1470 1 IN THE UNITED STATES DISTRICT COURT 2 DISTRICT OF WYOMING 3 -------------------------------------------------------- 4 THE ESTATES OF DEBORAH MARIE TOBIN and ALYSSA ANN TOBIN, deceased, by 5 TIMOTHY JOHN TOBIN, personal representative; and THE ESTATES OF 6 DONALD JACK SCHELL and RITA CHARLOTTE SCHELL, deceased, 7 by NEVA KAY HARDY, personal representative, 8 Plaintiffs, Case No. 00-CV-0025-BEA 9 vs. May 31, 2001 Volume VIII 10 SMITHKLINE BEECHAM PHARMACEUTICALS, 11 Defendant. ----------------------------------------------------------- 12 13 14 TRANSCRIPT OF TRIAL PROCEEDINGS 15 16 Transcript of Trial Proceedings in the above-entitled 17 matter before the Honorable William C. Beaman, Magistrate, 18 and a jury of eight, at Cheyenne, Wyoming, commencing on the 19 21st day of May, 2001. 20 21 22 23 Court Reporter: Ms. Janet Dew-Harris, RPR, FCRR Official Court Reporter 24 2120 Capitol Avenue Room 2228 25 Cheyenne, Wyoming 82001 (307) 635-3884 1471 1 A P P E A R A N C E S 2 For the Plaintiffs: MR. JAMES E. FITZGERALD Attorney at Law 3 THE FITZGERALD LAW FIRM 2108 Warren Avenue 4 Cheyenne, Wyoming 82001 5 MR. ANDY VICKERY Attorney at Law 6 VICKERY & WALDNER, LLP 2929 Allen Parkway 7 Suite 2410 Houston, Texas 77019 8 For the Defendant: MR. THOMAS G. GORMAN 9 MS. MISHA E. WESTBY Attorneys at Law 10 HIRST & APPLEGATE, P.C. 1720 Carey Avenue 11 Suite 200 Cheyenne, Wyoming 82001 12 MR. CHARLES F. PREUSS 13 MR. VERN ZVOLEFF Attorneys at Law 14 PREUSS SHANAGHER ZVOLEFF & ZIMMER 225 Bush Street 15 15th Floor San Francisco, California 94104 16 MS. TAMAR P. HALPERN, Ph.D. 17 Attorney at Law PHILLIPS LYTLE HITCHCOCK 18 BLAINE & HUBER, LLP 3400 HSBC Center 19 Buffalo, New York 14203 20 INDEX TO WITNESSES DEFENDANT'S PAGE 21 MARK SUHANY, M.D. Deposition of Mark Suhany, M.D. Read 1487 22 J. JOHN MANN, M.D. 23 Direct - Mr. Preuss 1527 24 25 1472 13:33:38 1 P R O C E E D I N G S 13:33:38 2 (Proceedings convened in chambers 13:33:38 3 1:15 p.m., May 31, 2001.) 13:33:38 4 THE COURT: Mr. Vickery. 13:33:38 5 MR. VICKERY: Your Honor, good morning -- it is 13:33:38 6 afternoon, isn't it? 13:33:38 7 MR. GORMAN: Yeah, someplace. 13:33:38 8 MR. VICKERY: We asked to see you this morning about 13:33:38 9 two things, and I've told Mr. Zvoleff and Mr. Preuss about 13:33:38 10 them already. 13:33:38 11 One of them is to give you a heads-up on an issue I 13:33:38 12 expect to arise tomorrow morning or Monday and that is we'll 13:33:38 13 offer the deposition testimony of Dr. Casey from the Miller 13:33:38 14 case in rebuttal in this case and I have a very short trial 13:33:38 15 brief as to why we would offer it and what the legal 13:33:38 16 authority is for offering that. 13:33:38 17 This is the man that was the chairman -- you will 13:33:38 18 recall Dr. Wheadon's testimony about the PDAC that met in 13:33:38 19 1991. And this man was the chairman of that committee and 13:33:38 20 Dr. Wheadon mentioned him by name in his testimony. And we 13:33:38 21 have his deposition which is important rebuttal evidence for 13:33:38 22 us. 13:33:38 23 THE COURT: His deposition in another case? 13:33:38 24 MR. VICKERY: Right, Rule 804(b)(1) addresses the 13:33:38 25 applicability of it, that and the advisory committee minutes, 1473 13:33:38 1 and I hope that when the Court reads my brief, you will 13:33:38 2 conclude that it is proper for us to do that. 13:33:38 3 But I wanted to let you know and them know now so 13:33:38 4 that -- where is Mr. Mathes -- so the Court would have time 13:33:38 5 to look at that issue before tomorrow afternoon. 13:33:38 6 THE COURT: Who is responding to this? Mr. Zvoleff 13:33:38 7 is sitting here on the edge of his chair. 13:33:38 8 MR. PREUSS: He is ready, Your Honor. 13:33:38 9 MR. ZVOLEFF: We're obviously opposed to it, Your 13:33:38 10 Honor. There's no justification for admitting this 13:33:38 11 deposition from another case in this case. We obviously were 13:33:38 12 not at the deposition, had no opportunity to attend it, to 13:33:38 13 cross or in any way develop the testimony of Dr. Casey. 13:33:38 14 But even more fundamentally, I have no idea -- there 13:33:38 15 is a brief description in the brief that we've been handed as 13:33:38 16 to why it should come in here and then he says he wants 13:33:38 17 Dr. Casey's deposition admitted. That's a pretty broad 13:33:38 18 request. I don't know what specific parts of it he wants 13:33:38 19 admitted, how he's going to argue that something in fact 13:33:38 20 rebuts something. 13:33:38 21 And finally, obviously this is not one of the 13:33:38 22 witnesses that was listed. It is a complete surprise at this 13:33:55 23 point. And it is totally inappropriate to admit in this case 13:33:55 24 without warning to us ahead of time a deposition in another 13:33:55 25 case from another party's expert. 1474 13:33:55 1 THE COURT: Is he offered as an expert, a rebuttal 13:33:55 2 expert? 13:33:55 3 MR. VICKERY: No, a fact witness. Mr. Zvoleff and I 13:33:55 4 did discuss Dr. Casey before this trial ever started. I had 13:33:55 5 said I intend to offer it in our case in chief and we 13:33:55 6 discussed it and he said he would object to it, and I backed 13:33:55 7 down and didn't offer it in my case in chief. I decided 13:33:55 8 based on Dr. Wheadon's testimony that it was appropriate 13:33:55 9 rebuttal testimony. And it is factual, not expert. 13:33:55 10 Secondly, the deposition itself is being Fed-Exed 13:33:55 11 from my office and I thought I would have it by 10:00 this 13:33:55 12 morning but I will have the proffers and an edited video 13:33:55 13 which probably is going to run 15 minutes or 20 at max. 13:33:55 14 THE COURT: A deposition and a video or it is a 13:33:55 15 deposition video? 13:33:55 16 MR. VICKERY: It is a deposition video. But I should 13:33:55 17 have that by Fed-Ex any moment. And of course, Mr. Zvoleff 13:33:55 18 will have the opportunity today or this evening to look at 13:33:55 19 that before we get to that point. 13:33:55 20 So -- 13:33:55 21 THE COURT: How does he cross-examine this witness? 13:33:55 22 MR. VICKERY: That's a very good question. And the 13:33:55 23 official commentary to Rule 804(b)(1) specifically says that 13:33:55 24 mutuality as an aspect of identity is now generally 13:33:55 25 discredited and the requirement of identity of the offering 1475 13:33:55 1 party disappears except as it might affect motive to develop 13:33:55 2 the testimony. 13:33:55 3 THE COURT: What does that mean? 13:33:55 4 MR. VICKERY: Well, what the rule itself says is that 13:33:55 5 you can use depositions from another case if the party in 13:33:55 6 that case had a similar motive and opportunity to develop it 13:33:55 7 by cross-examination. 13:33:55 8 Well, Phizer in that case did have a similar motive 13:33:55 9 and opportunity to develop it by cross-examination, as 13:33:55 10 SmithKline Beecham does in this case. 13:33:55 11 THE COURT: How do I know that? 13:33:55 12 MR. ZVOLEFF: Let me respond to that briefly. I 13:33:55 13 mean, he's Phizer's expert in the other case. The deposition 13:33:55 14 is a deposition of their expert. 13:33:55 15 THE COURT: Whose expert? 13:33:55 16 MR. ZVOLEFF: Of Phizer's expert. He's saying Phizer 13:33:55 17 had the motivation to develop the testimony. In the real 13:33:55 18 world I'm sure Phizer didn't even ask him any questions. 13:33:55 19 MR. VICKERY: They did. They did ask him questions. 13:33:55 20 MR. ZVOLEFF: At an expert's -- your own expert's 13:33:55 21 deposition what your motives are are quite different from 13:34:09 22 what your motives are in crossing a fact witness. 13:34:09 23 Now he's proffering him as a fact witness. And we 13:34:09 24 certainly are not in Phizer's shoes here where they were at 13:34:09 25 an expert depo of their own expert and we've had no 1476 13:34:09 1 opportunity to cross him, whatever facts he wants to bring 13:34:09 2 out, to put them in context. 13:34:09 3 Now, his trial brief -- let me touch one other thing 13:34:09 4 briefly. It is true he told me before the trial started he 13:34:09 5 wanted to proffer Dr. Casey's depo in his case in chief. And 13:34:09 6 in effect our discussion was, "You've got to be kidding me. 13:34:09 7 You can't do that. It is a deposition from another case. 13:34:09 8 There's no basis for it." 13:34:09 9 We didn't discuss it really in any more detail than 13:34:09 10 that and then he withdrew the proffer which I think was the 13:34:09 11 proper thing to do and is still the proper thing to do. 13:34:09 12 His trial brief argues that what he needs it for is 13:34:09 13 some testimony with respect to the PDAC panel. 13:34:09 14 Now, as he knows, Dr. Mann is here today who was an 13:34:09 15 advisor to that panel. If he wants to develop some of the 13:34:09 16 facts, he certainly has his cross today and I wouldn't be at 13:34:09 17 all surprised if it includes just this topic. 13:34:09 18 THE COURT: Well, let's wait until we see the 13:34:09 19 deposition, but I will tell you right now I don't think I 13:34:09 20 favor this at all. I have a concern about the nature of this 13:34:09 21 deposition testimony from the standpoint is it really factual 13:34:09 22 or does it get into the area of expertise. And of course our 13:34:09 23 procedure here is no expert rebuttal with a new expert that 13:34:09 24 hasn't been designated. 13:34:09 25 So is this really a 701 witness who is giving lay 1477 13:34:09 1 opinions or no opinions at all, just going to report, "I was 13:34:09 2 at a meeting. This thing transpired. Period"? If that's 13:34:09 3 what you're representing all he's going to say, that's fine 13:34:09 4 from the standpoint if he were here live, he could testify to 13:34:09 5 those things, and maybe you could bring him live. Cost you 13:34:09 6 lots of money. 13:34:09 7 MR. VICKERY: Couldn't get him. He's beyond the 13:34:09 8 subpoena power of the court and is a Phizer expert. There's 13:34:09 9 no way he would ever come. Nor would it be proper for me to 13:34:09 10 contact Phizer's expert and ask him to testify. 13:34:09 11 It may become moot if Dr. Mann acknowledges what the 13:34:09 12 facts are as Dr. Casey testified to them. 13:34:26 13 THE COURT: Well, the facts as you view them. 13:34:26 14 MR. VICKERY: No, as Dr. Casey testified to them. 13:34:26 15 Not as I view them, Your Honor. 13:34:26 16 THE COURT: That would be wonderful. In all 13:34:26 17 seriousness, Counsel, right now just from the arguments I've 13:34:26 18 heard back and forth, this is not something I'll probably go 13:34:26 19 along with. My mind isn't 100 percent closed, Mr. Vickery. 13:34:26 20 I will read what you have, take a look at the deposition. I 13:34:26 21 don't know if you want to supply anything in response other 13:34:26 22 than what you've said here, but it is going to take a lot to 13:34:26 23 get me to turn over on that -- 13:34:26 24 MR. VICKERY: I understand. 13:34:26 25 THE COURT: -- under these circumstances. 1478 13:34:26 1 MR. VICKERY: I wanted to give us lead time built in 13:34:26 2 to do that. 13:34:26 3 The other thing I think may well be moot but I wanted 13:34:26 4 to apprise the Court and counsel for SmithKline Beecham of a 13:34:26 5 matter that could generate additional local publicity, and I 13:34:26 6 didn't know if they would want some further instruction or 13:34:26 7 not. 13:34:26 8 Last Thursday there was a case decided by a 13:34:26 9 Magistrate judge in New South Wales. It is the case of Queen 13:34:26 10 versus David John Hawkins. It is a remarkably similar case 13:34:26 11 factually: Man was on Zoloft for one day, strangled his 13:34:26 12 wife. It is a criminal case, but the reason I was concerned 13:34:26 13 about it was, of course, this Court has been so sensitive 13:34:26 14 about publicity that might affect our jury. 13:34:26 15 I got three or four calls yesterday in my office and 13:34:26 16 my partner is monitoring all of that and didn't take any of 13:34:26 17 them, but my guess is that it is the kind of thing -- it is 13:34:26 18 big news, big news internationally because the judge 13:34:26 19 concluded that the Zoloft made this man murder his wife after 13:34:26 20 one day. 13:34:26 21 And so I wanted to alert you to it. I have a copy of 13:34:26 22 the judge's opinion if you would like it. I've given a copy 13:34:26 23 to Mr. Zvoleff. I thought they might want additional 13:34:26 24 admonition from the Court. He tells me they don't. 13:34:26 25 THE COURT: To whom? 1479 13:34:26 1 MR. VICKERY: To our jury to be extra sensitive. I 13:34:26 2 know you've told the jury not to listen to anything about 13:34:26 3 this case, but I was thinking if a Denver paper or a Cheyenne 13:34:26 4 paper picked up and started writing about some case in New 13:34:26 5 South Wales, a juror might read through the whole thing at 13:34:26 6 the end. 13:34:40 7 THE COURT: I'm smiling and looking at the local 13:34:40 8 counsel. Our newspaper pick that up? It wouldn't happen in 13:34:40 9 a hundred years unless somebody came and published it for 13:34:40 10 them. 13:34:40 11 MR. VICKERY: We're certainly not going to do that. 13:34:40 12 THE COURT: And really, they don't pick up on those 13:34:40 13 things at all. It might be of some international concern, 13:34:40 14 New Jersey or someplace like that, but other than this case 13:34:40 15 pending here, it would have to be big bold print in a black 13:34:40 16 box on the wire. 13:34:40 17 MR. VICKERY: It is moot, then? 13:34:40 18 THE COURT: I think so. 13:34:40 19 MR. VICKERY: My only concern is that it is likely to 13:34:40 20 be on the AP wire and the UPI wire. I read it this morning 13:34:40 21 and I thought I ought to bring it to the attention of the 13:34:40 22 Court and counsel. That's all I'm doing. 13:34:40 23 THE COURT: I appreciate that. And when I -- if I 13:34:40 24 don't forget to give them their usual admonition I'll tell 13:34:40 25 them again to be sure to ignore any media about such matters. 1480 13:34:40 1 I don't know if I want to say related matters. It almost 13:34:40 2 suggests that there's something else going on. So unless I 13:34:40 3 slip... 13:34:40 4 But that's fine. There's a remote chance that the 13:34:40 5 Casper Star-Tribune could pick this up. They're a little 13:34:40 6 more aggressive than our paper. But again, these things 13:34:40 7 would have to come out of the Denver media to get any 13:34:40 8 attention here, hopefully. 13:34:40 9 MR. VICKERY: Okay. 13:34:40 10 THE COURT: So I'm trying to be -- 13:34:40 11 MR. VICKERY: Just being cautious. 13:34:40 12 THE COURT: I'm being optimistic about that. 13:34:40 13 MR. VICKERY: Do you want that opinion, Your Honor? 13:34:40 14 THE COURT: No, even though that's a real Magistrate. 13:34:40 15 MR. GORMAN: I have one issue we need to discuss and 13:34:40 16 some information I just found out. As the Court will recall, 13:34:40 17 yesterday in my examination of Mrs. Lafferty about the 13:34:40 18 neighbor, Mrs. Powers, Dee Powers -- and I was a little 13:34:40 19 surprised -- I wasn't surprised now, but I shouldn't have 13:34:40 20 been surprised at the reaction I got from Jim and Andy when 13:34:40 21 that name even surfaced. 13:34:40 22 Well, who Mrs. Powers is, Mrs. Powers was a neighbor 13:34:40 23 of Don Schell's and had a dog they kept in their yard because 13:34:40 24 the dog barked at people who came into the alley. 13:34:40 25 This angered Mr. Schell, and he -- a person, a man, 1481 13:34:40 1 started calling the Powers' home. And they started out with 13:34:40 2 threats that "I'm going to kill the dog." They went to 13:34:40 3 threats that "I'm going to hurt the children, your children," 13:34:57 4 and threats that I'm going to hurt you. 13:34:57 5 So Mrs. Powers had the -- called the police, had told 13:34:57 6 them about the calls that she was getting and had the -- a 13:34:57 7 trace put on her phone and the trace revealed that it was Don 13:34:57 8 Schell making these calls. 13:34:57 9 THE COURT: It did? 13:34:57 10 MR. GORMAN: Yes, it did. It did. 13:34:57 11 THE COURT: It traced the phone number, correct? 13:34:57 12 MR. GORMAN: It traced it back to Mr. Schell. 13:34:57 13 THE COURT: Their telephone number? 13:34:57 14 MR. GORMAN: Their telephone number. 13:34:57 15 They went -- the policeman came, the policeman went 13:34:57 16 and talked to Don Schell about it because of the trace. 13:34:57 17 Now, what is significant about this, I found this 13:34:57 18 information out just before Mrs. Lafferty went on the witness 13:34:57 19 stand. I was puzzled at the response I got from the 13:34:57 20 plaintiff's counsel when the word "neighbor" was mentioned. 13:34:57 21 Both were on their feet. 13:34:57 22 I now have learned that this information was given to 13:34:57 23 Andy several weeks ago by Mrs. Lafferty herself when Andy 13:34:57 24 called her first to encourage her to come and testify in the 13:34:57 25 plaintiff's case in chief. And when she found out -- when he 1482 13:34:57 1 found out this information, according to Mrs. Lafferty, 13:34:57 2 discouraged her from coming at all. 13:34:57 3 MR. VICKERY: What? 13:34:57 4 THE COURT: Just a minute. 13:34:57 5 MR. VICKERY: I'm sorry, Judge. 13:34:57 6 THE COURT: Just a minute. Let's hear this out and 13:34:57 7 I'll take care of it. Don't you worry. 13:34:57 8 MR. GORMAN: So we would like to -- we have found 13:34:57 9 Mrs. Powers. We would like to call her because we think this 13:34:57 10 evidence is important. Certainly she would have been called 13:34:57 11 if we had known this evidence prior to trial. 13:34:57 12 And I think this falls into the same category as what 13:34:57 13 happened yesterday with Peggy Deans, Mrs. Deans and the 13:34:57 14 conversation Andy heard about before he put her on that the 13:34:57 15 Court let in. 13:34:57 16 So we would like to call Mrs. Powers before the end 13:34:57 17 of the week and get this testimony in the record. 13:34:57 18 THE COURT: What's the timeline of this occurrence? 13:34:57 19 MR. GORMAN: This happened in the early 1980s. 13:34:57 20 THE COURT: Early 1980s? 13:34:57 21 MR. GORMAN: Yes, around the time when he -- remember 13:34:57 22 we traced the depression back to '84? I think it was '81, 13:34:57 23 '82, in that time frame, Judge. 13:34:57 24 THE COURT: Well, without any recriminating comments, 13:34:57 25 I will hear your response. 1483 13:34:57 1 MR. VICKERY: I'm sorry. Judge, I did talk to Miss 13:34:57 2 Lafferty to try to encourage her to come and testify in our 13:34:57 3 case in chief. Miss Lafferty told me something that was very 13:35:11 4 alarming. She said a lady told her husband who told her that 13:35:11 5 Don Schell had shot a gun through her window. It sounded 13:35:11 6 like he had fired a bullet through his neighbor's window. 13:35:11 7 And I said, "Holy smokes. That doesn't sound like 13:35:11 8 Don Schell that everybody else has talked about. Let me get 13:35:11 9 to the bottom of this." 13:35:11 10 "You didn't talk to this lady, your husband did?" 13:35:11 11 That's what Mrs. Lafferty told me. I said fine. 13:35:11 12 I did get to the bottom of it, and the best I can 13:35:11 13 tell the bottom of it from Miss Hardy was there was some 13:35:11 14 incident with some dog and Don Schell shot a BB gun out of 13:35:11 15 his own window trying to chase the dog away. He did not fire 13:35:11 16 a .357 magnum through his neighbor's window. 13:35:11 17 With regard to Mrs. Lafferty, I urged her to come 13:35:11 18 testify in our case in chief. She sent me an e-mail that I 13:35:11 19 can show the Court saying she wasn't coming to testify in my 13:35:11 20 case because she didn't believe Paxil was responsible. I 13:35:11 21 sent her an e-mail in response -- she said, "I'm coming to 13:35:11 22 testify in the defense case." 13:35:11 23 I sent her an e-mail in response and I said, "My only 13:35:11 24 concern is that maybe the defense will decide all of a sudden 13:35:11 25 they don't want you. I think your testimony is important for 1484 13:35:11 1 the jury to hear. Would you please come on anyway?" 