7 Q. Are you one of those kinds of people who likes 11:00:04 8 to research and write, publish things in books or journal 11:00:06 9 articles? 11:00:11 10 A. Yes, I do. I have no idea where you're going 11:00:12 11 with the question, but it is really drawn from -- usually 11:00:14 12 the things that I work on aren't awfully abstract, they're 11:00:19 13 really drawn from clinical experience. 11:00:22 14 Q. Now, we've talked a little bit about the books 11:00:26 15 or several of your books. How many books total have you 11:00:28 16 published? 11:00:32 17 A. There's approximately 12 books published or in 11:00:34 18 press. There's a further 100 odd articles published or in 11:00:38 19 press and probably 100 further articles which are nonpeer 11:00:47 20 reviewed articles of one sort or the other. 11:00:53 21 Q. The first hundred you mentioned, are those 11:00:54 22 journal articles peer reviewed? 11:00:57 23 A. Yes, or most all of the ones I've listed in my 11:00:59 24 CV are, yes. 11:01:01 25 Q. And would you just explain for the jury the 11:01:03 22 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 significance of having an article published in a 11:01:05 3 professional journal that has been peer reviewed? 11:01:07 4 A. Yes. Well, the significance is that the article 11:01:10 5 has gone to the journal and the journal then sends the 11:01:15 6 article out to two or three other people in the field. 11:01:21 7 You usually don't know who it is the article has gone to. 11:01:24 8 And these other experts are asked for their 11:01:28 9 views on the issue of have you handled the research that 11:01:30 10 you actually describe in the article in the way the 11:01:35 11 research should have been handled. 11:01:38 12 Now, for instance, if an article were sent to me 11:01:43 13 to review, I would fairly regularly point out to the 11:01:45 14 editor of the journal in the review that I write that this 11:01:48 15 article that's actually come to me is one that has flaws, 11:01:54 16 for instance, that the authors really ought to have done 11:01:58 17 this and this and this. It may be too much to ask them to 11:02:02 18 go back and do the whole thing again, but if they're going 11:02:06 19 to describe the results, they're going to have to point 11:02:09 20 out the limitations of what they've done also, you know, 11:02:11 21 for instance. 11:02:14 22 But fairly often in the course of this process, 11:02:15 23 an article would be turned down by the journal, by a peer 11:02:18 24 reviewer such as me. 11:02:23 25 Q. Now, have you published in peer reviewed 11:02:25 23 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 journals articles which express the basic opinion that 11:02:30 3 you're going to give in this lawsuit that for some people 11:02:34 4 the SSRI drugs like Paxil pose an increased risk of 11:02:36 5 violence or suicide? 11:02:41 6 A. Yes, I have. The first of these articles dates 11:02:43 7 back to 1994. 11:02:46 8 Q. Have you ever had a journal article that you 11:02:48 9 have written where there hasn't been some peer reviewed 11:02:53 10 publication willing to publish it on these issues? 11:03:00 11 A. No. The -- no. All of the articles that I've 11:03:06 12 written on this issue have all been published in peer 11:03:09 13 reviewed journals other than one. There's one that has 11:03:14 14 been actually published by the British Medical Ethics 11:03:17 15 bulletin and that, I believe, was not peer reviewed. 11:03:22 16 Q. And you mentioned something about you reviewing 11:03:25 17 articles. Do you sit on the editorial boards of 11:03:27 18 professional journals, scientific journals, where you are 11:03:31 19 the reviewer rather than the author? 11:03:35 20 A. I regularly review. You don't have to be on the 11:03:38 21 editorial board to actually review articles. I regularly 11:03:45 22 review articles for about 30 or 40 journals in the field 11:03:45 23 of psychiatry. 11:03:49 24 Q. Could you give us two or three of the most 11:03:52 25 widely known journals? 11:03:53 24 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 A. British Journal of Psychiatry, journals such as 11:03:56 3 Psychological Medicine, the Journal of 11:04:03 4 Psychcopharmacology, the European Journal of 11:04:05 5 Neuropsychopharmacology. I could go on and on. 11:04:10 6 Q. I think we get the point. We've talked a little 11:04:16 7 bit about some of the research you've done with SmithKline 11:04:19 8 Beecham. 11:04:22 9 Have you conducted other research with SSRI 11:04:23 10 drugs? 11:04:26 11 A. Yes, I have. 11:04:27 12 Q. Have you ever conducted any research which 11:04:29 13 involved people who were not depressed -- depression has 11:04:33 14 nothing to do with what happens to them -- that are 11:04:37 15 perfectly healthy where they were on a SSRI drug and one 11:04:39 16 or more of them became suicidal? 11:04:45 17 A. Yes, I have, Mr. Vickery. I've done two trials. 11:04:48 18 One involves a SSRI given to a group of healthy 11:04:52 19 volunteers. These were nursing staff, medical staff and 11:04:56 20 administrative workers in the unit in which I work. 11:05:01 21 We took 20 volunteers, randomized them either to 11:05:09 22 a drug active on the serotonin system, in this case Zoloft 11:05:17 23 was the one we used, or a drug with no actions on the 11:05:22 24 serotonin system, and in this case the drug we used was a 11:05:25 25 drug called Reboxetine. 11:05:29 25 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Q. Let me stop you there because I think the jury 11:05:32 3 has already heard this word in one of the depositions. Is 11:05:35 4 that a crossover design study? 11:05:37 5 A. What we did was we took both of the pills and 11:05:40 6 made them up so they looked absolutely the same. You 11:05:44 7 couldn't tell which of the two drugs that people were on. 11:05:47 8 And half of the group had one drug and the other half had 11:05:51 9 the other drug for a two week period in a full clinical 11:05:58 10 dose. 11:06:03 11 They then halt the drug and they're drug-free 11:06:03 12 from whichever drug they've been on for a two-week period 11:06:06 13 and then they cross over and they have the other drug, the 11:06:10 14 one they haven't had before. So all the volunteers got 11:06:13 15 Zoloft and all the volunteers got reboxetine. Half got 11:06:19 16 Zoloft first and Reboxetine second and the other half got 11:06:24 17 Reboxetine first and Zoloft second. 11:06:30 18 Q. Did any of those volunteer people have 11:06:33 19 absolutely horrible experiences on the SSRI drug Zoloft? 11:06:35 20 A. Yes, two of the women in the study, and I have 11:06:39 21 to stress again, none of the people -- well, actually as 11:06:41 22 it turned out we found out afterwards courtesy of Phizer, 11:06:44 23 no less, but one of the people that we had actually 11:06:48 24 recruited had been mildly depressed five years beforehand, 11:06:52 25 but none of the others, and in particular neither of the 11:06:55 26 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 two people who became very, very suicidal on Zoloft, both 11:06:58 3 of them became suicidal on Zoloft, both of them were 11:07:04 4 women, but none of them had any nervous problems of any 11:07:08 5 sort before they went on this drug or ever before. 11:07:12 6 Q. And were the results of that study written up on 11:08:40 7 published in a peer reviewed journal? 11:08:40 8 A. Yes, we did two things. One is we wrote almost 11:08:40 9 instantly what had happened to these two volunteers, these 11:08:40 10 two women who had become very, very suicidal. We wrote 11:08:40 11 that instantly up and sent that off for peer review. The 11:08:40 12 rest of the study has been written up. We have a huge 11:08:40 13 amount of data, we've used all sorts of rating scales, 11:08:40 14 we've used measures to look at the personalities of all of 11:08:40 15 the people who had actually been involved, and we've 11:08:40 16 written that up now and that's gone off to a journal 11:08:40 17 called psychological medicine which is probably Europe's 11:08:40 18 premier peer reviewed journal. It hasn't actually been 11:08:40 19 accepted but that's where it's gone. 11:08:40 20 Q. Very good. Let's move to your opinions in this 11:08:40 21 case. I would like for you to -- I know it is going to 11:08:40 22 take some time for you to explain each and the basis but 11:08:40 23 let's get them all out there and then the jury can kind of 11:08:40 24 follow us where we're going. 11:08:40 25 First of all, with respect to general causation, 11:08:40 27 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 in your opinion, Dr. Healy, does Paxil cause some patients 11:08:48 3 to become homicidal or suicidal? 11:08:52 4 A. Yes, it does, Mr. Vickery. 11:08:56 5 MR. PREUSS: Counsel, could you turn it so 11:08:58 6 we can see that as well? 11:09:01 7 MR. VICKERY: Sure. 11:09:04 8 Q. (BY MR. VICKERY) Dr. Healy, were there people 11:09:44 9 who you believe either killed other people or killed 11:09:46 10 themselves as a result of ingesting Paxil before February 11:09:53 11 13th of 1998? 11:09:54 12 A. Yes, Mr. Vickery. We know for sure that there 11:09:56 13 were several hundred people who are logged with the FDA 11:10:01 14 who committed suicide or murder/suicide. On the SSRIs as 11:10:05 15 a group the figure is well over 3,000 people on Prozac, 11:10:10 16 Zoloft and Paxil. 11:10:14 17 Q. Now, are all the incidences of people who have 11:10:19 18 committed murder or suicide on these drugs actually found 11:10:22 19 in the FDA database? Does their system, it in other 11:10:25 20 words, pick up all of the instances? 11:10:29 21 A. No, Mr. Vickery. If you go into the FDA's 11:10:31 22 website, they themselves say that for serious problems 11:10:35 23 at -- 11:10:41 24 MR. PREUSS: Your Honor, I object. This 11:10:42 25 is clearly beyond the Rule 26 designation. 11:10:43 28 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 MR. VICKERY: I don't believe it is, Your 11:10:47 3 Honor. 11:10:48 4 THE COURT: Well, you will have to show 11:10:49 5 me. 11:10:51 6 MR. VICKERY: Let me defer and do that. 11:10:53 7 We will keep going. 11:10:54 8 THE COURT: All right. 11:10:57 9 Q. (BY MR. VICKERY) Second opinion: Do you 11:10:58 10 believe that SmithKline Beecham has conducted appropriate 11:11:05 11 tests and other forms of investigation with respect to the 11:11:12 12 question of whether and to what extent Paxil causes some 11:11:15 13 people to become homicidal or suicidal? 11:11:20 14 A. No, I think I'm very clear in my own mind that I 11:11:25 15 haven't and I think you will see from Dr. Blumhardt's 11:11:28 16 video deposition earlier on in the morning that there has 11:11:32 17 not been a single prospective clinical trial that's been 11:11:35 18 designed by SmithKline Beecham to look at the issue of 11:11:38 19 whether people become suicidal on this drug or not. 11:11:40 20 Q. Third: Do you believe that SmithKline Beecham 11:12:02 21 has given the warnings to the medical profession or others 11:12:04 22 as appropriate considering the risk of homicide, suicide? 11:12:09 23 A. No, I'm very clear in my mind that they haven't. 11:12:15 24 Again, you heard Mr. Preuss interviewing Christine 11:12:20 25 Blumhardt earlier on during the morning and he himself 11:12:23 29 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 refers to the fact that the suicide on the warning refers 11:12:27 3 to -- 11:12:29 4 MR. PREUSS: Objection, that was not my 11:12:30 5 voice on the video. 11:12:32 6 THE WITNESS: Then I'm very sorry, 11:12:34 7 Mr. Preuss. 11:12:36 8 Q. (BY MR. VICKERY) There was another lawyer 11:12:38 9 questioning Dr. Blumhardt. 11:12:39 10 A. Right. It is very clear that the warnings that 11:12:42 11 are on the label refer to suicide being caused by people 11:12:45 12 being depressed. There are no warnings there about what 11:12:51 13 this drug can cause. 11:12:53 14 Q. Finally, with respect to specific causation, did 11:13:06 15 Paxil cause Don Schell to murder or shoot -- murder has a 11:13:11 16 different connotation -- to shoot his wife, his daughter, 11:13:21 17 his granddaughter and then himself? 11:13:23 18 A. Yes, I believe that it did, Mr. Vickery. I 11:13:26 19 believe that if Mr. Schell didn't have the Paxil that he 11:13:29 20 had been given that he would be alive today and so would 11:13:33 21 his family. 11:13:37 22 Q. Now let's kind of take these one at a time, and 11:14:01 23 I want to actually start with the second one about their 11:14:04 24 failure to test. 11:14:06 25 First question: Why test? I guess you could 11:14:11 30 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 say the same thing about a warning. What was there at any 11:14:13 3 point in time that would cause them to want to test or 11:14:22 4 need to test? 11:14:24 5 A. Well, as I would have understood that issue 11:14:26 6 until fairly recently, it would have been very much on the 11:14:29 7 lines, as I think was indicated in the video yesterday, the 11:14:35 8 article produced by Martin Teicher and Jonathan Cole on 11:14:42 9 Prozac in 1990 was an article by two extremely senior 11:14:49 10 figures in the field. Jonathan Cole is probably the most 11:14:53 11 senior figure in the field. 11:14:57 12 And when people like this describe patients 11:14:58 13 becoming suicidal on Prozac, when they describe it in a 11:15:03 14 way that all but proves there and then that the Prozac has 11:15:08 15 caused these patients to become suicidal, when they're not 11:15:13 16 describing the usual kind of suicidality that happens in 11:15:17 17 the case of people who are depressed, when they're 11:15:22 18 describing a suicidality, when people working in the field 11:15:26 19 for years say, "Look, we've seen people depressed become 11:15:30 20 suicidal, but we've never seen anything like this," when 11:15:34 21 they describe patients who were suicidal before and they 11:15:38 22 say, "Doctor, I've been suicidal before but this is 11:15:43 23 ridiculous," then the field is generally put on notice 11:15:46 24 that there may be a problem with Prozac and other groups 11:15:49 25 of drugs -- all of the other drugs in this group of drugs. 11:15:51 31 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 I think it was clear from the video yesterday 11:15:59 3 that SmithKline, they took seriously in the first instance 11:16:01 4 this report by Martin Teicher and Jonathan Cole, as did 11:16:06 5 the rest of the field. 11:16:13 6 Now, over the course of the following year or 11:16:14 7 two, a range of other senior people came out and endorsed 11:16:15 8 what Cole and Teicher had found, so by the end of 1991, 11:16:19 9 before Paxil ends up on the market here you have a large 11:16:29 10 body of senior clinical people here in the US saying there 11:16:29 11 is a problem with this group of drugs. 11:16:33 12 Q. Tick them off for us, either by name or 11:16:36 13 institution that they come from. How many other people, 11:16:38 14 prestigious senior people from prestigious institutions in 11:16:42 15 the United States were writing about this problem in that 11:16:46 16 time frame from February of '90 when the Teicher and Cole 11:16:49 17 article came out until, say, November of '91 when your own 11:16:53 18 article was published? 11:16:56 19 A. Let's keep mainly to the US and let's not make 11:16:57 20 it too long a list. But we have people like Theodore Van 11:17:00 21 Putten who worked in the university of California. Van 11:17:07 22 Putten was recognized as a leading world expert on 11:17:13 23 akathisia, and in the series of people that he reported 11:17:17 24 on, he says Prozac is causing these people to become 11:17:21 25 suicidal and causing them to become suicidal because it 11:17:25 32 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 causes akathisia. 11:17:29 3 There was Tony Rothschild and Carol Lock, of 11:17:31 4 whom the senior author on this article was Carol Lock, 11:17:35 5 from Harvard again. And they did a challenge-rechallenge 11:17:39 6 study with Prozac. They had a number of people who had 11:17:44 7 become suicidal on Prozac. The problem cleared up when 11:17:47 8 the drug was halted. 11:17:51 9 They felt happy to do a thing that this court 11:17:53 10 would find fairly risky, I guess, which was to give these 11:17:58 11 people Prozac again. They felt happy to do it because in 11:18:04 12 all three instances the people had done things like jump 11:18:07 13 off buildings and ended up in wheelchairs with broken legs, 11:18:11 14 arms and ribs and couldn't move. So they felt safe giving 11:18:16 15 them the Prozac again to see did the same thing happen. 11:18:19 16 And yes, it did, in all three instances. 11:18:22 17 They found something else which was extremely 11:18:25 18 intriguing. They had a theory about what was actually 11:18:27 19 happening, which was that Prozac was flushing 5HT 11:18:31 20 serotonin onto the serotonin 1 receptor. They argued, if 11:18:35 21 we can block this, that maybe the problem would be eased 11:18:39 22 and in two of the three they were able to ease the problem 11:18:45 23 by using Inderal which is a drug that Dr. Suhany was 11:18:48 24 giving Mr. Schell when he had him on Prozac. 11:18:53 25 Q. Is that like an antidote? 11:18:57 33 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 A. It is not a proper antidote as such in that it 11:18:59 3 minimized the problem rather than cleared it up. 11:19:02 4 Q. I see. 11:19:07 5 A. Now, among the others who looked at this were 11:19:08 6 people like Mark Riddle who I believe at the moment is 11:19:10 7 with Johns Hopkins, was probably then with Yale, and this 11:19:14 8 was a group who -- well, Mark Riddle and others who have become 11:19:17 9 some of the senior figures for child psychopharmacology 11:19:22 10 here in the US. 11:19:27 11 They looked at a group of children who had 11:19:29 12 obsessive-compulsive disorder and this is a particularly 11:19:31 13 interesting series of reports because the Lilly defense, as 11:19:34 14 the SmithKline Beecham defense here has been it is the 11:19:37 15 depression not the drug, Riddle and his group looked at a 11:19:41 16 group of children with obsessive compulsive disorder who 11:19:44 17 were not depressed and this group of people, again, also 11:19:47 18 became suicidal. 11:19:52 19 That brings me to a further point which is that 11:19:54 20 Martin Teicher and Jonathan Cole reported on six different 11:19:56 21 people who became acutely suicidal on this drug. They 11:20:00 22 didn't report on all of the patients they had. They 11:20:03 23 didn't in particular report on a 15 year old boy being 11:20:06 24 treated for OCD who became suicidal and killed himself. 11:20:11 25 Q. Not one of their patients? 11:20:16 34 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 A. One of their patients but not one they 11:20:17 3 described. 11:20:19 4 Q. And being treated with? 11:20:20 5 A. Prozac. 11:20:21 6 Q. You have mentioned Riddle was from Yale, Teicher 11:20:22 7 and Cole were from Harvard, right? 11:20:25 8 A. Yes. 11:20:27 9 Q. Is Rothschild from Harvard? 11:20:28 10 A. Yes -- well, then he was but as I say, the 11:20:30 11 senior person there was Dr. Carol Lock and she's still 11:20:33 12 there. 11:20:41 13 Q. How about Van Putten, where was he from? 11:20:42 14 A. Van Putten was, as I said, I think UCLA I could 11:20:44 15 have the wrong part of the university but it was one of 11:20:48 16 the bits of the university of California. 11:20:51 17 Q. I think we get the point, but were there any 11:20:54 18 other major figures in that time period in the United 11:20:56 19 States that were writing about the similar problems? 11:21:00 20 A. Yes. There were people like John Mann writing 11:21:03 21 about the problem and saying, well, he hadn't seen it. It 11:21:06 22 seemed quite conceivable that this could be happening. 11:21:10 23 Q. Speaking of John Mann. Did you read Dr. Mann's 11:21:14 24 article, the Mann and Kapur article that came out in 11:21:18 25 September of 1991? Have you read it? 11:21:20 35 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 A. Yes, I did. 11:21:29 3 Q. Have you seen in that article and again in the 11:21:29 4 ACNP paper where he actually recommended four specific 11:21:29 5 ways to test for this? 11:21:31 6 A. Yes, I did, Mr. Vickery. Yes, I have seen them. 11:21:31 7 Yes. 11:21:35 8 Q. And has SmithKline Beecham ever done any one of 11:21:35 9 the four types of tests or studies that Dr. Mann himself 11:21:38 10 recommended? 11:21:43 11 A. No, they haven't. 11:21:43 12 Q. We have talked about why they should test. 11:21:59 13 Let's talk about how you would test. 11:21:59 14 What kind of a scientific study would be 11:21:59 15 appropriate to nail down a cause and effect relationship 11:21:59 16 between a psycho active drug like paroxetine or Paxil and 11:22:03 17 violent or suicidal behavior? 11:22:07 18 A. Well, let me begin by bringing out a how you 11:22:09 19 would test thing but that goes back to a why you would 11:22:15 20 test issue that you've asked me before. 11:22:18 21 As I said, as of 1990 SmithKline Beecham and all 11:22:20 22 of the rest of us were aware because of the article by 11:22:25 23 Teicher and Cole that there was an issue here. But in 11:22:29 24 actual fact, all of the companies that produce SSRIs had 11:22:33 25 during the 1980s done studies in healthy volunteers to see 11:22:37 36 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 what these drugs, the SSRIs do. 11:22:43 3 Now, I was completely unaware of what SmithKline 11:22:46 4 Beecham had done during this period of time until 11:22:48 5 recently, as I was unaware of what Phizer had done and all 11:22:51 6 of the other companies in the field. 11:22:55 7 One of the very good ways to actually test this 11:23:00 8 would be to do a study in healthy volunteers who aren't 11:23:02 9 depressed. 11:23:06 10 There is a problem, clearly, trying to look at a 11:23:07 11 group of people who are depressed who may also be 11:23:10 12 suicidal, trying to work out does the drug cause you to 11:23:12 13 become suicidal. Though I have to note here that it seems 11:23:15 14 that SmithKline Beecham, Eli Lilly and Phizer have no 11:23:19 15 problems saying that depression causes you to have 11:23:23 16 insomnia and our drug causes you to have insomnia. 11:23:24 17 Q. Yeah, we heard Dr. Blumhardt say that. 11:23:28 18 A. Depression causes sexual dysfunction and our 11:23:31 19 drug causes sexual dysfunction; depression causes loss of 11:23:34 20 appetite and our drug causes loss of appetite. They can 11:23:36 21 pick out what's been caused by the drug and what's been 11:23:39 22 caused by the illness. When it comes to people being 11:23:42 23 suicidal, it can't be caused by the drug, only the 11:23:46 24 illness. 11:23:48 25 One way to get around the illness is to go to a 11:23:49 37 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 group of healthy volunteers, which we did. And I've 11:23:52 3 discovered since that all of the companies have done an 11:23:55 4 extensive body of healthy volunteer work in this area and 11:23:58 5 I believe SmithKline Beecham had the grounds long before 11:24:01 6 1990 to think that their drug may be causing this problem. 11:24:03 7 Q. Let's pursue that just a minute. Have you as 11:24:08 8 part -- through your role as a witness in this case been 11:24:12 9 given access to their records of their studies on healthy 11:24:22 10 volunteers that otherwise is not in the public domain? 11:24:25 11 A. Yes, I have. 11:24:29 12 Q. Where did you see those records? 11:24:30 13 A. I went to Harlow where I was actually presented 11:24:31 14 with a vast amount of material. I've been told it is 11:24:35 15 something like 250,000 pages of material or something like 11:24:41 16 that. 11:24:43 17 Q. Is Harlow -- 11:24:44 18 A. In England. 11:24:45 19 Q. Let me ask you specifics. Is Harlow in England? 11:24:46 20 A. It is, yes. 11:24:49 21 Q. And how long were you given to look at this 11:24:49 22 material? 11:24:51 23 A. I think -- 11:24:52 24 MR. PREUSS: Objection, Your Honor, 11:24:53 25 leading and argumentative. 11:24:54 38 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 THE COURT: It is a little leading. 11:24:56 3 Go ahead. 11:24:57 4 MR. VICKERY: Let me rephrase it. 11:24:59 5 Q. (BY MR. VICKERY) Would you tell us how long you 11:25:00 6 were allowed to review these records? 11:25:02 7 MR. PREUSS: Objection, same objection, 11:25:04 8 Your Honor. 11:25:06 9 THE COURT: It is getting a little 11:25:10 10 technical. Overruled. Let the witness testify. 11:25:11 11 A. Right. Well, as I understand it, I had to put 11:25:15 12 in a report on my views in this particular case on 11:25:18 13 whatever date it was, March 15th. You actually let me 11:25:24 14 know what the date was. 11:25:27 15 And having actually asked you and I assume you 11:25:29 16 asked them could I have access to the records for some 11:25:33 17 months beforehand, I finally got the opportunity a week 11:25:35 18 before my final report had to be in. 11:25:38 19 I was told that I could have three days. My 11:25:41 20 problem is I also work clinically and I cannot just leave 11:25:43 21 the patients that I've got. I could only take two of 11:25:47 22 those three days because Harlow is close to 200 miles away 11:25:49 23 from where I live and work. So it was a major effort to 11:25:53 24 get there for even those two days. 11:25:57 25 But I put in a full two days working on them. 11:25:59 39 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 In the course of this afternoon I expect you will see -- 11:26:02 3 the court will be able to see some of the issues. For 11:26:08 4 instance, there's a Montgomery study which is not one of 11:26:11 5 the healthy volunteer studies but it is a reasonably small 11:26:15 6 piece of work that SmithKline Beecham had done and you 11:26:18 7 will see out of that particular study a heap of papers 11:26:26 8 this large. 11:26:26 9 MR. PREUSS: Objection, Your Honor, not in 11:26:26 10 the Rule 26, the Montgomery study. 11:26:26 11 THE COURT: Sustained. 11:26:29 12 MR. VICKERY: Let me move on to something 11:26:30 13 else. 11:26:31 14 THE COURT: The jury is directed to 11:26:31 15 disregard the testimony. 11:26:32 16 A. Let me rephrase. 11:26:34 17 Q. (BY MR. VICKERY) Let me ask you a question and 11:26:36 18 we'll get back on track here. 11:26:37 19 Of the material that you reviewed, can you tell 11:26:39 20 us approximately how many different study protocols on 11:26:42 21 healthy people that they had done that you were allowed to 11:26:46 22 review? 11:26:49 23 A. Well, I reviewed approximately 34 different 11:26:50 24 studies. I reviewed -- well, I tried to review all of the 11:26:54 25 studies that had been done by SmithKline Beecham with 11:26:59 40 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 healthy volunteers before the drug had actually been 11:27:02 3 licensed here in the US. 11:27:04 4 When I went there I was told that all of the 11:27:08 5 actual material would be there, but there were at least 11:27:10 6 four healthy volunteer trials from that period that 11:27:12 7 weren't there that I've since asked for and have not been 11:27:15 8 supplied to me. 11:27:19 9 Some of them indicate from the items I have 11:27:21 10 seen severe problems with volunteers dropping out after a 11:27:24 11 single dose of Paxil. 11:27:29 12 Q. Okay. Is there anything about the material that 11:27:32 13 you did review where they studied this drug on healthy 11:27:35 14 people that helps us answer the question of why should 11:27:39 15 they have done further testing? 11:27:42 16 A. Yes, there is. It became very clear that the 11:27:44 17 problem with the SSRI group of drugs is that they cause 11:27:49 18 some people to become agitated. They put you into a state 11:27:53 19 of mental turmoil. 