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