13:35:11 2 That was the reason for my outburst, because I urged 13:35:11 3 her to come on anyway. Since she is like 90 percent of the 13:35:11 4 defense witnesses, a may-call witness, I feared the defense 13:35:11 5 might say, "We're not going to call her." And so if she 13:35:11 6 declined to come for me the jury would not have her 13:35:11 7 testimony. 13:35:11 8 This incident, if it were a felony, it is beyond the 13:35:11 9 period it can be used for impeachment of a witness under the 13:35:11 10 rules of evidence. I don't see how it could possibly have 13:35:11 11 any probative value 20 years or 18 years before this 13:35:11 12 happened. 13:35:11 13 And certainly Miss Lafferty has been on the defense 13:35:11 14 witness list. They could have interviewed her as I did. 13:35:11 15 They could have heard the specious tale and tracked it down 13:35:11 16 as I did. But to allow it now, it is delayed in time, it has 13:35:11 17 no probative value. It is a surprise for them to put on 13:35:11 18 Miss Powers. 13:35:11 19 THE COURT: It is a surprise and it has limited 13:35:11 20 probative value. 13:35:11 21 MR. GORMAN: Well, as was the conversation that 13:35:25 22 Mrs. Deans testified about yesterday. It does have some 13:35:25 23 probative value in terms of we've heard a lot of testimony 13:35:25 24 from a lot of plaintiffs' witnesses on what a laid-back, 13:35:25 25 docile, loving kind of man Don Schell was. And the fact that 1485 13:35:25 1 this happened in '81 or '82 maybe goes to its weight and I 13:35:25 2 assume Andy or Jim can bring that out on cross-examination. 13:35:25 3 The reality is we did -- we had talked to 13:35:25 4 Mrs. Lafferty. We had talked to her several times. 13:35:25 5 Mrs. Lafferty never mentioned this to us. I was not aware of 13:35:25 6 this until immediately before she went on the witness stand. 13:35:25 7 And immediately before I came up here this afternoon I had 13:35:25 8 the chance to talk to her on the phone and learned from her 13:35:25 9 for the first time then that she was the source of that 13:35:25 10 information back to Andy. 13:35:25 11 THE COURT: She? 13:35:25 12 MR. GORMAN: Mrs. Lafferty. We have talked to 13:35:25 13 Mrs. Powers, and Mrs. Powers still lives in Gillette and told 13:35:25 14 us that if after today's visit with the Court, if the Court 13:35:25 15 allowed her to testify, she would. 13:35:25 16 THE COURT: I didn't say it was of no probative 13:35:25 17 value, I said it was of limited probative value because of 13:35:25 18 the time factor. I think it has more to do with anger over a 13:35:25 19 barking dog that angers lots of people under any 13:35:25 20 circumstances. But I know you want to offer it to refute the 13:35:25 21 testimony of numerous witnesses, as you said, Mr. Gorman, 13:35:25 22 about the personality traits of Mr. Schell. 13:35:25 23 It is a surprise to the plaintiff, at least 13:35:25 24 partially, that you're going to offer that information. I 13:35:25 25 will accept the fact that the defendant just found out about 1486 13:35:25 1 it. Under the circumstances it won't delay the trial. I 13:35:25 2 will let you offer Miss Powers as a witness for whatever it 13:35:25 3 is worth. 13:35:25 4 MR. GORMAN: Thank you, Judge. We will make the 13:35:25 5 arrangements to get her here. 13:35:25 6 THE COURT: This is probably going to be the last 13:35:25 7 time I'm going to do something like that in this case. No 13:35:25 8 more surprises, notwithstanding what you've found out. We're 13:35:25 9 about to wrap this up and you've done a real nice job so far. 13:35:25 10 I commend you all. You've tried a real nice case, so to put 13:35:25 11 it in the vernacular, we don't want to muck it up any more 13:35:25 12 than we've had the chance to do already. 13:35:25 13 We still going to run a little bit late. Want to go 13:35:25 14 to 5:30, quarter to 6:00? 13:35:25 15 MR. VICKERY: I don't know how long the direct will 13:35:38 16 be with Dr. Mann. 13:35:38 17 MR. GORMAN: We have that deposition to finish. 13:35:38 18 We're on page 16 of a 60-page deposition, so probably it 13:35:38 19 would be good to go a little late. 13:35:38 20 THE COURT: I'd tell you to read fast but I would be 13:35:38 21 thumped on the head by Miss Harris. 13:35:38 22 Let's go to work. We've already lost 15 minutes. 13:35:38 23 (Proceedings recessed in chambers 1:30 p.m. and 24 reconvened in the presence of the jury 13:42:26 25 1:40 p.m., May 31, 2001.) 1487 13:42:26 1 THE COURT: I believe when we recessed we were 13:42:28 2 reading the deposition of Dr. Suhany. If you want to resume, 13:42:33 3 you may do so. 13:42:36 4 MS. WESTBY: Thank you, Your Honor. 13:42:48 5 MR. ZVOLEFF: Good afternoon, Your Honor. 13:42:50 6 THE COURT: Afternoon. 13:42:52 7 MR. ZVOLEFF: We will resume reading at page 16, line 13:42:54 8 10. 13:42:57 9 Q. "Then it is my understanding that he would have switched 13:42:59 10 to Prozac at some point in between those two visits; is that 13:43:03 11 correct? 13:43:04 12 A. In between 1/23 and 2/2, yes. In fact, it says that he's 13:43:10 13 switched eight days before 2/2, so that must be very shortly 13:43:14 14 after he left the other appointment. 13:43:16 15 Q. Okay. Was it -- was it your -- would it have been your 13:43:19 16 instructions to him to switch to the Prozac if he were not 13:43:23 17 getting the relief that he needed or the effect from Desyrel? 13:43:28 18 A. It looks like that's what we both agreed at the 1/23 13:43:32 19 visit. 13:43:32 20 Q. Okay. Did the switch from Desyrel to Prozac have anything 13:43:36 21 to do with his thoughts of death? 13:43:39 22 A. No. 13:43:39 23 Q. Okay. Okay. Let's go on to 2/9 of '90. 13:43:45 24 A. Individual psychotherapy. Trial of increased Ativan, 6 13:43:48 25 milligrams per day. Caused too much sedation. 1488 13:43:52 1 Q. Doctor, excuse me for interrupting for a minute, but 13:43:57 2 Misha, did you all finish the 2/2 entry? I'm kind of going 13:44:02 3 along with you here." 13:44:09 4 MR. ZVOLEFF: Then the witness. 13:44:10 5 A. "Yes, is there something that --" 13:44:12 6 MR. ZVOLEFF: "Miss Westby: Yeah, I think we did, 13:44:15 7 Andy." 13:44:15 8 And skipping some, and back to the witness, line 13. 13:44:23 9 MR. VICKERY: Don't skip that, please. 13:44:26 10 MR. ZVOLEFF: Mr. Vickery, I apologize. 13:44:27 11 Q. "Maybe I just didn't get it but it says obvious -- 13:44:31 12 A. Somatic anxiety today. 13:44:32 13 Q. -- anxiety today? 13:44:33 14 A. Yes. 13:44:34 15 Q. Okay. 13:44:35 16 A. I can reread that if you would like. 13:44:37 17 Q. What's the word before anxiety, obvious something, anxiety 13:44:43 18 today? 13:44:43 19 A. Obvious somatic. That means of the body. 13:44:45 20 Q. Got you. 13:44:46 21 A. Okay. 13:44:46 22 Q. Thank you. 13:44:48 23 A. Sure. Ready for 2/9? 13:44:51 24 Q. Yes. 13:44:51 25 A. 2/9/1990. Individual psychotherapy. Trial of increased 1489 13:44:56 1 Ativan to 6 milligrams per day caused too much sedation and 13:45:00 2 memory loss. Anxiety relieved with 4 milligrams per day with 13:45:04 3 few side effects. Depression improving somewhat. Agreed to 13:45:07 4 continue Prozac trial. Discussed loss of, quote, drive, 13:45:12 5 unquote, related to achieving, quote, top, unquote, of 13:45:15 6 profession. Children grown. Financially stable. Will 13:45:18 7 continue to explore this. And schedule appointment 2/14. 13:45:22 8 Q. Okay. Now you're -- in this entry you talk about the fact 13:45:26 9 that the anxiety was relieved with the 4 milligrams of 13:45:29 10 Ativan; is that correct? 13:45:31 11 A. Yes. 13:45:32 12 Q. Okay. So there's no notation or no indication in this 13:45:36 13 record that he had increased anxiety on this day, correct? 13:45:40 14 A. Correct. In fact, the entry states that his anxiety is 13:45:43 15 relieved. 13:45:48 16 Q. Okay. And he is still taking Prozac at this time, 13:45:51 17 correct? 13:45:52 18 A. Yes, he would be taking Prozac and Ativan. What this 13:45:54 19 entry says is that Ativan, 6 milligrams a day, was too much, 13:45:59 20 but Ativan at 4 milligrams a day seemed to be working very 13:46:02 21 nicely. 13:46:03 22 Q. Okay. And since you had mentioned in the 2/2 entry that 13:46:06 23 the increased anxiety and decreased appetite or loss of 13:46:09 24 appetite were potentially side effects of Prozac and we get 13:46:18 25 down to 2/9 and the anxiety is relieved, is that an 1490 13:46:21 1 indication that the increased anxiety was not a side effect 13:46:25 2 of Prozac? 13:46:26 3 A. To my professional -- no. To my professional experience 13:46:30 4 the connection between anxiety and depression is difficult to 13:46:33 5 sort out. There are many cases of depression in which 13:46:36 6 anxiety is a prominent feature and the -- so that I think in 13:46:40 7 this -- in Mr. Schell's case, the anxiety being so prominent, 13:46:44 8 that's why I have recommended treating both with an anxiety 13:46:48 9 medication as well as with an antidepressant. 13:46:51 10 Q. Okay." 13:46:52 11 MR. VICKERY: Excuse me, Mr. Zvoleff. Would you 13:46:54 12 reread that last sentence? It was antianxiety. 13:47:00 13 A. "...treating both with an antianxiety medication as well 13:47:04 14 as with an antidepressant. 13:47:06 15 Q. But you would agree that he was experiencing anxiety prior 13:47:11 16 to the time he began taking Prozac, correct? 13:47:19 17 A. Oh, yes. In fact, I believe he's having anxiety even at 13:47:19 18 the initial consultation. 13:47:19 19 Q. And then he just seems to be going through cycles of 13:47:21 20 increased or decreased anxiety during his trial on Prozac or 13:47:25 21 his treatment on Prozac, would you agree with that? 13:47:29 22 A. Yes. And actually, that's common. 13:47:31 23 Q. Okay. And so basically what you're saying to me is that 13:47:37 24 anxiety may just be a function or a factor in his depression, 13:47:42 25 is that a fair statement? 1491 13:47:43 1 A. Yes. The anxiety symptoms may be from a -- from an 13:47:46 2 anxiety disorder that is separate from depression. The 13:47:49 3 anxiety symptoms may be part of the symptoms of depression, 13:47:53 4 and symptoms that look like anxiety can be due to side 13:47:56 5 effects of medication, so that's what I would be trying to 13:47:59 6 sort out with him. 13:48:00 7 Q. But you never made any specific finding that these were 13:48:03 8 side effects or that the increased anxiety was a side effect 13:48:07 9 of Prozac, correct? 13:48:11 10 A. And to this point in the record; that is correct. 13:48:14 11 Q. Okay. Let's go on to 2/14 of '90. 13:48:18 12 A. Okay. Individual psychotherapy. Overall improved, 13:48:22 13 although had increased anxiety during the weekend. And then 13:48:25 14 there's a notation S, which is without identified 13:48:29 15 precipitants. Continued to explore loss of drive and loss of 13:48:33 16 self-confidence. Discussed possibility of returning to work 13:48:36 17 part time. Will continue current treatment. Prescription 13:48:38 18 for Ativan, 1 milligram, 75. No refill. And an appointment 13:48:44 19 for 2/23. 13:48:48 20 Q. Okay. Let's go on to February 23rd of 1990. 13:48:52 21 A. Individual psychotherapy. Continued improved although had 13:48:55 22 increased anxiety yesterday without apparent precipitant. 13:49:00 23 Focused on fears surrounding return to work. Emphasize 13:49:03 24 progress he's made and he emphasized the importance of wife's 13:49:07 25 support. Plan to return to work 2/26. Will continue 1492 13:49:10 1 treatment and schedule appointment in one to two weeks. 13:49:13 2 Prescription for Prozac, 20 milligrams, number 30, no refill. 13:49:19 3 Prescription for Ativan, 1 milligram, number 50, no refill. 13:49:23 4 Q. Okay. When he's expressing specific dates or instances of 13:49:27 5 increased anxiety, what does that mean to you about the rest 13:49:31 6 of the time or what kind of anxiety he's experiencing, if 13:49:36 7 any, the rest of the time? 13:49:38 8 A. In general a notation like 'increased anxiety' by me would 13:49:42 9 indicate that there is some change in his condition that he 13:49:46 10 identified. And he identified it as occurring the previous 13:49:50 11 day. And then I would have asked what may have triggered 13:49:54 12 this, and apparently he could not identify anything. 13:49:56 13 Q. Let's go on with 3/2 of '90. 13:49:59 14 A. Individual psychotherapy. Unable to remain at work. 13:50:02 15 Increased anxiety. This week has developed trembling in 13:50:06 16 hands which seems unrelated to anxiety. Question, side 13:50:09 17 effect Prozac. However, depression continues to improve. 13:50:12 18 Will recommend continued Prozac and Ativan and will 13:50:15 19 supplement with trial Inderal for tremor. 13:50:18 20 And then I have written a prescription for Inderal, 13:50:22 21 20 milligrams, number 15, no refill. And schedule an 13:50:25 22 appointment for the following week. 13:50:26 23 Q. You note in this entry a hand tremor. Does that -- or no, 13:50:31 24 trembling in the hands? 13:50:34 25 A. Right. 1493 13:50:34 1 Q. Does that -- how do you -- how do you describe these kinds 13:50:37 2 of conditions? Could there possibly have been other things 13:50:41 3 going on? Is that going to be the most serious symptoms? 13:50:44 4 Tell me -- explain to me how you -- how you describe these 13:50:48 5 kinds of things in your notes. 13:50:51 6 A. The phrase 'developed' signals that this is something new 13:50:55 7 that either the patient is complaining about or that I 13:50:57 8 noticed myself in the consultation. Ordinarily, although, of 13:51:01 9 course, these are brief notes, I would try to write down any 13:51:04 10 change, any new symptom, any worsening symptoms. So if there 13:51:09 11 had been other new symptoms, I would likely have recorded 13:51:12 12 them. 13:51:12 13 Q. So then it would be your impression from these notes, the 13:51:15 14 trembling in hands was the only new symptom; is that correct? 13:51:19 15 A. That would be my impression. 13:51:21 16 Q. But you continued Prozac at this time? 13:51:23 17 A. Yes, even though I questioned to myself whether or not the 13:51:26 18 trembling in the hands might be a side effect of the Prozac. 13:51:30 19 Q. And this occurred, it looks like, approximately a month or 13:51:33 20 a little bit longer after he had initially started taking the 13:51:37 21 Prozac; is that accurate? 13:51:39 22 A. Yes, about a month. 13:51:40 23 Q. And what is Inderal? 13:51:41 24 A. Inderal is a medication that in this context can be 13:51:45 25 helpful in controlling hand tremors. Inderal is primarily 1494 13:51:50 1 used for the treatment of high blood pressure. 13:51:52 2 Q. Let's go to the next notation, 3/9 of '90. 13:52:01 3 A. Individual psychotherapy. Continued tremors until 13:52:01 4 Wednesday. P with a slash, that's post, meaning after first 13:52:03 5 dose of Inderal. However, dizziness and tiredness 13:52:11 6 secondary -- that's 2 with a little sort of degree -- that's 13:52:12 7 secondary to Inderal. And then I have a notation to myself. 13:52:16 8 It looks like a parenthesis with an exclamation point which 13:52:20 9 would be like a surprise to me. That's... 13:52:22 10 Discussed in detail advantages, disadvantages of 13:52:26 11 trial of new antidepressant; with incomplete effectiveness 13:52:31 12 and difficult side effects have recommended D/C, which is 13:52:35 13 discontinue, Prozac and continue trial of imipramine. 13:52:39 14 And then I have parentheses, depression mixed with 13:52:43 15 anxiety, close parentheses. Effects, side effects explained. 13:52:46 16 Patient understands. 13:52:48 17 Plan, then, is to discontinue Prozac, begin 13:52:51 18 imipramine, 50 milligrams advancing to 75 milligrams at 13:52:55 19 bedtime. Prescription for imipramine, 25 milligrams, number 13:52:59 20 25. No refill. To continue the Ativan and to schedule an 13:53:02 21 appointment on 3/15. And there's a box, Call Dan Mainprize, 13:53:09 22 it looks like, and a telephone number, 3/23. 13:53:12 23 Q. So then this is the point in your treatment of Don Schell 13:53:15 24 when you discontinued Prozac, correct? 13:53:17 25 A. Yes. 1495 13:53:18 1 Q. And up until this point the only motor response that you 13:53:21 2 had noticed was a hand tremor; is that correct? 13:53:24 3 A. According to my notes, yes. 13:53:25 4 Q. And you would not describe this as akathisia, would you? 13:53:29 5 A. I would not. 13:53:34 6 Q. Okay. Let's go on to the next note, 3/15 of 1990. 13:53:40 7 A. Individual psychotherapy. Reports significant improvement 13:53:44 8 since Monday. Improved mood, decreased anxiety, increased 13:53:49 9 concentration, increased appetite, even increased libido. 13:53:53 10 HA -- that would be headaches -- gone and tremors markedly 13:53:56 11 decreased. Has also decreased Ativan to 4 milligrams a day. 13:54:01 12 Again discussing themes of loss, especially 13:54:03 13 self-confidence. Will continue IMI -- that's imipramine -- 13:54:06 14 prescription, 25 milligrams, number 30. No refill. 13:54:09 15 Prescription Ativan, 1 milligram, number 60. No refill. May 13:54:12 16 increase imipramine to 100 milligrams at bedtime if needed. 13:54:18 17 Next appointment, one week, 3/22. 13:54:21 18 Q. And before we get too far in these records, I just wanted 13:54:24 19 to ask you one other question about the Prozac. 13:54:27 20 A. Yes. 13:54:28 21 Q. You describe in your notes of 3/9/90 incomplete 13:54:32 22 effectiveness of Prozac, but would you agree or wouldn't you 13:54:36 23 agree that there was some improvement with Prozac or that it 13:54:40 24 had some -- some value in the treatment of Don Schell? 13:54:43 25 A. According to the notes, he had received some benefit from 1496 13:54:45 1 Prozac, yes. 13:54:47 2 Q. Let's go on, then, to the notes of 3/20. 13:54:51 3 A. Okay. 3/20. This says a draft letter to Mildred Ramsey, 13:54:55 4 RN, OXY-U.S.A., Medical Department, P.O. Box 300, Tulsa, 13:55:01 5 Oklahoma, 74102. This seems to be not a session with Don 13:55:06 6 Schell but the draft of a letter that I'm sending to this 13:55:09 7 person. And this also talks about Dan Mainprize. 13:55:14 8 Dan Mainprize with the EAP contacted me Monday and 13:55:17 9 requested this letter. Don Schell has been under my care for 13:55:20 10 treatment MDD -- that means major depressive disorder -- 13:55:23 11 since 1 of '90. Unable to work since 1/26/90. Originally 13:55:28 12 had moderate positive response to Prozac but developed 13:55:31 13 significant side effects including tremor, agitation, 13:55:34 14 headache. Also depression did not respond completely to 13:55:37 15 Prozac. 13:55:38 16 Then little symbol would be like next paragraph. 13:55:41 17 Accordingly, I recommended a trial of imipramine early, 3 of 13:55:45 18 '90. At last appointment, 3/15, he demonstrated substantial 13:55:50 19 positive response. Next appointment is 3/22. If positive 13:55:53 20 response continues he may be able to return to work week of 13:55:56 21 3/26. 13:55:57 22 And then another paragraph symbol. Thank you, 13:56:00 23 advance assist. Kind of standard closing thing. 13:56:03 24 I will contact DP, presumably Dan Mainprize, after 13:56:08 25 next week appointment with DS, Donald Schell. Further 1497 13:56:11 1 assist, et cetera, kind of a closing. That was a letter. 13:56:14 2 Q. The next note looks like 3/22 of '90. 13:56:18 3 A. Yes. Individual psychotherapy. Continues to do well, 13:56:22 4 underlined. No major symptoms, depression. Decreased 13:56:25 5 anxiety. Variable mood rather than flat. Actually had done 13:56:28 6 paperwork at the office about two hours a day for three days. 13:56:32 7 And then a symbol of surprise. 13:56:35 8 No complaints side effects. Did increase imipramine 13:56:38 9 to 100 milligrams. That is HH, recommended. Will continue 13:56:48 10 current treatment and plan half day of work next week. 13:56:48 11 Prescription for imipramine, 50 milligrams, number 13:56:48 12 30, two at bedtime. No refill. Next appointment 3/29, it 13:56:53 13 looks like. 13:56:54 14 Q. Then it looks like the note from 3/27 is another letter; 13:56:57 15 is that correct? 