11:27:57 20 It is very clear from the healthy volunteer work 11:28:00 21 that SmithKline Beecham did with Paxil during the 1980s 11:28:02 22 that a significant proportion of the healthy volunteers 11:28:05 23 who went on this drug in a placebo controlled way or not 11:28:08 24 placebo controlled way became agitated, at least 1 in 4, a 11:28:13 25 significant proportion, 1 in 6 and in some instances well 11:28:21 41 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 over half of the volunteer that is go on Paxil drop out 11:28:25 3 because they couldn't tolerate the side effects and often 11:28:28 4 after only a single dose. 11:28:31 5 So, what we clearly have in the 1980s is a 11:28:32 6 record here that SmithKline Beecham were fully aware of 11:28:36 7 long before the Teicher and Cole article comes out that 11:28:39 8 this drug can agitate a significant number of people. 11:28:42 9 A significant number of people who wouldn't have 11:28:45 10 been inclined to complain, because SmithKline Beecham did 11:28:48 11 their studies on their own employees, by and large. 11:28:51 12 Q. I see. Okay. Now, let's move to how do you 11:28:55 13 test, from why test to how do you test. 11:28:59 14 What is the appropriate way, if you're going to 11:29:03 15 conduct a test, to design and conduct that test in an 11:29:06 16 ethical and proper way you could find out whether and to 11:29:12 17 what extent and to whom this drug poses such problems? 11:29:15 18 A. Well, one of the ways to do it is the healthy 11:29:21 19 volunteer way. 11:29:23 20 The second way which was worked on extensively 11:29:24 21 for over a year by Lilly and the FDA is to do what is 11:29:28 22 called a challenge/rechallenge protocol. 11:29:32 23 What you do, you take people who become 11:29:35 24 suicidal, for instance, on Prozac in the case of Lilly and 11:29:37 25 you re-randomize them then to either get Prozac again for 11:29:41 42 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 a second time or to get another drug that has no actions 11:29:46 3 on the serotonin system at all. 11:29:50 4 This would be what you refer to up here as a 11:29:53 5 rich population, not wealthy but these are the kind of 11:29:56 6 people who are the vulnerable group of people that you 11:29:59 7 really want to look at. 11:30:02 8 Lilly drew up the protocol for this, spent over 11:30:04 9 a year working on it. They lined up all the 11:30:07 10 investigators. They had the pills waiting in the blister 11:30:09 11 packs, had everything ready to run, designed a new scale 11:30:13 12 for the emergence of suicidal agitation that was vastly 11:30:17 13 superior to the Beck scale you heard mentioned in the 11:30:21 14 video. And everything was ready to run and Dr. Wheadon 11:30:25 15 whom you've also mentioned was involved in trying to 11:30:29 16 actually design this piece of work, but it has never been 11:30:31 17 conducted. 11:30:35 18 This is the kind of study Dr. Mann recommends 11:30:35 19 should be conducted, hasn't been conducted by any of the 11:30:39 20 companies. 11:30:42 21 Q. Now, let's talk about rechallenge. Is there a 11:30:44 22 lot of published scientific literature about challenge, 11:30:47 23 dechallenge and rechallenge as a means to prove cause and 11:30:52 24 effect from a drug? 11:30:55 25 A. Yes. Challenge, dechallenge and rechallenge of 11:30:58 43 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 dose-response curves, are the only way to prove cause and 11:31:01 3 effect. Randomized control trials won't do it for you. 11:31:08 4 Q. They won't? 11:31:12 5 A. No, they won't. 11:31:13 6 Q. What do they prove? 11:31:14 7 A. Let me give you an example, okay, and this will 11:31:15 8 help the court. 11:31:23 9 Let's say we take alcohol and everyone in this 11:31:23 10 court will know that we know that alcohol makes you drunk 11:31:23 11 because you take the drug and within, you know, half an 11:31:27 12 hour to an hour Mr. Preuss would have said from his 11:31:31 13 opening remarks this couldn't happen so quickly, you know, 11:31:34 14 on just a small bit of alcohol, maybe two gins or 11:31:37 15 whatever, but within a half an hour you know that this 11:31:40 16 drug is having an effect on you. 11:31:43 17 While the drug wears off, you realize the effect 11:31:45 18 wears off also. You then take your next drink, maybe the 11:31:48 19 next day, and you get the same effect. And everyone in 11:31:53 20 this court knows that alcohol does what it does because of 11:31:56 21 that. But -- 11:31:59 22 Q. Let me stop you and follow up on that a minute. 11:32:01 23 Let's say the first day I took my alcohol with 11:32:04 24 gin and I had too much and I became inebriated so I have a 11:32:07 25 pretty strong feeling that the alcohol in the gin caused 11:32:13 44 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 that, right? 11:32:15 3 What if the next day when I was rechallenging 11:32:18 4 myself I used vodka? Is that any different in terms of 11:32:21 5 proving the cause and effect? 11:32:26 6 A. Oh, absolutely. That makes it really much 11:32:27 7 clearer that it is nothing to do with juniper or whatever 11:32:29 8 is in gin and nothing to do with wheat or whatever is in 11:32:33 9 vodka, it is to do with the alcohol. This is actually the 11:32:38 10 common element in the whole thing. 11:32:41 11 Q. We have a challenge and dechallenge and you were 11:33:32 12 about to explain the rechallenge process? 11:33:32 13 A. Yes. If you say take gin one day and vodka the 11:33:32 14 next and you find it produces the same effect within hours 11:33:32 15 of having had it, you know that alcohol is actually 11:33:32 16 causing this problem. 11:33:32 17 Now, if you take one gin and you get a bit of a 11:33:32 18 problem, you take two gins and you get even more of a 11:33:32 19 problem, then this really confirms for you good and proper 11:33:32 20 it is the alcohol. 11:33:32 21 These are the ways pharmacologically, the 11:33:32 22 appropriate ways and the people who do randomized clinical 11:33:32 23 trials and epidemiologists and all, the FDA, everybody 11:33:32 24 will say to you, this is the appropriate way to prove 11:33:32 25 cause and effect. 11:33:32 45 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Now, there's a further angle on this. This 11:33:32 3 let's take a randomized control trial. Let's say we take 11:33:37 4 all of the lawyers here, right, and we give them an 11:33:38 5 alcohol that you don't taste as alcohol. We give them, 11:33:43 6 say, two beers, one with alcohol in it and the other that 11:33:46 7 hasn't got alcohol in it. So one is an alcohol beer and 11:33:51 8 the other is a placebo beer. 11:33:54 9 We take all of you group of lawyers. This would 11:33:57 10 be a randomized control trial where we have some of you on 11:34:03 11 alcohol, some of you not on alcohol, but you don't know 11:34:06 12 which of you are on alcohol and the jury isn't clear which 11:34:09 13 of you is on alcohol. 11:34:12 14 Everybody also probably knows when we break the 11:34:14 15 code that some of you lawyers who are highly suggestive 11:34:17 16 people who will have been on the placebo beer will have 11:34:20 17 been looking drunk to the jury because you will have been 11:34:24 18 picking up the mood of the group but we will know the 11:34:28 19 placebo has not been causing you to be drunk. 11:34:31 20 Randomized control trials can tell you something 11:34:34 21 about the frequency with which certain things happen, but 11:34:36 22 as regards proving cause and effect, for the thing the 11:34:39 23 jury, the court, all of us know alcohol actually causes, 11:34:45 24 randomized control trials can get in the way of you 11:34:48 25 actually being able to see it is actually the alcohol 11:34:52 46 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 doing this. 11:34:55 3 Q. I think I follow that. 11:34:56 4 Now, you've mentioned already the Rothschild and 11:34:58 5 lock article where they did rechallenge people with 11:35:02 6 Prozac. Is there any other evidence in the scientific 11:35:05 7 literature where the writers have relied on either 11:35:09 8 dechallenge or rechallenge as a means to say, "Hey, 11:35:13 9 there's a problem here"? 11:35:18 10 A. I'm not quite clear. 11:35:21 11 Q. Do any of the other articles -- 11:35:23 12 A. Yes, with -- 11:35:26 13 Q. -- contain those components? 11:35:28 14 A. Yes, with the Teicher Cole article, with the Van 11:35:30 15 Putton article and others, while they didn't go out 11:35:37 16 systematically to give Prozac to people and see does the 11:35:40 17 problem clear up once you withdraw the drug and reexpose 11:35:43 18 people to the drug, what they do actually report is that 11:35:46 19 the problem comes about with the drug, it can get worse if 11:35:49 20 you go up to a higher dose, which is the dose response 11:35:52 21 curve that I've actually outlined to you. It can clear up 11:35:55 22 when you halt the drug, and what they weren't aware at 11:35:59 23 this stage was whether it was actually being caused by the 11:36:02 24 drug or not. 11:36:04 25 And they've in some cases reexposed people by 11:36:05 47 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 accident to Prozac and the problem comes back. That 11:36:16 3 includes most all of the articles, including the one we 11:36:16 4 did. 11:36:18 5 We were involved in Wales in 1990, I was 11:36:19 6 involved before the issue of Prozac had hit the headlines 11:36:21 7 at all, and I was involved with two different people who 11:36:24 8 had become suicidal, one who had become suicidal on Luvox 11:36:27 9 and the other on Prozac. 11:36:34 10 I hadn't read the Teicher article. We reexposed 11:36:36 11 them to another drug acting on the serotonin system and 11:36:39 12 both people became suicidal again. 11:36:42 13 Q. In addition to doing the kind of study design 11:36:52 14 that Dr. Beasley and Dr. Wheadon worked on, the 11:36:54 15 rechallenge design, are there other ways SmithKline could 11:36:58 16 if they chose have investigated or studied this issue? 11:37:02 17 A. Yes, there were a number of other ways. 11:37:06 18 You could have done randomized control trials 11:37:09 19 with rating scales sensitive to the problem, and actually 11:37:12 20 very early on when the Prozac problem blew up, working 11:37:16 21 with SmithKline Beecham on the issue -- on the old age 11:37:21 22 trial that I actually referred to you earlier, the one 11:37:23 23 that was sealed and never saw the light of day, I 11:37:26 24 recommended to SmithKline Beecham that they should do a 11:37:29 25 study looking at whether their drug caused more or less, I 11:37:33 48 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 assume it would be less, agitation and akathisia than 11:37:38 3 Prozac. 11:37:41 4 Q. Why did you make that recommendation? Did you 11:37:42 5 think it would help their company in some way to conduct 11:37:44 6 such a study? 11:37:46 7 A. Well, it seemed very clear to me if they were to 11:37:48 8 do that kind of trial, those of us who want to prescribe 11:37:50 9 SSRIs who know about the hazards with the drug like Prozac 11:37:54 10 would have instantly switched if it turned out that Paxil 11:37:58 11 didn't cause the problem that Prozac did cause. We would 11:38:02 12 have instantly switched and I'm sure the whole field would 11:38:05 13 have. Everybody who was on Prozac, off Prozac and on to 11:38:08 14 Paxil. SmithKline Beecham would have made an awful lot 11:38:12 15 more money than they would have made. The patients would 11:38:14 16 have been an awful lot safer. It was, if they had 11:38:17 17 confidence in their drug causing less problems than 11:38:20 18 Prozac, this was the obvious study to do. 11:38:24 19 Q. Okay. You mentioned something I think we need 11:38:28 20 to follow up on now. I know there was a discussion with 11:38:29 21 Dr. Blumhardt on the deposition about it. And it is 11:38:32 22 rating scales. Can you just explain generally what a 11:38:35 23 rating scale is? 11:38:39 24 A. Yes. Well, when I give a drug, say, to anyone 11:38:41 25 here in the court in the course of a clinical trial, 11:38:52 49 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 there's a few different ways we can rate things. We can 11:38:54 3 rate them from my point of view, and I can look to see 11:39:03 4 have things changed in the patient that I, the physician, 11:39:06 5 want to see changed. They may not be things that the 11:39:10 6 patient actually wants to see changed. 11:39:14 7 The rating scale that's most commonly used from 11:39:16 8 this point of view is the one called a hamilton rating 11:39:18 9 scale of depression. One of the others in the field is a 11:39:24 10 rating scale called the Montgomery Asburg rating scale for 11:39:27 11 depression -- 11:39:31 12 MR. PREUSS: Your Honor, I object. This 11:39:31 13 is again beyond the Rule 26 as comparative analysis of the 11:39:33 14 various rating scales. 11:39:36 15 THE WITNESS: I'm not going to compare the 11:39:38 16 various rating scales. 11:39:39 17 MR. VICKERY: I didn't intend to compare 11:39:41 18 the various rating scales. 11:39:42 19 THE WITNESS: No, I'm trying to outline 11:39:44 20 for the court what ways you can rate. It doesn't compare. 11:39:46 21 Q. (BY MR. VICKERY) The Hamilton scale, I think we 11:39:50 22 heard, has four items. Let me just show it on the screen, 11:39:53 23 if I may. I have written down -- does the Hamilton scale 11:39:56 24 at 3 on the scale ask about suicide? 11:41:02 25 A. I should probably explain something else about 11:41:02 50 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 the Hamilton scale. It is a rating scale like a physician 11:41:02 3 like me would use to rate the things I want to see changed 11:41:02 4 in the patient as opposed to the things the patient wants 11:41:02 5 to see changed. It was actually made by Geigy 11:41:02 6 Pharmaceuticals rather than Max Hamilton. It is a 11:41:02 7 pharmaceutical produced scale probably. 11:41:02 8 Q. And does the physician or the patient make the 11:41:02 9 rating on whether they're suicidal or not? 11:41:02 10 A. It is the physician. It is me who actually 11:41:02 11 decides. 11:41:02 12 Q. And do they, as I've written down here, have a 11:41:02 13 choice anywhere from zero to 4? 11:41:02 14 A. Do I or they? 11:41:02 15 Q. You, the physician. 11:41:02 16 A. Only me who has a choice. This is a very 11:41:02 17 insensitive way to rate whether patients may be suicidal 11:41:02 18 or not. Who says so? Well, Eli Lilly says so, everybody 11:41:02 19 in the field says so, Stuart Montgomery says so, who has 11:41:02 20 been a consultant for SmithKline Beecham, everyone 11:41:02 21 says so. 11:41:08 22 Q. We've talking about why they should test. We've 11:41:08 23 talked about how you would test. 11:41:11 24 Has SmithKline Beecham done any prospective 11:41:12 25 study of the question of whether and to what extent Paxil 11:41:17 51 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 causes people to become homicidal or suicidal? 11:41:23 3 A. They haven't even gone near doing such a study. 11:41:26 4 There's been no study designed for this purpose. Not only 11:41:30 5 that, the retrospective studies that they've done -- the 11:41:33 6 ones that they've done since the problem cleared up, the 11:41:37 7 usual conventional clinical trials have been done which 11:41:40 8 Dr. Blumhardt said they looked very closely at efficacy, 11:41:43 9 whether the drug works, and safety, the rating scales they 11:41:48 10 use for checking safety, whether the drugs cause side 11:41:52 11 effects are woefully inadequate. They're recognized 11:41:54 12 generally at picking up at the most 1 in 10 of the side 11:41:58 13 effects that are actually happening to people. 11:42:02 14 So these trials, the retrospective ones, any of 11:42:04 15 them, they haven't done a single prospective study 11:42:10 16 designed to evaluate the safety of this drug, ever, from 11:42:13 17 the point of view of any side effect. 11:42:16 18 Q. Dr. Healy, you heard Dr. Blumhardt when I asked 11:42:19 19 her on the deposition say, "Well, yeah, but we haven't 11:42:22 20 done one but we funded a study by Dr. Verkes over there in 11:42:26 21 Holland." 11:42:31 22 Are you familiar with the Verkes study? 11:42:32 23 A. Yes, I am, Mr. Vickery. 11:42:34 24 Q. And I believe she said it was 91 patients that 11:42:35 25 were in the study for a year? 11:42:38 52 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 A. They weren't, Mr. Vickery. Most of them dropped 11:42:40 3 out during the course of the year so that by the end there 11:42:43 4 were only 19 people left. 11:42:45 5 This was not a study designed to look at whether 11:42:47 6 Paxil could make people suicidal or not. I don't want to 11:42:50 7 infer motives and I'm sure the lawyers for SmithKline 11:42:55 8 would get very worked up if I did. But if I wanted to 11:43:00 9 design a study to conceal the problem that Paxil may be 11:43:04 10 causing, I would put it into a group of patients who had 11:43:11 11 the recurrent brief depressive disorders that the Verkes 11:43:16 12 study looked at. 11:43:20 13 There were a number of other studies of this 11:43:23 14 that have been done -- at least one done by SmithKline 11:43:28 15 Beecham that I have referred to in my Rule 26 statement as 11:43:31 16 the Baldwin study. As a matter of fact, this is a 11:43:34 17 Montgomery study and is the one that Mr. Preuss mentioned 11:43:38 18 earlier. 11:43:41 19 Other studies have been done by Lilly in just 11:43:42 20 this group of patients, but the results haven't been 11:43:45 21 published. 11:43:50 22 Q. You mentioned Baldwin and Montgomery. Is 11:43:50 23 Dr. Stuart Montgomery is well-known psychopharmacologist 11:43:54 24 in the United Kingdom? 11:43:59 25 A. Dr. Stuart Montgomery is a very well-known 11:44:01 53 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 psychopharmacologist in the UK. At the time I was a 11:44:05 3 secretary for the British association for 11:44:07 4 psychopharmacology, Stuart Montgomery was the president 11:44:10 5 of the association. 11:44:13 6 Q. How about Dr. David Baldwin? Is he one of your 11:44:14 7 colleagues in the field of psychopharmacology in the 11:44:17 8 United Kingdom? 11:44:21 9 A. Yes, he is. We get on well. I've known David 11:44:23 10 Baldwin for ten or more years. At the time that he was 11:44:25 11 involved in the study that I keep calling the Baldwin 11:44:29 12 study but should be more appropriately called the 11:44:33 13 Montgomery study, he would have been very young, very 11:44:36 14 junior. He's much more senior now and better known than 11:44:41 15 he was then. 11:44:44 16 Q. Dr. Healy, is one of the things that your 11:44:45 17 opinion is based on in this case data from that study that 11:44:47 18 has never been published? 11:44:50 19 A. Yes, the data -- part of the study has been 11:44:52 20 published, but the data that I depend on that have 11:44:56 21 influenced me haven't been published. 11:45:00 22 Q. Are they data specifically relating to suicide? 11:45:03 23 A. They're data specifically related to people 11:45:07 24 being suicidal on Paxil. 11:45:09 25 Q. And how did you learn about that data if it has 11:45:11 54 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 never been published? 11:45:14 3 A. Well, about seven or eight years after the study 11:45:15 4 was conducted, much to my amazement, at a meeting in 11:45:18 5 London in September of 1999, Dr. Baldwin presented the 11:45:22 6 suicide data. I nearly fell out of my seat at the time, 11:45:26 7 but there you go. 11:45:31 8 Q. In other words, at a professional meeting he was 11:45:33 9 lecturing and presented that data? 11:45:34 10 A. He did, yes. 11:45:36 11 Q. And did you subsequently ask him to give you the 11:45:37 12 slides that contained the data that he presented? 11:45:39 13 A. Yes, I did. And you will see one of these 11:45:42 14 later. 11:45:44 15 Q. All right. And just generally, if you can put 11:45:45 16 it in a nutshell, what is the significance of that 11:45:48 17 unpublished data in terms of whether Paxil causes people 11:45:50 18 to become suicidal? 11:45:55 19 A. The significance is it is clear that this drug 11:45:57 20 does cause people to become suicidal. 11:46:08 21 It has a further significance in the light of 11:46:08 22 the Donovan study because it controls for one of the 11:46:08 23 factor that is SmithKline Beecham depend on to argue that 11:46:11 24 the Donovan study doesn't show what I think is shows, for 11:46:14 25 example, but of course there's a further significance to 11:46:19 55 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 all of this, Mr. Vickery, which I'm sure the court will 11:46:21 3 have grasped which is the fact of inconvenient data for 11:46:24 4 pharmaceutical companies being left unpublished and there 11:46:29 5 is a vast amount of inconvenient data that is unpublished. 11:46:32 6 Q. I want to move now -- we've been talking about 11:46:38 7 your opinion that SmithKline did not test reasonably. And 11:46:42 8 I want to move to the question of general causation that 11:46:56 9 this drug does cause homicide or suicide for some 11:46:56 10 patients. If all of these tests that have been 11:46:56 11 recommended have not been done, then what kind of 11:46:59 12 information can we rely upon to say in terms of reasonable 11:47:02 13 probability that there's a problem? 11:47:05 14 A. Well, what I think you'll find is that 11:47:07 15 patients -- I'm awfully sorry, Dr. Maltsberger -- I was 11:47:12 16 going to say that people like Dr. Maltsberger and I who 11:47:17 17 have used Paxil clinically have seen exactly the same 11:47:20 18 problems caused by it as we've seen caused by the other 11:47:24 19 SSRIs. 11:47:27 20 So there's a very good class basis actually, the 11:47:29 21 same thing you had gin and vodka, you get drunk from one 11:47:35 22 and the other, you assume it is the same thing. 11:47:40 23 We have seen similar problems on the SSRIs, all 11:47:43 24 of the SSRIs. The range of side effects from Paxil is the 11:47:46 25 same as the range of side effects from Prozac, it is the 11:47:50 56 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 same as the range of side effects from Zoloft and the 11:47:53 3 other SSRIs. 11:47:56 4 This group of drugs is broadly effective or 11:47:57 5 ineffective -- none of them, for instance, work for 11:48:00 6 hospital depression. If you look at the Physician's Desk 11:48:04 7 Reference for Paxil, it very clearly states as of 1998, 11:48:10 8 the year that Don Schell was put on this drug, that this 11:48:15 9 drug has not been shown to work for hospitalized 11:48:19 10 depression. None of the SSRIs have been shown to work for 11:48:23 11 hospitalized depression. The SSRIs have been shown to 11:48:26 12 work for obsessive-compulsive disorder, panic disorder, 11:48:28 13 social phobia, PTSD and a range of conditions like this. 11:48:29 14 We have a range of situations where if it has 11:48:34 15 feathers like a duck, quacks and things like that, you say 11:48:38 16 it is a duck. 11:48:42 17 Now, in terms of the evidence, we also have a 11:48:43 18 range of epidemiological evidence from Prozac. We have 11:48:46 19 epidemiological evidence from Paxil or as relates to 11:48:51 20 Paxil. We've also got the Montgomery study and we've also 11:48:59 21 got the healthy volunteer work on Paxil which is highly 11:49:03 22 relevant to just this issue. 11:49:06 23 Q. That's the stuff you saw in Harlow, England, 11:49:36 24 right? 11:49:36 25 A. Right is. 11:49:36 57 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Q. You have explained the significance of that. Is 11:49:36 3 there anything else of significance you gleaned from 11:49:36 4 reviewing that private healthy volunteer data that you 11:49:36 5 haven't shared with us that you need to? 11:49:36 6 A. Yes, absolutely. Well, I'm sure Mr. Vickery 11:49:36 7 there's more than one thing. 11:49:36 8 In terms of the arguments Mr. Preuss made 11:49:36 9 yesterday about Mr. Schell and the fact he didn't adhere 11:49:38 10 to treatment the way he should have done, one the extra 11:49:41 11 ordinarily interesting things about the healthy volunteer 11:49:44 12 data in Harlow was that they have a group of studies there 11:49:47 13 where totally healthy volunteers, people like members of 11:49:50 14 the court here, go on this drug for very brief periods of 11:49:54 15 time, a week or two at the most, and after only two weeks 11:49:57 16 on the drug SmithKline Beecham recognized that they're 11:50:02 17 having physical dependence on this drug so when the drug 11:50:06 18 is halted there are withdrawal syndromes. 11:50:13 19 MR. PREUSS: This is totally beyond Rule 11:50:16 20 26. 11:50:17 21 THE WITNESS: This is in my Rule 26. 11:50:18 22 THE COURT: Wait, wait, let your attorney 11:50:19 23 dot litigating here. 11:50:21 24 Your response. 11:50:24 25 MR. VICKERY: I think there is extensive 11:50:27 58 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 reference in his Rule 26 report to the healthy volunteer 11:50:29 3 study and its implications. 11:50:31 4 MR. PREUSS: Not as to dependence. 11:50:35 5 MR. VICKERY: Not as to dependency. I'm 11:50:37 6 sorry. Yes, he's right. 11:50:39 7 THE COURT: Sustained. 11:50:42 8 Q. (BY MR. VICKERY) Now, is there a series of 11:50:52 9 principles, and we don't have to get too scientific or 11:50:53 10 technical, but a series of principles that have been in 11:50:57 11 use for over a hundred years to help doctors and 11:51:00 12 scientists determine when something bad happens to someone 11:51:06 13 what caused it? 11:51:11 14 A. Yes, these are the ones that I've outlined 11:51:15 15 earlier on during the course of the last half hour or so, 11:51:18 16 but if the problem comes out fairly soon after you've had 11:51:22 17 the drug or fairly soon after you get the bacteria and you 11:51:26 18 catch the flu virus or whatever, if it comes on very soon 11:51:34 19 afterwards, within one or two doses, then all of us will 11:51:36 20 be inclined to think the drug has caused the problem. 11:51:40 21 This is just the opposite to what Mr. Preuss 11:51:44 22 said yesterday. Your common sense will say to you two 11:51:46 23 pills could not have caused this problem. Our common 11:51:49 24 sense, your common sense says to you every day of the week 11:51:53 25 if you have a pill and within a few hours of having had 11:51:56 59 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 this pill that things change, then you will be inclined to 11:51:58 3 think it was the pill that caused the problem. 11:52:04 4 Q. Let me stop and follow up with a question there. 11:52:07 5 Is there any kind of a physical, biological 11:52:09 6 effect on both men and women that these folks acknowledge 11:52:13 7 is caused by that pill within 30 minutes? 11:52:18 8 A. Yes, there is. It is very well-known that if 11:52:21 9 men have a premature ejaculation problem or women, either, 11:52:26 10 that you can take paroxetine and 30 minutes later a male 11:52:34 11 will be less likely to ejaculate and a woman will be less 11:52:39 12 likely to have an orgasm. Now, you don't have to be 11:52:45 13 on the drug for weeks before this will happen. You just 11:52:50 14 have to 30 minutes beforehand have the drug and this is 11:52:53 15 what you will find. 11:52:56 16 Now, this has led SmithKline Beecham to, of 11:52:57 17 course, consider the possibility of marketing their drug 11:53:00 18 for premature ejaculation and it is much more -- 11:53:03 19 MR. PREUSS: Objection, Your Honor, no 11:53:08 20 foundation in this whole line of questioning as to sexual 11:53:09 21 dysfunction. It is not under -- 11:53:12 22 THE COURT: I think it is confusing and we 11:53:15 23 are drifting far away from the subject matter. 