13:56:58 16 A. Yes, it looks like it is. 13:57:00 17 Q. Okay. 13:57:00 18 A. Draft letter to Mildred Ramsey, RN. This letter will 13:57:04 19 update you on Donald Schell's condition. At last 13:57:09 20 appointment, 3/22, he was responding well to new medication. 13:57:12 21 He will be able to return to work half days begin 3/26. 13:57:15 22 Next paragraph. His next appointment is 3/29 and we 13:57:19 23 will review his readiness to return to work full time. 13:57:22 24 Next paragraph, thank you for your cooperation. 13:57:25 25 Continue -- or contact further info, kind of a standard close 1498 13:57:29 1 again. 13:57:29 2 Q. And then 3/29? 13:57:32 3 A. Individual psychotherapy. Returned to work. First few 13:57:37 4 days quite good but in last two days has increased anxiety, 13:57:41 5 depression, self-doubts. Explored connections between old 13:57:45 6 job and these feelings. Also explored probable relationship 13:57:50 7 between these feelings and desire not to make same, quote, 13:57:54 8 trade-offs, unquote, as before. 13:57:57 9 Plan to continue half days next week. Next 13:58:00 10 appointment one week, 4/5. 13:58:03 11 Q. Do you know what -- can you be more specific about your 13:58:06 12 entry about 'old job' and 'same feelings' and 'trade-offs'? 13:58:09 13 Do you have any more information or remember anything more 13:58:11 14 about that entry? 13:58:13 15 A. I don't remember anything other than what's written. I 13:58:16 16 don't. 13:58:16 17 Q. All right. Let's go to 4/5. 13:58:18 18 A. Individual psychotherapy. Continues to do well. Work 13:58:22 19 fine with 7-hour days and even one 11-hour day in the field. 13:58:26 20 He knows he is, quote, thinking clearly, unquote, now and 13:58:31 21 wasn't able to before. One noticeable change is certainly 13:58:35 22 that he's less critical and demanding of himself. Did have 13:58:38 23 increased depressive period on Sunday, perhaps connected with 13:58:43 24 DA's -- that would be daughter's -- visit/departure and 13:58:49 25 perhaps with anxieties about work. 1499 13:58:51 1 Overall quite improved and ready to return to work 13:58:54 2 full time next week. Will continue current medication. 13:58:57 3 Prescription for imipramine, 50 milligrams, number 60, two at 13:59:01 4 bedtime. No refill. Prescription Ativan, 1 milligram, 13:59:04 5 number 100, tid to qid, three times a day to four times a 13:59:09 6 day. No refill. Next appointment two weeks, 4/19. 13:59:14 7 Q. Did it seem significant to you this was the first time he 13:59:18 8 had noted a potential connection to his depression with his 13:59:21 9 daughter's visits or departures? 13:59:23 10 A. At the time it must have seemed significant since I wrote 13:59:26 11 it down, and in this context this would be because the 13:59:29 12 patient himself had noticed it or at least we had connected 13:59:32 13 it together. 13:59:33 14 Q. Okay. And that would have been related to depression and 13:59:37 15 anxiety; is that correct? 13:59:39 16 A. Yeah. The notation says, 'Did have increased depressive 13:59:43 17 period on Sunday perhaps connected with daughter's 13:59:47 18 visit/departure and possibly with anxieties about work.' 13:59:53 19 Q. Let's continue on to 4/9. 13:59:55 20 A. That also appears to be a letter, draft letter to Mildred 13:59:58 21 Ramsey, RN. This letter updates you on Donald Schell and 14:00:03 22 confirmed phone 4/6. He continues to respond well to current 14:00:07 23 treatment. Half days at work have been successful. He will 14:00:10 24 be able to return to work full time 4/9. He will continue 14:00:14 25 follow-up treatment with me. 1500 14:00:16 1 Paragraph. Thanks, cooperation. Contact, further 14:00:19 2 info, et cetera. 14:00:20 3 Q. Then 4/9? 14:00:21 4 A. Yes. Individual psychotherapy. Reports first week of 14:00:25 5 work, quote, good. This week quote, not very good, unquote. 14:00:29 6 He has noticed increased anxiety, increased depression, 14:00:33 7 decreased self-confidence, again centered at work. No 14:00:37 8 obvious precipitants outside of work. Continued to discuss 14:00:41 9 how hardest on himself and made cognitive plans to make 14:00:46 10 changes. Will check serum imipramine level and continue 14:00:50 11 current medications pending results. Next appointment in two 14:00:52 12 weeks, 5/3. 14:00:54 13 Q. So he's still showing cycles of increased anxiety at this 14:00:57 14 point; is that correct? 14:00:58 15 A. Yes, according to the notes. 14:01:00 16 Q. And he is on imipramine at this point; is that correct? 14:01:04 17 A. Imipramine and Ativan, yes. 14:01:06 18 Q. Okay. Let's go to 4/23 of '90. 14:01:10 19 A. Okay. Phone call to patient. Serum IMI plus DMI -- 14:01:17 20 that's imipramine, and DMI is desmethylimipramine. That's a 14:01:23 21 metabolite of imipramine -- equals 88 NG, which is nanograms, 14:01:30 22 per milliliter. 14:01:31 23 I have the indication that that's low, meaning that's 14:01:33 24 below the therapeutic range, so advised to increase 14:01:40 25 imipramine to 150 milligrams at bedtime and keep scheduled 1501 14:01:41 1 appointment. 14:01:42 2 Q. Okay. 5/3 of '90? 14:01:44 3 A. Individual psychotherapy. Reports significant improvement 14:01:47 4 with increased imipramine to 150 milligrams at bedtime. 14:01:51 5 Depression decreased, anxiety much decreased. 14:01:54 6 Self-confidence returning. Concentration improved. Has 14:01:57 7 noted positive changes both at work and with family. 14:01:59 8 Beginning to review episode of depression and feels, quote, I 14:02:03 9 can be a better person because of this, unquote. Open 14:02:07 10 parentheses, that is, more concerned with others and not as, 14:02:10 11 quote, harsh, unquote, close parentheses. 14:02:14 12 No complaints of side effects. Will continue 14:02:16 13 imipramine at current dose and schedule appointment in three 14:02:20 14 weeks, 5/24. Prescription for imipramine, 50 milligrams, 14:02:23 15 100 -- number 100, three at bedtime. No refill. And note 14:02:28 16 that the patient has self-tapered Ativan to 2 and a half to 2 14:02:32 17 milligrams a day. 14:02:34 18 Q. Okay. Let's go on to the next page. I have the first 14:02:37 19 notation as 5/24 of '90. 14:02:41 20 A. Yes. Individual psychotherapy. Reports he is doing V -- 14:02:46 21 that would be in this context very well. No sustained 14:02:49 22 depressive symptoms, no significant anxiety. Increased 14:02:52 23 self-confidence. Tried to taper below Ativan 2 milligrams a 14:02:57 24 day, but anxiety increased too much. Resumption of 2 14:03:01 25 milligrams a day resolved all symptoms. Reviewed his 1502 14:03:05 1 increased comfort in handling work problems. But also 14:03:09 2 continue to support his ability to set limits and not 14:03:09 3 overextend himself. 14:03:10 4 Will continue current medications. Schedule 14:03:13 5 appointment one month, 6/21. 14:03:16 6 Prescription, imipramine, 50 milligrams, number 100, 14:03:19 7 three at bedtime. No refill. And prescription, Ativan, 1 14:03:23 8 milligram, number 60, one twice a day. No refills. 14:03:26 9 Q. Okay. 6/27/90. 14:03:30 10 A. Individual psychotherapy. Continues to do very well 14:03:33 11 without depressive symptoms, without significant anxiety. 14:03:36 12 Work going well. Received a raise. He, his wife and 14:03:40 13 daughter have all noticed positive changes in his 14:03:42 14 personality. There's a colon which would mean, for example, 14:03:45 15 less demanding, less critical, less irritable, more willing 14:03:50 16 to listen. 14:03:50 17 He tried decreasing Ativan to 1 milligram a day but 14:03:54 18 developed increased anxiety. Discussed plans to taper more 14:03:58 19 gradually, for example, to 1 and a half milligrams a day. 14:04:02 20 Will continue current medications. 14:04:04 21 Prescription, imipramine, 50 milligrams, 100, three 14:04:08 22 at bedtime. That's a monthly supply. No refill. And 14:04:11 23 prescription, Ativan, numbering 60, one twice a day. That's 14:04:13 24 again a monthly supply. No refill. With an appointment the 14:04:16 25 following month on 7/26. 1503 14:04:19 1 Q. Okay. And then the notation from 7/26. 14:04:23 2 A. Individual psychotherapy. Continued stable improvement. 14:04:27 3 No symptoms of depression, no significant anxiety. Work and 14:04:30 4 family fine. Beginning to talk of fears of relapse. 14:04:33 5 Education given regarding signs and treatment. Ativan 14:04:37 6 decreased to 1 milligram a day, occasionally 1 and a half 14:04:40 7 milligrams a day. Will continue current treatment. 14:04:44 8 Prescription, imipramine, 50 milligrams, number 100, 14:04:47 9 three at bedtime. No refill. And next appointment 9/6. 14:04:51 10 Q. Since you increased the dosage to 150 milligrams of 14:04:56 11 imipramine has Don Schell been on the same level since that 14:04:59 12 point? 14:05:00 13 A. Yes. 14:05:01 14 Q. Okay. The next note is 9/13. 14:05:05 15 A. Individual psychotherapy. Doing very well. No symptoms 14:05:09 16 depression or significant anxiety. Feels better than he has 14:05:12 17 in two-plus years. Now feels better than when he had last, 14:05:16 18 quote, recovered, unquote, on Prozac. Does have fears of 14:05:19 19 relapse during approaching winter. Plan to continue 14:05:22 20 imipramine into early next year. Ativan use decreased to 14:05:26 21 five per week, and then will continue current treatment. 14:05:29 22 Prescription, imipramine, 50 milligrams, number 10, 14:05:32 23 three at bedtime. Prescription, Ativan, 1 milligram, number 14:05:35 24 25. Next appointment in six weeks at -- on 10/25. 14:05:41 25 Q. Do you have any independent recollection or can you shed 1504 14:05:44 1 any light on Don Schell's previous treatment with Prozac that 14:05:47 2 you have noted here and other times in the records? 14:05:52 3 A. I don't have any independent recollection. The record 14:05:55 4 showed that he had taken Prozac previously when he had this, 14:05:58 5 quote, depressive reaction after he was taking Tylenol after 14:06:01 6 a growth had been removed from his eye. That was with the 14:06:05 7 previous psychiatrist. 14:06:06 8 And then of course we had -- and I mean, I -- Don 14:06:11 9 Schell and I had our own trial of Prozac with him for about 14:06:19 10 four or five weeks. So that's what I would mean by, quote, 14:06:19 11 recovered. In this context that would be his perception; 14:06:21 12 that is, that he feels better than he had when he had last, 14:06:24 13 quote, recovered on Prozac. 14:06:28 14 Q. Okay. The next entry is 10/25/90. 14:06:31 15 A. Individual psychotherapy. Continues to do very well. 14:06:35 16 Quote, I didn't think I could feel even better but I do, 14:06:38 17 unquote. Now beginning to sort out some of the precipitating 14:06:41 18 events. And then I have a bracket around, apparently, some 14:06:44 19 of these precipitating events: Brother-in-law died in 1987. 14:06:49 20 Didn't grieve. Quote, strong one, unquote, until 1988. Rs, 14:06:55 21 I'm thinking in this context meaning his wife, Rita's, 14:07:00 22 depression, '88 to '89, secondary to her mother's CA, in this 14:07:06 23 context presumably cancer; daughter's, quote, bad Pap smear, 14:07:09 24 unquote. And then there's a notation, now resolved, and then 14:07:12 25 that quote continues to the following page. 1505 14:07:14 1 Also has renewed self-confidence at work. Will be on 14:07:19 2 vacation three weeks in the next two months. Since doing 14:07:22 3 well will schedule appointment in two months, on 12/18. 4 And then my prescription for imipramine, 50 14:07:26 5 milligrams, number 100. One refill. That is a month's 14:07:30 6 supply and one refill. That's the end of that note. 14:07:33 7 Q. And it looks like the final note is 2/18 of '90. 14:07:37 8 A. Actually, it is 12/18 of '90. 14:07:41 9 Q. 12/90? I'm sorry. 14:07:44 10 A. Yes. Individual psychotherapy. Continues in complete 14:07:47 11 remission of depression. Has taken no Ativan for -- that's 14:07:50 12 times one month and feels very good about this. Facing 14:07:54 13 possible major change at work including possible relocation 14:07:57 14 with confidence rather than anxiety. Still plan to continue 14:08:00 15 medications throughout the winter. 14:08:02 16 Prescription, imipramine, 50 milligrams, number 100, 14:08:05 17 three at bedtime. One refill. Is to call for appointment in 14:08:10 18 about two months. 14:08:11 19 Q. So that would have been enough imipramine for two months, 14:08:13 20 correct? 14:08:14 21 A. Yes. That is a one-month supply of his current dose of 14:08:18 22 imipramine and one refill. 14:08:20 23 Q. And do you know if he ever called for that appointment in 14:08:23 24 two months? 14:08:25 25 A. I -- I don't know. In my records there's nothing to 1506 14:08:28 1 indicate one way or another, and I don't have any independent 14:08:32 2 recollection of that. 14:08:33 3 Q. Okay. And did you ever see Don Schell again following the 14:08:37 4 visit on 12/18 of '90? 14:08:40 5 A. According to my record, no. And I have no independent 14:08:44 6 recollection of anything different. 14:08:45 7 Q. According to the records -- or your records, the only 14:08:49 8 notations regarding ideas of death are in the first note of 14:08:54 9 1/16/1990. You never observed any suicidal or homicidal 14:09:00 10 ideation or behavior while Don was being treated with Prozac; 14:09:03 11 is that correct? 14:09:05 12 A. According to my notes, I would say that is correct. 14:09:08 13 Q. Okay. 14:09:09 14 A. Since I didn't note it down as a positive finding, which I 14:09:12 15 would certainly expect to do if it had been present. 14:09:15 16 Q. And was it your observation that work was a significant 14:09:19 17 stressor for Don Schell? 14:09:21 18 A. Clearly, all the way from the initial consultation to his 14:09:24 19 difficulties in returning to work. Clearly in his own mind 14:09:27 20 the depression and anxiety were quite related to work and his 14:09:30 21 ability to either be able to work or not. 14:09:32 22 Q. So you would also agree that work was a source of his 14:09:35 23 anxiety? 14:09:37 24 A. According to my notes and the way I understand them, yes. 14:09:40 25 It seems that on more than one occasion when he was either 1507 14:09:43 1 returning to work or getting ready to return to work that 14:09:46 2 some anxiety symptoms increased. That was the connection 14:09:50 3 that he made and that as he reported I would write down. 14:09:54 4 Q. And was work a significant component of his depression? 14:09:58 5 A. Well, I'm not sure what you mean by that. 14:10:00 6 Q. Well, okay. Would you -- it appears to me from the 14:10:04 7 records that work is the most frequently mentioned stressor 14:10:07 8 or cause of his problems. Would you agree with that? 14:10:11 9 A. I would say that it is the most frequently mentioned 14:10:13 10 stressor, yes. 14:10:15 11 Q. And do you believe that it was a significant cause or led 14:10:19 12 to his depression? 14:10:20 13 A. Cause is a difficult word for me in this context. The -- 14:10:24 14 a diagnosis that I made, major depressive disorder, in my 14:10:28 15 thinking then as well as my current thinking, is a 14:10:30 16 biological/biochemical illness. So to say that a particular 14:10:35 17 stressor, including a set of stressors at work, is causative 14:10:40 18 is not a link that I'm prepared to make. 14:10:43 19 On the other hand, as I also indicated in my 14:10:45 20 first consultation note -- and I still look at these issues 14:10:48 21 this way -- the psychological issues or the psychological 14:10:58 22 impact is important besides the alteration in the brain 14:10:58 23 chemistry. And so I approached Mr. Schell then from both 14:10:58 24 perspectives of trying to manage the biochemical 14:11:00 25 abnormalities with medication and trying to help him 1508 14:11:02 1 understand stressors and his response to them through 14:11:05 2 psychotherapy. 14:11:06 3 Q. Okay. Did you ever meet" -- 14:11:24 4 MR. ZVOLEFF: Mr. Vickery, can I skip the colloquy? 14:11:27 5 Start at 40, line 1. 14:11:29 6 Q. "Do you recall -- I don't remember hearing you mention it 14:11:31 7 in any of the records, but do you recall after having gone 14:11:35 8 through those records if you ever met Rita Schell or if she 14:11:40 9 was ever present at any of these visits? 14:11:43 10 A. According to my records, she would not have been present 14:11:46 11 at any of the visits because they're all labeled individual 14:11:50 12 psychotherapy. Whether or not she may have come to the 14:11:53 13 office and I may have met her incidentally, I have no 14:11:56 14 independent recollection. 14:11:58 15 Q. Okay. Did you -- 14:11:59 16 A. If I had seen -- excuse me. If I had seen them together 14:12:01 17 in terms of any kind of joint counseling session, I would 14:12:04 18 have recorded that information. 14:12:05 19 Q. Did you know the Schells socially at all? 14:12:08 20 A. No, I didn't. 14:12:09 21 Q. And you never saw Don Schell outside of the office? 14:12:11 22 A. I can't say with certainty. Gillette, when I was there, 14:12:15 23 is certainly a small community and I may have seen him in 14:12:19 24 passing, but I don't know whether I did or not. 14:12:22 25 Q. Do you recall anything, independent of the records from 1509 14:12:24 1 your visits with him, anything that struck you as unusual, 14:12:27 2 any particular concerns you had, anything that may be of 14:12:31 3 assistance to us? 14:12:33 4 A. No. 14:12:34 5 Q. And I think that we've already discussed this, but I just 14:12:37 6 want to make sure that it is clear for the record. Would you 14:12:40 7 describe what Don Schell experienced on Prozac as akathisia? 14:12:45 8 A. According to the information that I have in my record, I 14:12:48 9 would not describe it as akathisia." 14:12:53 10 MR. ZVOLEFF: Now switching to Mr. Vickery's 14:12:55 11 questions on line 15. 14:12:58 12 Q. "Doctor, this is Andy Vickery. Can you hear me okay? 14:13:02 13 A. Yes, sir, I can hear you fine. 14:13:04 14 Q. Why on earth would a guy leave Dallas, Texas and go to 14:13:09 15 Gillette, Wyoming? 14:13:10 16 A. Well, that -- we're on the record, right? 14:13:12 17 Q. No, I'm just joking. I'm just joking. They're both very 14:13:18 18 nice places. 14:13:19 19 A. Actually, Dallas was too big for us, we thought, and 14:13:23 20 Gillette turned out to be way too small. 14:13:27 21 Q. I hope you found the midpoint. 14:13:29 22 A. Well, I don't know -- I don't know if Las Vegas is the 14:13:30 23 midpoint, but it's suiting us just nicely right now. 14:13:30 24 Q. It is a very nice town. I assume from the fact that you 14:13:33 25 now live and work in Las Vegas that you will not be available 1510 14:13:37 1 to testify in Cheyenne, Wyoming in May of this year in this 14:13:40 2 trial? 14:13:40 3 A. I would prefer not. 14:13:42 4 Q. Okay. Well, if you're not available, then we can use this 14:13:47 5 deposition. I just had to make it clear on the record that 14:13:50 6 you did not plan on being there and would prefer not to be 14:13:53 7 there. 14:13:53 8 A. Yes, I would prefer that my deposition would suffice for 14:13:56 9 my physical presence. 14:13:58 10 Q. Now, let me ask this, sir. You are, of course, a trained 14:14:02 11 psychiatrist, right? 14:14:03 12 A. Yes, I am. 14:14:04 13 Q. And when you have someone with a major depressive disorder 14:14:07 14 such as you diagnosed for Donald Schell, are you always 14:14:10 15 sensitive to the possibility that that person would be 14:14:12 16 thinking about harming themselves or others? 14:14:15 17 A. Yes. 14:14:16 18 Q. Is that something that you look for, not only at the 14:14:19 19 initial intake session but periodically throughout your 14:14:22 20 treatment of that person? 14:14:26 21 A. Yes, typically. 14:14:27 22 Q. Did you ever see anything in Donald Schell that would 14:14:29 23 indicate that this patient was a risk for harming himself or 14:14:32 24 anyone else? 14:14:34 25 A. According to what I have detailed in my records, no, with 1511 14:14:38 1 the exception of the mention at the initial consultation that 14:14:41 2 he had been thinking about death, although not specifically 14:14:44 3 about suicide. 14:14:45 4 Q. And if I understood what you were saying there, looking 14:14:47 5 back on the first page of your records, there is a -- in your 14:14:51 6 shorthand way, a progression of thoughts, beginning with 14:14:54 7 thoughts of death being the most mild and ending with an 14:14:59 8 active suicide plan or attempt as the most severe, correct? 14:15:02 9 A. Yes. Plan is the most serious; plan and means to carry 14:15:05 10 out the plan. 14:15:06 11 Q. But when you say on the January 16th, 1990, visit, 14:15:10 12 positive ideas about death but without suicidal ideation or 14:15:16 13 other info, does that mean plan? 14:15:19 14 A. Actually, that's intent. 14:15:21 15 Q. Intent? 14:15:21 16 A. Yes. 14:15:22 17 Q. Does that mean that you affirmatively questioned him at 14:15:24 18 that time about that? 14:15:25 19 A. Yes, that would mean that. And that would be my standard 14:15:28 20 practice. 14:15:30 21 Q. Dr. Suhany, I note in going through these records that 14:15:33 22 apparently you saw this man about 18 different times for 14:15:37 23 individual psychotherapy throughout 1990? 14:15:40 24 A. I will accept your count of that, yes. 14:15:42 25 Q. About how long would you see him each time? 1512 14:15:45 1 A. Probably about an hour. Perhaps in some of the later 14:15:48 2 visits it was shorter than that, but certainly the early 14:15:55 3 visits would be about an hour. That was my standard of 14:15:56 4 private practice at that time in 1990. 14:15:58 5 Q. Tell us, if you would, just in your own words after 14:16:02 6 spending 18 hours with this man what adjectives would you use 14:16:05 7 to describe him? 14:16:07 8 A. Do you mean when he first came to see me or do you mean 14:16:10 9 toward the end of what appeared to me to be a successful 14:16:13 10 treatment? 14:16:14 11 Q. Let's take them both. When he first came to see you, how 14:16:17 12 would you describe, generally speaking, Donald Schell? 14:16:21 13 A. According to what my notes reflect, an anxious, depressed, 14:16:24 14 hard-working man. 14:16:25 15 Q. And did you believe that the anxiety and depression 14:16:28 16 related to the particular situation he was facing at work 14:16:32 17 then? 14:16:33 18 A. According to my notes, and, you know, also just trying to 14:16:37 19 understand what I've written, that the depression and anxiety 14:16:40 20 would have been related to concerns about his job, yes. 14:16:44 21 Q. Sir, I didn't see anything in your notes that -- let me 14:16:47 22 ask you this from your memory. Throughout the course of your 14:16:51 23 treatment of this man for a year did you ever see any 14:16:53 24 indication that he had problems with his marriage or with his 14:16:55 25 family? 1513 14:16:57 1 A. I have no independent recollection of that outside of my 14:17:00 2 notes. The notes talk about at one point that he values his 14:17:04 3 wife's support. There are a couple of notes about his 14:17:06 4 daughter. And beyond that, I have no other recollection and 14:17:09 5 there's nothing in the notes to indicate that. 14:17:12 6 Q. I noticed that when we went through. And when you write 14:17:15 7 down something like 'values his wife's support,' does that 14:17:18 8 mean that he is getting that support and appreciates it? 14:17:23 9 A. Well, let's see. Do you know which -- 14:17:25 10 Q. Yes, sir, I think I highlighted it for you. 14:17:31 11 A. All right. 14:17:31 12 Q. It is in the 2/23/90 visit. 14:17:34 13 A. Okay, actually the actual words he emphasized are the 14:17:38 14 importance of wife's support. That is -- the whole sentence 14:17:41 15 says emphasized progress he's made and he emphasized 14:17:46 16 importance of wife's support. 14:17:47 17 In that context it appears to me he believes his wife 14:17:50 18 is supportive and that that's been important to him. 14:17:54 19 Q. Did you believe he needed both the medication as well as 14:17:57 20 the individual psychotherapy? 14:17:58 21 A. Yes, I did. 14:17:59 22 Q. Can you explain why, why it is in your judgment that it is 14:18:03 23 helpful for someone to have both of these forms of therapy 14:18:06 24 together? 14:18:07 25 A. Yes. My experience to that point in 1990 had taught me 1514 14:18:11 1 that patients with clinical illness like major depression 14:18:14 2 need or will do better with a combination of treatment. Not 14:18:17 3 only the appropriate medication to regulate whatever 14:18:20 4 biomechanical/biological abnormality may be present, but also 14:18:25 5 psychotherapy, both to identify maladaptive ways of dealing 14:18:29 6 with stressors, as well as identify better coping skills, as 14:18:34 7 well as a relationship with a treating professional to 14:18:37 8 understand the clinical problem, and also, as we talk about 14:18:42 9 later on in the course of Mr. Schell's treatment, 14:18:44 10 understanding what needs to be done to prevent or minimize 14:18:47 11 relapse. 14:18:48 12 Q. Now, is that what -- what you in your profession refer to 14:18:53 13 as a therapeutic alliance? 14:18:55 14 A. Yes. 14:18:55 15 Q. And can you just sort of put that in plainspeak for us. 14:18:58 16 What is therapeutic alliance? 14:18:59 17 A. In plainspeak, a therapeutic alliance is a working 14:19:03 18 relationship between the patient and his doctor in which both 14:19:06 19 respect and trust each other. 14:19:07 20 Q. Did you believe that you had a good therapeutic alliance 14:19:10 21 with Donald Schell? 14:19:12 22 A. Absent any evidence to the contrary in my notes, yes. 14:19:15 23 Q. I didn't see any, but I just wanted your testimony on it. 14:19:19 24 Did this man want your help and did he want to get better? 14:19:22 25 A. I believe he did, both in terms of that it would appear 1515 14:19:25 1 that he himself contacted my office and that he was quite 14:19:29 2 faithful in working with me over a period of almost a year. 14:19:32 3 Q. Was he a compliant patient? 14:19:34 4 A. According to the record, yes. 14:19:36 5 Q. And what do we mean by that? 14:19:37 6 A. What I would mean by that is that when I have proposed a 14:19:41 7 plan he appears to have followed it, and what I also mean by 14:19:44 8 that is that he continued treatment with me. What I also 14:19:47 9 mean by that is it would appear from my record that he was 14:19:50 10 using the medication appropriately and not requesting extra 14:19:53 11 or saying, 'I don't need it because I didn't take as much,' 14:19:57 12 or anything like that. 14:19:59 13 That is, there seems to be no evidence like that in 14:20:01 14 the record and the prescription amounts would appear to be 14:20:05 15 consistent with what would be needed from visit to visit. 14:20:08 16 Q. Okay, sir. Now, let me ask you something. You mentioned 14:20:11 17 a Dr. B that had apparently given him some Prozac briefly in 14:20:16 18 the spring of '89. 14:20:18 19 A. Yes. 14:20:18 20 Q. Would that have been Dr. Buchanan rather than 14:20:21 21 Dr. Bresnahan? 14:20:24 22 A. It could have been. I have no independent recollection of 14:20:31 23 that. Dr. Bresnahan is a psychiatrist that I believe was in 14:20:31 24 town at that time, but if you have information that it was 14:20:34 25 Dr. Buchanan, that -- I have no way of knowing. 1516 14:20:40 1 Q. Do you know Dr. Buchanan? 14:20:43 2 A. I don't recall. 14:20:43 3 Q. Now, let's get specifically to the medications, if we can. 14:20:47 4 A. Yes. 14:20:48 5 Q. At the time he first came to see you he had already been 14:20:50 6 started by his GP on Desyrel and Ativan, correct? 14:20:55 7 A. Yes, that is correct. 14:20:56 8 Q. Can you tell me what classification of drugs Desyrel is 14:21:00 9 in? 14:21:00 10 A. Yes. It is an antidepressant. 14:21:04 11 Q. What kind? 14:21:04 12 A. What kind? 14:21:05 13 Q. Is it a tricyclic? 14:21:07 14 A. No, it is -- at the time in 1990 it was in class by 14:21:11 15 itself. It was not a traditional tricyclic antidepressant. 14:21:16 16 It was not the new kid on the block, SSRI, Prozac. And it 14:21:20 17 was not an even older type of medication, monoamine oxidase 14:21:27 18 inhibitor, MAOI. So it was in a class by itself. 14:21:31 19 Q. Did it have any effects, insofar as you can recollect, on 14:21:34 20 the serotonin system? 14:21:37 21 A. Certainly. It was designed to enhance serotonin, as most 14:21:39 22 antidepressants are. 14:21:41 23 Q. But in a different way rather than blocking the reuptake, 14:21:44 24 right? 14:21:45 25 A. I'm not sure. 1517 14:21:45 1 Q. In any event, you continued him on the Desyrel for a 14:21:49 2 period of time but then switched over to Prozac, correct? 14:21:53 3 A. That is correct. 14:21:54 4 Q. Was Prozac, to use your words, the new kid on the block in 14:21:59 5 1990? 14:21:59 6 A. I believe it was. I don't know if it was the newest 14:22:02 7 antidepressant in 1990, but it was certainly one of the newer 14:22:06 8 ones. And it was the first of what is now recognized as the 14:22:09 9 class of SSRIs, serotonin selective reuptake inhibitors. 14:22:15 10 Q. Dr. Suhany, have you, since Paxil came out in 1992, had 14:22:18 11 occasion to prescribe Paxil for patients? 14:22:21 12 A. Yes, I have. 14:22:21 13 Q. And I believe it is also an SSRI, right? 14:22:23 14 A. Yes, it is. 14:22:24 15 Q. How about Zoloft which also came out in '92? Have you had 14:22:29 16 occasion since 1992 to prescribe that for patients? 14:22:33 17 A. Yes, I have. 14:22:34 18 Q. And can you tell me whether or not Paxil is a more potent 14:22:39 19 inhibitor of the reuptake of serotonin than Prozac? 14:22:42 20 A. I don't know. 14:22:52 21 Q. All right. Now, let's back up a minute. At the time he 14:22:56 22 first came to you, in addition to being on the antidepressant 14:23:00 23 Desyrel, he was also on Ativan, correct? 14:23:03 24 A. That is correct. 14:23:03 25 Q. Is that in a classification of drugs known as 1518 14:23:06 1 benzodiazepines? 14:23:07 2 A. Yes, it is. 14:23:07 3 Q. Are they generally thought to be antianxiolytic 14:23:12 4 medication? 14:23:13 5 A. Yes, anxiolytic medications. 14:23:18 6 Q. That's a tenpenny word, too. Can you put that in 14:23:20 7 plainspeak for us? What do they do for you? 14:23:24 8 A. Antianxiety, depress anxiety. 14:23:26 9 Q. Do they also have a sedative or calming effect on a 14:23:30 10 person? 14:23:30 11 A. Yes, that would be another way of describing its 14:23:33 12 antianxiety effect, sedative effect reference to the fact it 14:23:42 13 helps people sleep at bedtime. 14:23:44 14 Q. Doctor, had you had occasion prior to Donald Schell to 14:23:48 15 prescribe Prozac for someone else? 14:23:52 16 A. I believe so, yes. 17 Q. Was it typical in your practice at that time, when you 14:23:53 18 were starting someone on Prozac, to give them Ativan or some 14:23:55 19 other benzodiazepine concomitantly; in other words, the first 14:24:00 20 period of time? 14:24:01 21 A. That would not have been my common practice in 1990 and it 14:24:05 22 isn't my common practice now. 14:24:08 23 Q. Were you aware of the fact in the spring of 1990 that the 14:24:11 24 maker of Prozac, Eli Lilly, had a warning in the Federal 14:24:15 25 Republic of Germany that recommended that doctors give 1519 14:24:20 1 sedatives along with Prozac in the initial period in order to 14:24:24 2 reduce the risk of suicide? 14:24:26 3 A. No, I was not aware of that. 14:24:28 4 Q. In any event, you start him on Prozac, let's see, when? 14:24:32 5 You start him on the 23rd of January; is that correct? 14:24:39 6 A. Sometime between the 23rd of January and the 22nd of 14:24:42 7 February. It looks like much closer -- 14:24:44 8 Q. You gave a prescription for Desyrel and Prozac, and he was 14:24:47 9 to, what, taper down on the Desyrel and if that didn't work, 14:24:51 10 then go to Prozac? 14:24:53 11 A. Yes, that was our plan as of 1/23. 14:24:56 12 Q. Now, when you see him on February 2nd, the next time after 14:25:00 13 that, would you just tell me there what are the two things 14:25:02 14 that you think may be side effects of Prozac according to 14:25:06 15 your entry? 14:25:07 16 A. Increased anxiety and loss of appetite. 14:25:10 17 Q. Okay, sir. When you write under February 2nd, 14:25:13 18 increased -- I'm sorry -- obvious somatic anxiety today, is 14:25:17 19 that an observation that you're making objectively rather 14:25:25 20 than reporting subjectively? 14:25:25 21 A. With the use of the word 'obvious' and the use of the word 14:25:26 22 'today,' I believe it is an observation that I'm making 14:25:29 23 rather than a self-report by the patient. 14:25:31 24 Q. Can you tell me what you would have seen or heard 14:25:33 25 typically from a patient like Mr. Schell to cause you to make 1520 14:25:37 1 that entry, obvious somatic anxiety today? 14:25:42 2 A. The kinds of things -- and I can't be certain that these 14:25:46 3 were present in Mr. Schell, but the kinds of things that I 14:25:48 4 would -- that I would mean by that kind of notation is really 14:25:52 5 physical signs of anxiety, such as trembling in hands, such 14:25:56 6 as like tapping fingers incessantly, you know, on a desk or 14:26:01 7 something, frequent and incessant-like foot tapping or other 14:26:04 8 jittery motions of the body, possibility some difficulties 14:26:08 9 with speech, like rapid speech or possibly, you know, a lot 14:26:11 10 of sighing, something that would indicate problems with 14:26:13 11 anxiety or nervousness. 14:26:14 12 Q. All right. But, in other words, something that you could 14:26:17 13 physically see; is that right? 14:26:18 14 A. My understanding of that notation would be that it was 14:26:23 15 something I saw that day, yes. 14:26:24 16 Q. And would it be fair to say that 11 years later, you know, 14:26:28 17 you don't recall specifically which one of those outward 14:26:31 18 symptoms you saw? 14:26:32 19 A. It is definitely fair to say that. I do not have 14:26:35 20 independent recollection. 14:26:37 21 Q. All right. Now, that is on February the 2nd, and the -- a 14:26:40 22 month later, on March the 2nd, you make another entry about 14:26:44 23 increased anxiety and also say, 'This week he has developed 14:26:50 24 trembling of hands.' What was -- 14:26:52 25 A. In, I believe that is. 1521 14:26:55 1 Q. What -- the fact that he had developed trembling of hands 14:26:58 2 recently? 14:26:58 3 A. The significance would be, first of all, that it was 14:27:01 4 something new; secondly, that either he had noticed it and 14:27:06 5 complained about it or that I had noticed it. 14:27:08 6 Q. Can you tell from your records which one that was, whether 14:27:12 7 it was something he reported to you or whether it was 14:27:14 8 something you observed? 14:27:15 9 A. I cannot tell based on the entry. 14:27:19 10 Q. Can you tell whether or not you believe that this was a 14:27:21 11 side effect of Prozac? 14:27:23 12 A. I questioned myself whether it was. 14:27:25 13 Q. And you gave him some medication that day to help deal 14:27:27 14 with that side effect, didn't you? 14:27:29 15 A. Yes, which makes me assume, although I will caution you it 14:27:32 16 is an assumption, that I myself saw a tremor or a trembling 14:27:37 17 that day since I had recommended a specific treatment. 14:27:39 18 Q. The treatment that you gave was a category of medicines 14:27:42 19 known as beta-blockers, correct? 14:27:45 20 A. That is correct. 14:27:45 21 Q. And specifically a medicine called Inderal? 14:27:48 22 A. Yes. 14:27:49 23 Q. Can you just explain for us in plain terms what a 14:27:52 24 beta-blocker is? 14:27:54 25 A. Beta-blockers are used primary for difficulties in 1522 14:27:58 1 cardiovascular systems, particularly in patients with high 14:28:02 2 blood pressure. And it slows down their heart rate and so it 14:28:06 3 makes their blood pressure decrease. In this context, 4 beta-blockers have been know for a long time to decrease what 14:28:08 5 are usually called bodily or somatic symptoms of anxiety, 14:28:12 6 particularly tremors, butterflies in the stomach, difficulty 14:28:16 7 with speech. Some patients have been given Inderal for 14:28:20 8 so-called performance anxiety. 14:28:24 9 Q. Is propranolol a beta-blocker? 14:28:31 10 A. Propranolol is the generic form of Inderal. 14:28:35 11 Q. Have you -- 14:28:35 12 A. It is the same medication 14:28:37 13 Q. Have you seen in the literature recommendations that 14:28:38 14 beta-blockers be used to treat SSRI-induced movement 14:28:41 15 disorders? 14:28:41 16 A. You mean did I have that information in 1990? 14:28:44 17 Q. Well, your point is well taken. Did you have that 14:28:47 18 information in 1990? 14:28:48 19 A. I believe I did. 14:28:49 20 Q. Have you subsequently in the years since then learned that 14:28:56 21 that is a selective treatment for SSRI-induced movement 14:29:00 22 disorders? 14:29:01 23 A. I'm aware of some of those kinds of reports. 14:29:04 24 Q. Now, Miss Westby asked you whether or not you would 14:29:08 25 diagnose this trembling you noticed as akathisia. Have you 1523 14:29:11 1 ever made a diagnosis in any patient of akathisia? 14:29:14 2 A. Yes, I have. 14:29:15 3 Q. Can you tell us what are the diagnostic criteria for 14:29:17 4 akathisia? 14:29:18 5 A. Yes. The primary feature of akathisia is an inability to 14:29:22 6 sit down or otherwise control gross motor behavior. Along 14:29:25 7 with that, patients themselves report intense discomfort and 14:29:29 8 inability to stop themselves from, like, pacing around or 14:29:32 9 from sitting down -- or not being able to sit down, actually. 14:29:35 10 So it is both a physical symptom as well as a discomfort that 14:29:39 11 patients feel. 14:29:40 12 Q. And are those diagnostic criteria taken from a big, old 14:29:44 13 book you have in your office called the DSM-IV? 14:29:48 14 A. Well, I don't think that akathisia is described in the 14:29:50 15 DSM-IV since it is not a clinical syndrome, but it is, 14:29:54 16 rather, a side effect of medications. 14:29:56 17 Q. Actually, I think you will find it under 14:29:58 18 neuroleptic-induced akathisia in the new version, but in any 14:30:02 19 event, is akathisia by definition something that is drug 14:30:05 20 induced? 14:30:13 21 A. Yes. 14:30:13 22 Q. Were you in early 1990 familiar with the literature 14:30:13 23 concerning Prozac and akathisia? 14:30:13 24 A. No. 14:30:13 25 Q. In February of '90, that's when you had him on Prozac, 1524 14:30:16 1 right? 14:30:17 2 A. Yes, that's when we started. 14:30:20 3 Q. And in that very month an article came out in a journal by 14:30:24 4 Dr. Teicher and Dr. Cole about suicides, the possible 14:30:27 5 connection between Prozac and suicide. Did you read that 14:30:30 6 article then? 14:30:33 7 A. I don't know. 14:30:33 8 Q. Are you aware of that article now? 14:30:35 9 A. Not by the information that you've given me." 14:30:36 10 MR. ZVOLEFF: Okay, sir. 14:30:43 11 MR. VICKERY: Down to line 21. 14:30:46 12 Q. "Dr. Suhany, in your practice in Gillette would drug 14:30:50 13 representatives periodically call on you to tell you about 14:30:53 14 their medications? 14:30:54 15 A. Not commonly in my private practice. 14:30:56 16 Q. Do you know whether or not anyone from Eli Lilly had ever 14:30:59 17 contacted you prior to February of 1990 to give you 14:31:03 18 information or promotional literature about Prozac? 14:31:06 19 A. I don't know for sure, but I would expect, yes." 14:31:12 20 MR. ZVOLEFF: Now to Miss Westby's follow-up 14:31:15 21 questions on line 16. 14:31:18 22 MS. WESTBY: Yes. 14:31:19 23 Q. "You were talking with Dr. Vickery about the entry on 14:31:22 24 2/2/90, obvious somatic anxiety today? 14:31:26 25 A. Yes. 1525 14:31:26 1 Q. The only actual description of a physical symptom in any 14:31:29 2 of your notes is the trembling in the hands, is that correct, 14:31:33 3 which occurs in your note on 3/2 of '90? 14:31:36 4 A. Yes, as near as I can tell and remember in looking at 14:31:39 5 those notes today. 