11:53:17 24 Q. (BY MR. VICKERY) Let me move to some of the 11:53:20 25 other factors we've talked about, temporal relation being 11:53:21 60 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 one of them. If you take the drug, within an expectable 11:53:25 3 period of time after you have a bad result, do red flags 11:53:28 4 go up? 11:53:32 5 A. Yes, there's two ways this can happen. The drug 11:53:33 6 can do it fairly systematic within a half hour, a day, two 11:53:35 7 days. In the case of Don Schell, for instance, I wouldn't 11:53:38 8 be here today, Mr. Vickery, if there Schell had been on 11:53:43 9 this drug for weeks or months and then the problem had 11:53:46 10 happened. If you had actually come to me and said look, 11:53:49 11 could this drug have caused a problem. I would have said 11:53:53 12 no, it hasn't. I'm here today precisely because very 11:53:56 13 shortly after this man goes on the drug, the problem 11:53:59 14 happens. In the vast majority of the SSRI cases I've got 11:54:01 15 involved in I've given the view that the drug hasn't 11:54:05 16 caused the problem for reasons just like that, you don't 11:54:07 17 have the close temporal relationship between the drug and 11:54:09 18 the problem that all of us know means the drug is involved 11:54:13 19 in this particular problem. 11:54:17 20 Q. Now -- 11:54:18 21 A. But -- 11:54:19 22 Q. Is there another -- 11:54:20 23 A. There's another aspect to that I really want to 11:54:21 24 bring out. 11:54:24 25 Q. What is it? 11:54:25 61 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 A. There's the systematic -- this drug, Paxil, 11:54:26 3 SmithKline Beecham have found in the healthy volunteer 11:54:29 4 work on a single dose will make people agitate. 11:54:32 5 There's another possibility here which even if 11:54:35 6 that weren't there, even if the healthy volunteer work 11:54:37 7 weren't there, even if the randomized control trial work 11:54:40 8 weren't there for any of the SSRIs, that everybody in this 11:54:44 9 court knows will play a part in the adverse effects of the 11:54:46 10 drug, particularly ones that seem to come on fairly 11:54:54 11 shortly after you have the drug. 11:54:59 12 And this is what we refer to as an allergic 11:55:00 13 reaction to the drug, it is idiosyncratic, you can't 11:55:03 14 predict it but it happens. Loads of people in this 11:55:09 15 courtroom will have had allergic reactions to one drug or 11:55:12 16 another. 11:55:16 17 Q. There's some people who by their body chemistry 11:55:17 18 or constitution are just at greater risk for this kind of 11:55:19 19 reaction, is that what you're saying? 11:55:23 20 A. Yes, absolutely. Yes. 11:55:25 21 Q. Now, one of the other factors that you mentioned 11:55:26 22 that I think folks have used for a long time is dose 11:55:29 23 response relationships. 11:55:32 24 A. Yes. 11:55:35 25 Q. Can you just explain for us what is the 11:55:35 62 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 significance of dose-response relationships when you're 11:55:37 3 trying to determine cause and effect. 11:55:41 4 A. Well, when you try to determine cause and 11:55:44 5 effect, the -- it is the obvious thing that we all know: 11:55:46 6 You have one gin and you think, did that do something to 11:55:54 7 me or not. You have two gins and it is quite clear that 11:55:58 8 it did and you link the alcohol that you've just had to 11:56:02 9 what it has done. This is a dose-response relationship. 11:56:05 10 It is the strongest thing in pharmacology aside 11:56:10 11 from challenge, dechallenge, rechallenge. 11:56:15 12 The FDA will license the drug without any 11:56:19 13 randomized control trials at all if the company shows a 11:56:21 14 dose-response relationship. A little bit of the drug 11:56:30 15 causes this is and a bigger bit causes more of it. 11:56:30 16 In the case of the healthy volunteer work that 11:56:31 17 SmithKline have done, and particularly in the case of one 11:56:33 18 of the studies that I didn't get to see for whatever 11:56:36 19 reason, there seems to be a -- well, it is explained away 11:56:38 20 by the FDA that you've got a series of 21 volunteers, 11:56:42 21 healthy medical and dental students given paroxetine in 11:56:48 22 10, 20, 30, 40, 50, 60 milligram doses, just a single 11:56:54 23 dose. 11:56:58 24 12 of them have reactions after a single dose that 11:56:59 25 the investigator describes as severe. The FDA comment on 11:57:05 63 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 this is that there seems to be a dose relationship here, 11:57:10 3 the more of the drug you give, the more of the problems 11:57:13 4 we're having. 11:57:16 5 And the problems that they were having, the side 11:57:18 6 effects that were severe were side effects produced by the 11:57:20 7 drug acting on the brain. 11:57:26 8 Q. And were they side effects that could lead to 11:57:28 9 violent or suicidal behavior? 11:57:30 10 A. It is very hard to know after just one dose and 11:57:32 11 the amount of material I've been allowed to see, which is 11:57:35 12 really only half a page, really doesn't put me in a good 11:57:37 13 position but after one dose in a number of other trials 11:57:41 14 they've done they've produced agitation in volunteers and 11:57:44 15 this is exactly the kind of condition that will lead to 11:57:48 16 violent, suicidal and homicidal behavior. 11:57:52 17 Q. Is another one of these factors that you 11:57:55 18 consider as you're analyzing it whether it makes sense in 11:57:57 19 terms of biological means; in other words, whether there's 11:58:01 20 some biologically plausible way to explain what is 11:58:05 21 happening to this person? 11:58:08 22 A. Yes. The field generally is always more -- if 11:58:14 23 we do a clinical trial -- I guess the best example and it 11:58:19 24 is actually one that you brought out earlier, is when 11:58:26 25 there's a group of drug which we also use called the MAOIs 11:58:30 64 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 and one of the interesting things about the SSRI group of 11:58:34 3 drugs and the MAOI group of drugs is they do opposite 11:58:38 4 things to the serotonin system. 11:58:42 5 One of the interesting things about that is that 11:58:45 6 it seems to be the people who react very badly to the 11:58:46 7 SSRIs react better to MAOIs. There's a real problem when 11:58:50 8 you put the MAOIs and SSRIs together or when you put the 11:58:54 9 MAOIs with cheese. It is an interesting -- 11:58:59 10 Q. A cheese. 11:59:03 11 A. It is a beautiful story, back in the 1960s it 11:59:04 12 was very clear that people were dropping dead because they 11:59:07 13 had a MAOI drug and they ate cheese. The response from 11:59:10 14 psychiatrists like me, the field generally, was well it is 11:59:15 15 nothing to do with our wonderful drugs. We always blame 11:59:20 16 the patient in some way or other. 11:59:24 17 And even though the evidence was there of people 11:59:26 18 when they took the MAOIs and had had cheese their blood 11:59:29 19 pressure going up, and then when they took cheese again 11:59:32 20 later, the blood pressure going up, people didn't believe 11:59:36 21 it until someone worked out how the cheese was actually 11:59:38 22 doing it. 11:59:42 23 Now, this is what Christine Blumhardt outlined 11:59:43 24 here. You don't need RCTs when you know just what is 11:59:48 25 happening with the interaction of MAOIs and cheese or 11:59:52 65 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 MAOIs and SSRIs. If you have a good theory about what is 11:59:55 3 happening, good enough to let you intervene with an 12:00:00 4 antidote of some sort to block the problem, you don't need 12:00:03 5 to do RCTs because RCTs don't prove cause and effect at 12:00:07 6 all. 12:00:12 7 Scientific for this purpose they're useless, 12:00:12 8 but -- 12:00:15 9 Q. So do you have, then, a biologically plausible 12:00:16 10 explanation for why this class of drugs, SSRIs, would 12:00:19 11 precipitate akathisia, which in turn would lead to 12:00:24 12 violence and suicide? 12:00:27 13 A. Yes. Well let me -- we don't -- I can't nail 12:00:29 14 this one done for you absolutely conclusively, 12:00:34 15 Mr. Vickery, but I will do as good as I can. 12:00:37 16 The problem of akathisia on these drugs, drugs 12:00:40 17 acting on the serotonin system was outlined first as far 12:00:43 18 back as 1955. There has not been a single scientific 12:00:48 19 meeting on this issue since then. There's been no 12:00:51 20 pharmaceutical company that has done any work on this 12:00:56 21 issue since then. The amount of research that's been 12:00:59 22 funded by the pharmaceutical companies on this issue since 12:01:01 23 then is close to zero relatively speaking. 12:01:04 24 But what you've got in the case of the SSRIs -- 12:01:07 25 now, there will be a little bit of dispute -- well, there 12:01:11 66 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 is a bit of dispute between the experts at SmithKline and 12:01:14 3 myself on this issue. They want to define akathisia in a 12:01:17 4 very, very particular way which would implicate a system 12:01:26 5 called the dopamine system. I'm going to offer you and 12:01:26 6 the court a view of what akathisia is later on during the 12:01:29 7 course of the day, and what we're going to see is that you 12:01:33 8 don't need to have the dopamine system involved at all. 12:01:36 9 Drugs active on the serotonin system only with 12:01:41 10 no action on the dopamine system can cause this problem. 12:01:44 11 Why might they do it, well -- 12:01:48 12 MR. PREUSS: I'll object. He has 12:01:50 13 expressed no opinions on this on the Rule 26. I would ask 12:01:51 14 me proceed by question and answer rather than long 12:01:54 15 narratives here. 12:01:57 16 THE COURT: I concur. Sustained. 12:01:58 17 MR. VICKERY: It is about two minutes and 12:02:04 18 we're about to change gears, Your Honor. 12:02:05 19 THE WITNESS: Would you like to ask the 12:02:08 20 question again and I'll give a brief answer? 12:02:09 21 MR. VICKERY: No, let's move on to 12:02:12 22 something else here. 12:02:13 23 Q. (BY MR. VICKERY) Dr. Healy, is it difficult for 12:02:34 24 you to find yourself in the position, having done the work 12:02:36 25 you have done with SmithKline Beecham in the past -- to 12:02:39 67 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 find yourself in the position in an American court of law 12:02:42 3 in testifying basically against them for the failure that 12:02:46 4 we've outlined here? 12:02:48 5 A. No, Mr. Vickery, it is not. I'm a person who 12:03:03 6 has made a living out of doing psychopharmacology research 12:03:08 7 and using psychopharmacotherapeutic agents including SSRIs 12:03:12 8 to treat people. I am not a psychotherapist hostile to 12:03:19 9 drug treatment. I use the antidepressants to treat people 12:03:23 10 who are depressed. I use SSRI antidepressants to treat 12:03:27 11 people who are depressed. I believe in order to treat 12:03:31 12 people properly I need to be able to let them know about 12:03:34 13 the hazards of these drugs as well as the good points. 12:03:36 14 In order to know who is going to do well on 12:03:40 15 these drugs -- and I've got some people doing fabulously 12:03:42 16 on SSRIs and have been doing so for years, I wouldn't 12:03:47 17 begin to think about halting them. But in order to know 12:03:50 18 who is going to do well, you have to do the research which 12:03:53 19 at the same time is going to pick out who has the problem. 12:03:55 20 My concern with all of this is that this kind of 12:03:58 21 research isn't being done. I'm concerned to hold on to 12:04:01 22 the drugs we have, I think the only way the public is 12:04:05 23 going to let us hold onto these drugs is if we're honest 12:04:08 24 about the hazards. I want to be able to warn the patients 12:04:13 25 that I treat about what could go wrong and what steps they 12:04:16 68 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 can take to minimize the problems. 12:04:20 3 But I don't think that the SSRIs are a bad group 12:04:22 4 of drugs. As I've indicated earlier to you, in the vast 12:04:24 5 majority of legal cases where I've been asked to give a 12:04:27 6 view, I have said these drugs do not cause the problems 12:04:31 7 that the plaintiffs think they're causing. 12:04:33 8 Q. Now, let me stop you and follow up on something 12:04:35 9 else you mentioned a minute ago. You said it is important 12:04:39 10 to know in terms of determining cause and effect -- is 12:04:41 11 there something that can be given, if not an antidote, to 12:04:46 12 reduce the risk? Is there, in fact, documented in the 12:04:49 13 scientific literature about the SSRIs and these problems, 12:04:54 14 instances where drugs have been given that, to use my 12:04:58 15 phrase, take the edge off of the akathisia? 12:05:03 16 A. Yes, there's a few different things you can do, 12:05:06 17 Mr. Vickery, once you recognize there may be a problem. 12:05:08 18 Dr. David Dunner in for SmithKline has outlined 12:05:11 19 that one of the things to do for people whom you think may 12:05:15 20 be at risk, people who are anxious to begin with, is to 12:05:19 21 lower the dose. This was a thing that was said by the 12:05:22 22 representative for SmithKline Beecham on the stand here 12:05:24 23 yesterday. He said that for anxious people you want to 12:05:27 24 begin them off at a lower dose until their body adjusts to 12:05:30 25 the problem. 12:05:34 69 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 This is the dose-response curve that I outlined 12:05:36 3 to you earlier. This makes absolute and eminent sense. 12:05:39 4 Aside from doing that, you can give sedatives 12:05:43 5 and right from the start -- 12:05:45 6 MR. PREUSS: Objection, again, nothing in 12:05:47 7 Rule 26 about coprescribing sedatives with SSRIs as far as 12:05:48 8 his opinions. 12:05:53 9 MR. VICKERY: I believe there is, Judge, 12:05:54 10 but I just can't point that out right now. 12:05:55 11 Q. (BY MR. VICKERY) Let me ask you this. I know 12:06:01 12 that your Rule 26 discusses the scientific literature and 12:06:02 13 it discusses the case of Don Schell at great length and 12:06:07 14 his medical history. 12:06:12 15 A. Yes. 12:06:13 16 Q. Have you reviewed his medical history? 12:06:13 17 A. Yes, I have reviewed his medical history. 12:06:15 18 Q. Did you review the treatment that he got for a 12:06:17 19 year under the care of a competent psychiatrist named 12:06:20 20 Dr. Suhany? 12:06:23 21 A. Yes, and there were a number of different drugs 12:06:24 22 Mr. Schell was put on that would have minimize the effects 12:06:34 23 of the Prozac he was taking. There was the Inderal which 12:06:34 24 had actually been discovered in the McLean hospital by 12:06:36 25 Carol Lock. There was Trazodone which has been recognized 12:06:42 70 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 by others as minimizing the problems that Prozac and other 12:06:45 3 SSRIs can cause. 12:06:49 4 There was the Ativan that Dr. Suhany had 12:06:51 5 Mr. Schell on and that he had been on earlier. This would 12:07:00 6 also minimize the problem and in my Rule 26 statement 12:07:03 7 going through the literature I note that Lilly and other 12:07:06 8 companies in their trials have coprescribed 12:07:09 9 benzodiazepines with SSRIs specifically to minimize the 12:07:13 10 problems of agitation caused by the SSRIs, this is in 12:07:16 11 their clinical trials. 12:07:20 12 Q. Fine, thank you. 12:07:23 13 THE COURT: Is this a good time to break? 12:07:24 14 MR. VICKERY: It is a perfect time, Your 12:07:26 15 Honor. 12:07:28 16 THE COURT: Let's do that. 12:07:28 17 THE WITNESS: Is this for lunch? 12:07:29 18 THE COURT: We will stand in recess until 12:07:32 19 1:15 p.m. 12:07:34 20 (Trial proceedings recessed 12:00 noon 12:07:37 21 and reconvened be (following out of the presence of 12:07:41 22 the jury in chambers.) 13:32:48 23 THE COURT: We're on the record with 13:32:48 24 regard to an issue with regard to demonstrative /OEFD, 13:32:48 25 slides that the plaintiff wishes to present to the jury 13:32:48 71 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 through the testimony of his expert witness Dr. Heally. 13:32:48 3 What's the status of this? 13:32:48 4 SPEAKER 2: During the lunch break we've 13:32:48 5 had a chance to go through the slides, primarily miss Hal 13:32:48 6 person, and look at them. And there are a number of them, 13:32:48 7 in fact, the majority of them that we are were not in the 13:32:48 8 Rule 26 report nor in the deposition. 13:32:48 9 Now, there are some that refer to articles that 13:32:48 10 were referenced in the deposition, but they appear to 13:32:48 11 reflect calculations that were never done and we were 13:32:48 12 never told about. 13:32:48 13 So although it is true they may have on the 13:32:48 14 bottom an article reference, the Cal /HRAEUGSs, et cetera, 13:32:48 15 we never saw. 13:32:48 16 They are a problem, and I think it probably 13:32:48 17 reflects the fact, as counsel said, this is part of a 13:32:48 18 speech that Dr. Heally routinely gives apparently and were 13:32:48 19 probably prepared a year, year and a half ago and were not 13:32:48 20 necessarily tailored to his Rule 26 report in this case. 13:32:48 21 SPEAKER 1: Judge, I will say this. We 13:32:48 22 had a stipulation about visual aides to be produced within 13:32:48 23 a time certain. I did it. They did T if they're now 13:32:48 24 going to say -- you can't even though we had a 13:32:48 25 stipulation, the power point slides you presented pursuant 13:32:48 72 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 to that stipulation may not be used unless they were 13:32:48 3 referenced in the Rule 26 report, that's fine, I won't use 13:32:48 4 them. I just want to alert the court and counsel that I 13:32:48 5 will take exactly the same position with respect to every 13:32:48 6 single power point slide that they have prepared for their 13:32:48 7 experts that they presented to us pursuant to the same 13:32:48 8 stipulation. 13:32:48 9 THE COURT: All right. Well, we're not 13:32:48 10 going to get into this school yard stuff. Here is the 13:32:48 11 situation: Any demonstrative evidence, and you all should 13:32:48 12 have reviewed it, you've all reviewed your demonstrative 13:32:48 13 evidence through the exchanges, yes or no, prior to today? 13:32:48 14 SPEAKER 1: Yes. 13:32:48 15 SPEAKER 2: Yes. 13:32:48 16 THE COURT: All right. This problem, 13:32:48 17 then, was known before. 13:32:48 18 SPEAKER 2: We moved with respect to 13:32:48 19 these slides and the court's order, as I understood it, 13:32:48 20 was that we would take the slides up as they came up 13:32:48 21 during testimony. And we referenced these in our motion 13:32:48 22 in limine with respect to the experts and not going along 13:32:48 23 with the Rule 26 report. 13:34:31 24 THE COURT: Any demonstrative evidence, if 13:34:31 25 it comes from an expert and it is based upon an expert's 13:34:31 73 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 opinion and contains data or bases for that opinion, that 13:34:31 3 information has to be previously designated by the orders 13:34:31 4 of this court which I said a long time ago I would 13:34:31 5 strictly enforce. 13:34:31 6 If it has been previously designated, it goes 13:34:31 7 forward. If it hasn't, notwithstanding any stipulation, 13:34:31 8 it doesn't go forward. If defendants have demonstrative 13:34:31 9 evidence that contains information that hasn't been 13:34:31 10 previously designated, it is out. 13:34:31 11 SPEAKER 1: Very well. /EUFPLT one other 13:34:31 12 issue that's of extreme importance. And that was the 13:34:31 13 innuendo this morning and maybe more than that by 13:34:31 14 Dr. Heally with respect to not giving him documents when 13:34:31 15 he was there and that is very, very troubling and very 13:34:31 16 upsetting because Vern handled the discussions with Andy. 13:34:31 17 The request was oral, it was late. There was a period of 13:34:31 18 time before we could make arrangements or he could tell us 13:34:31 19 when he could be there, but to suggest that we were 13:34:31 20 withholding documents from him when it was virtually at 13:34:31 21 the close of discovery and after that, and then a final 13:34:31 22 request after the expert reports were due and at that time 13:34:31 23 we said, "You're too late." And I don't know how we can 13:34:31 24 correct it, but -- 13:34:31 25 THE COURT: I've already given that some 13:34:31 74 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 thought. 13:34:31 3 Go ahead, Mr. Vic /REU. 13:34:31 4 SPEAKER 1: If I may respond, Your Honor, 13:34:31 5 we were told that all of their healthy volunteer stuff 13:34:31 6 would be in Harlow, England. Dr. Heally goes to Harlow, 13:34:31 7 England. It is not there. There are three reports that 13:34:31 8 are not there. He can identify what these reports are 13:34:31 9 because they're referenced in the materials that are 13:34:31 10 there, but the reports themselves are not there. 13:34:31 11 Now, unfortunately, by the time it took them to 13:34:31 12 get all of this stuff assembled, but the time heally could 13:34:31 13 see if was about a week before his report was due. So 13:34:31 14 here's the situation where we go there thinking all the 13:34:31 15 material is there, it is not there, there are three things 13:34:31 16 that are of extreme significance that aren't there, and so 13:34:31 17 we did indeed ask, hay, here are three things that were 13:34:31 18 missing there. Please send them to us." And they were 13:34:31 19 never provided. 13:34:31 20 So I don't think anybody has taken any cheap 13:34:31 21 shot here at the defendant. We went fully expecting that 13:34:31 22 all of those relevant stuff would be there. 13:34:47 23 THE COURT: Let me tell you. I don't 13:34:47 24 expect Dr. Heally to be the one to raise the issue at all, 13:34:47 25 especially in front of the jury. And I didn't like it. 13:34:47 75 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 It drew my attention immediately. He was advocating and 13:34:47 3 when he has a license to practice law and he is standing 13:34:47 4 out there at the podium outside of the presence of the 13:34:47 5 jury, he can raise such things. 13:34:47 6 We've gone through a long discovery process and 13:34:47 7 this has never been raised to me as an issue one way or 13:34:47 8 the other, through a motion to compel or for sanctions or 13:34:47 9 anything else. And I think it is very improper for 13:34:47 10 Dr. Heally -- it was more than an innuendo about his two 13:34:47 11 to three references as to this during his testimony. And 13:34:47 12 it was unsolicited, maybe prepared, but it was unsolicited 13:34:47 13 by your questions. 13:34:47 14 SPEAKER 1: It was. 13:34:47 15 THE COURT: I will have no more of that. 13:34:47 16 We're not going to say another word about it because it 13:34:47 17 will draw too much attention to it. I think it was fine 13:34:47 18 that you didn't make the objection at that time. That's 13:34:47 19 at least my personal feeling. 13:34:47 20 But to go back and make an issue of it right now 13:34:47 21 would be improper. You use your own discretion as to 13:34:47 22 whether you question him about that on cross-examination. 13:34:47 23 But we won't have it again and I expect immediate 13:34:47 24 objection if anything like that comes from him /EUFPLT you 13:34:47 25 will get it. 13:34:47 76 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 THE COURT: All right. In a kind and 13:34:47 3 gentle way /EUFPLT in a kind and gentle way, sir. 13:34:47 4 THE COURT: Okay. (Proceedings in chambers 13:34:47 5 recessed 1:20 p.m..) (following in the presence of the 13:34:47 6 jury.) Reconvened 1:25. 13:34:47 7 THE COURT: Once again, Dr. Healy, you're 13:34:47 8 still under oath. 13:34:47 9 Q. (BY SPEAKER 1) Dr. Healy, before lunch we 13:34:47 10 talked about two of the four opinions you have in this 13:34:47 11 case, the general causation opinion that you have that 13:34:47 12 Paxil causes homicide and suicide in some patients and the 13:34:47 13 opinion that /SK*B did not test. 13:34:47 14 I want to move to the third opinion, warnings. 13:34:47 15 Can you tell us why a warning is important? 13:34:47 16 A. Yes. I think there's a very real risk that both 13:34:47 17 clinical prescribers of the drug and also patients may 13:34:47 18 feel when they go on any of the antidepressants and become 13:34:47 19 suicidal or have other odd, strange thoughts, that it is 13:34:47 20 their illness that is actually causing this. Many 13:34:47 21 clinicians will witness what is happening to patients and 13:35:02 22 they will conclude that it is the illness. Many patients 13:35:02 23 in whom this happens to them will conclude that it is 13:35:02 24 their illness, too. 13:35:02 25 My doctor wouldn't have put me on anything that 13:35:02 77 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 could do me harm. 13:35:02 3 In order to reduce the risk of this happening, 13:35:07 4 in order to reduce the risk of the misperception on 13:35:09 5 the part of both the clinician and the patient, the needs, 13:35:12 6 I believe, based on all the /OU there needs, I believe, 13:35:16 7 based on all the data there needs to be a specific 13:35:20 8 recommendation or warning that while the illness may cause 13:35:23 9 a problem, that the drug, and in this case Paxil, may also 13:35:25 10 cause a problem. It may cause a problem and particularly 13:35:29 11 cause a problem in people who aren't suicidal to begin 13:35:37 12 with. 13:35:40 13 Q. People like Don Schell? 13:35:40 14 A. People like Don Schell, for example. You see, 13:35:42 15 it may be that the person becomes suicidal and they halt 13:35:47 16 the drug and don't actually do anything. If you don't 13:35:50 17 have a warning that clearly directs the physician and/or 13:35:53 18 the patient they're all going to be left feeling, perhaps 13:35:58 19 the person's husband, wife, children or parents are all 13:36:01 20 going to be left thinking that yes, they've got this flaw 13:36:04 21 in them, there is some dark recess to the mind we didn't 13:36:07 22 know about -- 13:36:11 23 Q. Let me see if I can break it down. Is it the 13:36:12 24 fundamental difference between whether -- I'm feeling real 13:36:15 25 bad, I'm the patient, and whether it is my disease that 13:36:18 78 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 made me feel this way or the drug? Is that the 13:36:21 3 fundamental distinction? 13:36:23 4 A. Yes, people need to know that it is the pill in 13:36:25 5 order to be able to halt the pill that may be actually 13:36:28 6 causing this kind of problem. 13:36:32 7 Physicians need to know to be able to warn the 13:36:34 8 patient, "Look, if this kind of thing happens you need to 13:36:38 9 halt the pill immediately. Beyond that, even if you halt the 13:36:41 10 pill and things -- even without being told there could 13:36:45 11 be -- if you aren't told, if there isn't a warning, if 13:36:49 12 physicians haven't been educated that the drug had cause 13:36:51 13 the problem, the patient and the physician may end up 13:36:54 14 thinking yes, they have this suicidal streak in them when 13:36:57 15 they don't, they only have it when they're put on this 13:37:00 16 drug. 13:37:02 17 Q. Now, I know that we've done this already with 13:37:03 18 Mr. Haase and there's no sense in doing anything 13:37:05 19 cumulative, and I am not going to put the warning up 13:37:12 20 again -- not a warning -- the label up again. 13:37:12 21 You have seen the Paxil label that was in effect 13:37:14 22 in 1998, right? 13:37:16 23 A. Yes, I have. 13:37:18 24 Q. And it is in evidence for the jury. They will 13:37:20 25 all have it. 13:37:22 79 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 (Following out of the presence 13:44:21 3 of the jury in chambers.) 13:44:21 4 THE COURT: We're on the record with 13:44:21 5 regard to an issue with regard to demonstrative evidence, 13:44:21 6 slides that the plaintiff wishes to present to the jury 13:44:21 7 through the testimony of his expert witness Dr. Healy. 