14:31:40 6 Q. Okay. So when you were describing some of the typical 14:31:44 7 physical symptoms that generally represent anxiety or 14:31:48 8 physical or somatic anxiety, you don't know specifically what 14:31:51 9 you meant by that entry, those were just some general ideas 14:31:56 10 of what may have been meant by that entry; isn't that 14:31:59 11 correct? 14:31:59 12 A. Yes, as I think I tried to say earlier. But that is what 14:32:02 13 I meant. 14:32:03 14 Q. Okay. 14:32:04 15 A. I can't be certain what exactly I observed on 2/2. I was 14:32:08 16 listing categories of things I might have observed that would 14:32:12 17 lead me to make that entry. 14:32:14 18 Q. But you don't have any specific entry about any kind of 14:32:17 19 physical symptom on 2/2; is that correct? 14:32:23 20 A. That is correct. 14:32:23 21 Q. And the only entry that appears anywhere in the records is 14:32:26 22 on 3/2 and that is trembling in hands; is that correct? 14:32:30 23 A. 3/2, and I think there's some mention in the next 14:32:33 24 appointment, 3/9, that the tremors continued until after he 14:32:37 25 took Inderal, but then he couldn't take Inderal." 1526 14:32:51 1 MS. WESTBY: I will start on 24 -- "That's all the 14:32:53 2 questions" -- 14:32:54 3 MR. ZVOLEFF: 61, line 1. 14:32:55 4 A. "Oh just -- I was just looking, just to be completely 14:32:58 5 fair. On 3/15 there also is a mention that the tremors have 14:33:01 6 markedly decreased. That's after the switch to imipramine. 14:33:05 7 Q. Okay. But still the only physical symptom that's noted is 14:33:09 8 trembling in hands and either the fact that it is there or it 14:33:13 9 is decreasing; is that true? 14:33:14 10 A. That is true." 14:33:16 11 MR. ZVOLEFF: Now, down to line 20 on 61, by 14:33:22 12 Mr. Vickery. 14:33:24 13 Q. "Doctor, the entry on 2/2/90, the list of symptoms that 14:33:29 14 you ran down that would cause you to write obvious somatic 14:33:32 15 anxiety today, first of all, they're all some kind of outward 14:33:38 16 manifested motor movement, correct? 14:33:40 17 A. I believe so, yes. 14:33:41 18 Q. And they include both foot tapping and jitteriness, right? 14:33:46 19 A. I believe I mentioned that, yes." 14:33:56 20 MR. ZVOLEFF: That's all, Your Honor. 14:33:56 21 THE COURT: Thank you very much. 14:34:06 22 Mr. Preuss, call your next witness. 14:34:08 23 MR. PREUSS: Yes, Your Honor. Defendant will call 14:34:10 24 John Mann at this time. 25 (Witness sworn.) 1527 1 THE CLERK: Please state your name and spell it for 14:35:33 2 the record. 14:35:33 3 THE WITNESS: My name is John Mann, 14:35:39 4 M A N N. 5 6 JOHN MANN, M.D., Ph.D. 7 called as a witness on behalf of the Defendant, being first 8 duly sworn, testified as follows: 9 DIRECT EXAMINATION 14:35:41 10 Q. (BY MR. PREUSS) Good afternoon, Dr. Mann. 14:35:42 11 A. Good afternoon. 14:35:43 12 Q. You're a physician? 14:35:44 13 A. I am. 14:35:45 14 Q. Medical doctor? 14:35:46 15 A. That's correct. 14:35:46 16 Q. Where were you born and raised, sir? 14:35:49 17 A. I was born and raised in Australia, northern Australia. 14:35:53 18 Q. Did you receive your education there, sir? 14:35:55 19 A. Yes, I did; went to high school, medical school, did 14:36:00 20 postgraduate studies there, residency training. 14:36:04 21 Q. All right. And in what area did you do your residency, 14:36:08 22 sir? 14:36:09 23 A. First I did internal medicine and then I did psychiatry, 14:36:13 24 and then I did a doctorate in neurochemistry. 14:36:16 25 Q. And both your internal medicine and psychiatry residency 1528 14:36:20 1 was at the Royal Melbourne Hospital; is that correct? 14:36:24 2 A. Yes, that's correct. 14:36:25 3 Q. And then you went on from there to get a doctorate at the 14:36:28 4 University of Melbourne? 14:36:31 5 A. Yes, I did. 14:36:33 6 Q. And what was the thesis of your doctorate, sir? 14:36:36 7 A. It was looking at aspects of brain chemistry involved in 14:36:39 8 certain psychiatric conditions such as depression, 14:36:43 9 schizophrenia and some neurological disorders like 14:36:48 10 Huntington's disease. 14:36:49 11 Q. Now, are the degrees of educational achievement in 14:36:58 12 Australia the same as they are here and if not, could you 14:36:58 13 tell us how you would translate those? 14:36:58 14 A. Well, in Australia you graduate with a degree called a 14:37:01 15 Bachelor of Medicine and Bachelor of Surgery. And then if 14:37:04 16 you do a doctorate, it is a Doctorate of Medicine. 14:37:08 17 Q. Would that be like our Ph.D.? 14:37:10 18 A. It is similar to the M.D./Ph.D. designation in the states. 14:37:15 19 Q. So you were licensed to practice medicine, psychiatry in 14:37:19 20 particular, in Australia, then? 14:37:21 21 A. Yes, I was actually -- I have done the board examinations 14:37:24 22 in both internal medicine and psychiatry. 14:37:28 23 Q. What happened to make you come to this country, sir? 14:37:32 24 A. I wasn't chased out. I was interested in pursuing a 14:37:39 25 career in medical research, so that in Australia you go into 1529 14:37:44 1 medical school straight out of high school, so by the time 14:37:47 2 you finish medical school you're still a kid. And I thought 14:37:53 3 it is a long way from the rest of the world. I thought it 14:37:56 4 would be interesting to spend a couple of years doing 14:37:58 5 research overseas. 14:38:01 6 And there was an Australian guy from the States came 14:38:07 7 and gave a lecture, and I talked to him about it and he gave 14:38:11 8 me a job. 14:38:12 9 Q. Where was that job, sir? 14:38:14 10 A. That was in New York, New York University Medical School. 14:38:18 11 Q. And that was -- what was the nature of the job you had 14:38:20 12 there? 14:38:20 13 A. Well, I came as a research fellow and then after a while 14:38:25 14 got promoted to assistant professor. 14:38:28 15 Q. About what time are we talking about when you came here 14:38:31 16 and started that? 14:38:32 17 A. That was 1978, and at the end of -- in 1980 he left for a 14:38:38 18 position as chairman in another state. And I wasn't sure 14:38:45 19 what to do because in Australia people generally got 14:38:52 20 educated, grew up, got married, had their job and retired all 14:38:56 21 in the same place. Nobody ever moved from one state to 14:38:59 22 another. That was pretty unusual. 14:39:00 23 So I was pretty surprised when he got up and left 14:39:04 24 after two years. But I was fortunate, somebody gave me a 14:39:08 25 position at Cornell to do a similar type of work, and so I 1530 14:39:12 1 stayed on. 14:39:13 2 Q. All right. So you moved then from New York University 14:39:16 3 Medical School to Cornell? 14:39:18 4 A. That's correct. I was there for ten years, and by then I 14:39:24 5 had three kids that had been in the States too long to pick 14:39:29 6 up and move back to Australia, so here I am. 14:39:33 7 Q. So you've been here ever since? 14:39:35 8 A. That's correct. 14:39:36 9 Q. And what was your research interest while you were at 14:39:40 10 Cornell, sir? 14:39:42 11 A. Well, all along the department where I trained in 14:39:46 12 Australia had a tradition of studying depression, and in 14:39:52 13 particular the treatment of depression. Lithium, that a lot 14:39:58 14 of people in the courtroom probably have heard of which is 14:40:01 15 used for the treatment of manic depression, was discovered by 14:40:06 16 an Australian in that department. 14:40:08 17 So the first clinic for the use of the lithium in 14:40:11 18 people with depression and manic depression was in a 14:40:17 19 hospital. So I developed an interest in depression, and with 14:40:21 20 the doctorate I got sort of into the chemical side of 14:40:24 21 depression and how depression worked. 14:40:30 22 Q. After Cornell where did you go, sir? 14:40:33 23 A. I was there for ten years, which is a long time, and the 14:40:36 24 research was going pretty well. I got a center grant at 14:40:40 25 Cornell and discovered something about the States, which is 1531 14:40:43 1 that there's a sort of free agent market out there. And I 14:40:50 2 got an offer and went to the University of Pittsburgh which 14:40:52 3 was very active in promoting research at the time. 14:40:55 4 Q. And you continue to pursue your research activities at the 14:40:59 5 University of Pittsburgh? 14:41:00 6 A. I was there for five years. The kids weren't too happy 14:41:04 7 because they liked New York. They had grown up there. Their 14:41:07 8 friends were there. So, you know, we liked to have kids at 14:41:12 9 home so we -- or nearby, not too far away, so I looked for 14:41:18 10 another job and got a job back in New York at Columbia. And 14:41:22 11 I've been there ever since, seven years. 14:41:24 12 Q. So you and your family live in New York? 14:41:27 13 A. Yes, pretty much everybody. 14:41:28 14 Q. What are the ages of your children, sir? 14:41:31 15 A. Well, I have a daughter who is 27, a son who is 25 and a 14:41:37 16 21-year-old son. 14:41:40 17 Q. The 21-year-old is the last one at home? 14:41:42 18 A. Yes, right. We're not in a rush to let him go. 14:41:49 19 Q. Now, since coming to the United States have you 14:41:51 20 licensed -- have you licensed yourself to practice medicine 14:41:55 21 here, sir? 14:41:56 22 A. Yes, I have a medical license in New York state and in the 14:42:00 23 Commonwealth of Pennsylvania. 14:42:02 24 Q. And have you been board certified in this country? 14:42:05 25 A. I have, in psychiatry and neurology with the specialty in 1532 14:42:09 1 psychiatry. 14:42:13 2 Q. All right. What are your present positions at Columbia 14:42:16 3 University, sir? 14:42:18 4 A. I'm a professor of psychiatry and radiology and chief of 14:42:25 5 the Division of Neuroscience in the university, but also I 14:42:26 6 have an appointment at New York State Psychiatric Institute 14:42:29 7 which is part of the medical campus of Columbia University 14:42:32 8 and there I head one of the departments. 14:42:39 9 Q. You mentioned radiology. How does that tie into your 14:42:42 10 pursuit of psychiatry? 14:42:44 11 A. I spent a let of time studying about the chemistry of 14:42:47 12 conditions like depression and the biochemical factors that 14:42:51 13 predispose people to suicide. I became interested in trying 14:42:55 14 to figure out ways of imaging the brain so that clinicians 14:43:01 15 could do biochemical radiological assessments of patients and 14:43:05 16 try to figure out which depressed patients are going to be at 14:43:07 17 risk for suicide. 14:43:09 18 Q. Basically looking into the brain, then? 14:43:11 19 A. That's correct, taking a picture of the biochemistry of 14:43:15 20 the brain. We can do that now. 14:43:17 21 Q. You indicated that you were chair or chief of the 14:43:22 22 Department of Neuroscience at New York Psychiatric Institute; 14:43:26 23 is that correct? 14:43:27 24 A. It is. 14:43:27 25 Q. And that's affiliated with Columbia, right? 1533 14:43:31 1 A. That's correct. 14:43:31 2 Q. And what kinds of responsibilities do you have as the 14:43:34 3 chief of that department, sir? 14:43:36 4 A. I'm responsible for about 150 staff and faculty, for the 14:43:44 5 productivity of those individuals in terms of science, for 14:43:48 6 the quality of the work, for compliance with the regulations 14:43:53 7 involving the ethics of doing research with patients and so 14:43:58 8 on and so forth, the safety of the research. 14:44:01 9 Q. Now, do you have a private practice, sir? 14:44:04 10 A. Yes, I do. 14:44:05 11 Q. And what does that involve? 14:44:07 12 A. That involves some hours in the later part of the day, in 14:44:12 13 the evenings a few days a week taking care of patients who 14:44:15 14 suffer from almost all -- mostly depressions, fairly severe 14:44:21 15 depressions, often with suicidal feelings or history of 14:44:25 16 suicidal behavior. 14:44:27 17 Q. And do you use antidepressants for therapy of those 14:44:30 18 patients, sir? 14:44:30 19 A. Yes, I do. 14:44:31 20 Q. Would that include SSRIs? 14:44:34 21 A. Yes. 14:44:34 22 Q. And Paxil? 14:44:36 23 A. It includes Paxil. 14:44:39 24 Q. Now, I see from your CV, sir, that you published a number 14:44:43 25 of articles in the medical journals; is that correct? 1534 14:44:47 1 A. Yes. 14:44:49 2 Q. Well over 200, I believe. How many of those focus on your 14:44:52 3 interest in suicide and depression? 14:44:57 4 A. The vast majority would be on either suicide or 14:45:02 5 depression. 14:45:02 6 Q. And you serve, I see, on ten different editorial boards. 14:45:06 7 Is that correct? 14:45:07 8 A. It is possible. 14:45:08 9 Q. And what does it mean to serve on an editorial board of a 14:45:11 10 journal, sir? 14:45:12 11 A. Mostly it involves reviewing papers that are submitted to 14:45:19 12 the journal by people who want to publish in that journal. 14:45:24 13 There are editorial meetings usually once a year and there's 14:45:28 14 discussion as to what the direction of the journal should be, 14:45:34 15 what papers it should try to attract, the quality of papers 14:45:37 16 it is attracting and publishing. 14:45:39 17 Q. I see that you're the biological editor for the Journal of 14:45:43 18 Suicide and Life-Threatening Behavior. What responsibilities 14:45:46 19 do you have as a biological editor, sir? 14:45:48 20 A. It means that I tend to see all of the biological papers, 14:45:56 21 papers that look at the biology of suicidal behavior, why 14:45:59 22 people commit suicide, why they don't commit suicide. 14:46:06 23 Q. And your CV indicates that you've had a number of honors. 14:46:09 24 Can you tell me about the Erma T. Hershal Trust Research 14:46:14 25 Science Award? What did that involve, sir? 1535 14:46:18 1 A. That was an award to help a young investigator develop a 14:46:24 2 research career. It provides funding for research for a 14:46:31 3 number of years, so instead of spending all day seeing 14:46:33 4 patients and trying to make a living, there was some 14:46:36 5 opportunity to have a few hours off to do some more research. 14:46:40 6 Q. And it looks like you were the recipient of that award for 14:46:43 7 a four-year period? 14:46:45 8 A. That's correct. 14:46:46 9 Q. How about the award of being a fellow of the American 14:46:50 10 Psychiatric Association? What did that involve? 14:46:54 11 A. That's an honorific promotion given by the American 14:47:02 12 Psychiatric Association to a limited number of individuals 14:47:03 13 each year. 14:47:05 14 Q. And in 1996 you received an award from the American 14:47:08 15 Association of Suicidology known as the Lewis Dublin Award. 14:47:13 16 What did that involve, sir? 14:47:16 17 A. That was for research into the factors that predispose 14:47:20 18 people to suicidal behavior. 14:47:22 19 Q. Are you still pursuing your research interests at this 14:47:26 20 time, sir? 14:47:27 21 A. Yes, I am. 14:47:28 22 Q. And what's your main focus at this time, sir? 14:47:36 23 A. I've devoted my career, really, to trying to discover the 14:47:39 24 reason why people who have become depressed are at risk for 14:47:44 25 suicidal behavior. Not everybody who is depressed is at risk 1536 14:47:54 1 for suicidal behavior. Most people who are depressed never 14:47:54 2 make a suicide attempt, but a lot do. And there are many 14:47:56 3 people who have depression every year in the United States 14:47:59 4 and they account for over 20,000 suicides each year. So I've 14:48:03 5 dedicated my career to trying to find out why they do that 14:48:06 6 and how to prevent it. 14:48:08 7 Q. And do you obtain grants from time to time to pursue that 14:48:12 8 interest, sir? 14:48:13 9 A. Yes, we try to do that. 14:48:15 10 Q. Have you received any from GlaxoSmithKline for your 14:48:18 11 research? 14:48:19 12 A. No. 14:48:23 13 Q. Tell me why you have chosen to devote your professional 14:48:27 14 life toward the study of suicide and why it occurs and how it 14:48:30 15 can be treated. 14:48:31 16 A. Suicide is not a consequence of stressors in life. It 14:48:38 17 almost invariably occurs in people who already have a 14:48:41 18 psychiatric illness, and we know that by many studies that 14:48:46 19 have gone and interviewed the families to find out why people 14:48:51 20 killed themselves. 14:48:51 21 It turns out that you read in the paper that someone 14:48:55 22 killed himself and he was the most popular kid in school and 14:48:58 23 a great athlete and doing well academically. When you 14:49:02 24 interview the family and find out more about this sad death, 14:49:05 25 you find it is not like that at all. 1537 14:49:08 1 It turns out that in young people and in older 14:49:11 2 people, by far the commonest association of suicide is with a 14:49:16 3 psychiatric illness. In fact, we find there is a diagnosable 14:49:20 4 psychiatric illness in over 90 percent of people, so that the 14:49:23 5 path, the way in which you're going to prevent suicide, is 14:49:26 6 not by improving parenting in the U.S. or by cutting down 14:49:33 7 violence on television. 14:49:34 8 It is first and foremost by treating psychiatric 14:49:38 9 conditions better and getting people better because people 14:49:42 10 who don't have a psychiatric illness almost never commit 14:49:45 11 suicide. It is exceedingly rare. 14:49:49 12 Q. Doctor, we talked about your work on editorial boards and 14:49:54 13 some of your achievements. Have you been asked to serve on 14:49:57 14 any task forces that have focused their investigation on the 14:50:01 15 causes and prevention of suicide? 14:50:08 16 A. Well, I served on -- as an ad hoc member of an advisory 14:50:15 17 committee for the FDA in 1991 which looked at the question of 14:50:20 18 whether antidepressants, in particular Prozac, had an effect 14:50:26 19 in promoting suicidal behavior. 14:50:29 20 I was the chairman of a task force set up by the 14:50:33 21 American College of Neuropsychopharmacology, which is a bit 14:50:37 22 of a mouthful. I'm sorry. But it is a group of about 4 or 14:50:41 23 500 individuals that are supposedly the main experts in the 14:50:45 24 country on the action of medications on the brain. 14:50:49 25 And this organization was also interested in the 1538 14:50:52 1 question of whether -- what medications did in terms of 14:50:57 2 preventing or perhaps promoting the risk for suicidal 14:51:02 3 behavior that were being used by doctors. And that was -- 14:51:05 4 that report was completed in 1992. 14:51:11 5 Most recently, as we speak now, there's a committee 14:51:14 6 of about 10 or 12 individuals -- I'm not sure of the exact 14:51:18 7 number -- which has been convened by an organization called 14:51:21 8 the Institute of Medicine which is probably the leading 14:51:28 9 organization in the country -- it is located in Washington -- 14:51:30 10 that provides advice to the government on major health 14:51:32 11 issues. 14:51:36 12 And it has been commissioned by the Centers for 14:51:39 13 Disease Control in Atlanta and Surgeon General's office and 14:51:43 14 the National Institute of Mental Health, the National 14:51:45 15 Institute of Drug Abuse and so on to produce a report on 14:51:50 16 suicide in the United States to try and see what do we know 14:51:54 17 about suicide, what causes suicide, what more research needs 14:51:59 18 to be done and what can we do best to prevent it. 14:52:03 19 Q. Can we refer to the second task force, of the American 14:52:07 20 College of Neuropsychopharmacology as the ACNP? 14:52:12 21 A. Yes, ACNP. 14:52:14 22 Q. Thank you. Let's talk a little bit about depression and 14:52:18 23 suicide, Doctor. Is depression a serious health concern in 14:52:23 24 this country? 14:52:24 25 A. Depression, meaning depression the illness, is a major 1539 14:52:26 1 health concern in the United States and worldwide. It has 14:52:32 2 been estimated that depression is the leading cause of 14:52:35 3 disability throughout the world. 14:52:37 4 In other words, it is -- depression, the illness, 14:52:43 5 causes more disability than heart disease, infectious 14:52:47 6 diseases, cancer, malnutrition worldwide, recurrent unipolar 14:52:54 7 depression, just exactly the sort of illness, the same 14:52:59 8 illness that the late Donald Schell suffered from. 14:53:04 9 It is a terrible illness. People who have depression 14:53:07 10 will tell you that the pain of depression is worse than the 14:53:15 11 pain of a physical illness. They would rather have the pain 14:53:15 12 of a physical illness than the pain of depression. And it is 14:53:16 13 very hard to conceive of how unpleasant this condition is and 14:53:21 14 how much suffering it causes without actually, you know, 14:53:25 15 having seen people who suffer from it or without having had 14:53:28 16 it yourself. 14:53:29 17 And it is very common. There are 11 million people 14:53:33 18 estimated each year who suffer from depression in the United 14:53:35 19 States, and it is tremendously undertreated. Most people 14:53:39 20 with depression in the United States do not receive proper 14:53:43 21 treatment for their depression. 14:53:47 22 Q. And how quickly can a major depressive episode develop, 14:53:52 23 Doctor? 14:53:53 24 A. It is quite variable. It can come on quickly or it can 14:53:57 25 come on slowly. It can come on gradually over months so the 1540 14:54:01 1 person hardly realizes that it is creeping up on them and 14:54:05 2 that they're getting more and more disabled. They might 14:54:08 3 continue to try and work and push through it. 14:54:11 4 Alternatively, it can come on like that. I had a 14:54:14 5 patient who told me that she was washing the dishes in her 14:54:17 6 kitchen and when she started washing the dishes she felt 14:54:21 7 fine. When she finished washing the dishes, she was really 14:54:24 8 depressed and that depression lasted for a couple of years 14:54:27 9 until she came to see me, took some medication and got 14:54:31 10 better. I had two patients who actually got on the plane and 14:54:34 11 when the plane took off, they felt fine. When the plane 14:54:38 12 lands, they were depressed. 14:54:40 13 So in some people it comes on gradually and in other 14:54:45 14 people it can come on rapidly. 14:54:49 15 Q. How is the risk of suicide associated with depression, 14:54:52 16 sir? 14:54:53 17 A. About 60 percent of individuals who kill themselves do so 14:54:56 18 at a time when they're suffering from a depression. So there 14:54:59 19 are two parts to this story. One is that the depression is 14:55:02 20 often associated with feeling -- the pain of depression is so 14:55:07 21 severe, the person often feels suicidal. They don't want to 14:55:11 22 go on living. 14:55:12 23 One of the peculiar things about depression is you 14:55:16 24 always feel hopeless, pessimistic, the cup always looks half 14:55:20 25 empty. The individual when depressed can't conceive of 1541 14:55:24 1 getting bettter. The motivation for seeking treatment is 14:55:28 2 impaired because sometimes it is hard to get out of bed, hard 14:55:32 3 to get dressed, have a shower. 14:55:34 4 If you're not depressed, it is amazing that that can 14:55:38 5 be the case. People say, "Pull your socks up and get out and 14:55:42 6 do more." Depressed people can't do that. The engine 14:55:45 7 doesn't work, so pushing the gas pedal to the floor isn't 14:55:48 8 going to have any effect. 14:55:50 9 Because they feel pessimistic and don't seek 14:55:52 10 treatment, they often have other feelings as well. They feel 14:55:55 11 guilty. They feel responsible for being depressed. The 14:55:59 12 failure to seek treatment is a big problem. We know that the 14:56:02 13 vast majority of depressed patients who kill themselves have 14:56:05 14 not had adequate antidepressant treatment. 14:56:08 15 In fact, most studies show that it is approximately 14:56:11 16 about 10 or 12 percent of individuals who die during a 14:56:14 17 depression, depressive illness have been receiving inadequate 14:56:19 18 doses of antidepressants, so most of them haven't been 14:56:23 19 getting anything and the ones that have been getting it 14:56:26 20 haven't been getting enough. 14:56:27 21 Q. How many suicides occur every year in this country? 14:56:32 22 A. Just over 30,000 a year. 14:56:34 23 Q. And how many of those are related to depressed patients? 14:56:36 24 A. About 60 percent. 14:56:45 25 Q. Do patients that commit suicide in general give any hints 1542 14:56:48 1 that they are suicidal before they take their own lives, sir? 14:56:52 2 A. A lot of patients do tell somebody that life isn't worth 14:56:56 3 living before they commit suicide. A lot of people think 14:56:59 4 that if people say that, that means they're not going to do 14:57:03 5 it. It is exactly the opposite. If somebody says they feel 14:57:06 6 like dying, life is not worth living or they want to kill 14:57:09 7 themselves, they have to be taken seriously. 14:57:12 8 Then there are a group of patients who will say 14:57:14 9 absolutely nothing and, in fact, they will do so 14:57:18 10 deliberately. They're very often men, middle-aged or older 14:57:21 11 men, because they've already decided in their own mind that 14:57:24 12 they're going to kill themselves and the reason they don't 14:57:27 13 tell anybody is that they don't want anybody to stop them. 14:57:30 14 So sometimes the most dangerous -- patients who are 14:57:34 15 the most dangerous to themselves are precisely the patients 14:57:38 16 that conceal that fact. 14:57:40 17 Q. Doctor, when people are depressed, what is it about 14:57:44 18 depressed individuals that makes it difficult for them to 14:57:47 19 seek treatment? 14:57:49 20 A. Well, as I said, there are a whole set of factors. First 14:57:55 21 of all, when you're depressed and it is hard to get out of 14:57:58 22 bed and have a shower, it is also hard to pick up the 14:58:05 23 telephone and call your doctor. Patient after patient will 14:58:05 24 tell you when they feel fine that, you know, they left it too 14:58:08 25 long to get help, they left it to the point where they didn't 1543 14:58:11 1 have the "go" in them, the energy or the drive to pick up the 14:58:17 2 telephone and call the doctor. If it is too much to get out 14:58:20 3 of bed and it is so hard to put your clothes on, it is also 14:58:24 4 hard to call the doctor. 14:58:25 5 Plus, they often feel responsible for the illness. 14:58:29 6 They think it is their own fault that they're depressed. 14:58:32 7 That doesn't sound like a medical problem anymore. 14:58:35 8 And finally they're pessimistic. They think if they 14:58:39 9 seek treatment, what's the point, it is probably not going to 14:58:42 10 work, so why bother. 14:58:47 11 And the family doesn't know any better very often, 14:58:51 12 not unless they're fortunate to have gotten information or 14:58:54 13 education. The family often says, "Get out of the house and 14:58:56 14 why don't you try going back to work and maybe you'll feel 14:59:00 15 better and it will give you a lift." 14:59:02 16 That's exactly the opposite. The person just feels 14:59:05 17 more guilty that they can't do it. There's lots of things 14:59:08 18 that can -- the motivation and drive to seek treatment is 14:59:14 19 extremely fragile and part of that task is to sort of educate 14:59:19 20 people so that they know they should get help and the family 14:59:23 21 should bring them along. 14:59:25 22 Q. Doctor, in recent years has there been any change in the 14:59:30 23 suicide rates in this country? 14:59:32 24 A. There has been over the last ten years for which we have 14:59:35 25 data, which is 1988 to 1998, there's been a little bit of a 1544 14:59:40 1 drop in the suicide rate in the United States. It has fallen 14:59:45 2 about 9 percent. That doesn't sound like a lot, but that's a 14:59:48 3 lot of people's lives. 14:59:49 4 Q. During that time what has happened to the use of SSRIs in 14:59:52 5 the treatment of depression? 14:59:54 6 A. Well, in the same period of time the number of 14:59:56 7 prescriptions for SSRIs in the United States went from about 14:59:59 8 2 million to about 70 million, so there's been a mammoth 15:00:07 9 increase in the amount of use of these medications, 15:00:10 10 astronomical. And they've gone from just a small part of the 15:00:15 11 prescriptions for antidepressants to by far the leading 15:00:18 12 choice for the treatment of depression in the United States, 15:00:21 13 and a similar pattern has happened overseas. 15:00:25 14 Q. All right. Has there been any attempt to determine 15:00:28 15 whether the fall in suicide rates is related in any way to 15:00:31 16 the upswing in the use of SSRIs for the treatment of 15:00:35 17 depression and suicidal thoughts? 15:00:37 18 A. Yes, there have been a couple of studies done, in Hungary, 15:00:42 19 in Sweden, in Norway, in Denmark looking at the increase in 15:00:47 20 prescription rates and relating that to the decrease in 15:00:50 21 suicide rates. 15:00:51 22 Now, for example, in Sweden, the prescription rates 15:00:54 23 for antidepressants, SSRIs went up considerably. The suicide 15:01:00 24 rate in Sweden which was actually a lot higher than the 15:01:04 25 United States has dropped by 25 percent. 1545 15:01:07 1 The prediction -- somebody predicted what the drop in 15:01:11 2 Sweden would be if the prescription rates went up and, in 15:01:15 3 fact, that prediction turned out to be exactly correct. 15:01:19 4 And similar observations have been observed in 15:01:21 5 Hungary. And interestingly, social factors that typically 15:01:24 6 have been associated with more suicide, like drug use, like 15:01:28 7 unemployment, you know, things that create problems for 15:01:31 8 people in their lives, those problems have actually gotten 15:01:35 9 worse over that period of time in those countries. 15:01:37 10 So the suicide rate actually dropped despite the fact 15:01:41 11 that there were social factors and other circumstances that 15:01:45 12 would potentially make the suicide rate greater. And that's 15:01:48 13 been related to the use of these types of antidepressants. 15:01:51 14 Q. And does that make sense to you as an expert in depression 15:01:54 15 and suicide, sir? 15:01:56 16 A. Yes, it does. In fact, we've just been doing the same 15:01:59 17 analysis for the United States, and statistically the results 15:02:05 18 are very consistent with the observations in Europe. 15:02:16 19 Q. As part of your research activities and your interest, 15:02:19 20 have you looked into the neurobiology of suicide? 15:02:23 21 A. Yes, that's how I originally got into this field. It 15:02:25 22 turns out that, of course, depression, which is a terrible 15:02:28 23 illness, is really -- it is an illness. It is not because 15:02:30 24 your mother didn't treat you right or toilet training didn't 15:02:35 25 go smoothly. It is an illness that often has an inherited 1546 15:02:41 1 component to it, tends to be -- people tend to have repeated 15:02:44 2 episodes. Most people are well between the episodes. It is 15:02:48 3 a medical problem that affects the brain chemistry. It is 15:02:51 4 not anybody's fault. 15:02:59 5 And in studying the biology of depression we've 15:02:59 6 learned a lot about that. We discovered that there was a 15:03:03 7 biochemical abnormality in the brain that also distinguished 15:03:06 8 those people who were at risk for suicide. I would suggest 15:03:10 9 we draw a picture, if that would be helpful. 15:03:13 10 Q. Sure. 15:03:32 11 A. No microphone. Doesn't matter. 15:03:34 12 Q. It will if she can't hear you. 15:03:38 13 A. I'll try to speak up. Here is the brain, this is the 15:03:40 14 front, here are the eyes. This gives you a bit of 15:03:44 15 orientation. 15:03:45 16 Now, depression has many symptoms. People can't eat 15:03:48 17 properly, they lose interest, can't concentrate, their memory 15:03:52 18 isn't as good, their appetite is lousy. A lot of things go 15:03:56 19 wrong in the brain in depression and sure enough, depression 15:04:00 20 involves abnormalities in several areas of the brain because 15:04:02 21 that fits with a lot of things going wrong. 15:04:05 22 But suicide is a particularly specific thing. It is 15:04:09 23 a decision that a person makes, are they going to live or 15:04:13 24 die, and that involves what we call decision-making. Now, it 15:04:16 25 is not a good idea to kill yourself, and most people don't, 1547 15:04:20 1 even though they feel like it when they're depressed. 15:04:23 2 So why do some people go ahead and kill themselves 15:04:26 3 and other people don't? There's a fundamental difference in 15:04:29 4 what we call their ability to restrain themselves. We call 15:04:32 5 it inhibition, technically, but it is basically their 15:04:36 6 restraint system. It is like a seat belt in the car that 15:04:39 7 keeps you in the seat in case of an emergency. 15:04:42 8 Well, we have a seat belt or restraint system in the 15:04:45 9 brain and it is located in this area about here. And what we 15:04:50 10 found is that -- first of all, we found that people who 15:04:54 11 committed suicide or people that made very lethal suicide 15:04:58 12 attempts and survived had a deficiency of a chemical in the 15:05:02 13 brain of serotonin, didn't have as much serotonin as people 15:05:08 14 who never made a suicide attempt. 15:05:10 15 It is an interesting difference. It is also true for 15:05:12 16 other psychiatric conditions where suicide is a probable 15:05:15 17 because it is not just depression. They all share the common 15:05:18 18 feature of not enough serotonin. 15:05:21 19 We went and set up a program like brain, organ 15:05:25 20 donation. We approached families like transplant teams do. 15:05:30 21 We asked after the medical examiner -- loved one committed 15:05:33 22 suicide and the medical examiner has finished the 15:05:35 23 examination, we said, "Could we look at the brain after the 15:05:38 24 examination is over and do some chemical analyses?" 15:05:41 25 And those people said yes, and we did do that. And 1548 15:05:44 1 we found that there was a biochemical abnormality right here, 15:05:48 2 not all over the brain, but right here; not enough serotonin 15:05:52 3 coming into this bit of the brain over here. So that's 15:05:58 4 really important because that means there's a chance of 15:06:01 5 helping people before they kill themselves. 15:06:04 6 So why do I have a title of professor of radiology? 15:06:08 7 Because I got interested in trying to image the brain while 15:06:11 8 people are alive and then the doctor can take the patient and 15:06:15 9 write an order, just like you need a lung scan, you need a 15:06:18 10 bone scan, kidney scan, okay, you're feeling very depressed 15:06:22 11 and you feel life isn't worth living. 15:06:24 12 This isn't in clinical practice yet, but you can see 15:06:28 13 where we're going with this, we will do a scan and see if 15:06:31 14 this area is functioning properly. If this area is not 15:06:34 15 functioning properly, you have a very serious and potentially 15:06:38 16 fatal illness and you need to take your pills and show up for 15:06:42 17 appointments, and if you don't come, we're going to call you 15:06:45 18 up and find out why you're not there and those sorts of 15:06:49 19 things. 15:06:49 20 If you have recurring episodes of depression -- 15:06:51 21 because the rule of thumb is if people have recurring 15:06:53 22 episodes and they're particularly at risk, we don't let them 15:06:58 23 get to the next episode of depression. We keep the 15:07:00 24 medication going and prevent the next episode from happening 15:07:03 25 because it is easier to prevent an episode of depression from 1549 15:07:06 1 happening than it is to treat it when it appears. 15:07:08 2 There's important treatment implications. That's why 15:07:11 3 everybody got so excited about SSRIs. SSRIs selectively 15:07:15 4 increase, among other things, the amount of serotonin, and we 15:07:19 5 thought that not only will that help the depression, but by 15:07:21 6 increasing the amount of serotonin, it will make this bit 15:07:24 7 function better. 15:07:25 8 And since the depression doesn't respond immediately 15:07:28 9 to the antidepressant, it takes, you know, a week, two weeks, 15:07:33 10 three weeks, five weeks, six weeks to work, the patient is at 15:07:37 11 risk in the meantime and this might reduce the risk by 15:07:51 12 improving the serotonin function in this area of brain. 15:07:51 13 MR. PREUSS: Your Honor, may I mark that diagram as 15:07:51 14 Defendant's LL and ask that it be admitted? 15:07:52 15 THE COURT: Any objection? 15:07:55 16 MR. VICKERY: On this one, Your Honor, I would rather 15:07:57 17 wait until I have an opportunity to cross him about it, if I 15:07:59 18 may. 15:08:00 19 THE COURT: Very well. 15:08:01 20 MR. PREUSS: I will just mark it for now, Your Honor. 15:08:03 21 THE COURT: That would be fine. 15:08:17 22 Q. (BY MR. PREUSS) Now, Doctor, we talked about depression 15:08:19 23 and we talked about suicide. I would like to add aggression 15:08:22 24 and homicide. Is there any relationship among those four 15:08:25 25 terms? 1550 15:08:28 1 A. Well, it is our belief that the same kind of restraint 15:08:33 2 mechanism that applies here in terms of making decisions as 15:08:38 3 to whether or not one acts on feeling suicidal applies to 15:08:42 4 other important decisions in life, including in individuals 15:08:47 5 who are likely to commit suicide -- commit homicide, 15:08:51 6 particularly impulsive homicide. 15:08:54 7 And it has been shown by others that there are 15:08:56 8 serotonin deficiencies in individuals who are impulsive in 15:09:00 9 terms of a homicide, also in terms of other types of very 15:09:05 10 serious aggression. 15:09:11 11 So it may be that an individual who has a very 15:09:13 12 powerful feeling driving them to do something that's not a 15:09:17 13 good idea, whether that be homicide, suicide or serious 15:09:24 14 suicide attempt or serious aggressive act towards a person or 15:09:29 15 something, that this particular area of the brain plays an 15:09:32 16 important role in preventing that happening. 15:09:35 17 Q. Doctor, I would like to talk a bit about antidepressant 15:09:38 18 treatment. Can you give us a short history of the 15:09:41 19 development of antidepressant medication, sir? 15:09:45 20 A. Sure. I will try and be brief and reasonably clear. 15:09:53 21 Until about 1958, which sounds like a long time ago 15:09:58 22 but it is not that long ago, there were really no effective 15:10:04 23 treatments for depression, no real antidepressants except for 15:10:11 24 shock treatment. 15:10:13 25 Q. You talking about electric shock treatment? 1551 15:10:18 1 A. Electroshock treatment. About the same time two classes 15:10:21 2 of medications were discovered independently. One group was 15:10:25 3 called MAOIs, MAO inhibitors. A lot of people know about 15:10:30 4 them because you have to be on a diet that excludes cheese 15:10:33 5 and a lot of other things because if you eat foods like 15:10:37 6 cheese that contain tyramine with an MAOI inhibitor, the MAO 15:10:42 7 is something that breaks down the stuff tyramine. And if you 15:10:45 8 ingest a lot of it and you have no MAO available to break it 15:10:49 9 down, your blood pressure can go through the roof and you can 15:10:52 10 die or have a stroke or some sort of other serious 15:10:56 11 complication. 15:10:57 12 But these antidepressants really worked. So that was 15:11:00 13 a tremendous thing. People who had been in hospitals with 15:11:03 14 depressions and not responsive to anything just got better 15:11:06 15 and walked out of the hospital. They're still on the market. 15:11:14 16 Around about the same time another class of 15:11:16 17 antidepressants were discovered, what we call the tricyclic 15:11:21 18 antidepressants, or the TCAs, of which the commonest examples 15:11:25 19 are amitriptyline and imipramine. And for many years 15:11:29 20 amitriptyline was the number one prescribed antidepressant in 15:11:33 21 the United States. 