13:44:21 8 What's the status of this? 13:44:21 9 MR. ZVOLEFF: During the lunch break we've 13:44:21 10 had a chance to go through the slides, primarily miss 13:44:21 11 Halpern, and look at them. And there are a number of 13:44:21 12 them, in fact, the majority of them that we are were not 13:44:21 13 in the Rule 26 report nor in the deposition. 13:44:21 14 Now, there are some that refer to articles that 13:44:21 15 were referenced in the deposition, but they appear to 13:44:21 16 reflect calculations that were never done and we were 13:44:21 17 never told about. 13:44:21 18 So although it is true they may have on the 13:44:21 19 bottom an article reference, the calculations, et cetera, 13:44:21 20 we never saw. 13:44:21 21 They are a problem, and I think it probably 13:44:21 22 reflects the fact, as counsel said, this is part of a 13:44:21 23 speech that Dr. Healy routinely gives apparently and were 13:44:21 24 probably prepared a year, year and a half ago and were not 13:44:21 25 necessarily tailored to his Rule 26 report in this case. 13:44:21 80 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 MR. VICKERY: Judge, I will say this. We 13:44:21 3 had a stipulation about visual aides to be produced within 13:44:21 4 a time certain. I did it. They did T if they're now 13:44:21 5 going to say -- you can't even though we had a 13:44:21 6 stipulation, the power point slides you presented pursuant 13:44:21 7 to that stipulation may not be used unless they were 13:44:21 8 referenced in the Rule 26 report, that's fine, I won't use 13:44:21 9 them. I just want to alert the court and counsel that I 13:44:21 10 will take exactly the same position with respect to every 13:44:21 11 single power point slide that they have prepared for their 13:44:21 12 experts that they presented to us pursuant to the same 13:44:21 13 stipulation. 13:44:21 14 THE COURT: All right. Well, we're not 13:44:21 15 going to get into this school yard stuff. Here is the 13:44:21 16 situation: Any demonstrative evidence, and you all should 13:44:21 17 have reviewed it, you've all reviewed your demonstrative 13:44:21 18 evidence through the exchanges, yes or no, prior to today? 13:44:21 19 MR. VICKERY: Yes. 13:44:21 20 MR. ZVOLEFF: Yes. 13:44:21 21 THE COURT: All right. This problem, 13:44:21 22 then, was known before. 13:44:21 23 MR. ZVOLEFF: We moved with respect to 13:44:21 24 these slides and the court's order, as I understood it, 13:44:21 25 was that we would take the slides up as they came up 13:44:21 81 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 during testimony. And we referenced these in our motion 13:44:21 3 in limine with respect to the experts and not going along 13:44:21 4 with the Rule 26 report. 13:44:33 5 THE COURT: Any demonstrative evidence, if 13:44:33 6 it comes from an expert and it is based upon an expert's 13:44:33 7 opinion and contains data or bases for that opinion, that 13:44:33 8 information has to be previously designated by the orders 13:44:33 9 of this court which I said a long time ago I would 13:44:33 10 strictly enforce. 13:44:33 11 If it has been previously designated, it goes 13:44:33 12 forward. If it hasn't, notwithstanding any stipulation, 13:44:33 13 it doesn't go forward. If defendants have demonstrative 13:44:33 14 evidence that contains information that hasn't been 13:44:33 15 previously designated, it is out. 13:44:33 16 MR. VICKERY: Very well. 13:44:33 17 MR. PREUSS: One other issue that's of 13:44:33 18 extreme importance. And that was the innuendo this 13:44:33 19 morning and maybe more than that by Dr. Healy with respect 13:44:33 20 to not giving him documents when he was there and that is 13:44:33 21 very, very troubling and very upsetting because Vern 13:44:33 22 handled the discussions with Andy. The request was oral, 13:44:33 23 it was late. There was a period of time before we could 13:44:33 24 make arrangements or he could tell us when he could be 13:44:33 25 there, but to suggest that we were withholding documents 13:44:33 82 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 from him when it was virtually at the close of discovery 13:44:33 3 and after that, and then a final request after the expert 13:44:33 4 reports were due and at that time we said, "You're too 13:44:33 5 late." And I don't know how we can correct it, but -- 13:44:33 6 THE COURT: I've already given that some 13:44:33 7 thought. 13:44:33 8 Go ahead, Mr. Vickery. 13:44:33 9 MR. VICKERY: If I may respond, Your 13:44:33 10 Honor, we were told that all of their healthy volunteer 13:44:33 11 stuff would be in Harlow, England. Dr. Healy goes to 13:44:33 12 Harlow, England. It is not there. There are three 13:44:33 13 reports that are not there. He can identify what these 13:44:33 14 reports are because they're referenced in the materials 13:44:33 15 that are there, but the reports themselves are not there. 13:44:33 16 Now, unfortunately, by the time it took them to 13:44:33 17 get all of this stuff assembled, but the time Healy could 13:44:33 18 see if was about a week before his report was due. So 13:44:33 19 here's the situation where we go there thinking all the 13:44:33 20 material is there, it is not there, there are three things 13:44:33 21 that are of extreme significance that aren't there, and so 13:44:33 22 we did indeed ask, hay, here are three things that were 13:44:33 23 missing there. Please send them to us." And they were 13:44:33 24 never provided. 13:44:33 25 So I don't think anybody has taken any cheap 13:44:33 83 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 shot here at the defendant. We went fully expecting that 13:44:33 3 all of those relevant stuff would be there. 13:44:47 4 THE COURT: Let me tell you. I don't 13:44:47 5 expect Dr. Healy to be the one to raise the issue at all, 13:44:47 6 especially in front of the jury. And I didn't like it. 13:44:47 7 It drew my attention immediately. He was advocating and 13:44:47 8 when he has a license to practice law and he is standing 13:44:47 9 out there at the podium outside of the presence of the 13:44:47 10 jury, he can raise such things. 13:44:47 11 We've gone through a long discovery process and 13:44:47 12 this has never been raised to me as an issue one way or 13:44:47 13 the other, through a motion to compel or for sanctions or 13:44:47 14 anything else. And I think it is very improper for 13:44:47 15 Dr. Healy -- it was more than an innuendo about his two to 13:44:47 16 three references as to this during his testimony. And it 13:44:47 17 was unsolicited, maybe prepared, but it was unsolicited by 13:44:47 18 your questions. 13:44:47 19 MR. VICKERY: It was. 13:44:47 20 THE COURT: I will have no more of that. 13:44:47 21 We're not going to say another word about it because it 13:44:47 22 will draw too much attention to it. I think it was fine 13:44:47 23 that you didn't make the objection at that time. That's 13:44:47 24 at least my personal feeling. 13:44:47 25 But to go back and make an issue of it right now 13:44:47 84 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 would be improper. You use your own discretion as to 13:44:47 3 whether you question him about that on cross-examination. 13:44:47 4 But we won't have it again and I expect immediate 13:44:47 5 objection if anything like that comes from him. 13:44:47 6 MR. PREUSS: You will get it. 13:44:47 7 THE COURT: All right. In a kind and 13:44:47 8 gentle way. 13:44:47 9 MR. PREUSS: In a kind and gentle way, 13:44:47 10 sir. 13:44:47 11 THE COURT: Okay. 13:44:47 12 (Proceedings in chambers recessed 1:20 p.m..) 13:44:47 13 (Following in the presence of the jury.) 13:44:47 14 (Trial proceedings reconvened 13:44:47 15 1:25 p.m., May 22, 2001.) 13:44:47 16 THE COURT: Once again, Dr. Healy, you're 13:44:47 17 still under oath. 13:44:47 18 Q. (BY MR. VICKERY) Dr. Healy, before lunch we 13:44:47 19 talked about two of the four opinions you have in this 13:44:47 20 case, the general causation opinion that you have that 13:44:47 21 Paxil causes homicide and suicide in some patients and the 13:44:47 22 opinion that SmithKline Beecham did not test. 13:44:47 23 I want to move to the third opinion, warnings. 13:44:47 24 Can you tell us why a warning is important? 13:44:47 25 A. Yes. I think there's a very real risk that both 13:44:47 85 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 clinical prescribers of the drug and also patients may 13:44:47 3 feel when they go on any of the antidepressants and become 13:44:47 4 suicidal or have other odd, strange thoughts, that it is 13:44:47 5 their illness that is actually causing this. Many 13:44:47 6 clinicians will witness what is happening to patients and 13:45:03 7 they will conclude that it is the illness. Many patients 13:45:03 8 in whom this happens to them will conclude that it is 13:45:03 9 their illness, too. 13:45:03 10 My doctor wouldn't have put me on anything that 13:45:03 11 could do me harm. 13:45:03 12 In order to reduce the risk of this happening, 13:45:03 13 in order to reduce the risk of the misperception on 13:45:03 14 the part of both the clinician and the patient, there 13:45:03 15 needs, I believe, based on all the data there needs to be 13:45:03 16 a specific recommendation or warning that while the 13:45:03 17 illness may cause a problem, that the drug, and in this 13:45:03 18 case Paxil, may also cause a problem. It may cause a 13:45:03 19 problem and particularly cause a problem in people who 13:45:03 20 aren't suicidal to begin with. 13:45:03 21 Q. People like Don Schell? 13:45:03 22 A. People like Don Schell, for example. You see, 13:45:03 23 it may be that the person becomes suicidal and they halt 13:45:03 24 the drug and don't actually do anything. If you don't 13:45:03 25 have a warning that clearly directs the physician and/or 13:45:03 86 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 the patient they're all going to be left feeling, perhaps 13:45:03 3 the person's husband, wife, children or parents are all 13:45:03 4 going to be left thinking that yes, they've got this flaw 13:45:03 5 in them, there is some dark recess to the mind we didn't 13:45:03 6 know about -- 13:45:03 7 Q. Let me see if I can break it down. Is it the 13:45:03 8 fundamental difference between whether -- I'm feeling real 13:45:03 9 bad, I'm the patient, and whether it is my disease that 13:45:03 10 made me feel this way or the drug? Is that the 13:45:03 11 fundamental distinction? 13:45:03 12 A. Yes, people need to know that it is the pill in 13:45:03 13 order to be able to halt the pill that may be actually 13:45:03 14 causing this kind of problem. 13:45:03 15 Physicians need to know to be able to warn the 13:45:03 16 patient, "Look, if this kind of thing happens you need to 13:45:03 17 halt the pill." Beyond that, even if you halt the pill 13:45:03 18 and things -- even without being told there could be -- if 13:45:03 19 you aren't told, if there isn't a warning, if physicians 13:45:03 20 haven't been educated that the drug had cause the problem, 13:45:03 21 the patient and the physician may end up thinking yes, 13:45:03 22 they have this suicidal streak in them when they don't, 13:45:03 23 they only have it when they're put on this drug. 13:45:03 24 Q. Now, I know that we've done this already with 13:45:03 25 Mr. Haase and there's no sense in doing anything 13:45:03 87 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 cumulative, and I am not going to put the warning up 13:45:16 3 again -- not a warning -- the label up again. 13:45:16 4 You have seen the Paxil label that was in effect 13:45:16 5 in 1998, right? 13:45:16 6 A. Yes, I have. 13:45:16 7 Q. And it is in evidence for the jury. They will 13:45:16 8 all have it. Is there anything in there to alert the 13:45:16 9 physician that this drug they're about to prescribe could 13:45:16 10 for some patients cause them to be homicidal or suicidal? 13:45:16 11 A. Absolutely nothing. 13:45:16 12 Q. There is in the precautions section, and we went 13:45:16 13 over it again yesterday, something that says it is a risk 13:45:16 14 of depression, the depression could make them do that. 13:45:16 15 A. Yes, that's the case. 13:45:16 16 Q. Is that adequate? Is that enough? 13:45:16 17 A. No, it is not, because many people get put on 13:45:16 18 this drug for stress reactions of various sorts. We may 13:45:16 19 well argue about what Mr. Schell had, but his G P, 13:45:16 20 Dr. Patel, when he saw him that day thought he was anxious 13:45:16 21 and had a stress reaction. Many people get put on Paxil 13:45:16 22 for this reason. 13:45:16 23 Many people who aren't depressed at all get put 13:45:16 24 on this drug. They have also the risk of becoming 13:45:16 25 suicidal. 13:45:16 88 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Q. That ends that topic and I want to move to 13:45:16 3 specific causation and your opinion that Paxil was a cause 13:45:16 4 in these deaths. 13:45:16 5 Why do you say that? What leads you to believe 13:45:16 6 that the two Paxil pills that Don Schell took precipitated 13:45:16 7 this homicidal, suicidal behavior? 13:45:16 8 A. Well, there are a number of reasons, 13:45:16 9 Mr. Vickery. As I read the records that you sent me, I 13:45:16 10 believe that Mr. Schell, over the course of about 10 or 15 13:45:16 11 years or so had a number of nervous episodes. Whether we 13:45:16 12 call them depression or whether we call them anxiety as 13:45:16 13 his G P Dr. Patel did is an issue that I'm sure we're 13:45:16 14 going to argue about further. 13:45:16 15 But from my perspective, these episodes were 13:45:16 16 mild to moderately severe. They were self-limiting 13:45:16 17 episodes. 13:45:16 18 Q. Let me stop you there. What do you mean when 13:45:16 19 you say that these prior incidents when he saw other 13:45:16 20 doctors, whether it is for anxiety or depression, were 13:45:16 21 self-limited? What does that mean? 13:45:16 22 A. They cleared up fairly quickly once he was put 13:45:16 23 on the right drug for him, and it would appear from what 13:45:16 24 SmithKline Beecham have been able to bring out of the 13:45:16 25 further history that I didn't know about when I first gave 13:45:32 89 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 my views, in that he saw sister Claire, for instance, when 13:45:32 3 you may have had a nervous incident -- 13:45:32 4 MR. PREUSS: Objection, that was not part 13:45:32 5 of the foundation he gave his written opinions on. 13:45:32 6 Q. (BY MR. VICKERY) Let's don't get into -- I'm 13:45:32 7 sure he'll ask you about it if it is something they've dug 13:45:32 8 up since then. Let's confine ourself to things you were 13:45:32 9 able to see before your report. 13:45:32 10 Let me ask you this: You're a trained 13:45:32 11 psychiatrist? 13:45:32 12 A. I am, yes. 13:45:32 13 Q. And do you have occasion in your clinical 13:45:32 14 practice in the UK to see patients who are referred to you 13:45:32 15 by primary care doctors who have seen them for conditions 13:45:32 16 like what Mr. Schell had? 13:45:32 17 A. Absolutely, yes. 13:45:32 18 Q. Is that a significant part of your clinical 13:45:32 19 practice? 13:45:32 20 A. Yes, it is a very large part of my clinical 13:45:32 21 practice. 13:45:32 22 Q. And from the materials that you had to review 13:45:32 23 prior to finalizing the Rule 26 report, was Donald Schell 13:45:32 24 a sick man? Did he have some chronic major depressive 13:45:32 25 illness? 13:45:32 90 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 A. No, Donald Schell, you can -- you can argue that 13:45:32 3 he had a major depressive illness, but I believe he had a 13:45:32 4 mild form of it. He certainly did not have a disorder 13:45:32 5 that put him at risk of suicide or homicide, at a 13:45:32 6 significant risk of suicide or homicide. 13:45:32 7 Q. We have heard some talk of maybe he needed 13:45:32 8 longer term treatment, longer term psychotherapy or 13:45:32 9 medications. Do you believe he did? 13:45:32 10 A. No, I don't. 13:45:32 11 Q. Let's go to the second reason. You said there 13:45:32 12 were a number of reasons that caused you to believe that 13:45:32 13 Paxil triggered this behavior. The first relates to his 13:45:32 14 prior condition. What is the second? 13:45:32 15 A. Yes, the second relates to his previous exposure 13:45:32 16 to Prozac which seems to have been an adverse exposure 13:45:32 17 that left Dr. Suhany concluding that this was not the 13:45:32 18 right drug for him, and Dr. Suhany changing him off of 13:45:32 19 that drug. 13:45:32 20 Don Schell, I believe, manifested some of the 13:45:32 21 typical precursors of violence and suicide that this group 13:45:32 22 of drugs can cause while he was on Prozac. 13:45:32 23 Q. Let me stop you. I want to follow up on that 13:45:32 24 one for a minute. 13:45:32 25 As you heard in my opening statement, Dr. Suhany 13:45:32 91 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 himself won't be here for a while. You have read his 13:45:32 3 deposition, have you not? 13:45:45 4 A. Yes, I have. 13:45:45 5 Q. And looked at his records? 13:45:45 6 A. And looked at his records. 13:45:45 7 Q. Did Mr. Schell have a bad reaction on the Prozac 13:45:45 8 that Dr. Suhany gave him within the first week? 13:45:45 9 A. Yes, he did. It becomes clear that Mr. Schell 13:45:45 10 within the first -- within a relatively brief period of 13:45:45 11 going on prozac becomes, as Dr. Suhany describes it, more 13:45:45 12 anxious. He talks in terms of him being somatically 13:45:45 13 anxious which is the kind of agitation that I've been 13:45:45 14 referring to. 13:45:45 15 Q. What does that word somatic mean? 13:45:45 16 A. It means that he's manifesting a number of 13:45:45 17 different features of anxiety. He seems to be restless, 13:45:45 18 to some extent. He's got -- he's jittery. It is more 13:45:45 19 than a quaver in his voice. It goes through his body. 13:45:45 20 His hands shake. He's generally more perspirant and 13:45:45 21 things like that. 13:45:45 22 Q. And did Dr. Suhany attribute that to being a 13:45:45 23 side effect of Prozac? 13:45:45 24 A. Yes, he did. 13:45:45 25 MR. PREUSS: Objection, Your Honor. This 13:45:45 92 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 isn't from the records. He's testifying as to what 13:45:45 3 Dr. Suhany did and it is improper foundation. 13:45:45 4 MR. VICKERY: Are you finished? I'm 13:45:45 5 sorry. It is in Dr. Suhany's deposition. He's read 13:45:45 6 Dr. Suhany's deposition, he referenced it and as the court 13:45:45 7 will rule we discussed before whether any portions of 13:45:45 8 Suhany's deposition could be read now and I'm just asking 13:45:45 9 him consistent with that discussion in chambers about his 13:45:45 10 reading of Dr. Suhany's deposition. 13:45:45 11 THE COURT: Observation overruled. 13:45:45 12 Q. (BY MR. VICKERY) Did Dr. Suhany attribute 13:45:45 13 this -- I think you called it obvious somatic anxiety as a 13:45:45 14 side effect of Prozac? 13:45:45 15 A. Yes, he did. And he took -- we have the 13:45:45 16 ultimate evidence that he did in that he specifically 13:45:45 17 halted Mr. Schell's Prozac and notes that the problem 13:45:45 18 cleared up. 13:45:45 19 Q. So is that like a dechallenge, that dechallenge 13:45:45 20 stuff we're talking about this morning? 13:45:45 21 A. Absolutely. 13:45:45 22 Q. Did Dr. Suhany have Mr. Schell on some kind of 13:45:45 23 other medication, to use my phrase, to take the edge off? 13:45:45 24 A. Yes, he did. During the period of time 13:45:45 25 Dr. Suhany saw Mr. Schell he was at various points on 13:45:45 93 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Trazodone which is an antidote to Paxil. He was put on 13:45:45 3 Inderol because of the handshake he had on Prozac. 13:45:45 4 But Inderal is a drug which blocks the serotonin 13:45:58 5 1, 5HT 1 receptor and is the one that doctors from Harvard 13:45:58 6 felt might minimize the problems that Prozac caused. 13:45:58 7 So he put Mr. Schell on this drug and he also 13:45:58 8 had him on Ativan which is a further drug that good 13:45:58 9 clinical sense at this point in time, in both of the US 13:45:58 10 and the UK in people having problems during the first few 13:45:58 11 days or weeks of going on a drug like Prozac, they were 13:45:58 12 being prescribed -- coprescribed benzodiazepines and 13:45:58 13 Dr. Suhany put Mr. Schell on a benzodiazepine. 13:45:58 14 Q. In spite of having these other medications at 13:45:58 15 the same time, did he still manifest the anxiety to the 13:45:58 16 point that Dr. Suhany took him off of Prozac? 13:45:58 17 A. Yes, he did. 13:45:58 18 Q. And in what way does that prior experience cause 13:45:58 19 you to believe that when he had Paxil, then, later that 13:45:58 20 his problem was Paxil? 13:45:58 21 A. Well, this is very strong suggestive evidence 13:45:58 22 that Mr. Schell is the kind of person who is going to have 13:45:58 23 these kinds of problems from a SSRI, so when he later goes 13:46:03 24 on a further SSRI, uncovered with the antidote -- I mean, 13:46:03 25 he isn't going on it with the other antidote that he had 13:46:08 94 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 been put on before when he was on the Prozac, it is -- it 13:46:12 3 makes perfect sense that this drug has caused the kind of 13:46:18 4 problems that we then see happen. 13:46:22 5 Q. Now, Dr. Patel did give him Ambien for sleep? 13:46:25 6 A. He did, yes. 13:46:29 7 Q. And he had Ambien in his blood at the same time? 13:46:30 8 A. He did, yes. 13:46:33 9 Q. Would that be effective as the antidote like the 13:46:34 10 benzodiazepine? 13:46:37 11 A. No, it wouldn't. Ambien was a drug which was -- 13:46:38 12 when concerns grew about the use of benzodiazepines, Ambien 13:46:43 13 was one of the drugs brought along as a sleeping pill 13:46:48 14 rather than the benzodiazepine sleeping pills. 13:46:51 15 But one of the things you get with Ambien, what 13:46:53 16 they tried to do was to hold onto the bit of the 13:46:57 17 benzodiazepine molecule that puts you to sleep but removed 13:47:01 18 the bit that is anxiolytic, the bit that makes you less 13:47:04 19 anxious, the bit that would cover the anxiety being 13:47:09 20 introduced by the SSRI. 13:47:13 21 Q. Let's talk about similarities and differences 13:48:19 22 between the Paxil and the Prozac. Which of those two -- 13:48:19 23 let me ask this question first. I'm sorry. 13:48:19 24 Do you believe that the treatment emergent 13:48:19 25 violence and suicide has something to do with the impact 13:48:19 95 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 of these medications on the serotonin system? 13:48:19 3 A. Yes, I do. 13:48:19 4 Q. And which of these two medications is the more 13:48:19 5 potent medication in terms of impacting the serotonin 13:48:19 6 system? 13:48:19 7 A. Paxil is more potent than Prozac. 13:48:19 8 Q. So if the -- if it is the impact on the 13:48:19 9 serotonin system that triggers this, would that at least 13:48:19 10 cause you to think that Paxil would be equally, if not 13:48:19 11 more, problematic for the patient? 13:48:19 12 A. I think what you can expect from Paxil is that 13:48:19 13 where the problem is being caused, it may happen even 13:48:19 14 earlier than it will happen with Prozac. 13:48:19 15 Q. You mean because of its potency it might happen 13:48:24 16 earlier? 13:48:24 17 A. Yes, you might have the same problem taking a 13:48:24 18 few more days to appear on Prozac but happening earlier on 13:48:25 19 Paxil. 13:48:29 20 Q. Is that analogous to that dose relationship 13:48:30 21 stuff we were talking about this morning? 13:48:35 22 A. Yes, to some extent it is. There's two ways you 13:48:37 23 can clearly get a dose -- 13:48:39 24 MR. PREUSS: Your Honor, object again. 13:48:41 25 He's going beyond his Rule 26 in terms of the early 13:48:42 96 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 manifestation testimony. 13:48:46 3 MR. VICKERY: Your Honor, the dose 13:48:50 4 response relationship is all over his Rule 26 report and 13:48:52 5 his deposition. I'm puzzled by that. 13:48:55 6 THE COURT: This is a big issue. You have 13:49:05 7 to point it out to me, where that information is. 13:49:07 8 MR. PREUSS: Page 217, lines 12 through 13:49:18 9 20. 13:49:20 10 MR. VICKERY: Let me read to the court if 13:49:33 11 I may from page 9 and 10 of the general causation argument 13:49:34 12 filed with the Rule 26 report. 13:49:38 13 In general, across clinical trials with SSRIs in 13:49:40 14 both depressed and nondepressed populations, the results 13:49:44 15 show a consistent pattern of drug-induced conditions 13:49:47 16 variously described as agitation, anxiety, nervousness, 13:49:51 17 hyperkinesis, tremor. These show a regular onset after 13:49:55 18 treatment starts and a dose-response relationship with the 13:50:00 19 problem clearing on discontinuation. 13:50:02 20 MR. PREUSS: Your Honor that all had to do 13:50:15 21 with the Pfizer problem, nothing to do with Paxil, the 13:50:17 22 Pfizer data. 13:50:22 23 THE COURT: Objection overruled. 13:50:23 24 MR. PREUSS: And we couldn't see that 13:50:24 25 because of confidentiality. 13:50:26 97 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 THE COURT: I will let the testimony 13:50:29 3 stand. 13:50:31 4 Q. (BY MR. VICKERY) I'm sorry. I think we 13:50:32 5 interrupted that colloquy there. 13:50:33 6 Is this problem of the potency causing the 13:50:36 7 aggression or suicidality quicker analogous or akin to the 13:50:40 8 dose-response relationship we were talking about? 13:50:47 9 A. Yes, it is. 13:50:50 10 Q. In what way? 13:50:50 11 A. Well, there are two ways to get a dose-response 13:50:51 12 relationship. One is if you use dose -- let's say you use 13:50:55 13 10 milligrams of the pill, and if 20 milligrams of the 13:51:01 14 pill causes more of a problem, that's what we actually 13:51:06 15 talked about earlier on this morning. 13:51:08 16 The other way to do it, of course, is to get a 13:51:10 17 drug which acts more potently on the receptor that 13:51:13 18 you're interested in or you think may actually be causing 13:51:20 19 the problem. 13:51:22 20 Q. Does Paxil operate more potently on the 5HT2 13:51:23 21 receptor? 13:51:29 22 A. What it acts more potently on is the serotonin 13:51:29 23 transport system causing more serotonin to be available at 13:51:34 24 the 5HT 2 receptor quicker than Prozac does. 13:51:38 25 Q. You mentioned this morning the effects of LSD on 13:51:43 98 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 that receptor. Are Paxil's effects there analogous to 13:51:47 3 those? 13:51:52 4 A. Well -- 13:51:52 5 MR. PREUSS: Objection, Your Honor, we 13:51:54 6 objected this morning on the same issue, that the LSD 13:51:56 7 issue is not a part of this report, the addictive nature. 13:51:59 8 MR. VICKERY: I think it is, Judge. Let 13:52:04 9 me just dig it out. 13:52:06 10 I won't waste the Court's time looking for it 13:52:26 11 but -- in all fairness let's not waste the court's and the 13:52:30 12 jury's time looking for it. I will withdraw that 13:52:34 13 question. 13:52:36 14 Q. (BY MR. VICKERY) Dr. Healy, are you fully aware 13:52:45 15 of the pharmacological differences, as fully aware as 13:52:47 16 anyone in your field can be today, between Zoloft, Paxil 13:52:51 17 and Prozac? 13:52:54 18 A. Yes, I am. 13:52:56 19 Q. Are there similarities and differences? 13:52:57 20 A. There are both similarities and differences. 13:52:59 21 Q. And have you written and published a book about 13:53:01 22 them? 13:53:04 23 A. Not specifically about that, but about the 13:53:05 24 general differences between molecules, how minor changes 13:53:08 25 to a molecule can produce a completely different effect. 13:53:11 99 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Q. With respect to their ability to precipitate 13:53:20 3 violent or suicidal behavior, are they similar or 13:53:23 4 different? 13:53:26 5 A. Similar. 13:53:27 6 Q. This morning you said you firmly believe that 13:54:06 7 but for the Paxil that he received that Mr. Schell and his 13:54:09 8 family would still be alive. Do you still hold that view? 13:54:13 9 A. Yes, I do. 13:54:18 10 Q. Do you hold that view to a degree of reasonable 13:54:26 11 medical probability? 