15:11:34 22 These medications were also a tremendous 15:11:36 23 breakthrough. They didn't require a diet, so that was a big 15:11:40 24 convenience. In that sense they were a lot safer. 15:11:43 25 However, they did do nasty things to your heart, 1552 15:11:46 1 especially if there was something wrong with your heart to 15:11:48 2 begin with, or if you were feeling really depressed and 15:11:51 3 looking around for some way of committing suicide and you 15:11:53 4 decided to swallow your antidepressant medication, which a 15:11:57 5 few will do every year, and if you swallowed a month's supply 15:12:02 6 of these pills, there was a pretty good chance that you would 15:12:05 7 be dead. So these pills were dangerous on overdose. 15:12:11 8 The next development occurred basically at the end of 15:12:14 9 the '80s and the beginning of the '90s and that was the 15:12:17 10 introduction of the SSRIs. SSRIs had several big advantages 15:12:21 11 over the pills that were currently available. 15:12:23 12 First of all, you could swallow a heck of a lot of 15:12:27 13 that medication and it wouldn't kill you, so that if the 15:12:30 14 treatment wasn't working or you felt suicidal and decided to 15:12:33 15 swallow the pills you had a much better chance of surviving, 15:12:41 16 live another day and getting more help. 15:12:43 17 The second area was that the tricyclic 15:12:46 18 antidepressants had side effects that weren't dangerous but 15:12:50 19 were a nuisance. They produced a very dry mouth, people were 15:12:55 20 constipated and constantly taking odd things to try and 15:12:59 21 overcome the constipation. And when you're depressed you 15:13:01 22 don't care because the depression is so horrible these side 15:13:09 23 effects are nothing. When you've been well for a while and 15:13:09 24 you have to take these pills for months or years, then these 15:13:10 25 side effects really become a nuisance. 1553 15:13:13 1 Anyone who has taken penicillin for ten days knows 15:13:17 2 how difficult it is to take penicillin for ten days. Imagine 15:13:21 3 if the doctor tells you you have to take it indefinitely. 15:13:26 4 The SSRIs didn't produce the dry mouth, the 15:13:29 5 constipation, so on and so forth. The SSRIs do have their 15:13:32 6 own set of side effects and people don't love them either. 15:13:36 7 There's some sexual dysfunction in a lot of people and they 15:13:41 8 might produce a bit of a tremor in some people. And they 15:13:44 9 speed up the rate at which your intestine moves so some 15:13:47 10 people get a bit of diarrhea and stuff like that. 15:13:51 11 They're not perfect but they're better tolerated in 15:13:54 12 general than the tricyclic antidepressants, and as I said, 15:13:58 13 they're safer if people swallow too much of them. 15:14:03 14 Q. Are there differences among the various SSRIs, sir? 15:14:07 15 A. There are differences amongst the SSRIs. They share a 15:14:10 16 common property of being an SSRI, which means selective 15:14:14 17 serotonin reuptake inhibitor. That means they block the 15:14:20 18 reuptake of serotonin into the nerve terminal which basically 15:14:23 19 is a way of magnifying the serotonin function in the brain. 15:14:27 20 So if you haven't got enough serotonin, it makes more 15:14:30 21 use of the serotonin that you've got. So it is like, you 15:14:32 22 know, if you work -- if you have eight hours working on the 15:14:35 23 job, you can double your productivity if you keep working at 15:14:39 24 the same pace by working 12 hours, right, go up by 50 15:14:43 25 percent. 1554 15:14:43 1 It is the same thing with an SSRI. You haven't 15:14:46 2 increased the labor force but you've made the force work for 15:14:49 3 longer hours. That's what it does by preventing the reuptake 15:14:53 4 which terminates the signal. It leaves the serotonin around 15:14:55 5 for longer, signalling the brain and so on. 15:14:59 6 So -- 15:15:02 7 Q. Are there studies that show that the benefits and side 15:15:06 8 effects among the various SSRIs differ one from another? 15:15:11 9 A. Well, there are studies that show that. Just to finish up 15:15:16 10 what I was staying in answer to the last question, each of 15:15:19 11 these SSRIs, if you laid them side by side and looked at 15:15:24 12 them, each looks different. It is not surprising to know 15:15:28 13 that they -- some may be broken down into a compound that may 15:15:32 14 be active, like the parent, and then a -- like you have two 15:15:37 15 different drugs in your body, and then others are broken down 15:15:40 16 into a compound which is inactive. 15:15:43 17 Paxil is an example of that group. Some have a very 15:15:47 18 long half-life, like Prozac, which has a half-life of two or 15:15:51 19 three days. Its metabolite, it is broken down into an active 15:15:57 20 compound which has a half-life of five to seven days, so the 15:16:00 21 stuff hangs around forever, take it once a week. So Paxil 15:16:07 22 breaks down into something which is inactive. 15:16:09 23 These are fundamental differences. There are studies 15:16:12 24 which have shown, for example, Paxil may produce more sexual 15:16:16 25 dysfunction. On the other hand, you may have more nausea on, 1555 15:16:21 1 say, Prozac. And there are also differences in their 15:16:25 2 efficacy. 15:16:26 3 Q. Can one patient, say, not respond to one SSRI, be switched 15:16:31 4 to another and then have a favorable response? 15:16:34 5 A. That's certainly been a very common clinical experience. 15:16:38 6 Q. And would the same apply to an adverse experience where 15:16:41 7 they might get it on one and switch to another and not have 15:16:44 8 one? 15:16:44 9 A. That's also been a very common clinical experience. 15:16:47 10 Q. With respect to SSRIs, does each SSRI need independent 15:16:53 11 approval by the FDA? 15:16:56 12 A. Yes, they do, so that each one of these compounds when it 15:17:01 13 was -- it comes along and people want to or companies want to 15:17:06 14 market it, they have to conduct the same rigorous set of 15:17:09 15 studies to prove the safety and the efficacy of that SSRI. 15:17:15 16 So you might think, boy, that's a tremendous waste of 15:17:18 17 time. If we know one works, then they're all going to work. 15:17:21 18 But the fact of the matter is that they all have different 15:17:24 19 structures and they all have different potentials for adverse 15:17:28 20 effects and toxic effects. 15:17:29 21 And a classic example is one of the earliest of the 15:17:34 22 SSRIs called zimelidine. Most of you haven't heard of 15:17:38 23 zimelidine because it didn't make it to the market in the 15:17:40 24 United States for reasons that had nothing to do with its 15:17:43 25 efficacy. 1556 15:17:45 1 But zimelidine turned out to produce a potentially 15:17:49 2 fatal and sometimes fatal neurological disorder, illness. 15:17:54 3 And it is interesting because it is only zimelidine. All the 15:18:04 4 other SSRIs don't produce it. So you've got to show that 15:18:04 5 your SSRI is effective, works, and that your SSRI is safe, 15:18:07 6 independently of all of the others. 15:18:12 7 Q. Doctor, can a scientist such as yourself reach conclusions 15:18:18 8 about whether Paxil causes suicidality, homicidal activity, 15:18:22 9 akathisia, agitation based on studies with other SSRIs? 15:18:28 10 A. Well, as I said before, the effects of medications have to 15:18:36 11 be independently evaluated. You cannot assume that because 15:18:42 12 two medications shared the same property that they will 15:18:48 13 automatically have exactly the same therapeutic effect and 15:18:52 14 that they will have exactly the same set of adverse effects. 15:18:57 15 While they may share one common property, they may be 15:19:00 16 different in a whole host of other ways and those other ways 15:19:04 17 may be the things that you really need to know about. 15:19:08 18 Q. And so is it fair to say if you want to know what Paxil 15:19:12 19 will do, you need to study Paxil? 15:19:14 20 A. That is correct. 15:19:14 21 Q. Before getting to the Paxil studies themselves, sir, when 15:19:17 22 did you first become involved in looking at the question of 15:19:20 23 whether antidepressants caused suicide? 15:19:27 24 A. Well, I became stimulated to look into this subject by the 15:19:35 25 Teicher study, you probably heard of it already, which was a 1557 15:19:42 1 paper that reported a series of cases in which individuals 15:19:46 2 became suicidal in the course of taking an antidepressant, in 15:19:52 3 that case Prozac. 15:19:55 4 And as a result of that -- to me, that was an 15:20:01 5 extremely important question because if antidepressants were 15:20:06 6 the backbone of preventing suicide, then clinicians really 15:20:14 7 needed to know they were safe to use and patients needed to 15:20:17 8 know that they were safe to take. 15:20:20 9 Because, as we already spoke about, the hesitancy and 15:20:23 10 the fragile commitment that patients often have to seeking 15:20:29 11 antidepressant treatment and sticking with antidepressant 15:20:33 12 treatment, is you then tell them, "Well, you have to take 15:20:35 13 this but there's a chance you might kill yourself," then who 15:20:38 14 is going to want to take it? And who is going to encourage 15:20:43 15 their spouse, friend, family member to take antidepressants? 15:20:47 16 So this was really a critical question to answer, so 15:20:50 17 we did a review of the literature. And lo and behold, it 15:20:56 18 turned out that these kinds of case reports had been coming 15:21:00 19 out for years and they had involved practically every class 15:21:04 20 of medication used to treat virtually every kind of 15:21:11 21 psychiatric illness. 15:21:12 22 Not only that, if you asked the question, well 15:21:16 23 maybe -- now, is there a relationship between the dose of 15:21:20 24 these kinds of medications like Prozac and the appearance of 15:21:25 25 this suicidal feeling that people in some of these case 1558 15:21:30 1 reports had come up with, there was no relationship. 15:21:34 2 What about the timing? You think that from the start 15:21:36 3 of the medication, it might appear after you take it. But 15:21:40 4 some reports said it appeared in a few hours. Others were 15:21:45 5 days, weeks, months. There was no relationship between the 15:21:48 6 timing, the dose, the class of medication, none of that. 15:21:53 7 Actually -- and all of that is summarized in great 15:21:57 8 detail in an article that is somewhere floating around this 15:22:03 9 courtroom that I wrote with another physician called 15:22:06 10 Dr. Kapur. 15:22:07 11 In that article we also reviewed the whole story that 15:22:10 12 I told you about serotonin, that you would think a serotonin 15:22:12 13 deficiency would be corrected by drugs that would enhance 15:22:15 14 serotonin function, so it didn't make any sense that SSRIs 15:22:18 15 should place people at risk for suicidal behavior. Actually, 15:22:23 16 SSRIs should do the opposite. 15:22:25 17 There were at least four studies in the literature at 15:22:27 18 that time that had looked at suicidality in people taking 15:22:31 19 SSRIs that found that the suicidality improved faster on the 15:22:35 20 SSRI than it did on the other type of medication like the 15:22:38 21 tricyclic antidepressant, all of which fit in with what we 15:22:43 22 expected. 15:22:44 23 So it really didn't make any sense. About the only 15:22:47 24 study that came up that caused a bit of concern was a study 15:22:51 25 of a drug called maprotiline. I'm sorry to throw all of 1559 15:22:55 1 these facts at you, but it is important to understand some of 15:22:58 2 the information on which we're making these judgments. 15:23:01 3 But what is maprotiline? Maprotiline is an 15:23:05 4 antidepressant, a tricyclic antidepressant. It is a drug 15:23:09 5 that has virtually no effect on serotonin at all so it is not 15:23:12 6 at all an SSRI. It is the opposite. It is a norepinephrine 15:23:20 7 selective reuptake inhibitor. It is like a different drug to 15:23:28 8 the SSRI. 15:23:28 9 And in the one study with that drug, which was a 15:23:28 10 randomized controlled, prospective clinical trial -- which I 15:23:31 11 think you've already heard about this technical jargon 15:23:34 12 before -- the best type of design of a study, that turned out 15:23:38 13 to produce more suicides and suicides attempts in a one-year 15:23:42 14 treatment program in depressed people than placebo. 15:23:45 15 So at the end of that review, we found that there 15:23:50 16 really wasn't much evidence linking -- we couldn't find any 15:23:53 17 credible evidence linking SSRIs to suicidality. We found a 15:23:57 18 question about this maprotiline medication and there had been 15:24:02 19 some reports with drugs used for schizophrenia or psychotic 15:24:07 20 symptoms which sometimes occur in depression, and so these 15:24:10 21 drugs are sometimes used in depression, that these 15:24:14 22 antipsychotic medications which produce a funny syndrome 15:24:18 23 called akathisia which is a motor restlessness in about 20 to 15:24:21 24 70 percent of cases, which means a lot of patients get it. A 15:24:25 25 few of those cases when it is very, very severe appear to 1560 15:24:28 1 become suicidal or even aggressive and potentially violent. 15:24:33 2 So those two classes of medications there was some 15:24:37 3 concerns that arose out of that study. 15:24:39 4 Q. All right. Just to recap some, the article you're 15:24:44 5 referring to is an article by yourself and a Dr. Kapur, 15:24:48 6 K A P U R? 15:24:49 7 A. Yes. 15:24:49 8 Q. And the title of it is Emergence of Suicidal Ideation and 15:24:54 9 Behavior in Antidepressant Pharmacotherapy? 15:24:59 10 A. That's correct. 15:25:00 11 MR. PREUSS: For the record, that's SBFF-51. 15:25:03 12 Q. (BY MR. PREUSS) That was prompted by Dr. Teicher's case 15:25:06 13 reports; is that right? 15:25:07 14 A. Yes, that's correct. 15:25:10 15 Q. And at the conclusion -- you reviewed more than the SSRIs, 15:25:14 16 correct? 15:25:15 17 A. Yes. We also looked at antianxiety drugs, you know, drugs 15:25:21 18 that belong to the family of Valium and Ativan and so on, so 15:25:25 19 forth. And there were reports that those drugs potentially 15:25:30 20 increased suicidality, produced paradoxical rage attacks in 15:25:35 21 people, disinhibited people, and so on and so forth. 15:25:39 22 Q. Following the completion of your review and the 15:25:43 23 publication of the article, was it your opinion at that time 15:25:45 24 that Prozac, which was the only SSRI out at the time, causes 15:25:49 25 suicidal thoughts or acts? 1561 15:25:52 1 A. That was not my opinion. In fact, my view was that it 15:25:55 2 didn't do that. We quoted one other article of relevance in 15:25:59 3 the paper that you've just cited which was a study that was 15:26:06 4 done by an analysis of the -- all the control studies that 15:26:14 5 had been done with Prozac, and that study asked that very 15:26:17 6 question. 15:26:18 7 It said, you know, how much suicidality emerges in 15:26:22 8 people while they're being treated with Prozac and how much 15:26:25 9 of it goes away. 15:26:27 10 And in both of those types of analyses Prozac had a 15:26:31 11 very significant beneficial effect in reducing suicidality in 15:26:35 12 patients, and in those patients where suicidality wasn't much 15:26:40 13 of a problem to begin with, it actually prevented it becoming 15:26:44 14 a problem far better than placebo and comparably to tricyclic 15:26:52 15 antidepressants. 15:26:54 16 So on the basis of those -- that, you know, 15:26:57 17 information, to produce credible scientific evidence linking 15:27:03 18 Prozac to the induction of suicidal behavior was not 15:27:11 19 possible. It didn't seem connected. 15:27:14 20 Q. Did you make some recommendations in the 1991 article that 15:27:17 21 you wrote with Dr. Kapur, sir? 15:27:19 22 A. Well, yes, we did. First of all, we recommended there 15:27:22 23 should be more studies because at that time, unlike today, 15:27:27 24 there was -- there were relatively fewer studies and there 15:27:33 25 were a lot more antidepressants about to come onto the market 1562 15:27:36 1 and these kinds of questions needed to be reviewed with each 15:27:40 2 of those. 15:27:42 3 So, for example, Prozac was on the market but the 15:27:44 4 other SSRIs were just in the pipeline, and as I said before, 15:27:48 5 each of those SSRIs needed to be examined and each of the 15:27:52 6 non-new SSRIs needed to be examined as well independently. 15:27:57 7 Q. We're talking about the 1991 time frame when your article 15:28:00 8 came out? 15:28:01 9 A. That's correct. 15:28:01 10 Q. And that was before Paxil was made available to 15:28:05 11 psychiatrists for prescription, right? 15:28:08 12 A. That's correct. 15:28:09 13 Q. Now, you mentioned earlier, sir, that you participated in 15:28:13 14 the FDA task force looking at the issue of whether SSRIs can 15:28:24 15 cause suicide, correct? 15:28:26 16 A. Yes. 15:28:26 17 Q. Can you tell me what that committee did with respect to 15:28:29 18 ascertaining an answer to that question? 15:28:32 19 A. Okay. Well, I'm -- I can't give you a lot of detail 15:28:43 20 because that was ten years ago and a lot of things have 15:28:43 21 happened. 15:28:43 22 But the committee was given the task of answering the 15:28:49 23 question whether antidepressants had the potential for 15:28:56 24 aggravating the risk of suicide, and if they did, was this 15:29:05 25 characteristic of one particular type of antidepressant or 1563 15:29:08 1 was this something that was characteristic of all 15:29:14 2 antidepressants, and if the answer to those questions was 15:29:18 3 yes, what are we going to do about it. 15:29:21 4 Q. So this did not involve just an inquiry as to SSRIs but 15:29:25 5 other antidepressants as well? 15:29:33 6 A. Well, there was a broader view of the matter, but in the 15:29:35 7 end it would be fair to say that the predominance of the 15:29:38 8 attention focused on the SSRIs and, in particular, as it 15:29:43 9 turned out, mostly on Prozac because most of the case reports 15:29:48 10 that sort of were the precipitant, if you like, for having 15:29:56 11 this review related to Prozac. 15:30:00 12 Q. Were the Teicher case reports a reason for convening this 15:30:05 13 task force -- or advisory committee? Excuse me. 15:30:11 14 A. I think it would be fair to say that although there were 15:30:14 15 other case reports as well involving a variety of types of 15:30:17 16 medications that appeared over the years, for a variety -- 15:30:22 17 for some reason the success and the rapid acceptance of 15:30:30 18 Prozac as an effective, well-tolerated antidepressant focused 15:30:37 19 unusual attention on the introduction of this medication. 15:30:39 20 And so the Teicher report had quite an impact on the 15:30:43 21 field and the thinking of people in regulatory agencies such 15:30:49 22 as the FDA and scientific organizations such as the ACNP, so 15:30:54 23 on and so forth. 15:30:56 24 Q. What was your particular role with respect to this 15:30:59 25 advisory committee, sir? 1564 15:31:01 1 A. I was not a regular member of that committee, and -- but I 15:31:09 2 was asked to serve as an ad hoc member of the committee for 15:31:13 3 purposes of this particular review. 15:31:14 4 Q. And was there a hearing on the issue? 15:31:16 5 A. Yes, there was a one-day hearing. 15:31:18 6 Q. Did you attend that? 15:31:19 7 A. I was there. 15:31:19 8 Q. And did the committee vote on the question of whether 15:31:23 9 antidepressants cause suicide or the intensification of 15:31:28 10 suicide or violent behavior? 15:31:30 11 A. A vote was held on the question. 15:31:33 12 Q. And how did that vote come out? 15:31:35 13 A. To the best of my recollection, it was a unanimous vote 15:31:39 14 indicating that there was no such connection. 15:31:43 15 Q. And you did not vote, though; is that right? 