13:54:26 12 A. Yes, I do. 13 MR. VICKERY: I will pass the witness. 13:54:26 14 THE COURT: Thank you very much. 13:54:26 15 Q. (BY MR. PREUSS) Good afternoon, Doctor. 13:55:02 16 A. Good afternoon, Mr. Preuss. 13:55:04 17 Q. You're not board certified as a physician in 13:55:07 18 this country, are you? 13:55:10 19 A. No, I am not. 13:55:11 20 Q. And you cannot practice medicine in this 13:55:12 21 country, can you? 13:55:16 22 A. No, I can't. 13:55:17 23 Q. Which means you can't write any prescriptions; 13:55:18 24 isn't that correct? 13:55:20 25 A. That's correct. 13:55:21 100 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Q. And that's because United States has different 13:55:21 3 regulations and rules that govern the practice of medicine 13:55:23 4 than Wales? 13:55:26 5 A. I assume it has, yes. 13:55:28 6 Q. And you're not an epidemiologist, are you, sir? 13:55:30 7 A. No, I not an epidemiologist but I know a good 13:55:33 8 deal about epidemiological principles. 13:55:37 9 Q. You do not have a degree in epidemiology, do 13:55:40 10 you? 13:55:42 11 A. No, I do not. 13:55:42 12 Q. You don't teach epidemiology, do you? 13:55:44 13 A. In terms of teaching psychopharmacology I will 13:55:47 14 teach epidemiological principles in terms of how to 13:55:50 15 outline drug adverse events. 13:55:53 16 Q. And you are not a statistician, are you? 13:56:06 17 A. No, I'm not. 13:56:09 18 Q. You don't usually analyze your own data if 13:56:10 19 you're doing research, do you? 13:56:13 20 A. No, I don't. 13:56:15 21 Q. You've been retained by Mr. Vickery in the 13:56:15 22 Schell case here? 13:56:18 23 A. I have, Mr. Preuss. 13:56:19 24 Q. And you have been retained by him in the past? 13:56:20 25 A. I have, Mr. Preuss, yes. 13:56:22 101 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Q. And you've been called to testify in a case in 13:56:24 3 Hawaii; isn't that correct? 13:56:26 4 A. That's correct. 13:56:29 5 Q. And when were you first engaged by Mr. Vickery, 13:56:29 6 sir, for any matter? 13:56:32 7 A. I believe January -- now you ask me the -- I 13:56:39 8 believe it was somewhere around May 1997. 13:56:42 9 Q. You're aware in this country the FDA regulates 13:56:50 10 what medicines can and can't be sold, correct? 13:56:53 11 A. Yes. 13:56:57 12 Q. And you don't claim any expertise in labeling in 13:56:57 13 this country, do you? 13:57:00 14 A. I don't claim expertise in labeling, no. 13:57:01 15 Q. Or the warning process at all as far as 13:57:04 16 pharmaceuticals are concerned? 13:57:07 17 A. I don't claim expertise in the warning process 13:57:09 18 from a FDA point of view. I do -- 13:57:12 19 Q. Thank you, Doctor. 13:57:16 20 You're not generally recognized as a FDA expert; 13:57:18 21 isn't that correct? 13:57:22 22 A. That's correct. 13:57:23 23 Q. And you never advised a drug manufacturer in 13:57:23 24 this country on FDA matters, have you? 13:57:25 25 A. No, I haven't. 13:57:27 102 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Q. And you understand that the FDA controls the 13:57:28 3 labeling process in this country? 13:57:33 4 A. Yes, I do. 13:57:34 5 Q. And you've never consulted with the FDA, have 13:57:35 6 you? 13:57:37 7 A. No, I have not. 13:57:37 8 Q. Or been employed by them in any way? 13:57:39 9 A. No. 13:57:41 10 Q. And you've never participated in any FDA 13:57:43 11 regulated proceeding addressing what constitutes an 13:57:45 12 adequate warning, have you? 13:57:49 13 A. No, I haven't. 13:57:50 14 Q. And would it be fair to say, Doctor, you have 13:57:58 15 little if any involvement with the regulatory standards 13:58:00 16 which govern the pharmaceutical company conduct here in 13:58:03 17 this country? 13:58:05 18 A. That would be fair. 13:58:06 19 Q. And you haven't drafted a product label that has 13:58:08 20 been used anywhere in the world, have you? 13:58:11 21 A. No, I haven't. 13:58:14 22 Q. And you haven't been involved in the regulation 13:58:15 23 or approval of a product labeling with a prescription 13:58:18 24 medication anywhere in the world, have you? 13:58:21 25 A. Well, I have been invited by the regulators in 13:58:24 103 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 the United Kingdom to submit an appropriate warning for 13:58:26 3 the SSRI group of drugs and I have done so. 13:58:31 4 Q. I would like to read from your deposition, page 13:58:34 5 346, lines 18 through 22 -- 13:58:36 6 MR. VICKERY: Hold on just a minute, 13:58:41 7 Mr. Preuss. 13:58:42 8 Q. (BY MR. PREUSS) Question: You haven't been 13:59:19 9 involved in the regulation or approval of product labeling 13:59:21 10 or prescription medication -- 13:59:24 11 A. Could you tell me where you are, Mr. Preuss? 13:59:27 12 Q. I'm sorry. Lines 18 through 22, sir, page 346. 13:59:29 13 A. 346? Sorry. I'm on the wrong page. 13:59:35 14 MR. VICKERY: Objection, Your Honor. 13:59:39 15 Under the rule of completeness I would ask that if 13:59:40 16 Mr. Preuss is going to offer this, he offer the two or 13:59:43 17 three questions before beginning on line 4 of that page. 13:59:45 18 MR. PREUSS: It is an isolated question 13:59:56 19 and answer, Your Honor. 13:59:57 20 MR. VICKERY: Judge, it is not isolated at 13:59:59 21 all. It is in context. 14:00:00 22 THE COURT: Well, go ahead and read it. 14:00:02 23 Let the witness refer back to it and read it out loud and 14:00:06 24 we'll see what it is. 14:00:10 25 MR. PREUSS: From where, Your Honor? 14:00:11 104 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 THE COURT: What did you suggest, line 4. 14:00:13 3 MR. VICKERY: 346, from line 4 if he wants 14:00:15 4 to put it in context. 14:00:17 5 Q. (BY MR. PREUSS) Question: Indeed, you've never 14:00:20 6 been involved with the drafting of product labeling for 14:00:22 7 any prescription medication in the United States? 14:00:24 8 Answer: United States, no, but clearly I've had 14:00:26 9 some involvement, however peripheral with the issue in 14:00:29 10 the UK. 14:00:32 11 Question: Have you ever drafted a product label 14:00:33 12 that's been used on prescription medication? 14:00:42 13 Answer: No, I have drafted a form of words 14:00:42 14 about warning on the SSRIs. 14:00:42 15 Question: Have you drafted a product label that 14:00:43 16 is in use anywhere in the world? 14:00:45 17 Answer: No. 14:00:48 18 Question: You haven't been involved with the 14:00:49 19 regulation or approval of product labeling of prescription 14:00:51 20 medication anywhere in the world? 14:00:54 21 Answer: That's correct. 14:00:56 22 Doctor, let's turn to a new area. As I 14:01:05 23 understand your testimony, you still prescribe SSRIs, 14:01:07 24 correct? 14:01:10 25 A. I do, indeed. 14:01:11 105 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Q. And Paxil is a SSRI? 14:01:12 3 A. It is, yes. 14:01:14 4 Q. You believe that SSRI have an important role in 14:01:14 5 the treatment of depression, do you not? 14:01:16 6 A. I believe they've got a role in the treatment of 14:01:18 7 a range of nervous problems. 14:01:21 8 Q. Including depression? 14:01:23 9 A. Including depression. 14:01:24 10 Q. And you agree that SSRIs have a place in the 14:01:26 11 management of depressive suicidality, do you not? 14:01:28 12 A. I do indeed, yes. 14:01:33 13 Q. And as I understand it, you've seen roughly 1200 14:01:34 14 newly depressed patients in the last ten years, sir? 14:01:37 15 A. That was my estimate when I was deposed and I 14:01:42 16 haven't had any reason to actually revisit that estimate. 14:01:44 17 Q. So that 1200 is about right? 14:01:48 18 A. Probably. 14:01:55 19 Q. You prescribe SSRIs to about half of them? 14:01:56 20 A. Of the group of antidepressants it is among 14:01:58 21 there -- there are a multitude of drugs that I would use. 14:02:00 22 Q. And those patients that you see that have prior 14:02:06 23 histories of SSRIs, more than half of them use Paxil; 14:02:08 24 isn't that correct? 14:02:14 25 A. Sorry, could you repeat that to me? 14:02:15 106 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Q. In the group of patients that you see that are 14:02:17 3 on SSRIs when you see them, more than half of those are on 14:02:20 4 Paxil, are they not? 14:02:24 5 A. Yes, they're referred to me by their G Ps on 14:02:25 6 Paxil. This tends to mean, though, that the drug is not 14:02:31 7 working in those patients and I'm being asked what to do. 14:02:35 8 Q. And you prescribe Paxil to your own patients, 14:02:39 9 correct? 14:02:42 10 A. I have been prescribing -- of the SSRIs I have 14:02:42 11 been prescribing it much less frequently than the others 14:02:46 12 because of problems with physical dependence. 14:02:48 13 Q. And the question was, you prescribe it to your 14:02:51 14 own patients; is that correct, sir? 14:02:53 15 A. Yes, but I haven't prescribed it that regularly 14:02:57 16 in recent years, no. 14:03:00 17 Q. I would like to read from the deposition, page 14:03:14 18 347, lines 25 through line 1 on page 348. 14:03:16 19 A. Did you wish me to read? 14:03:32 20 Q. I'm waiting for your counsel? 14:03:35 21 MR. VICKERY: I'm there, line 25. 14:03:37 22 MR. PREUSS: Line 25 to line 1, page 346. 14:03:39 23 Q. (BY MR. PREUSS) Question: Do you still 14:03:43 24 prescribe Paxil. 14:03:44 25 Answer: Yes, I would prescribe Paxil. 14:03:45 107 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Was that your testimony when you were deposed? 14:03:48 3 A. Yes, it was and it is the testimony I've offered 14:03:51 4 you as well this afternoon. 14:03:53 5 Q. And you believe Paxil is an effective treatment 14:03:54 6 for depression, do you not? 14:03:57 7 A. It is not a treatment for severe or hospital 14:03:59 8 depression as your own product labeling indicates. 14:04:02 9 Q. With that exclusion, it is effective for 14:04:05 10 depression on non-hospital based patients? 14:04:07 11 A. For milder cases it may be effective for some 14:04:10 12 patients. 14:04:14 13 Q. You prescribe it when you do in the hope it will 14:04:14 14 reduce depression, do you not? 14:04:17 15 A. Yes, I do. 14:04:19 16 Q. By reducing depression, you would reduce the 14:04:19 17 risk of potential suicide? 14:04:22 18 A. When I prescribe it, I am aware I may be at the 14:04:24 19 same time increasing the risk of suicide. 14:04:28 20 Q. You prescribe it with the idea that it will help 14:04:30 21 depression and there by help reduce the risk of suicide, 14:04:32 22 do you not, sir? 14:04:36 23 A. Not especially. Mr. Preuss, can I explain the 14:04:37 24 answer to you? 14:04:41 25 Q. I think we will move on, sir. 14:04:42 108 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 You believe that Paxil can reduce suicidal 14:04:45 3 thoughts and make people less suicidal, don't you? 14:04:48 4 A. I believe, Mr. Preuss, that for the group of 14:04:53 5 patients who are most suicidal the drug is ineffective. 14:04:54 6 Your own product labeling suggests that. But within the 14:04:58 7 group of patients who are more mildly depressed, some of 14:05:01 8 whom may be somewhat suicidal, yes, it may reduce that 14:05:04 9 suicidal ideation. 14:05:07 10 Q. And Paxil has an antianxiety effect, does it 14:05:09 11 not? 14:05:13 12 A. It has over the longer term. In the short term 14:05:13 13 it may greatly increase the level of anxiety and 14:05:16 14 agitation. 14:05:19 15 Q. I would like to read from page 44, lines 20 14:05:23 16 through 23. 14:05:26 17 MR. VICKERY: Hold on there. 14:05:28 18 A. We have a problem. I don't have that page in 14:05:33 19 this copy of the deposition. Mine ends on page 41 and 14:05:35 20 starts on page 46. 14:05:45 21 Q. I apologize. Let's use this one? 14:06:20 22 A. We have the same problem with this one, 14:06:31 23 unfortunately. Unless I'm doing something very strange. 14:06:31 24 MR. VICKERY: I object to it anyway, Your 14:06:32 25 Honor. It is inappropriate use of deposition testimony. 14:06:33 109 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 It is fully consistent with the testimony he just gave so 14:06:35 3 it is not impeachment. 14:06:38 4 THE COURT: Overruled. 14:06:40 5 MR. VICKERY: Should I hand -- may I hand 14:06:43 6 the witness my copy, then, so he can read along. 14:06:44 7 THE COURT: Yes, you may. 14:06:47 8 THE COURT: Mr. Preuss, state the page and 14:06:55 9 line again. 14:06:56 10 MR. PREUSS: Certainly, Your Honor. Page 14:06:57 11 44, lines 21 through 23. 14:06:59 12 A. Give me just one minute to coordinate here. 14:07:02 13 Q. (BY MR. PREUSS) "Let me reask the question: 14:07:10 14 Does Paxil have an anxiolytic effect. 14:07:12 15 Answer: Paxil has an anxiolytic effect." 14:07:17 16 Doctor, you would agree, would you not, that 14:07:39 17 long before antidepressant medications were around that 14:07:39 18 people committed suicide for no apparent reason? 14:07:39 19 A. Yes, I would agree with that. 14:07:41 20 Q. In your expert reports you're familiar with 14:09:01 21 that, are you not, sir? 14:09:01 22 A. I would hope so. 14:09:01 23 Q. In those two reports that you submitted, you do 14:09:01 24 not cite to any single case report of a single person that 14:09:01 25 took Paxil and had suicidal thoughts; isn't that correct? 14:09:01 110 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 A. In the original form you asked me for -- when I 14:09:01 3 was being deposed I was asked for further case reports, 14:09:01 4 which I offered. 14:09:01 5 Q. My question, sir, was at the time that you 14:09:01 6 filled out your reports in this case, your expert reports, 14:09:01 7 you did not cite to a single published case report of a 14:09:01 8 person that took Paxil and had suicidal thoughts; isn't 14:09:01 9 that correct, sir? 14:09:01 10 A. That is correct. 14:09:01 11 Q. And same question as to suicidal attempt? 14:09:01 12 A. That is correct. 14:09:01 13 Q. Same question as to committing suicide, actually 14:09:01 14 completing it? 14:09:01 15 A. That's correct. 14:09:01 16 Q. Same question as to homicidal thoughts? 14:09:01 17 A. Correct. 14:09:01 18 Q. Same question as to attempted homicide? 14:09:01 19 A. That is correct. 14:09:01 20 Q. Same question as to committed homicide? 14:09:01 21 A. That is correct. 14:09:01 22 Q. Same question as to committed murder/suicide? 14:09:01 23 A. That is correct. 14:09:01 24 Q. And in addition, Doctor, you didn't cite to a 14:09:01 25 single article in those reports in the worldwide 14:09:07 111 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 literature that demonstrates a causal connection between 14:09:07 3 Paxil and homicide; isn't that correct? 14:09:09 4 A. That is correct. 14:09:12 5 Q. And you didn't cite to a single article in the 14:09:12 6 worldwide scientific literature that demonstrates a causal 14:09:14 7 connection between Paxil and homicidal attempts or 14:09:18 8 homicidal thoughts; isn't that correct? 14:09:21 9 A. That is correct. 14:09:24 10 Q. And you cited to no article in the worldwide 14:09:24 11 literature linking Paxil to aggression, did you? 14:09:27 12 A. That is correct. 14:09:31 13 Q. Now you have written in those reports that Paxil 14:09:39 14 causes three different conditions: Akathisia, emotional 14:09:41 15 indifference and psychotic decompensation; isn't that 14:09:45 16 correct? 14:09:49 17 A. That's correct. 14:09:50 18 Q. And it is your belief that any one of those 14:09:50 19 three can lead to potential for violence or suicide, isn't 14:09:52 20 that right? 14:09:56 21 A. That is correct. 14:09:57 22 Q. In this particular case you believe that 14:09:57 23 akathisia may be the one that's involved; is that correct? 14:09:58 24 A. Well, I think you can't tease these things 14:10:02 25 actually apart all that cleanly. In almost any case, 14:10:05 112 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Mr. Preuss. I think I made that clear during the course 14:10:10 3 of the deposition. 14:10:15 4 Q. Are you saying that we're dealing here with 14:10:16 5 emotional blunting? 14:10:18 6 A. I think that Mr. Schell may well have been 14:10:21 7 emotionally labile and may well have psychotically 14:10:25 8 decompensated. 14:10:30 9 Q. And that particular term, emotional blunting, 14:10:32 10 has not really been defined, has it? 14:10:35 11 A. It hasn't been clearly defined. 14:10:38 12 Q. You didn't cite to a single article, did you, in 14:10:40 13 your report linking Paxil to emotional indifference or 14:10:42 14 emotional blunting, as you refer to it? 14:10:46 15 A. No, I didn't. 14:10:49 16 Q. And not only with respect to articles, but you 14:11:29 17 didn't cite any case report in the entire worldwide 14:11:29 18 literature linking Paxil to emotional blunting or 14:11:29 19 emotional indifference; isn't that correct? 14:11:29 20 A. That is correct. 14:11:29 21 Q. Let's turn to psychotic decompensation, sir. 14:11:29 22 You didn't cite to a single scientific article linking 14:11:29 23 Paxil to psychotic decompensation; isn't that correct, in 14:11:29 24 your reports? 14:11:29 25 A. That's correct. 14:11:29 113 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Q. Who are a single articles that talks about a 14:11:29 3 case report linking Paxil to psychotic decompensation; 14:11:29 4 isn't that correct? 14:11:29 5 A. That's correct. 14:11:29 6 Q. Let's talk about akathisia then. Is it your 14:11:32 7 testimony that akathisia has a motor component? 14:11:32 8 A. No, it is not my testimony. 14:11:34 9 Q. Have you written anywhere that akathisia has a 14:11:39 10 motor component? 14:11:42 11 A. Akathisia may well have a motor component. It 14:11:43 12 is not my testimony that it is necessary that it has a 14:11:46 13 motor component. 14:11:49 14 Q. It may or may not, is that your testimony? 14:11:50 15 A. Yes, it is. 14:11:52 16 Q. Would you agree that traditionally akathisia is 14:11:55 17 believed to have a motor component as well as a subjective 14:11:58 18 component? 14:12:02 19 A. Traditionally if you look at the main books on 14:12:03 20 this, it is thought to primarily have a subjective 14:12:11 21 component. The motor component is particularly associated 14:12:11 22 with the use of antipsychotic drugs and once the 14:12:13 23 phenomenon gets described as being produced by SSRIs, 14:12:16 24 there is much less emphasis on a motor component. It is 14:12:20 25 much less of a feature of the descriptions of akathisia 14:12:24 114 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 induced by SSRIs. 14:12:27 3 Q. And hand tremors are not akathisia, are they? 14:12:30 4 A. Hand tremors may be a manifestation that the 14:12:34 5 person is in a state of turmoil. They may also be just 14:12:37 6 simply hand tremors. 14:12:41 7 Q. Refer to you page 243, line 4 through 5. 14:12:56 8 THE COURT: What were the lines again, 14:13:04 9 Mr. Preuss. 14:13:05 10 MR. PREUSS: 4 through 5, Your Honor. 14:13:06 11 Q. (BY MR. PREUSS) Question: So a hand tremor is 14:13:19 12 not akathisia? 14:13:21 13 Answer: -- 14:13:23 14 A. I'm on page 242. Sorry. What page? 14:13:25 15 Q. 243. Question: "So a hand tremor is not 14:13:28 16 akathisia? 14:13:31 17 Answer: No, it is not." 14:13:32 18 Was that your testimony, sir? 14:13:34 19 MR. VICKERY: Excuse me, Counsel. I 14:13:36 20 object, Your Honor. The lawyer then says, "So you can go 14:13:37 21 on," and there's an explanation that follows right after, 14:13:42 22 that the very next line. 14:13:44 23 THE COURT: I will let you take that up on 14:13:50 24 redirect. But I will -- request Mr. Preuss to read what 14:13:51 25 lines. 14:13:55 115 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 MR. VICKERY: Just the rest of the answer, 14:13:57 3 the lawyer on line 6 says, "You can go on," and then the 14:13:58 4 answer continues on line 7 and goes down through page 244, 14:14:02 5 line 15. 14:14:06 6 THE COURT: Read the whole answer. 14:14:10 7 MR. PREUSS: Yes, Your Honor. 14:14:12 8 Q. (BY MR. PREUSS) "So you can go on. 14:14:13 9 Answer: Right, akathisia as has been generally 14:14:15 10 understood by the field -- and there are two or three 14:14:18 11 books which deal with this. There's a book literally 14:14:20 12 called Akathisia by Herman Sacfda. And there's another 14:14:23 13 book, for my money the best book, on the Extrapyramidal 14:14:27 14 Problems Caused by Antipsychotics, called something like 14:14:33 15 that. It is a guide to the problems caused by 14:14:33 16 antipsychotics. I should know the title offhand, but it 14:14:35 17 is by David Cunningham Owens from Edinburgh, and in his 14:14:39 18 opinion akathisia is closer to dysphoria than it is to 14:14:43 19 dyskinesia, which is an unpleasant emotional state. For 14:14:46 20 most clinicians in the field their view tends to be an 14:14:50 21 inner restlessness of some sort. You don't have to have 14:14:54 22 obvious motor manifestations. 23 My definitions of akathisia come back to three 14:14:56 24 or four quotes, which the first description of it in the 14:14:59 25 literature, when it is produced by Reserpine -- and I can 14:15:06 116 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 provide the quotes for you during whatever the break we 14:15:11 3 have -- but the first patients where it is actually 14:15:13 4 described is -- what later gets termed akathisia is he 14:15:16 5 reacted to the drug with marked anxiety and weeping and he 14:15:19 6 reported strange and unusual impulses and worries about 14:15:22 7 the things that he might do, okay. 14:15:24 8 So these -- I think people who define akathisia 14:15:26 9 have to include these descriptions from patients which are 14:15:30 10 the first in the field." 14:15:33 11 Is it your view that Don Schell's hand tremors 14:15:37 12 were akathisia? 14:15:41 13 A. My view is that Don Schell's hand tremors are 14:15:44 14 potentially one of the manifestations of the somatic 14:15:51 15 anxiety that Dr. Suhany described. 14:15:56 16 Q. Could you answer the question, please? 14:16:00 17 A. They may also be independently tremors as all 14:16:01 18 the SSRIs can cause tremors quite separately to causing 14:16:04 19 akathisia. So they could have been either, Mr. Preuss. 14:16:08 20 Q. And Dr. Suhany in his deposition indicated -- 14:16:12 21 which you read, right? 14:16:15 22 A. Yes. 14:16:16 23 Q. Indicated that in his view Don Schell did not 14:16:16 24 have akathisia; isn't that correct? 14:16:19 25 A. As I indicate on page 242 here in the bit just 14:16:21 117 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 before you read that he's using a particular use of the 14:16:24 3 word "akathisia." 14:16:27 4 Q. You know what uses using? 14:16:30 5 A. I think I know what use he's using of that word, 14:16:32 6 yes. 14:16:35 7 Q. So you have defined at least in this litigation 14:16:48 8 that akathisia is something as simple as agitation; isn't 14:16:50 9 that correct? 14:16:53 10 A. Yes. Part of the reason for doing this is that 14:16:53 11 that in the healthy volunteer studies SmithKline Beecham 14:16:58 12 defined akathisia under the heading agitation. That's 14:17:01 13 what they called it. 14:17:04 14 Q. Is it correct, Doctor, we don't even know what 14:17:08 15 causes akathisia? 14:17:11 16 A. It is correct that we haven't investigated it 14:17:12 17 properly and the field hasn't moved on to the point where 14:17:17 18 I can give you crystal clear answers on just that issue, 14:17:20 19 Mr. Preuss, yes. 14:17:24 20 Q. In your expert reports, Doctor, you didn't cite 14:17:25 21 to a single article in the peer reviewed literature that a 14:17:27 22 person taking Paxil developed akathisia or agitation which 14:17:30 23 in turn led to suicide or homicide, did you? 14:17:33 24 A. No, I didn't. 14:17:36 25 Q. And the same question as to whether you could 14:17:45 118 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 cite to a single case report in the literature of a person 14:17:47 3 taking Paxil, getting akathisia which developed into 14:17:49 4 suicide or homicide? You couldn't cite to one, could you? 14:17:58 5 A. Well, now we're -- I was asked there and then 14:17:58 6 and I said I was aware that there was some reports of 14:18:01 7 people becoming agitated on probably becoming suicidal. I 14:18:04 8 didn't have the reports at my fingertips; that is correct. 14:18:12 9 Q. You understood at the time of your deposition 14:18:16 10 you had already submitted your reports, correct? 14:18:17 11 A. That's correct. 14:18:19 12 Q. And you did not cite any case report in there, 14:18:20 13 did you? 14:18:22 14 A. No, I didn't. 14:18:23 15 Q. You agree that every SSRI drug you discussed has 14:18:42 16 a different chemical formula, correct? 14:18:42 17 A. That is correct. 14:18:42 18 Q. And they have different chemical structures as 14:18:42 19 well, right? 14:18:45 20 A. That is correct. 14:18:45 21 Q. And you would agree that changing even one atom 14:18:46 22 in a chemical structure of a drug could alter the biologic 14:18:49 23 effects that that drug produces; isn't that correct? 14:18:53 24 A. I have written a book on just that, Mr. Preuss. 14:18:56 25 Q. But you believe that SSRIs can differ in their 14:19:00 119 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 ability to creating agitation in people that ingest them; 14:19:03 3 isn't that correct? 14:19:07 4 A. That is correct. 14:19:07 5 Q. And you believe Paxil and Prozac differ in their 14:19:07 6 ability to creating agitation, do you not? 14:19:11 7 A. Yes, I do. 14:19:15 8 Q. And you believe that Prozac is the most 14:19:16 9 agitating of all SSRIs; isn't that correct? 14:19:18 10 A. Yes. 14:19:21 11 Q. You believe Zoloft is up there with Prozac but 14:19:22 12 not quite as high as Prozac; isn't that correct? 14:19:25 13 A. That is correct. 14:19:27 14 Q. And you believe that Paxil is less likely to 14:19:27 15 cause agitation than either Prozac or Zoloft; isn't that 14:19:29 16 correct? 14:19:33 17 A. That is correct. 14:19:33 18 Q. When Prozac was approved for sale years 14:19:49 19 before -- withdraw the question. Prozac was approved 14:19:49 20 years before Paxil was; isn't that correct? 14:19:49 21 A. That is correct. 14:19:50 22 Q. You understand the regulatory structure enough 14:19:50 23 to know that SmithKline can't just rely on Prozac NDA to 14:19:52 24 get Paxil approved? 14:19:57 25 A. That's absolutely correct. Given how weak the 14:19:59 120 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 antidepressant effects of Prozac were, it was entirely 14:20:01 3 appropriate for the FDA to insist on further studies. 14:20:06 4 Q. You understand that each manufacturer has to 14:20:08 5 submit its owe data on its product for approval; is that 14:20:10 6 correct? 14:20:14 7 A. That's correct. 14:20:15 8 Q. So that the FDA approval for Paxil was based on 14:20:15 9 FDA review of Paxil studies, correct? 14:20:18 10 A. That is correct. 14:20:21 11 Q. The FDA approves the various drugs for different 14:20:27 12 indications, right? 14:20:30 13 A. That is correct. 14:20:30 14 Q. And Paxil is approved for a number of 14:20:31 15 indications; isn't that correct, in this country? 14:20:34 16 A. It is, that's true. 14:20:38 17 Q. General anxiety disorder, social anxiety 14:20:41 18 disorder, depression? 14:20:43 19 A. Yes. 14:20:44 20 Q. Obsessive compulsive disease? 14:20:45 21 A. Yes. 14:20:48 22 Q. And Prozac, for example, isn't approved for any 14:20:49 23 anxiety use; isn't that correct? 14:20:51 24 A. I'm not immediately clear on what exact 14:20:53 25 conditions Prozac is approved for. 14:20:57 121 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Q. Prozac and Paxil have different chemical 14:21:00 3 formulas? 14:21:03 4 A. That is correct. 14:21:04 5 Q. And different chemical structures? 14:21:04 6 A. That is correct. 14:21:07 7 Q. And different pharmacologic effects, correct? 14:21:07 8 A. Different pharmacologic effects, this isn't one 14:21:10 9 I can answer yes or no unfortunately for you. There are 14:21:13 10 differences in the pharmacokinetic effects, differences in 14:21:16 11 the pharmacodynamic effects, but functional effects, they 14:21:19 12 share a broad range of common functional pharmacological 14:21:24 13 effects. 14:21:32 14 Q. You said that Prozac and Paxil have different 14:21:33 15 pharmacokinetic characteristics; is that right? 14:21:35 16 A. Yes, I did. 14:21:37 17 Q. Doctor, you would agree that they different in 14:21:46 18 that they block the reuptake of serotonin, correct? 14:21:48 19 A. That's correct. 14:21:53 20 Q. Same question with respect to norepinephrine? 14:21:54 21 A. That's correct. 14:21:57 22 Q. That's another neurotransmitter? 14:21:58 23 A. That's correct. 14:22:00 24 Q. Same with respect to dopamine, correct? 14:22:01 25 A. That is correct. 14:22:04 122 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Q. And they differ in the way they're metabolized, 14:22:06 3 do they not? 14:22:10 4 A. That's correct. 14:22:11 5 Q. And Paxil, for example, does not have an active 14:22:13 6 metabolite, isn't that right? 14:22:16 7 A. That's correct. 14:22:19 8 Q. And Prozac does? 14:22:20 9 A. That is correct. 14:22:22 10 Q. And so does Zoloft, right? 14:22:22 11 A. Yes. 14:22:23 12 Q. There are other differences as well, are there 14:22:28 13 not? Somebody may react positively to one SSRI and not 14:22:30 14 positively to another; isn't that correct? 14:22:33 15 A. That's possible. Equally, someone can react not 14:22:35 16 too badly to one SSRI and much worse to another. 14:22:39 17 Q. That's right. Now, you spoke of dose-response 14:22:42 18 this morning with respect to Paxil, did you not? 14:22:45 19 A. Yes, I did. 14:22:48 20 Q. At the time you were deposed you had no opinion 14:22:49 21 in that regard, did you? 14:22:51 22 A. It may kind of depend on the context. Would you 14:22:55 23 like to show me the part of the deposition? I have a 14:22:58 24 feeling you might. 14:23:01 25 Q. Page 217, lines 12 through 20? 14:23:02 123 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 MR. VICKERY: 217. 14:23:25 3 MR. PREUSS: Yes, 217, lines 12 through 14:23:26 4 20. 14:23:28 5 "Question: Let me ask again. Is it going to be 14:24:06 6 your opinion to a reasonable degree of scientific 14:24:06 7 certainty that there is a clear dose-response relationship 14:24:06 8 between Paxil and suicidality? 14:24:06 9 Answer: I haven't formed a specific view about 14:24:06 10 Paxil and the dose-response relationship between it and 14:24:06 11 suicide at this point in time." 14:24:06 12 Did you give that testimony? 14:24:06 13 A. Yes, I did. 14:24:06 14 Q. And yet you commented on dose-response this 14:24:06 15 morning, did you not? 14:24:06 16 A. I did indeed, yes. 14:24:06 17 MR. PREUSS: Ask that that testimony be 14:24:06 18 stricken, Your Honor. 14:24:06 19 MR. VICKERY: Your Honor, I would respond 14:24:09 20 as follows: He talked about dose-response this morning in 14:24:09 21 terms of dose-response relationship between akathisia, 14:24:12 22 agitation, those kinds of side effects, not this question 14:24:15 23 here which was specifically limited to suicide. 14:24:20 24 So it would be inappropriate to strike that 14:24:23 25 testimony. 14:24:25 124 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 THE COURT: The testimony this morning was 14:25:22 3 it related to Paxil. 14:25:22 4 MR. VICKERY: It was related to all SSRIs, 14:25:22 5 including Paxil. The distinction is the one question he 14:25:22 6 asked him was related to dose-response to suicide as 14:25:22 7 opposed to dose-response to those states that might lead 14:25:22 8 to suicide. That's the distinction. 14:25:22 9 MR. PREUSS: Your Honor, the testimony was 14:25:22 10 related to Paxil and dose-response this morning and the 14:25:22 11 clear implication in the testimony that Paxil was part of 14:25:22 12 that. He had no opinion in his deposition and yet he puts 14:25:22 13 it in in the morning. It is totally improper. 14:25:22 14 MR. VICKERY: The specific question asked 14:25:22 15 in the deposition was did he have an opinion about 14:25:22 16 dose-response and suicide and he did not say that this 14:25:22 17 morning. He didn't say that. He said that there's a 14:25:22 18 clear dose-response relationship between those conditions 14:25:22 19 that have led to suicide. 14:25:22 20 THE COURT: It is a fine line. Overruled. 14:25:26 21 MR. PREUSS: Just a minute, Doctor. 14:25:27 22 THE COURT: Would you state for us what 14:25:58 23 you handed the witness. 14:25:59 24 MR. PREUSS: Yes, Your Honor, I handed the 14:26:01 25 witness and counsel a binder of articles that I'm going to 14:26:02 125 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 be asking him about and it is really merely for expediency 14:26:05 3 so that he would have it right there as we move through 14:26:09 4 these. 14:26:11 5 Q. (BY MR. PREUSS) Now, in 1994, sir, you wrote an 14:26:13 6 article entitled fluoxetine and suicide controversy, been 14:26:15 7 identified as SBFF 92. Is that correct? 14:26:19 8 A. Yes, I wrote an article, yes, of that title. 14:26:25 9 Q. And that was in 1994? 14:26:32 10 A. That's 1994. 14:26:34 11 Q. And fluoxetine is the same as Prozac, right? 14:26:35 12 A. That's correct. 14:26:39 13 Q. So we can use that interchangeably? 14:26:39 14 A. We can. 14:26:42 15 Q. And it discusses Prozac and suicide, does it 14:26:46 16 not? 14:26:48 17 A. It does. 14:26:48 18 Q. In this you make reference to the Teicher 14:26:54 19 article that you referenced this morning as being a 14:26:58 20 watershed article that manufacturers of SSRIs paid 14:27:00 21 attention to, right? 14:27:05 22 A. Yes, you will have to point me to the spot. You 14:27:07 23 mean the place where I actually refer to it at the start 14:27:10 24 of the article? 14:27:13 25 Q. Well, at the start and in other sections. 14:27:14 126 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 A. Yes, okay. 14:27:18 3 Q. All right. And the Teicher article dealt with a 14:27:19 4 case report; isn't that correct? 14:27:24 5 A. The Teicher article dealt with a series of six 14:27:25 6 case studies. 14:27:30 7 Q. Okay. And on page 227, do you see that? 14:27:32 8 A. Well, it actually depends where. 14:27:40 9 Q. 227. On the right-hand column you say case 14:27:42 10 reports are clearly an unreliable form of information; 14:27:46 11 isn't that correct? 14:27:50 12 A. That is correct. But it is in the context of 14:27:50 13 distinguishing anecdotal case reports from case studies. 14:27:52 14 Q. You used the word "case reports," not case 14:27:57 15 studies, didn't you? 14:28:00 16 A. I'm using the word "case reports" here in the 14:28:01 17 context of talking about anecdotal case reports. 14:28:03 18 Q. And you were critical of the Teicher reports, if 14:28:07 19 you go down a little further, right, where you say, "While 14:28:11 20 the initial reports by Teicher of suicidal ideation after 14:28:14 21 fluoxetine administration were clearly compromised on many 14:28:19 22 of these criteria." Do you see that? 14:28:22 23 A. Yes, I do. 14:28:24 24 Q. And in fact, you proposed table 2 as a way to 14:28:25 25 try to encourage reporting in a more reliable fashion for 14:28:28 127 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 scientists; isn't that right? 14:28:31 3 A. That's correct. 14:28:34 4 Q. On number 5, still on page 227, you say, "In 14:28:38 5 reply to the case reports, the fluoxetine induced 14:28:42 6 suicidality, Beasley and colleagues scrutinized the Eli 14:28:45 7 Lilly database for evidence of increased suicidality in 14:28:50 8 patients receiving fluoxetine. No such evidence has been 14:28:53 9 found. These data" -- 14:28:56 10 A. Could you point out where we are? I've lost 14:29:01 11 you. 14:29:04 12 Q. Same page, left-hand column, number 5. You want 14:29:05 13 me to start over? 14:29:08 14 A. No, no, I don't. 14:29:09 15 Q. Well, I will for context. "In reply to these 14:29:13 16 case reports of fluoxetine induced suicidality, Beasley 14:29:16 17 and colleagues scrutinized the Eli Lilly database for 14:29:19 18 evidence of increased suicidality in patients receiving 14:29:23 19 fluoxetine. No such evidence has been found. These data 14:29:26 20 from several thousand patients and the evidence that 14:29:30 21 fluoxetine reduces suicide ideation must on any scientific 14:29:32 22 scale outweigh the dubious evidence of a handful of case 14:29:36 23 reports." 14:29:39 24 And you believed that statement to be true at 14:29:41 25 the time you wrote it in 1994, didn't you? 14:29:48 128 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 A. No, I was making that statement ironically. The 14:29:48 3 follow-up correspondence to this article -- 14:29:49 4 Q. You mean you didn't mean what you said here in 14:29:52 5 an article you published in a peer reviewed scientific 14:29:54 6 article, sir? 14:29:57 7 A. I think this is to some extent and this is an 14:29:57 8 unfortunate way to put it -- have I lost sound -- was 14:30:00 9 poking fun at the way the issue had been handled by Lilly. 14:30:05 10 I thought it had been handled at this point in time -- 14:30:10 11 that it had been handled in a manner that was 14:30:14 12 irresponsible. 14:30:17 13 Q. Did I read this correctly, sir? 14:30:18 14 A. Well, there's a whole lot of ways to read 14:30:20 15 things. 14:30:24 16 Q. Did I read it correctly? 14:30:24 17 A. Well, you have the words, but you don't have the 14:30:26 18 correct tone of voice, Mr. Preuss. 14:30:28 19 Q. So somebody that reads that is supposed to 14:30:34 20 understand the interpretation, is that your testimony? 14:30:36 21 A. If you read the whole article, that will be 14:30:38 22 crystal clear to them. If it isn't crystal clear and 14:30:40 23 they're slow on the up take, if they read the follow-up 14:30:43 24 response, it is spelled out in detail. 14:30:47 25 Q. If you turn to the last paragraph on page 230, 14:30:49 129 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 sir, it says, "Such reactions to fluoxetine are rare and 14:30:52 3 undue concern over them may lead to more suicides by 14:31:05 4 virtue of patients giving up treatment." Do you agree 14:31:08 5 with that statement, sir? 14:31:11 6 A. In the context of the rest of the paragraph 14:31:12 7 which is that "It is this author's opinion that 14:31:16 8 acknowledging that such reactions may occur with all 14:31:20 9 psychotropic drugs and developing management guidelines 14:31:23 10 for such reactions is essential for all parties involved 14:31:27 11 in the therapy," that's the patient, the physician and the 14:31:30 12 pharmaceutical company. 14:31:34 13 Q. Which opinion is reactions to fluoxetine are 14 rare and undue concern could lead to more suicides by 14:31:44 15 patients giving up treatment? 14:31:45 16 A. Undue concern, if the warnings were clearly 14:31:48 17 there, then undue concern could be a problem. If the 14:31:51 18 warnings aren't there, we should be duly concerned. 14:31:54 19 Q. All right. Then could you please turn to 225 on 14:31:59 20 the left-hand column. You see the next to last paragraph 14:32:02 21 there, sentence, "Available post marketing surveillance 14:32:17 22 data from individual SSRIs do not suggest that any of the 14:32:21 23 SSRIs are particularly liable to cause aggressive, 14:32:24 24 impulsive or suicidal acts." Was that your statement at 14:32:28 25 the time, sir? 14:32:32 130 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 A. This statement need to be borne in context which 14:32:40 3 is that everybody recognizes that post marketing 14:32:43 4 surveillance studies are not a good way to pick up adverse 14:32:46 5 reactions. The fact that the post marketing surveillance 14:32:49 6 work doesn't implicate one SSRI more than the others, 14:32:56 7 which is how you need to read that particular sentence, 14:32:59 8 isn't anything to alleviate my mind on this issue of its 14:33:02 9 worries and shouldn't alleviate yours. 14:33:09 10 Q. Doctor, did I read it correctly and were those 14:33:11 11 your words in 1994 in the article that you published in a 14:33:14 12 peer review journal? 14:33:17 13 A. Yes, it is. 14:33:19 14 Q. Thank you. Now, Doctor, I believe if you would 14:33:20 15 turn again to page 227 on the right-hand column, on the 14:33:39 16 last paragraph there, it says, "Across all reports there 14:33:48 17 is a broad correspondence regarding the time of emergence 14:33:53 18 of suicidal ideation. About 10 to 14 days after 14:33:59 19 initiation of fluoxetine treatment. Is that correct? 14:34:04 20 A. That's correct. 14:34:09 21 Q. And Don Schell, according to your theory, 14:34:09 22 exhibited suicidal behavior in less than two days, 14:34:11 23 correct? 14:34:14 24 A. According to my testimony, he had agitation on 14:34:15 25 Prozac in the 10 to 14 day period. I explained I would 14:34:22 131 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 expect Paxil if it was going to cause problems, to cause 14:34:25 3 it earlier. 14:34:29 4 Q. Have you published that anywhere, sir, on Paxil? 14:34:33 5 A. No, I haven't. 14:34:36 6 Q. And you did not express that opinion in your 14:34:37 7 expert reports in this case, did you? 14:34:40 8 A. No one asked me for it. My view is clearly -- 14:34:42 9 Q. You had the opportunity to express whatever 14:34:45 10 opinions you wanted to in that report and you didn't put 14:34:47 11 it in there, did you, Doctor? 14:34:49 12 A. I expressed the opinion that I thought Paxil had 14:34:51 13 caused the problem for Mr. Schell, yes. 14:34:54 14 Q. But nothing with respect to the time, did you, 14:34:56 15 sir? 14:34:58 16 A. I can't see that that's an issue if I think that 14:35:00 17 the drug has caused the problem, Mr. Preuss. 14:35:02 18 Q. And the answer to my question is, "No, I didn't 14:35:05 19 put anything as to time in the expert report," correct? 14:35:07 20 A. I didn't put a specific point on time. But as 14:35:10 21 I've explained to Mr. Vickery, we wouldn't be here if it 14:35:12 22 had happened much later. 14:35:15 23 Q. Doctor, I would like to refer you, if I could, 14:35:17 24 to joint Exhibit 209? 14:35:26 25 A. Where will I find it? 14:35:26 132 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Q. It is tab 3: Is that a declaration or affidavit 14:35:38 3 that you prepared in connection with the Pierre matter? 14:35:47 4 A. It is, yes. 14:35:52 5 Q. And that involved where you were dealing with an 14:35:53 6 attorney over a criminal matter, right? 14:35:58 7 A. That is correct. 14:36:01 8 Q. And you were offering an opinion as to whether 14:36:01 9 Prozac could have been involved in the crime, correct? 14:36:04 10 A. That is correct. 14:36:08 11 Q. And you state on paragraph 11, first Prozac 14:36:10 12 causes a state of agitation or akathisia that fills the 14:36:17 13 individual with unusual impulses and has been associated 14:36:22 14 with suicide, homicide and other violent actions. 14:36:25 15 Typically this problem has its onset after a week or two 14:36:28 16 of Prozac treatment." Was that your statement, sir? 14:36:31 17 A. That is my statement. 14:36:34 18 Q. And on 14 you say, "However, this disinhibition 14:36:35 19 or change of personality, while possible" -- how do you 14:36:39 20 say it? 14:36:48 21 A. Whilst. 14:36:49 22 Q. -- "whilst possible in Mr. Pierre's case in this 14:36:50 23 instance is in the ordinary course of events something 14:36:52 24 that would be expected to happen after and I take of 14:36:55 25 Prozac for some weeks rather than acutely a few hours 14:36:57 133 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 after the first dose." Is that also your statement there, 14:37:01 3 sir? 14:37:05 4 A. It is my statement. 14:37:05 5 Q. Could you refer to your 1999 article entitled 14:37:27 6 suicide in the course of treatment of depression, SBFF 88, 14:37:30 7 please. 14:37:34 8 A. Yes, I have it. 14:37:35 9 Q. And if you would, sir, turn to page 98 in the 14:37:56 10 left-hand column. Again, this case has to do with Prozac, 14:38:02 11 does it not? 14:38:12 12 A. Which bit would you have me look at? 14:38:15 13 Q. It starts at -- with the sentence -- see the 14:38:19 14 paragraph, "As regards" -- if you go down five or six 14:38:23 15 lines, there's a statement, "There seems some possibility 14:38:28 16 that at least one SSRI, fluoxetine, may be associated with 14:38:30 17 higher rates of suicidality in certain individuals. It 14:38:34 18 remains unclear whether this is a problem likely to affect 14:38:38 19 all SSRIs or only those SSRIs used in particular 14:38:41 20 populations." 14:38:45 21 Was that your statement at the time? 14:38:47 22 A. That's my statement at the time, yes. 14:38:49 23 Q. And you stand by that statement? 14:38:50 24 A. That needs to be seen in the context of how one 14:38:53 25 writes scientific articles. And how one writes scientific 14:38:55 134 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 articles, Mr. Preuss, is if, for instance, I was a 14:39:00 3 Republican from Wyoming trying to get some proposal 14:39:03 4 through the Clinton Gore white house, one would phrase the 14:39:07 5 issues in a way that didn't raise the hackles of people 14:39:12 6 who might have particular beliefs in the case of this 14:39:16 7 article, we referred to the peer review process earlier 14:39:21 8 and I knew this article was going to be peer reviewed by a 14:39:24 9 particular individual and I was going to have to choose my 14:39:28 10 words very carefully in that context. 14:39:30 11 Q. So you didn't really say what you meant? 14:39:32 12 A. I said what I knew would get into print, given 14:39:34 13 that many of the reviewers of this kind of article are 14:39:39 14 going to be consultants to the pharmaceutical industry. 14:39:44 15 Q. Well, do you write differently in the medical 14:39:46 16 literature for your peers there than you do in terms of 14:39:48 17 giving oral opinions in a court of law, sir? 14:39:52 18 A. No, I don't. What must be very clear to you and 14:39:55 19 to the rest of the court from what I've said this 14:40:00 20 morning -- 14:40:04 21 Q. I think you've answered the question, Doctor. 14:40:05 22 A. All right, fine. 14:40:10 23 Q. That phrase you believe to be an accurate 14:40:20 24 statement, do you not, sir? 14:40:23 25 A. That's a phrase that's put in this article which 14:40:24 135 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 is a political compromise. 14:40:26 3 Q. Let's turn to SBFF 94 which I think should be 14:40:34 4 right after another article of yours entitled the 14:40:37 5 emergence of antidepressant induced suicidality. Do you 14:40:39 6 see that? 14:40:44 7 A. Yes. 14:40:45 8 Q. And again, you're talking about reports linking 14:40:45 9 Prozac to suicide, correct? 14:40:48 10 A. I'm talking about reports in this -- this is -- 14:40:51 11 yes, I'm talking about reports linking Prozac, Zoloft and 14:40:55 12 Paxil to suicidality. 14:40:59 13 Q. Where is Paxil cited, sir? 14:41:05 14 A. We've been through this in my deposition, 14:41:07 15 Mr. Preuss. I can't particularly remember which one has 14:41:09 16 the Paxil, but it is in here. Yes, reference 13. 14:41:14 17 Q. And that was an article that was not cited in 14:41:43 18 your expert report, was it? 14:41:45 19 A. Well, Mr. Preuss, in my expert report I cited 14:41:47 20 this article which contains that article, so from my point 14:41:50 21 of view, when I wrote my expert report there's clearly an 14:41:54 22 issue about how exhaustive one can be with these things. 14:41:58 23 I thought I had given you a fairly comprehensive list of 14:42:02 24 all of the things that I relied upon. 14:42:05 25 Q. All right. And again, you were talking about a 14:42:11 136 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 possibility of association of SSRIs, including Zoloft and 14:42:13 3 Paxil, and suicidality, right? 14:42:19 4 A. That's how one phrases things in scientific 14:42:21 5 articles, yes. 14:42:31 6 Q. So when you come in here is it still your 14:42:31 7 opinion scientifically it is only a possibility; is that 14:42:31 8 right? 14:42:33 9 A. No, it is my view these drugs can cause this 14:42:33 10 problem for some people. 14:42:36 11 Q. You agree with me, Doctor, in this article you 14:42:37 12 published for the peers in the scientific literature, you 14:42:39 13 again use the word "possibility" like you did in the '99 14:42:42 14 article we just discussed? 14:42:45 15 A. Can you point me to the particular spot you're 14:42:47 16 looking at? 14:42:49 17 Q. I can. Right-hand column, first page of the 14:42:50 18 article, it says, "On this basis there would seem, 14:42:52 19 therefore, to be a possibility that other SSRIs might 14:42:55 20 similarly induce suicidality." 14:42:59 21 A. Yes, this is saying quite clearly, I think, that 14:43:02 22 other SSRIs probably will induce suicidality. 14:43:05 23 Q. Your words were possibility, correct? 14:43:09 24 A. Yes, it is. 14:43:11 25 Q. And that's not the word you've used in this 14:43:12 137 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 courtroom? 14:43:14 3 A. I believe it is consistent with what I've said 14:43:14 4 in this courtroom. 14:43:17 5 Q. Is it only a possibility in your view as you sit 14:43:18 6 here today testifying in this courtroom? 14:43:20 7 A. No, it is not a possibility, it is obviously -- 14:43:22 8 as far as I'm concerned these drugs do cause a problem and 14:43:28 9 the scientific evidence, both the challenge/dechallenge, 14:43:32 10 dose-response, randomized control trials and 14:43:37 11 epidemiological evidence make this as clear as it can be 14:43:41 12 scientifically or legally or any other way. 14:43:44 13 Q. In the article you talk about possibility; isn't 14:43:49 14 that correct? 14:43:51 15 A. I talked about that because this is going out 14:43:51 16 for peer review and people may get very offended, people 14:43:53 17 who are consultants to the pharmaceutical industry. 14:43:56 18 Q. And you are -- well, this gets reviewed by your 14:43:59 19 peers, right? 14:44:02 20 A. It gets reviewed by my peers, most of whom -- 14:44:02 21 most of my peers would also be consultants to the 14:44:06 22 pharmaceutical industry. 14:44:08 23 Q. So your testimony here is different from what 14:44:10 24 you would tell your scientific peers; is that correct? 14:44:12 25 A. No, it is not at all different. 14:44:15 138 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Q. You don't use the word "possibility" in here, as 14:44:17 3 I understand it? 14:44:20 4 A. When you're writing a peer reviewed article, 14:44:21 5 Mr. Preuss, like this you're engaged in a political 14:44:23 6 exercise. You want some part of the truth at least to get 14:44:26 7 out and see the light of day. 14:44:29 8 Q. Doctor, turn to page 127 of your deposition, 14:44:38 9 please. 14:44:41 10 A. Unfortunately, Mr. Preuss, I cannot turn to page 14:44:50 11 127. This copy does not have a page 127. 14:44:53 12 MR. PREUSS: I need a new copier. 14:44:57 13 THE WITNESS: We both need one. 14:45:03 14 Q. (BY MR. PREUSS) Try again, Doctor. Maybe one 14:45:13 15 for three. 14:45:14 16 A. Whatever. You want me to go to page 127? 14:45:23 17 Q. Yeah, from line 22 to line 16? 14:45:31 18 A. You will have to give me just a moment to find 14:45:40 19 it. 14:45:42 20 THE COURT: Say that again, line 22. 14:45:43 21 MR. PREUSS: Yeah, I'm sorry. 14:45:45 22 Q. (BY MR. PREUSS) Page 127, line 22 to page 129, 14:45:50 23 line 16. 14:45:58 24 A. Sorry, can you do it again? Let me make a note. 14:46:00 25 My piece of paper is on the floor. 14:46:07 139 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Q. I will get it. 14:46:09 3 A. Right, wonderful. Thanks very much. 14:46:10 4 Now, 127? 14:46:34 5 Q. 127, line 22, please, to 129, line 16. 14:46:37 6 A. What is to happen now? 14:46:59 7 Q. I would like you to read that and when you've 14:47:01 8 read that, let me know. You can read it to yourself, 14:47:03 9 please. 14:47:06 10 A. Right. 14:47:43 11 Q. And that discussion revolves around your use of 14:47:43 12 the word "possibility" in the articles we just discussed, 14:47:47 13 the '99 and 2000 articles, right? 14:47:50 14 A. Yes, it actually revolves around that, 14:47:54 15 Mr. Preuss. 14:47:56 16 Q. And you say, and I'm quoting from line 4 -- 14:47:57 17 yeah, line 5, page 129 down to line 16, and you say, "Now, 14:48:00 18 a possibility -- there are scientific conventions which 14:48:08 19 broadly speaking say it is probable that the earth is 14:48:12 20 round. They leave open the possibility that the earth may 14:48:15 21 be flat. It is very rare in any scientific article to 14:48:18 22 have people make absolute black and white statements, so 14:48:22 23 you've got to interpret the phrase here as being dictated 14:48:25 24 by the scientific convention which is the possibility 14:48:28 25 there are other SSRIs that may cause similar problems. 14:48:31 140 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Did I read that correctly? 14:48:36 3 A. Well, it again depends on the -- 14:48:38 4 Q. Did I read that correctly? 14:48:40 5 A. It depends on the tone of voice, Mr. Preuss. 14:48:42 6 Q. I'm sorry, the way I read it, did I read it 14:48:44 7 correctly? 14:48:51 8 A. You read the words that are there, but you can 14:48:53 9 change the meaning if you change the tone of voice. 14:48:55 10 Q. The question is just like the earth may be flat, 14:48:58 11 there's the possibility that Paxil may cause suicide, 14:49:01 12 correct? 14:49:04 13 A. No, it is the other way around. In a scientific 14:49:11 14 article I would say it is possible that the earth is round 14:49:11 15 and the jury would understand that I mean absolutely for 14:49:11 16 certain the earth is round in the same way I'm saying 14:49:16 17 there's a possibility that other SSRIs make people 14:49:19 18 suicidal and I expect the jury to understand that I mean 14:49:22 19 it is absolutely certain that other SSRIs cause people to 14:49:25 20 suicidal and homicidal. 14:49:31 21 I keep losing sound here. 14:49:33 22 THE CLERK: It is just the P A system. 14:49:35 23 THE COURT: I got blamed the last time. 14:49:38 24 THE COURT: Clerk tells me we've had a 14:49:45 25 problem for a long time in this courtroom. It comes and 14:49:47 141 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 goes. If you have a problem, Dr. Healy, just keep on 14:49:50 3 going. 14:49:55 4 THE WITNESS: If you find it hard to hear 14:49:56 5 me because this happens, I'll ask you to ask me to speak 14:49:57 6 louder. 14:50:03 7 THE COURT: I would rather the jury just 14:50:04 8 raise your hand at the witness if you can't hear him and 14:50:06 9 he'll speak louder. 14:50:10 10 Q. (BY MR. PREUSS) With respect to this quote, 14:50:11 11 sir, you indicated it is possible the earth is round, 14:50:12 12 correct? 14:50:16 13 A. I believe that the earth is round, most 14:50:17 14 scientists -- 14:50:19 15 Q. There's a possibility that the earth is flat, 14:50:20 16 rights? 14:50:22 17 A. Most scientists writing a scientific article 14:50:23 18 would leave open the possibility that the earth is flat. 14:50:26 19 They would leave open the possibility, Mr. Preuss, that 14:50:29 20 we're not here in this courtroom today absolutely for 14:50:31 21 certain. 14:50:34 22 Q. To make sure, on SBFF 94, the possibility is 14:50:58 23 that other SSRIs might include suicidal ideation, which 14:51:02 24 would be Paxil, possibility? 14:51:05 25 A. The possibility I refer to is the earth is round 14:51:08 142 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 and in the same context I say it is possible that other 14:51:10 3 SSRIs will make people suicidal. 14:51:13 4 Q. And, Doctor, you say the probability is the 14:51:15 5 earth is round in the testimony I just read you. 14:51:18 6 A. I said if I was to write an article that what we 14:51:21 7 would say, probably the earth is round, yes. But we 14:51:24 8 wouldn't say for certain that the earth was round. 14:51:30 9 Q. You've never in the published literature written 14:51:41 10 a statement that Paxil causes suicide; isn't that correct? 14:51:43 11 A. That's probably correct. I've certainly 14:51:46 12 written that SSRIs cause suicide and in that context would 14:51:51 13 include Paxil. 14:51:54 14 Q. The answer to my question is you have not 14:51:55 15 written that Paxil causes suicide in any article? 14:51:57 16 A. I haven't seen fit to distinguish Paxil from the 14:52:00 17 rest of the SSRIs. 14:52:03 18 Q. The answer is yes, you have not written in the 14:52:05 19 literature that Paxil causes suicide; isn't that correct, 14:52:07 20 sir? 14:52:10 21 A. That's absolutely correct, sir. 14:52:11 22 Q. Now, at your deposition you referred to some 14:52:15 23 additional information that you received that caused you 14:52:17 24 to feel that your opinion was reinforced, and in 14:52:20 25 particular, the healthy volunteer studies, correct? 14:52:26 143 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 A. Yes, that is correct. 14:52:29 3 Q. Now, Doctor, with respect to all of the 14:52:30 4 arrangements with respect to getting that data and having 14:52:32 5 it prepared for you to look at and what transpired there, 14:52:35 6 you were not part of any of the discussions among counsel 14:52:40 7 as to what was to be done, how it was to be done or the 14:52:42 8 circumstances surrounding it; isn't that correct? 14:52:46 9 A. That is correct. 14:52:49 10 Q. You reviewed that in March of this year? 14:53:02 11 A. You will probably be able to give me the precise 14:53:04 12 date. I think it was around March. 14:53:07 13 Q. And my information indicates that you reviewed 14:53:08 14 about 235 file boxes that had about 155,000 pages, does 14:53:10 15 that sound about right? 14:53:17 16 A. That sounds about right, 235 boxes, certainly, 14:53:18 17 and when quote add number of pages, in terms of hundreds 14:53:25 18 of thousands. 14:53:31 19 Q. And involved 62 healthy volunteer studies? 14:53:31 20 A. It may have involved 62 healthy volunteer 14:53:35 21 studies. I focused, as I explained earlier, to ones that 14:53:38 22 were prior to Paxil being licensed here in the US. 14:53:43 23 Q. You made your selection, but there were 66 from 14:53:46 24 which you could make your choice? 14:53:48 25 A. I picked about 35. 14:53:50 144 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Q. And those included thousands of patients using 14:53:52 3 Paxil? 14:53:54 4 A. I haven't actually totaled it up. I don't 14:53:56 5 believe -- actually, they aren't all patients, they're 14:53:59 6 healthy volunteers. And I don't think it came to 14:54:03 7 thousands, no. 14:54:07 8 Q. You spent two days reviewing materials. Your 14:54:08 9 schedule wouldn't permit you to stay there an extra day, 14:54:11 10 right? 14:54:14 11 A. I stayed down in Harlow overnight and I operated 14:54:14 12 from as early as I could in the morning to as late as I 14:54:17 13 could in the evening, yes. 14:54:20 14 Q. And you had to get back to your business after 14:54:21 15 two days? 14:54:23 16 A. That's right. 14:54:24 17 Q. Okay. Now, in these healthy volunteer studies 14:54:25 18 people were given Paxil and the reactions to the drug was 14:54:29 19 recorded, right? 14:54:33 20 A. Certain proportions to the reactions to the drug 14:54:41 21 were recorded. I have no confidence that the full range 14:54:44 22 of reactions to these drugs was recorded. 14:54:52 23 Q. You have no knowledge one way or the other, 14:54:52 24 right? 14:54:52 25 A. I'm fully confident that it wasn't. 14:54:52 145 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Q. And the individuals in the study received one or 14:54:54 3 two doses? 14:54:56 4 A. The individuals in some instances were on the 14:54:57 5 drugs for two or three weeks, but in many of the studies 14:54:59 6 received only one or two doses. 14:55:02 7 Q. And some of the doses were 20 or 30 or 40 14:55:06 8 milligrams, even some as high as 60, right? 14:55:10 9 A. Very, very few as high as 60. The paroxetine 14:55:13 10 study I referred to in the morning was one that wasn't 14:55:17 11 there and that involved a dose as high as 60 milligrams. I 14:55:21 12 had of course had sighted that before I ever went to Harlow. 14:55:25 13 As you will know. But no, for the most part, the doses 14:55:29 14 being used were 20 to 30 milligrams, I would guess in 95 14:55:33 15 percent of the healthy volunteers that I looked at. 14:55:38 16 Q. But some, whatever remaining percentage, some 14:55:42 17 had had 40 and even a few at 60, right? 14:55:45 18 A. A very small proportion, but nothing that would 14:55:48 19 influence the overall picture. 14:55:51 20 Q. All right. And not one of those healthy 14:55:53 21 volunteers experienced suicidal ideation, isn't that 14:55:56 22 right? 14:55:59 23 A. Neither you nor I know that, Mr. Preuss. It is 14:56:01 24 clear that a great number of healthy volunteers, almost 14:56:03 25 exclusively on paroxetine dropped out. We do know that 14:56:07 146 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 suicidal ideation wasn't recorded. We don't know that it 14:56:11 3 didn't happen. 14:56:15 4 Q. Not one of the volunteers attempted suicide 14:56:21 5 while on Paxil, isn't that right, sir? 14:56:24 6 A. It is correct that not one of the volunteers 14:56:26 7 actually attempted suicide while on Paxil but shortly 14:56:28 8 after halting Paxil I believe one of them did. 14:56:32 9 Q. That was three months later, right? 14:56:41 10 A. Yes, but there's a withdrawal syndrome from 14:56:43 11 Paxil, including agitation, abnormal dreams and night 14:56:46 12 mares that comes through in spades in these healthy 14:56:51 13 volunteer studies. 14:56:54 14 Q. You're saying Paxil is still active for three 14:56:55 15 months? 14:56:58 16 A. In up to 80 percent of the volunteers on this 14:56:58 17 drug for only two weeks produces withdrawal syndromes in 14:57:01 18 these healthy volunteers. I'm saying in my clinical 14:57:05 19 experience I've seen people on this drug for short periods 14:57:08 20 of time and I've seen them have troubles three months 14:57:10 21 later, yes. 14:57:15 22 Q. And you don't know anything about the particular 14:57:20 23 circumstances of that one patient, do you? 14:57:22 24 A. No, I don't. 14:57:25 25 Q. Now, again -- 14:57:25 147 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 A. Let's repeat, it is a healthy volunteer, not a 14:57:26 3 patient. 14:57:30 4 Q. Thank you. You didn't see one healthy volunteer 14:57:32 5 experience suicidal ideation, did you? 14:57:38 6 A. It is not reported. It is reported by 14:57:41 7 SmithKline Beecham employees and Dataline. This is not 14:57:44 8 recorded. Apprehension, agitation, restlessness and 14:57:46 9 akathisia are all recorded. 14:57:51 10 Q. I would like to have you turn to page 194, sir. 14:57:53 11 A. Of which? 14:57:58 12 Q. Your deposition. 14:57:59 13 A. Mr. Preuss, we're jinxed, even in this large 14:58:08 14 copy I don't have page 194. I may have it -- except 14:58:12 15 you've removed that. I have another copy of the 14:58:16 16 deposition here. Let's see ifs in that. We are in luck. 14:58:18 17 It is in this one. 14:58:39 18 Q. 194, lines 12 through 195, line 4, please. 14:58:40 19 A. Sorry, 194, line 12? 14:58:47 20 Q. Yes. 14:58:50 21 A. To line -- 14:58:50 22 Q. 4 on 195? 14:58:55 23 A. "Did you review a single report of a patient on 14:58:56 24 paroxetine who experienced suicidal ideation? 14:58:59 25 There is a single report of a patient on 14:59:02 148 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 paroxetine who experienced violent dreams. 14:59:05 3 I'm sorry. Who experiences violent dreams. 14:59:09 4 Dreams, okay, but my question was did you review a report 14:59:13 5 of any patient who experienced suicidal ideation. No. 14:59:16 6 Did you review a report of any patient who experienced a 14:59:21 7 suicide attempt. 14:59:23 8 No. 14:59:25 9 Did you review a report of any patient who 14:59:26 10 committed suicide. 14:59:29 11 No." 14:59:30 12 What line did you want me to go to? 14:59:31 13 Q. That was it. Thank you. 14:59:33 14 Didn't you testify in your deposition you felt 14:59:49 15 it would be extra ordinary if anyone actually reported a 14:59:50 16 suicidal ideation or made a suicide attempt? 14:59:54 17 A. In the context of company employees who are 14:59:58 18 healthy volunteers taking this drug, I thought it would be 15:00:01 19 extra ordinary if anyone had taken one dose and gone out 15:00:05 20 and committed suicide. In our experience reported 15:00:09 21 suicidal ideation -- you have to realize the context of 15:00:11 22 this, which is that patients as I've outlined earlier, 15:00:15 23 people who go on these drugs when these things begin to 15:00:18 24 happen don't necessarily blame the drug. They worry about 15:00:21 25 whether it is themselves and they don't report these 15:00:29 149 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 things to treating physicians or anyone else. SmithKline 15:00:29 3 Beecham employees experiencing suicidal ideation probably 15:00:31 4 kept it quiet. 15:00:34 5 Q. You have no basis for that whatsoever, do you, 15:00:35 6 Doctor? 15:00:38 7 A. I do, yes. We have done a healthy volunteer, 15:00:39 8 Mr. Preuss. 15:00:41 9 Q. With respect to that particular study, do you, 15:00:42 10 sir, you have no personal information on that, do you? 15:00:44 11 A. I am reasonably confident that given what we 15:00:46 12 know. 15:00:49 13 Q. Do you have any personal information, Doctor? 15:00:49 14 A. About what. 15:00:51 15 Q. About what you just said? 15:00:52 16 A. I am reasonably confident it will have happened. 15:00:54 17 Q. The question is do you have any personal 15:00:57 18 information, sir? 15:00:58 19 A. I don't have any reports written by SmithKline 15:00:59 20 that this happened. 15:01:00 21 Q. And you have no personal information at all 15:01:01 22 yourself any way, anyhow, right? 15:01:03 23 A. About what? 15:01:06 24 Q. About what you just said? 15:01:06 25 A. Which bit of what I just said? 15:01:08 150 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Q. With respect to not reporting things. 15:01:10 3 A. It is very, very clear that the clinical 15:01:13 4 trialist for SmithKline and the other companies who have 15:01:19 5 done healthy volunteer work where there have been GIT physicians 15:01:22 6 or ENT physicians -- the GIT identifies gut problems on paroxetine -- 15:01:26 7 Q. My question is do you have any personal 15:01:33 8 knowledge with respect to SmithKline's healthy volunteer 15:01:35 9 studies they're not reporting or recording? 15:01:40 10 A. I'm absolutely confident they're not recording. 15:01:42 11 Q. Do you have any personal knowledge, you are he 15:01:45 12 speculating? 15:01:47 13 A. No, I'm not. Let's be very clear. We can go 15:01:48 14 into this in detail if you want. None of these healthy 15:01:51 15 volunteer studies were supervised by a psychiatrist or 15:01:54 16 psychologist or anyone with any expertise in looking at 15:01:57 17 the issues that are of concern to this court here today. 15:02:00 18 No one who is supervising any of these clinical 15:02:05 19 trials had any inkling or sensitivity to this kind of 15:02:08 20 problem. 15:02:14 21 Q. You don't know that, you don't know the 15:02:15 22 clinicians what they did, what they did at the time the 15:02:16 23 tests were run, do you, you have no knowledge of that? 15:02:20 24 A. I know who most of the clinicians were, I asked 15:02:22 25 about it when I was there. 15:02:25 151 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Q. When? 15:02:27 3 A. When I was there in Harlow. 15:02:27 4 Q. When you were looking at the documents? 15:02:29 5 A. Yes. 15:02:30 6 Q. And you know all of those physicians? 15:02:31 7 A. I know that none of them were psychiatrists. 15:02:33 8 Q. You don't know whether they didn't record or 15:02:36 9 people didn't report to them? You have no personal 15:02:37 10 knowledge of that, do you, sir? 15:02:40 11 A. I'm very, very clear that the people who were 15:02:41 12 doing the studies weren't trained to pick up the issues 15:02:44 13 that are of concern to us here today. 15:02:47 14 Q. That's your opinion, right? 15:02:50 15 A. I'm absolutely sure about this opinion. 15:02:52 16 Q. That's your opinion? 15:02:55 17 A. Yes. 15:02:56 18 Q. And by the way, the healthy volunteers in your 15:02:57 19 study were employees of your organization; isn't that 15:02:59 20 correct? 15:03:04 21 A. No, this is a -- it is hard to -- well, it is 15:03:04 22 hard to put the right word for this. This is is view that 15:03:09 23 has been put out by Pfizer. None of the volunteers, bar 15:03:12 24 one, was in any way employed by me or my organization. 15:03:17 25 Pfizer had gone around the place talking about this 15:03:21 152 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 particular study saying that these people were all 15:03:24 3 employed by me. They weren't. 15:03:27 4 Q. Doctor, none of the healthy volunteers 15:03:31 5 experienced homicidal ideation, did they? 15:03:34 6 A. What we have, one person experienced violent 15:03:37 7 dreams. That for my money sounds like very close to 15:03:42 8 homicidal ideation. 15:03:45 9 Q. Are dreams ideation in your mind? 15:03:47 10 A. Absolutely, yes. 15:03:50 11 Q. Unexpressed dreams are suicidal ideation or 15:03:52 12 homicidal ideation? 15:03:56 13 A. This person expressed the fact that they were 15:03:58 14 having violent dreams, and recall, this is not a patient. 15:04:00 15 This is a healthy volunteer. 15:04:05 16 Q. And none of the volunteers committed homicide 15:04:07 17 did they, Doctor? 15:04:10 18 A. I hope not. It is quite possible that they 15:04:11 19 weren't followed up for the full withdrawal period that 15:04:13 20 can happen with this drug. And abnormal dreams and 15:04:16 21 nightmares occurred during the withdrawal period on this 15:04:20 22 drug also. 15:04:23 23 Q. On one person, right? 15:04:24 24 A. That's all that's recorded, yes, which -- 15:04:25 25 abnormal dreams and nightmares is actually recorded 15:04:27 153 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 throughout a range of different studies. The specific 15:04:31 3 reference to the fact that these dreams were violent is 15:04:38 4 only recorded on one person. 15:04:41 5 Q. Now, Doctor, you said you observed a lot of 15:04:43 6 reports of agitation? 15:04:47 7 A. Where? 15:04:51 8 Q. In the healthy volunteer study? 15:04:52 9 A. Yes, yes, I did. 15:04:54 10 Q. And you would have no evidence to cite to me 15:04:56 11 that agitation or akathisia on Paxil can degenerate into a 15:04:59 12 more severe form that causes suicide or homicide, can you? 15:05:04 13 A. I can say to you that I believe that all of the 15:05:08 14 SSRIs as a class produce a comparable agitation and that 15:05:11 15 this is a precursor of suicide and homicide. 15:05:23 16 Q. And you can't cite me to any article in the 15:05:23 17 literature that relates that to Paxil, can you? 15:05:23 18 A. No, but I can cite you to the fact that I said 15:05:24 19 SSRIs do it and that includes Paxil. If I hadn't thought 15:05:28 20 that Paxil would have included, I would have taken care to 15:05:31 21 mention it. 15:05:33 22 Q. There's no pending question. 15:05:34 23 THE COURT: I would like to instruct the 15:05:36 24 witness not to volunteer information, just answer the 15:05:37 25 question that's been posed. 15:05:39 154 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 THE WITNESS: I'm awfully sorry, Your 15:05:42 3 Honor. 15:05:44 4 THE COURT: Thank you. 15:05:44 5 Q. (BY MR. PREUSS) You mentioned the Baldwin 15:05:57 6 study? 15:05:58 7 A. I did. 15:05:59 8 Q. You never read that report before you finalized 15:05:59 9 your report in this case, did you? 15:06:02 10 A. No, I didn't but I've had a chance to read it 15:06:05 11 since. 15:06:07 12 Q. Your opinion was expressed before you ever read 15:06:07 13 the study, right? 15:06:09 14 A. That is correct. But I had seen the key data 15:06:11 15 from the study. It would have been hard for me to read 15:06:15 16 the study given that the key data were unpublished. 15:06:17 17 Q. And you never saw any of the statistical 15:06:22 18 analysis on that data before you finalized your report, 15:06:24 19 right? 15:06:29 20 A. That's correct. It would have been extremely 15:06:30 21 hard for me to see it given it remained unpublished, 15:06:33 22 Mr. Preuss. 15:06:36 23 Q. You understand the results that have study were 15:06:38 24 not statistically significant; isn't that correct? 15:06:39 25 A. I understand that even though there were 15:06:42 155 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 something like 47 suicide attempts on paroxetine and 12 on 15:06:44 3 placebo and the jury will understand there's a big 15:06:48 4 difference, there, that given the fact the study was 15:06:50 5 terminated early because of these problems, that it didn't 15:06:54 6 reach statistical significance. 15:06:56 7 Q. And not being statistically significant means 15:06:58 8 that you cannot reasonably rely on that information as a 15:07:01 9 scientist; isn't that correct, Doctor? 15:07:04 10 A. The fact that the company chose to terminate the 15:07:06 11 study early and not publish the results, I think, can be 15:07:08 12 relied on as a scientist. 15:07:12 13 Q. My question was as a scientist, sir, you cannot 15:07:14 14 reasonably rely on any study that is not statistically 15:07:19 15 significant, isn't that right? 15:07:22 16 A. Of course I can. I can rely on evidence that is 15:07:24 17 consistent with the rest of the evidence in the field. 15:07:26 18 Q. So if it is not statistically significant in 15:07:29 19 your view, it is still reliable information; is that 15:07:32 20 correct? 15:07:35 21 A. It may well be reliable information, yes. 15:07:36 22 Q. And you think it is in this case? 15:07:38 23 A. I think it is in this case. 15:07:40 24 Q. And you think that that view on statistical 15:07:41 25 significance is held by your peers? 15:07:44 156 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 A. Oh, absolutely. And the fact that most of these 15:07:46 3 studies, paroxetine, if it was submitted to the FDA, 15:07:50 4 didn't reach statistical significance to show that the 15:07:54 5 drug works for depression, didn't stop the FDA licensing 15:07:57 6 it on the basis of some studies that did reach statistical 15:08:01 7 significance. 15:08:05 8 Q. You expressed some opinions on specific 15:08:11 9 causation, have you not, sir? 15:08:13 10 A. I have indeed. 15:08:16 11 THE COURT: Before we go into this, 15:08:17 12 Mr. Preuss, we will take our afternoon recess. Court will 15:08:18 13 stand in recess for 15 minutes. 15:08:21 14 (Recess taken 3:00 p.m. until 3:15 p.m.) 15:08:26 15 MR. PREUSS: May I begin, Your Honor. 15:26:40 16 THE COURT: Yes, you may begin. 15:26:42 17 Q. (BY MR. PREUSS) Dr. Healy, you offered some 15:26:43 18 opinions on the specific causation issue as to Don 15:26:45 19 Schell's murder/suicide. Do you recall that? 15:26:48 20 A. Yes, I did, Mr. Preuss. 15:26:51 21 Q. I want to ask you what records you reviewed and 15:26:55 22 didn't review. My understanding is that based on what you 15:26:57 23 filed in your expert reports that you have not read the 15:26:59 24 records of Dr. Bagnarello; isn't that correct? 15:27:04 25 A. At the time I offered my opinion, that was 15:27:08 157 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 correct. I have since read some records, yes. 15:27:10 3 Q. As of the time of your report you had not read 15:28:02 4 that, is that right? 15:28:02 5 A. That is correct. 15:28:02 6 Q. Did you incorporate Dr. Bagnarello's records 15:28:02 7 into the opinions you rendered here today? 15:28:02 8 A. Yes, I have. Well -- can I -- may I rephrase my 15:28:02 9 answer, Mr. Preuss? I sit on this stand ready to get down 15:28:02 10 off of it or else to say to you that I don't believe that 15:28:02 11 this drug -- this drug Paxil caused this problem for 15:28:02 12 Mr. Schell if anything is offered to me that would cause 15:28:02 13 me to change my mind. 15:28:02 14 Dr. Bagnarello's report has not caused me to 15:28:02 15 change my mind. 15:28:02 16 Q. You understood, though, that your opinion was to 15:28:02 17 be based on material that was put in your expert report 15:28:05 18 and that we would be relying on that when we took your 15:28:07 19 deposition, is that right? 15:28:10 20 A. That's correct. 15:28:13 21 Q. And after that occurred you have apparently read 15:28:13 22 Dr. Bagnarello's record which you've incorporated into 15:28:15 23 your testimony today? 15:28:19 24 A. In the sense that if anything had come to hand 15:28:20 25 that caused me to revise my opinion, I would certainly say 15:28:22 158 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 to you that I did not believe this drug had caused the 15:28:31 3 problem, if anything had been brought to my attention 15:28:31 4 which would indicate that. 15:28:33 5 Q. All right. Let me ask you this: How about 15:28:34 6 Dr. Ray Lougar, have you read his records? 15:28:37 7 A. I have read, seen -- 15:28:41 8 Q. As of the time of your report had you read them? 15:28:43 9 A. Absolutely not, no. 15:28:45 10 Q. Are you read them since. 15:28:46 11 A. I'm not sure what I read, Mr. Preuss. I've seen 15:28:47 12 three pages of medical notes that are hard to read. I've 15:28:50 13 read Dr. Merrill's report, your expert in this case who 15:28:53 14 refers to Dr. Lougar and Dr. Bagnarello. I'm not sure -- 15:29:00 15 on what I read was nothing that particularly said this is 15:29:05 16 Dr. Bagnarello's notes, these are Dr. Lougar's notes. 15:29:08 17 Q. You still have the deposition there. Let's go 15:29:29 18 back to page 295, if you would. Are you there? 15:29:31 19 A. Yes, I am. 15:29:50 20 Q. You were asked what doctor records you had been 15:29:51 21 shown and you said you had the records of Patel, Suhany 15:29:53 22 and Buchanan, right? 15:29:57 23 A. That's correct. 15:29:59 24 Q. And then you were asked, "Is that all?" And you 15:29:59 25 said, "I think so"? 15:30:02 159 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 A. That is correct. 15:30:05 3 Q. And now we know you've taken a look subsequent 15:30:05 4 to that at Bagnarello's and what is your testimony as to 15:30:08 5 Dr. Lougar, you have or have not read them since your 15:30:12 6 deposition? 15:30:15 7 A. I think you would have to show me Dr. Lougar's 15:30:17 8 records, Mr. Preuss, and I would be happy to confirm 15:30:20 9 whether I had seen these or not. 15:30:23 10 Q. Have you looked at additional records, then, 15:30:26 11 besides Dr. Bagnarello's since your deposition? 15:30:28 12 A. I have seen three pages of medical notes. I am 15:30:33 13 not absolutely certain who these notes come from. 15:30:39 14 Q. How about Dr. Buchanan? 15:30:43 15 A. I'm not sure. I would have to have a look. 15:30:44 16 Q. How about the employee records of Don Schell, 15:30:50 17 have you looked at those? 15:30:52 18 A. No, I haven't. 15:30:53 19 Q. And those records could show time off from work, 15:30:56 20 right? 15:30:58 21 A. Yes. 15:30:59 22 Q. And somebody who is unable to work because of 15:31:00 23 their depression has a serious depression, wouldn't you 15:31:05 24 agree? 15:31:08 25 A. No, I wouldn't. 15:31:09 160 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Q. Across the board you wouldn't agree? 15:31:11 3 A. Across the board I wouldn't agree, yes. 15:31:12 4 Q. So being off work because you are mentally so 15:31:14 5 wound up you can't work is not a significant factor to 15:31:20 6 you? 15:31:23 7 A. It is a factor. Clearly it is a factor. But 15:31:23 8 for me serious depression means that you have to be 15:31:28 9 hospitalized and there's no hint that Mr. Schell was 15:31:31 10 anything close to hospitalization. 15:31:41 11 Q. Even though he was off work for a period of a 15:31:43 12 month several times over the course of his prior episodes, 15:31:46 13 that's not significant to you? 15:31:49 14 A. Well, Mr. Preuss, you've outlined that 10 15:31:51 15 percent of the population of the U.S.A. may be depressed 15:31:57 16 during the course of any one year. Even if we say half of 15:32:03 17 those, I'm sure it is about half of those, will take some 15:32:06 18 time off work during the course of their depressive 15:32:08 19 episode. That would give us 9 to 10 million severely 15:32:11 20 depressed figure and should by the figures you've 15:32:14 21 introduced give us 2 million suicides in the US annually, 15:32:17 22 but it doesn't. We have 30,000 suicide. We're going to 15:32:20 23 have to look closely at the term depression. Clearly 15:32:27 24 being off work means you don't have a minor problem. But 15:32:31 25 off work for half a year until quite recently could leave 15:32:35 161 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 you categorized as having a mild depression. 15:32:39 3 Q. And you're familiar with the DSM? 15:32:43 4 A. I am familiar with the DSM, yes. 15:32:46 5 Q. And being off work is a factor in determining 15:32:49 6 whether an individual has a major depression, severe in 15:32:51 7 nature, is it not? 15:32:54 8 A. For the DSM. 15:32:55 9 Q. Right. And that's used here in the United 15:32:57 10 States? 15:33:00 11 A. That's a document that is used in the United 15:33:00 12 States. 15:33:04 13 Q. And is it your testimony that the absences from 15:33:05 14 work which you could have ascertained directly from 15:33:07 15 looking at his employment records is not particularly 15:33:11 16 significant to you in assessing Don Schell's depressive 15:33:14 17 history? Is that correct? 15:33:17 18 A. Yes. Mr. Schell -- the crucial factor to me in 15:33:18 19 trying to assess -- 15:33:22 20 Q. Your answer is it is not significant; is that 15:33:23 21 right? 15:33:25 22 A. It is not a factor on which I put much weight. 15:33:25 23 Q. Okay, thank you. 15:33:29 24 Now, how about the deposition of Kevin Nelson? 15:33:30 25 You haven't read that, have you? 15:33:35 162 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 A. No, I haven't. 15:33:37 3 Q. You haven't read the deposition of Sherry 15:33:37 4 McGrath, right? 15:33:40 5 A. I have not read the deposition -- I hadn't at 15:33:41 6 the time I offered you my report. I have since. 15:33:43 7 Q. You have since? 15:33:46 8 A. Yes. 15:33:47 9 Q. And did you rely on that in rendering your 15:33:47 10 opinion here today? 15:33:49 11 A. No. 15:33:50 12 Q. Did you read the deposition of father Og? 15:33:54 13 A. I had since my report read the deposition, yes. 15:33:57 14 Q. And did you rely on that in any way? 15:34:00 15 A. No, I didn't. 15:34:02 16 Q. And did you read the deposition of Ron Wagner? 15:34:04 17 A. No. I have read a great number of depositions, 15:34:14 18 Mr. Preuss. I don't believe I've read that one, but I'm 15:34:14 19 not certain. 15:34:15 20 Q. And have you read the documents from the 15:34:18 21 Campbell County Memorial Hospital? 15:34:20 22 A. Now, they may be the ones I've seen in the 15:34:22 23 course of the last day or two, now that you mention it. 15:34:25 24 Q. You just don't know, right? 15:34:28 25 A. I suspect they are, but I'm not certain. 15:34:30 163 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Q. All right. Well, you understood that you were 15:34:33 3 to have based your opinion on information you had reviewed 15:34:35 4 as of the time your reports were submitted, right? 15:34:39 5 A. Yes, and that's what I believe I've done. 15:34:41 6 Q. But you've read documents since that time which 15:34:44 7 you've incorporated in the opinions you've expressed 15:34:47 8 today, right? 15:34:50 9 A. No, I haven't incorporated them in the views 15:34:51 10 I've offered you here today. What I've said to you is, 15:34:53 11 Mr. Preuss, if you or anyone else produces any further 15:34:56 12 material for me that would cause me to change my mind, I 15:34:59 13 am able in this court to say based on what you've now 15:35:02 14 shown me that this drug did not cause the problem. 15:35:05 15 I'm in this position but I think your experts, 15:35:07 16 given the arguments that they've outlined, aren't in the 15:35:12 17 position to say that the drug caused the problem. 15:35:16 18 Q. You would agree, Doctor, wouldn't you that it is 15:35:19 19 important to read whatever information might be available 15:35:23 20 before rendering an opinion? 15:35:25 21 A. Mr. Preuss, I believe I read whatever 15:35:27 22 information was available. I certainly asked for all the 15:35:30 23 information that was available at the time that I offered 15:35:34 24 my opinions. 15:35:37 25 Q. So you asked for it but may have not gotten it? 15:35:37 164 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 A. That's quite possible. 15:35:41 3 Q. And that would have been obtained through 15:35:42 4 Mr. Vickery, right? 15:35:44 5 A. Yes. 15:35:45 6 MR. PREUSS: No further questions. Thank 15:35:46 7 you. 15:35:47 8 THE COURT: Redirect. 15:35:49 9 MR. VICKERY: Yes, I do, Your Honor. 15:35:51 10 Q. (BY MR. VICKERY) I just want to follow up on a 15:36:12 11 few things that Mr. Preuss asked you about. Do you 15:36:14 12 remember him asking you about emotional blunting and I 15:36:27 13 believe you used the word "lability." 15:36:32 14 A. Yes. 15:36:36 15 Q. Are those the same thing? 15:36:36 16 A. No, they're slightly different. You see, 15:36:37 17 Mr. Vickery, the problem for us all here today is there's 15:36:40 18 a range of reactions that these drugs cause that much more 15:36:43 19 research should have been done on. There's clearly a 15:36:50 20 change in the emotional state of many people that go on 15:36:53 21 these drugs that can happen in the first few hours or 15:36:56 22 first few days on the drug and this can involve feelings 15:36:59 23 of lack of concern which would be more the emotional 15:37:01 24 blunting end of things and feelings of your mood swinging 15:37:05 25 from being seemingly quite okay one minute to 30 minutes 15:37:08 165 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 later being extremely depressed, suicidal and crying. 15:37:12 3 That would be the emotionally labile bit. 15:37:16 4 Q. You were asked about some articles you wrote, 15:37:23 5 and I want to have a look at a couple of provisions. 15:37:25 6 First, the 1994 article, tab 2? 15:37:35 7 MR. VICKERY: Your Honor, we seem to have 15:38:27 8 lost power. 15:38:28 9 MR. GORMAN: Misha will fix it for you. 15:38:40 10 MR. VICKERY: I will stay out of the way. 15:38:43 11 Thank you. 15:38:46 12 Q. (BY MR. VICKERY) This is an article you wrote 15:39:08 13 in 1994, I believe? 15:39:11 14 A. Yes, it is. 15:39:12 15 Q. And I just wanted to ask you first of all about 15:39:13 16 the table of contents and what the significance is of each 15:39:16 17 of these matters that you've considered in reviewing the 15:39:20 18 evidence. 15:39:23 19 First of all, the toxicity indices. What is 15:39:24 20 that and why would you consider that in reviewing the 15:39:28 21 evidence on whether these drugs cause suicides? 15:39:31 22 A. Well, one of the issues was that the older group 15:39:37 23 of drugs was dangerous in overdose, and from that point of 15:39:39 24 view the SSRIs when they came onstream for clinicians like 15:39:44 25 me looked a very helpful group of drugs in that in 15:39:48 166 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 overdose at least you couldn't kill yourself with them. 15:39:52 3 Q. Okay. Another topic on there is serotonin and 15:39:56 4 suicide. How long had serotonin and suicide been linked 15:39:59 5 together in the scientific literature? 15:40:03 6 A. Yes, the issues are of interest. They were 15:40:06 7 linked first by George Ashcroft from Edinburgh. George 15:40:08 8 Ashcroft -- and there was work later done by Mary Asburg 15:40:15 9 from Sweden. She was probably -- that's about the 15:40:21 10 mid-1990s. Gorge Ashcroft was the early 1960s. 15:40:24 11 Ashcroft and a range of other people working in 15:40:31 12 this field concluded fairly early on by 1970 that there 15:40:33 13 was nothing wrong with the serotonin people -- with the 15:40:36 14 serotonin system in people who were depressed. 15:40:39 15 Mary Asburg went on to show that in people who 15:40:45 16 could be violent, there may be a lowering of serotonin. 15:40:47 17 MR. PREUSS: I will object it is beyond 15:40:50 18 the -- it is hearsay for one thing and it is way beyond 15:40:52 19 the expert report and three it is not appropriate redirect 15:40:55 20 because I didn't go into these areas at all on this 15:40:58 21 particular article. 15:41:05 22 MR. VICKERY: Well, Your Honor, he went 15:41:05 23 into the article. 15:41:05 24 MR. PREUSS: No question about that. 15:41:05 25 MR. VICKERY: I think once he goes into 15:41:06 167 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 the article, he opens the door to what is in the article. 15:41:07 3 THE COURT: Well, I think that should be 15:41:10 4 very limited and stay directly to the cross-examination. 15:41:12 5 MR. VICKERY: Okay. 15:41:16 6 Q. (BY MR. VICKERY) Let me move on, then, to the 15:41:17 7 next frame here. I have highlighted here the passage that 15:41:19 8 Mr. Preuss read from page 225, "Available post-marketing 15:41:28 9 surveillance data from individual countries do not suggest 15:41:36 10 that any of the SSRIs are particularly liable to cause 15:41:39 11 aggressive, impulsive or suicidal acts." 15:41:42 12 Could you read the next sentence? 15:41:46 13 A. "If it is later" -- I need to point out, 15:41:49 14 Mr. Vickery, that this means that it hasn't been shown 15:41:52 15 that one is more likely than the other. 15:41:56 16 "If it is later established that they or other 15:41:58 17 antidepressants do cause such effects, the question would 15:42:01 18 arise as to whether this is a direct or indirect effect." 15:42:05 19 Q. Now, that was 1994. In the intervening time has 15:42:09 20 it been established by scientific evidence that these 15:42:11 21 drugs do cause this problem? 15:42:16 22 A. Well, as of then I believe it was conclusively 15:42:19 23 established that these drugs do cause the problem. A 15:42:23 24 great deal of further evidence has come to light on the 15:42:26 25 frequency with which they cause the problem. 15:42:31 168 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Q. I wanted to ask you about another provision. I 15:42:39 3 think it is in this one. You were asked about a page on 15:42:43 4 229? 15:43:04 5 MR. VICKERY: And I unfortunately, Your 15:43:09 6 Honor, didn't write down exactly which passage he asked 15:43:11 7 about. 15:43:14 8 Q. (BY MR. VICKERY) But I would invite your 15:43:16 9 attention to the right-hand column under the Conclusions 15:43:17 10 and Recommendations, and would you just read the paragraph 15:43:19 11 that starts, "Suicidal ideation..." 15:43:23 12 A. "Suicidal ideation associated with fluoxetine is 15:43:29 13 probably not a direct effect of fluoxetine, but is 15:43:52 14 mediated through the induction of 15:43:56 15 akathisia/agitation/panic. This may occur through changes 15:43:58 16 of 5HT1A or 5HT2 receptors. The effects may be 15:43:38 17 successfully blocked by propranolol." That's Inderal. 15:43:44 18 Q. Let's look at tab 4, which I believe is your 15:44:05 19 1999 article. 15:44:08 20 A. No, I believe it is tab 1. 15:44:09 21 Q. I'm sorry, you were asked about the 2000 15:44:13 22 article. I wanted to go to that one next. 15:44:16 23 Now, I have highlighted what Mr. Preuss asked 15:44:39 24 you to read here, and let me read that and then ask you to 15:44:41 25 read the two follow-up sentences. 15:44:46 169 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 "On this basis, there would seem, therefore, to 15:44:48 3 be a possibility that other SSRIs might similarly induce 15:44:52 4 suicidality. A metaanalysis of trials involving the SNRI 15:44:56 5 milnucipran compared with SSRIs show a significantly 15:45:02 6 increased rate of suicidality on treatment with SSRIs." 15:45:06 7 That's your footnote 14. Can you tell us what 15:45:11 8 article that is? 15:45:13 9 A. Yes, that's the Kasper 1997 article which is reported 15:45:18 10 from the Pierre Fabre database, approximately at that time 15:45:22 11 8,000 patients and looking at the number of suicide 15:45:28 12 attempts in people who go on SSRIs versus milnucipran, 15:45:32 13 which is a drug they have in Europe but you in the US 15:45:37 14 don't have and we in the UK don't have either, are 15:45:41 15 tricyclic antidepressants which were also used in those 15:45:43 16 trials. 15:45:48 17 Q. Let me read the next sentence: "A randomized 15:45:48 18 placebo controlled trial of paroxetine in recurrent major 15:45:51 19 depression showed a higher rate of suicide attempts on 15:45:56 20 paroxetine than on placebo in this group of patients." 15:45:59 21 Now, is that the Baldwin data that wasn't 15:46:07 22 published but you got from Dr. Baldwin from the speech 15:46:10 23 that he gave? 15:46:13 24 A. Yes, it is. 15:46:14 25 Q. You were asked questions about scientific 15:46:41 170 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 literature that you discussed with counsel at your 15:46:44 3 depositions. Do you remember that discussion? 15:46:46 4 A. Yes, I do. 15:46:48 5 Q. Did you in your report and in your deposition 15:46:49 6 discuss with them Dr. Lane's 1997 article? 15:46:58 7 A. Yes, I did. 15:47:01 8 Q. And would you tell the -- 15:47:02 9 MR. PREUSS: Objection, Your Honor. The 15:47:03 10 Lane material is not part of his expert disclosure. I 15:47:04 11 would object to any testimony relating to lane. 15:47:09 12 MR. VICKERY: It most certainly is. The 15:47:13 13 lane report is cited in his expert report and was, I 15:47:14 14 believe, discussed at his deposition. 15:47:18 15 MR. PREUSS: Your Honor, the designation 15:48:06 16 says Roger Lane on sertraline as well as correspondence by 15:48:06 17 Dr. Lane and Professor Ulrik Malt of Norway. This is not 15:48:06 18 that article and it was not cited in -- as something he 15:48:06 19 relied on in his deposition. 15:48:06 20 MR. VICKERY: Let me dig it up, Your 15:48:18 21 Honor. 15:48:20 22 MR. PREUSS: In addition, it is beyond the 15:48:20 23 scope of the cross. 15:48:21 24 MR. VICKERY: Let me respond to that. The 15:48:22 25 scope of cross was what articles did you rely on, what 15:48:24 171 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 scientific articles about Paxil did you rely on at the 15:48:27 3 time of your deposition and report. This article which is 15:48:30 4 a review of all of the scientific literature was disclosed 15:48:33 5 in his report and it is a comprehensive review of that 15:48:36 6 literature. 15:48:40 7 What I'm about to show you is that it reviews 11 15:48:41 8 different articles on Paxil. 15:48:45 9 MR. PREUSS: Well, Your Honor, we've been 15:48:47 10 over that deposition thoroughly. I have asked him the 15:48:49 11 questions based on the deposition. The deposition does 15:48:51 12 not have any testimony that he relies on lane for the 15:48:54 13 opinions in this case. 15:48:57 14 MR. VICKERY: There are 42 footnotes in 15:49:19 15 the thing, Judge. Let me just move on. It is not worth 15:49:21 16 that fight. 15:49:24 17 Q. (BY MR. VICKERY) You were asked about your 15:49:54 18 review of the healthy volunteer studies, and you said 15:49:55 19 something about the kinds of physicians that were running 15:49:58 20 the studies somehow affects the kinds of maladies that 15:50:03 21 they report and I don't think you got an opportunity to 15:50:08 22 fully explain what you mean. 15:50:10 23 Can you tell us how the kind of physician that's 15:50:11 24 running the study affects the kind of side effects that 15:50:15 25 are noted? 15:50:18 172 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 MR. PREUSS: Objection, no foundation, 15:50:19 3 hearsay, speculation, Your Honor. 15:50:21 4 THE COURT: Do you have any foundation? 15:50:25 5 MR. VICKERY: Yes, let me lay the 15:50:27 6 foundation, Your Honor. 15:50:28 7 Q. (BY MR. VICKERY) Did you notice or take heed of 15:50:29 8 what kinds of physicians were running these studies? 15:50:32 9 A. Yes, I did. 15:50:37 10 Q. Why was that important to you? 15:50:37 11 A. Because it is clear from the healthy volunteer 15:50:39 12 work that I've reviewed across companies that the 15:50:43 13 orientation or specific discipline that the physician 15:50:47 14 comes from, whether they're an ENT consultant or a 15:50:52 15 gastrointerstinal consultant, that this heavily 15:50:56 16 influences, as you would expect, the kind of problems that 15:51:01 17 they see with the drug. 15:51:04 18 Q. Let me ask you a follow-up. If it is an ENT 15:51:07 19 doctor that's running the study, what kinds of problems do 15:51:10 20 you see cropping up? 15:51:14 21 A. You see them noticing that the patient -- the 15:51:15 22 patient on SSRIs have jaw dyskinesias, jaw problems, pain 15:51:21 23 in the throat, trouble swallowing, and they find this 15:51:25 24 happening in half or more of the people that go on the 15:51:28 25 drug. 15:51:32 173 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Whereas, if it is a GIT consultant or someone 15:51:32 3 else, they don't seem to notice this problem at all. On 15:51:35 4 the other hand, GIT physicians notice nausea, vomiting, diarrhea and 15:51:39 5 things like that and they don't notice the jaw problems, 15:51:43 6 the throat problems or the other problems that they're not 15:51:46 7 trained to notice. 15:51:49 8 Now, the crucial point for me in all of this, 15:51:50 9 trying to review what the evidence showed, was that there 15:51:53 10 was no psychiatrist or even psychologist involved in 15:51:55 11 running the particular studies for SmithKline who had the 15:52:02 12 expertise to look at what behavioral problems, what the 15:52:05 13 impact on the psyche of the person of these drugs might 15:52:08 14 be. 15:52:13 15 Q. Okay. You were asked another question 15:52:14 16 specifically about your 1994 article in which you were 15:52:16 17 describing Dr. Beasley's metaanalysis over at Lilly? 15:52:20 18 A. Yes, I was. 15:52:26 19 Q. Have you learned a lot about that means -- first 15:52:27 20 of all, tell us, what is a metaanalysis? 15:52:31 21 A. This is an approach to the data that SmithKline 15:52:37 22 have taken, for instance, and Lilly took where you take, I 15:52:40 23 would have assumed in the first instance, but that you 15:52:47 24 take all the trials that you have done and you have a look 15:52:50 25 at whether certain -- you add them all together and you 15:52:53 174 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 have a look at whether certain problems occur more often 15:52:56 3 on your drug or on the other drug that it is being 15:53:00 4 compared with or placebo. 15:53:03 5 Q. Since you wrote about that in 1994, have you 15:53:07 6 learned about other things that compromise the scientific 15:53:09 7 integrity of the Beasley metaanalysis? 15:53:14 8 A. Well, I've always made it clear that a met that 15:53:17 9 analytic approach, when Dr. Beasley wrote his article 15:53:21 10 first in the British Medical Journal, I made it clear this 15:53:25 11 was not the correct approach to the problem. It is the 15:53:28 12 approach that Dr. Montgomery has taken for SmithKline in a 15:53:31 13 1995 article, but -- 15:53:34 14 Q. Let me chase that down a minute. When that 15:53:36 15 article appeared in the British Medical Journal did you 15:53:38 16 write a letter to the editor complaining that they 15:53:41 17 published it? 15:53:44 18 A. I wrote that there were flaws with the study and 15:53:45 19 the British Medical Journal published -- 15:53:48 20 MR. PREUSS: Objection, again. He's 15:53:51 21 talking about the Montgomery study. 15:53:52 22 MR. VICKERY: No, I'm talking about the 15:53:54 23 Beasley study. 15:53:55 24 THE COURT: It got a little confusing 15:53:56 25 because the witness did mention Montgomery so I can 15:53:58 175 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 understand that. He is referring to the Beasley study. 15:54:08 3 MR. VICKERY: Right. 15:54:08 4 THE COURT: And he wrote a letter to the 15:54:08 5 editor of the London Times or -- 15:54:08 6 MR. VICKERY: No, British Medical Journal, 15:54:09 7 considerably different than the London Times, Your Honor. 15:54:11 8 THE COURT: Complaining or voicing 15:54:14 9 concern. 15:54:15 10 MR. VICKERY: Right. 15:54:16 11 THE COURT: Go ahead. 15:54:16 12 Q. (BY MR. VICKERY) And did Dr. Beasley respond to 15:54:18 13 your letter? 15:54:20 14 A. Yes, he did. 15:54:21 15 Q. And did the British Medical Journal publish his 15:54:22 16 response to your letter? 15:54:25 17 A. They did. 15:54:29 18 Q. And what did Dr. Beasley say in his response was 15:54:29 19 the appropriate, the quote, scientifically appropriate way 15:54:31 20 to study this issue? 15:54:35 21 A. He conceded that what I had suggested which was 15:54:37 22 challenge/rechallenge was an appropriate way to handle the 15:54:40 23 issue. 15:54:44 24 Q. And is this the same Dr. Beasley who along with 15:54:45 25 Dr. Wheadon wrote a challenge/rechallenge protocol at Eli 15:54:48 176 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Lilly? 15:54:53 3 A. Yes, it is. 15:54:54 4 Q. Now, since 1994 when you wrote those comments 15:54:54 5 that Mr. Preuss asked you about, have you learned other 15:54:57 6 things that cause you to have even less confidence in the 15:55:01 7 Beasley work? 15:55:06 8 A. I have gone to a number of things. The first 15:55:08 9 thing which I mentioned at my deposition -- 15:55:12 10 MR. PREUSS: Again, Your Honor, objection, 15:55:15 11 it is not part of his expert report again. It is beyond 15:55:16 12 the scope of cross and it is hearsay. 15:55:20 13 MR. VICKERY: The cross -- 15:55:24 14 THE COURT: Repeat the question. 15:55:24 15 Q. (BY MR. VICKERY) What have you learned since 15:55:26 16 1994 when you wrote the provision about the Beasley 15:55:27 17 article that Mr. Preuss read to you during your cross that 15:55:31 18 causes you to put even less confidence in Beasley's work? 15:55:35 19 THE COURT: Is the witness going to 15:55:41 20 testify to matters that he's disclosed in his expert 15:55:41 21 designation or how am I going to know that? That's a 15:55:44 22 pretty broad question. 15:55:48 23 MR. VICKERY: That is a good question. I 15:55:51 24 think that miss Halpern questioned him about that at the 15:55:52 25 deposition, but I would take her word for it if she chose 15:55:55 177 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 not to. 15:55:59 3 MS. HALPERN: I don't recall any answer 15:56:01 4 from Dr. Healy with regard to this. 15:56:02 5 MR. VICKERY: I understand the court's 15:56:13 6 dilemma. I'll pass it rather than lead into that dilemma. 15:56:14 7 That concludes the redirect, Your Honor. 15:56:44 8 THE COURT: Any recross. 15:56:51 9 MR. PREUSS: Just a couple yes, sir, Your 15:56:52 10 Honor. 15:56:53 11 Q. (BY MR. PREUSS) Do you think the individuals 15:56:54 12 that were supervising the studies that you looked at and 15:56:55 13 the healthy volunteers of SmithKline would be able to 15:56:58 14 recognize suicide, homicide attempts or actual events? 15:57:00 15 A. I don't think that they had the skill to elicit 15:57:07 16 whether people were becoming suicidal. 15:57:10 17 Q. And even if they told them that? 15:57:14 18 A. There are certain problems with healthy 15:57:17 19 volunteers actually reporting these things. 15:57:20 20 MR. PREUSS: Thank you, sir. 15:57:23 21 THE COURT: Anything else, Mr. Vickery. 15:57:31 22 MR. VICKERY: No, Your Honor, that 15:57:32 23 concludes it. 15:57:33 24 THE COURT: Thank you, Dr. Healy. You may 15:57:34 25 step down. 15:57:36 5 THE COURT: Who is the next witness. 16:58:27 6 MR. VICKERY: Dr. Maltsberger. He will be 16:58:29 7 a fairly long witness. 16:58:30 8 THE COURT: Let's not waist the time. We 16:58:32 9 can start on his qualifications. 16:58:34 10 MR. VICKERY: I knew you would say that. 16:58:35 11 THE COURT: I knew you knew that, too. 16:58:38 12 MR. VICKERY: Dr. Terry Maltsberger. 16:58:40 13 (Witness sworn.) 16:59:19 14 THE CLERK: State your name and spell it 16:59:19 15 for the record, please. 16:59:20 16 THE WITNESS: My name is John Terry 16:59:21 17 Maltsberger. And John is J O H N, Terry is T E R Y and 16:59:24 18 Maltsberger is M A L T S B E R G E R. 16:59:32 19 Q. (BY MR. VICKERY) It is Dr. Maltsberger, is it 16:59:38 20 not? 16:59:40 21 A. Yes. 16:59:40 22 Q. Would you please recite for us your educational 16:59:40 23 background following high school. 16:59:43 24 A. Well, I graduated from Princeton university in 16:59:46 25 1955, from the Harvard medical school in 1959. I was a 16:59:48 195 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 general intern at the Pennsylvania hospital in 16:59:57 3 Philadelphia between 1959 and 1960, and then I went into 17:00:00 4 psychiatric training in Boston at the Massachusetts mental 17:00:06 5 health center where I did three years of adult psychiatry, 17:00:10 6 including one year as chief resident. And then I did two 17:00:14 7 years in child psychiatry after that. 17:00:18 8 I'm a graduate of the Boston psychoanalytic 17:00:21 9 institute. 17:00:28 10 Q. What does that mean? Would you explain. Is 17:00:28 11 that further on past your residency? 17:00:30 12 A. Yes. It is a subspecialty training for 17:00:31 13 intensive talk therapy for certain kinds of selected 17:00:39 14 patients that are likely to benefit from it. 17:00:44 15 Q. Have you practiced in and around the Boston area 17:00:46 16 since you've completed all of your training, 17:00:50 17 Dr. Maltsberger? 17:00:52 18 A. Ever since. 17:00:53 19 Q. What has been the nature of your clinical 17:00:54 20 practice? 17:00:57 21 A. Well, I am a general psychiatrist. It is true I 17:00:58 22 practice psychoanalysis but that's not the major part of 17:01:04 23 my professional effort. Mostly I see adults, and I've had 17:01:09 24 a special interest in depression for many years, going 17:01:14 25 back to the time when I was in residency training, and in 17:01:17 196 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 particular an interest in suicidal patients. 17:01:25 3 Q. How is it that you became interested in 17:01:27 4 depression, and particularly in suicide? 17:01:30 5 A. When I was a first year resident in training it 17:01:34 6 fell to me to be on duty one weekend in the hospital, and 17:01:38 7 one of the patients managed to get off the ward and she 17:01:44 8 went down into a hidden place in the basement where she 17:01:50 9 had hidden a bottle of chloroform and she tied a sweater 17:01:56 10 over her face and killed herself with the chloroform. 17:02:01 11 And it fell to me to deal with it. 17:02:06 12 Q. Was she your patient before she did that? 17:02:08 13 A. She was not my patient. She was one of the 17:02:10 14 other doctor's patients, but she was a patient of our 17:02:12 15 group and it was such a horrible experience that by the 17:02:16 16 time I recovered my balance, I decided the only way to 17:02:20 17 deal with it was to learn as much about suicide as I could 17:02:24 18 and I and a couple of colleagues began to study it and it 17:02:29 19 more or less took on a life of its own and I have now a 17:02:36 20 specialty in suicide. 17:02:40 21 Q. Now, how many years has that been since that 17:02:41 22 incident with that patient that started you down this road 17:02:47 23 to studying suicide? 17:02:49 24 A. That must have been in 1960, so that was a long 17:02:51 25 time ago. 17:02:54 197 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 Q. Forty-one years? 17:02:56 3 A. I'm afraid so. 17:02:57 4 Q. Over that 41 years, Dr. Maltsberger, how much of 17:03:00 5 your time has been spent in learning about this phenomenon 17:03:04 6 of suicide? 17:03:07 7 A. Well, it has been the principal area in all of 17:03:09 8 psychiatry and indeed psychoanalysis that I've studied. 17:03:16 9 It has been a major professional commitment and I see more 17:03:21 10 suicidal patients than the average psychiatrist does. In 17:03:29 11 fact, I'm often a consultant to doctors in Boston and to 17:03:34 12 the different psychiatric hospitals near Boston and 17:03:39 13 sometimes further away when there are difficult, 17:03:45 14 complicated, suicidal cases and somebody wants another 17:03:49 15 opinion. 17:03:53 16 Q. Dr. Maltsberger, in those 41 years that you've 17:03:54 17 been taking care of patients at suicidal risk have you 17:03:58 18 ever lost a patient to suicide? 17:04:02 19 A. Well, I'm happy to say that I have never lost 17:04:04 20 one of my own patients to suicide, knock on wood. 17:04:06 21 Q. Have you hung around, for lack of a better word, 17:04:19 22 with doctors that have similar interests. Are there 17:04:22 23 groups or organizations that you all belong to? 17:04:25 24 A. Yes, there are two principle ones in the United 17:04:27 25 States, one is the American association of suicidology 17:04:29 198 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 which people may belong to if they're interested in 17:04:36 3 suicide studies, if they want to come to the annual 17:04:38 4 meeting. We have a journal called suicide and life 17:04:41 5 threatening behavior. I have the honor to be on the 17:04:48 6 editorial board for that. 17:04:50 7 Q. How long have you belonged to that organization? 17:04:57 8 A. Oh, goodness, a good 15 years or more. 17:04:58 9 Q. When was it founded? 17:05:01 10 A. It is now about 50 years old, a little older. 17:05:02 11 Q. Do you make it a point to go to the annual 17:05:10 12 meetings? 17:05:12 13 A. I haven't missed one in a long time. 17:05:13 14 Q. Do you regularly receive the journal? 17:05:15 15 A. Yes. 17:05:17 16 Q. You read the journal? 17:05:17 17 A. I do. 17:05:19 18 Q. Do you do peer reviews for other people 17:05:20 19 submitting articles to that journal? 17:05:24 20 A. To that journal and other journals also, for 17:05:26 21 several other journals. 17:05:29 22 Q. And have you yourself authored articles from 17:05:30 23 time to time on the subject of suicide? 17:05:33 24 A. I have. 17:05:34 25 Q. Now, you started to tell us there were two 17:05:35 199 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 organizations you belong to. What is the other one? 17:05:38 3 A. The other one is called the American foundation 17:05:40 4 for suicide prevention, and the best way to explain it to 17:05:43 5 the jury is to compare it to the American cancer society. 17:05:47 6 We are an organization that tries to raise money to fund 17:05:51 7 research for suicide prevention and we also have a lot of 17:05:59 8 education programs that we promote for the public and for 17:06:04 9 doctors and with a special interest recently for what we 17:06:09 10 can do about the problem of suicide in schools. 17:06:14 11 I have the honor to be the secretary of the 17:06:18 12 board at the moment and the chairman of the New England 17:06:21 13 division, and the codirector of something called the 17:06:30 14 suicide database in which we collect cases of suicide and 17:06:31 15 study them as exhaustively as we can. 17:06:39 16 We have 26 cases of people who committed suicide 17:06:42 17 when they were in active treatment with psychiatrists or 17:06:47 18 psychologists. Those doctors have come to meetings, have 17:06:50 19 written the cases up. We have massive data and we've 17:06:56 20 learned a lot about the state of mind that people are in 17:06:59 21 when they take their lives. 17:07:04 22 THE COURT: Okay. 17:07:11 23 MR. VICKERY: I can go on if the court 17:07:11 24 likes. Whatever. 17:07:13 25 THE COURT: No, we will take our evening 17:07:14 200 1 *UNEDITED REALTIME ROUGH DRAFT*UNEDITED REALTIME ROUGH DRAFT* 2 recess now. 17:07:16 3 Ladies and gentlemen of the jury, please 17:07:17 4 remember the admonition not to talk about this, not to 17:07:17 5 read about it in the media or listen to it on the TV or 17:07:22 6 radio, and we will adjourn until 9:00 a.m. tomorrow 17:07:26 7 morning. 17:07:30 8 (Trial proceedings recessed 17:07:31 9 5:00 p.m., May 22, 2001.) 17:07:33 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25