15:31:46 16 A. That's correct. 15:31:46 17 Q. And what was your opinion at the time? 15:31:49 18 A. I agreed with the conclusions of the committee. 15:31:55 19 Q. Doctor, if I might, I would like to turn your attention 15:31:57 20 now to the -- what we've abbreviated as the ACNP task force 15:32:03 21 that you served on. That was in 1991 and 1992? 15:32:08 22 A. Yes, that's correct. 15:32:09 23 Q. And what was the mission or purpose of that task force, 15:32:13 24 sir? 15:32:14 25 A. The task force -- well, the ACNP regarded itself as the -- 1565 15:32:20 1 as an important opinion former in the scientific and medical 15:32:27 2 community and wanted to follow up and supplement the findings 15:32:33 3 that the FDA committee -- 15:32:38 4 Q. The one we just talked about? 15:32:40 5 A. Yes, the one we just spoke about by obtaining additional 15:32:44 6 information and data that had been unpublished by 15:32:49 7 pharmaceutical companies on tricyclics that were in the 15:32:52 8 pipeline because thousands of patients had been studied in 15:32:55 9 order to determine the safety and efficacy of these -- I said 15:33:02 10 tricyclics. I meant SSRIs. 15:33:05 11 Thousands of patients had been studied in the United 15:33:08 12 States and overseas under controlled clinical trial 15:33:12 13 conditions, where the patient and the doctor didn't know 15:33:15 14 which medication the patient was receiving so nobody was 15:33:18 15 biased, looking at the safety and efficacy of these other 15:33:22 16 drugs. 15:33:23 17 So the question is we've got all this other 15:33:25 18 information. The question is really important. How safe and 15:33:28 19 how effective are these medications? Let's tap into this 15:33:32 20 additional information and find out. 15:33:34 21 So that's what the committee did. We spent quite a 15:33:38 22 bit of time gathering data from various drug companies and 15:33:44 23 formulating it into the publication of the committee's 15:33:49 24 findings. 15:33:49 25 Q. Did you obtain information from SmithKline on Paxil? 1566 15:33:53 1 A. We did. 15:33:54 2 Q. And who were members of this task force in addition to 15:33:58 3 yourself? Was that -- I mean, were a number of people or how 15:34:03 4 large a group was it? 15:34:04 5 A. It wasn't a big group. I think I recall there were four 15:34:10 6 members of the group. I was the chairperson of the task 15:34:16 7 force. Another member was Fred Goodwin who had been the 15:34:19 8 former director of the National Institutes of Mental Health 15:34:28 9 and the former administrator of the -- in the administration 15:34:28 10 for drug abuse, mental health and alcoholism. 15:34:37 11 And then there was a Dr. Charles O'Brien who is a 15:34:41 12 distinguished expert in psychopharmacology and actually 15:34:48 13 become a president of the ACNP who was at the University of 15:34:52 14 Pennsylvania. 15:34:53 15 And the fourth member was Dr. Donald Robinson who had 15:34:57 16 been a chairman of pharmacology, I think, in Virginia, and he 15:35:04 17 may have at the time had a position with Bristol-Myers. 15:35:12 18 Q. And did this task force look at the medical literature 15:35:16 19 again? 15:35:17 20 A. Yes. The report reviewed both the so-called case reports, 15:35:25 21 including the Teicher report, and as well as information from 15:35:32 22 controlled clinical studies, randomized controlled, 15:35:36 23 double-blind clinical studies. 15:35:38 24 Q. With respect to case reports, can you form any causation 15:35:41 25 conclusions from case reports alone, sir? 1567 15:35:46 1 A. No. Case reports are a clue to the medical profession 15:35:54 2 about something. There may be a relationship between A and B 15:35:58 3 because you see it in one, two, three, four, five patients, 15:36:06 4 whatever. 15:36:07 5 Then you try and figure out whether it is correct or 15:36:10 6 incorrect. There are a number of ways of going about this, 15:36:19 7 but in the particular problem that we're talking about today, 15:36:22 8 which is the safety and efficacy of these kinds of 15:36:25 9 medications, the best way to figure out the answer to that 15:36:28 10 question, the only way to figure out the answer to that 15:36:31 11 question is that you do a randomized, double-blind, 15:36:34 12 controlled clinical trial. 15:36:36 13 Q. How long did the task force work together before issuing 15:36:40 14 its report, sir? 15:36:47 15 A. Well, it took us, I think, about five months. 15:36:56 16 Q. Now, did you publish what has been called a consensus 15:37:01 17 statement with respect to the issue of suicidal behavior and 15:37:04 18 psychotropic medication? 15:37:07 19 A. Yes, we did. 15:37:08 20 Q. Can you recognize that just from this distance? 15:37:11 21 A. You got to be kidding. These glasses aren't that good. 15:37:14 22 Can you read the title? 15:37:16 23 Q. Suicidal Behavior and Psychotropic Medication accepted as 15:37:19 24 a consensus statement by the ACNP council, March 2nd, 1992? 15:37:26 25 A. That's the paper. 1568 15:37:27 1 MR. PREUSS: For the record, Your Honor, SBFF -- 15:37:31 2 MR. VICKERY: That's a Joint Exhibit. 15:37:32 3 MR. PREUSS: I'm sorry. Joint Exhibit 5. 15:37:36 4 MR. VICKERY: 245. 15:37:45 5 Q. (BY MR. PREUSS) And what was your role with respect to 15:37:47 6 the writing of this consensus statement, sir? 15:37:52 7 A. Well, like the other members, I contributed to the 15:37:55 8 writing. It was then reviewed by the council of the ACNP 15:38:01 9 which is the executive, as it were, and they all signed off 15:38:05 10 on it, and so it represents the collective views, as it were, 15:38:11 11 of that college. 15:38:13 12 Q. And what conclusion did the statement make as to whether 15:38:19 13 or not SSRIs cause suicides or suicidal ideation? 15:38:25 14 A. The conclusion was that you could not decide that on the 15:38:31 15 basis of the available evidence that SSRIs cause -- just 15:38:36 16 going to look at my copy -- you could not conclude on the 15:38:43 17 basis of the evidence available that SSRIs cause suicidal 15:38:51 18 behavior. 15:38:52 19 In fact, it says here, "There is no evidence that 15:38:57 20 antidepressants such as selective serotonin reuptake 15:39:00 21 inhibitors, for example, fluoxetine, trigger emergent 15:39:04 22 suicidal ideation over and above the rates that may be 15:39:07 23 associated with depression." 15:39:10 24 Q. Okay. And did your committee, special committee, task 15:39:18 25 force, come out with some recommendations, sir? 1569 15:39:24 1 A. Well, yes, I think that the committee made a plea for 15:39:31 2 essentially good clinical practice. A plea which involved 15:39:37 3 the recognition that we're treating conditions such as 15:39:42 4 depression and alcoholism and schizophrenia and so on that 15:39:46 5 are associated with a serious complication, meaning death by 15:39:51 6 suicide, and that some people who survive have done 15:39:55 7 themselves a lot of harm and their families have suffered a 15:39:57 8 great deal, so that clinicians need to be aware of this risk, 15:40:02 9 need to ask the patient about it, need to warn the patient 15:40:04 10 about it and involve the family in that process and so on and 15:40:09 11 so forth. 15:40:10 12 So essentially that's what it boiled down to. That 15:40:12 13 was actually consistent with the statement that I made at the 15:40:17 14 hearing where I suggested that a letter encouraging good 15:40:21 15 clinical practice be sent to physicians throughout the United 15:40:26 16 States. In fact the FDA sent out a kind of memorandum on 15:40:30 17 that subject. 15:40:31 18 Q. Did the -- 15:40:32 19 THE COURT: Mr. Preuss, I'm going to interrupt you. 15:40:35 20 I wasn't watching the clock well enough. Time has flown by. 15:40:38 21 Let's take our afternoon recess at this time. We will stand 15:40:41 22 in recess for 15 minutes. 15:40:48 23 (Recess taken 3:40 p.m. until 4:00 p.m.) 16:06:02 24 THE COURT: Counsel and the Court talking yesterday 16:06:04 25 about running a little bit past 5:00, but I'm not so sure I 1570 16:06:08 1 mentioned it to the jury. If I did, good for me. If I 16:06:11 2 didn't, here is a little surprise. We might go a little past 16:06:16 3 5:00 tonight, might be 5:30, quarter to 6:00. 16:06:21 4 I will try to keep a better eye on the clock as I was 16:06:24 5 busy working on the computer and we shot by the 3:00 recess 16:06:29 6 by 35 minutes. So I will try to watch the clock better. 16:06:33 7 Dr. Mann, you understand, of course, you're still 16:06:35 8 under oath. 16:06:36 9 Mr. Preuss, you may proceed. 16:06:38 10 MR. PREUSS: Thank you, Your Honor. 16:06:40 11 Q. (BY MR. PREUSS) Dr. Mann, before the break we were 16:06:42 12 talking about the consensus statement by the ACNP task force 16:06:47 13 which came out in 1992. Did the task force make any 16:06:52 14 recommendations with respect to the need for additional 16:06:56 15 research in this area, sir? 16:06:59 16 A. Yes, it did. It -- the task force recommended four types 16:07:05 17 of studies which might shed more light on the question of 16:07:11 18 what is the relative efficacy and safety of antidepressant 16:07:18 19 medications in particular with regard to their effects on 16:07:23 20 suicidality. 16:07:26 21 And if I could use the board, I could show -- 16:07:29 22 Q. Just we will go to the board in a second. Just a couple 16:07:34 23 questions here. 16:07:35 24 From the time of your '91 article with Dr. Kapur and 16:07:38 25 your work on the advisory committee and now completing the 1571 16:07:42 1 work on the task force, did your opinions change at all with 16:07:46 2 respect to SSRIs and their relationship to suicide or 16:07:50 3 suicidal behavior, sir? 16:07:52 4 A. Well, it appeared to me that the original findings with 16:07:56 5 regard to Prozac were certainly no weaker than we were 16:08:04 6 before, but important additional information which wasn't 16:08:08 7 available then emerged with regard to several of the other 16:08:11 8 SSRIs in terms of their potential for reducing the risk of 16:08:19 9 suicidality, improving suicidality, preventing emergent 10 suicidality. 16:08:28 11 Q. And am I correct that Paxil did not become available to 16:08:32 12 psychiatrists for prescribing until about a year after this 16:08:36 13 consensus statement? 16:08:38 14 A. That's correct. 16:08:38 15 Q. Now, Doctor, if you could go to the easel, I would like to 16:08:41 16 review with you the recommendations of the task force with 16:08:44 17 respect to further study as it relates to Paxil in 16:08:47 18 particular. 16:08:56 19 MR. PREUSS: Would like to mark this next for 16:08:58 20 identification as LL, Your Honor. 16:08:59 21 MR. GORMAN: MM. 16:09:00 22 THE COURT: All right, thank you. 16:09:22 23 Q. (BY MR. PREUSS) Maybe at the start, if you would, Doctor, 16:09:24 24 briefly put the '91 Mann and Kapur, '91 FDA committee and 16:09:33 25 lastly the ACNP task force? 1572 16:09:38 1 A. Say that again. 16:09:38 2 Q. The '91 Mann and Kapur and the '91 FDA ad hoc committee 16:10:07 3 and the 1991-'92 ACNP task force. 16:10:15 4 There were four recommendations for further study in 16:10:18 5 that study; is that correct? 16:10:21 6 A. That is correct. 16:10:22 7 Q. What was the first? 16:10:23 8 A. The first was to go back and have a look at the studies 16:10:25 9 that had already been done because each of the new 16:10:29 10 medications that had come onto the market or were going to 16:10:35 11 come onto the market actually had been tested in thousands of 16:10:39 12 patients in these randomized controlled clinical trials. 16:10:42 13 And the occurrence of those trials was that they 16:10:48 14 avoided weighting one treatment group on one drug or another 16:10:52 15 drug or the placebo with, say, the sickest patients because 16:10:56 16 if you were just putting patients in, you wouldn't want to 16:10:58 17 put the sick patients on a placebo so you would want to put 16:11:02 18 them on an active drug. So you biased the results and you 16:11:05 19 wouldn't really know whether the drug worked and the drug 16:11:08 20 would be treating all the sickest patients and the placebo 16:11:12 21 would be treating the healthy or least sick patients and it 16:11:16 22 wouldn't be a level playing field. 16:11:19 23 The randomized trials get rid of that. Let's say the 16:11:23 24 doctor or the patient had certain biases. If either one 16:11:28 25 doesn't know which one they're on, the doctor or the patient, 1573 16:11:31 1 there's no bias. So it is the method for getting the most 16:11:35 2 reliable information. 16:11:36 3 Q. Is that what you mean by double blind, that neither the 16:11:39 4 patient nor the doctor knows what the patient is getting? 16:11:42 5 A. That's correct. Double blind means the patient doesn't 16:11:45 6 know and the doctor doesn't know. So when the doctors 16:11:48 7 evaluate how well the drug is doing, they can't be biased 16:11:52 8 because they're not sure which one the patient is on. 16:11:55 9 We have little tricks for checking that. We ask the 16:12:03 10 doctor, "Take a guess which drug you thought they were on," 16:12:03 11 and we ask the patients the same thing and we see if the 16:12:05 12 answers are just random. 16:12:07 13 Q. The first area that you mentioned in your task force 16:12:10 14 report? 16:12:10 15 A. Right, was to go back and do what we call -- you can call 16:12:14 16 it metaanalysis or some type of reanalysis of the data that 16:12:21 17 you've already gone and collected, all of these thousands of 16:12:26 18 patients. In fact, that's done and that has been done. I'll 16:12:38 19 just list here, the first of these studies was done by a 16:12:44 20 Spanish guy, Professor Lopez-Ibor. 16:12:49 21 Q. We're talking about studies relating to Paxil, are we not? 16:12:52 22 A. Yes, I'm only going to talk about Paxil because you can 16:12:55 23 talk about every SSRI, but to keep things simple, since we 16:12:58 24 just want to know what the results are with Paxil, I'm just 16:13:06 25 going to talk about Paxil. 1574 16:13:08 1 The first analysis was done by Professor Lopez-Ibor. 16:13:13 2 What did he do? He went and looked at about 4,000 patients 16:13:17 3 that had gone through these trials worldwide where Paxil was 16:13:20 4 compared to placebo and to another active antidepressant. In 16:13:26 5 the majority of the cases that was a tricyclic 16:13:31 6 antidepressant. 16:13:36 7 And what he found in all -- not all of the studies. 16:13:39 8 What he found, he went and looked -- and you may have already 16:13:41 9 heard from other witnesses discussing this whole question -- 16:13:44 10 MR. VICKERY: Excuse me, Doctor. If I may interrupt, 16:13:47 11 Your Honor, we have indeed heard from another witness about 16:13:50 12 this. This is cumulative of the testimony of Dr. Wang. He 16:13:53 13 went through this one and all the others that I suspect 16:13:56 14 Dr. Mann is about to reiterate again. 16:14:00 15 MR. PREUSS: We will move briefly through these. 16:14:01 16 THE COURT: It is all right to lay a background. 16:14:03 17 Let's proceed. 16:14:04 18 THE WITNESS: Thank you, Your Honor. I will try and 16:14:06 19 be quick. 16:14:07 20 THE COURT: That's all right. 16:14:08 21 A. So what happened was he used a particular item which was 16:14:11 22 this Item 3 on this depression rating scale which asks people 16:14:16 23 are you feeling that life isn't, you know, worth living, do 16:14:21 24 you have any plans for doing away with yourself and have you 16:14:24 25 ever attempted suicide, so on and so forth. 1575 16:14:28 1 And what he found was that the Paxil did at least as 16:14:34 2 well as the other types of antidepressants, and both of 16:14:38 3 those -- and the new antidepressant Paxil and the old 16:14:43 4 antidepressants did a lot better than the placebo. 16:14:50 5 He did some other analyses, but they overlap with 16:14:56 6 stuff that was found by Montgomery who actually did the same 16:15:00 7 kind of analysis with this Item 3, but he had developed the 16:15:04 8 depression rating scale called the Montgomery-Asburg rating 16:15:07 9 scale, and in that there's Item 10 and Item 10 is better than 16:15:16 10 Item 3 because Item 10 focuses only on suicidal thoughts and 16:15:20 11 it rates them from zero to 6, so a big spread in score so you 16:15:28 12 can score people more precisely. 16:15:33 13 Not that you need to because the results were just so 16:15:36 14 striking. In the studies of thousands of patients, they 16:15:40 15 actually came up with a whole set of results which showed 16:15:42 16 that, one, Paxil clearly has a beneficial effect on 16:15:46 17 suicidality in depressed patients; two, that Paxil in 16:15:52 18 depressed patients who enter this treatment not feeling 16:15:56 19 suicidal, zero, the score is zero, it prevented the 16:16:03 20 development of suicidal feelings during the course of 16:16:06 21 treatment significantly better than the placebo. And as a 16:16:10 22 matter of fact, it was even better than the other types of 16:16:13 23 antidepressants. It was better, it was faster and it was 16:16:19 24 better and so there was an actual advantage for Paxil. 16:16:45 25 Q. That would be with respect to newly emergent suicide? 1576 16:16:45 1 A. That would be with respect to causing the suicidality to 16:16:45 2 fade away and preventing it appearing. 16:16:45 3 Q. Then there was another study by two individuals, Dunner 16:16:49 4 and Kumar, another one of these so-called metaanalyses, and 16:16:55 5 this is a study which appeared later -- forgive me if I'm off 16:16:58 6 by a year or two, but I think it appeared in about 1998 -- 16:17:04 7 that did analysis of even more patients and also showed that 16:17:10 8 there were certain advantages, therapeutic advantages of 16:17:14 9 Paxil clearly over placebo. 16:17:17 10 It definitely works. It prevents people becoming 16:17:20 11 suicidal, if they weren't suicidal when the treatment starts, 16:17:24 12 and it works for -- seemed to have an advantage potentially 16:17:28 13 in working a little faster. And that was both versus 16:17:32 14 tricyclic antidepressants, as well as other types of 16:17:40 15 antidepressants. 16:17:40 16 So these studies involved thousands of patients and 16:17:40 17 they avoided the biases by being prospective, double blind, 16:17:44 18 randomized, placebo controlled; all of those important 16:17:49 19 scientific requirements. 16:17:55 20 Now, finally, there's a study that should be 16:17:57 21 mentioned and that's a study by somebody called Arif Kahn 16:18:02 22 from Washington state, and what Dr. Kahn does was went and 16:18:07 23 under the Freedom of Information Act, he got from the FDA all 16:18:10 24 of the raw data that was supplied by all of the drug 16:18:14 25 companies for all of the new psychotropic medications. That 1577 16:18:19 1 included antidepressants, antianxiety drugs, antipsychotic 16:18:23 2 drugs, the whole kit and caboodle. 16:18:26 3 And then he looked at -- and what is published as 16:18:31 4 antidepressants and suicidality. He had in the published 16:18:34 5 study, as I recall, about 20,000 patients. And he has now 16:18:40 6 got a paper that he hasn't published yet, but that has 16:18:44 7 another 18,000 patients. 16:18:45 8 In all of that huge, massive amount of data, which is 16:18:48 9 all of the information that we've got in the United States, 16:18:50 10 there was absolutely no evidence that there was a higher rate 16:18:56 11 of suicide or suicide attempts among the SSRIs or the 16:19:02 12 tricyclic antidepressants compared to people that were on 16:19:06 13 placebo. 16:19:08 14 So there's absolutely no evidence from any of these 16:19:11 15 kinds of studies that these drugs do harm and in fact, it is 16:19:16 16 the exact opposite. The best and the most unbiased data that 16:19:21 17 we've got from the American studies and also from the 16:19:24 18 European studies, because that's -- Montgomery included those 16:19:28 19 data and so did Lopez-Ibor -- you don't see these drugs doing 16:19:34 20 harm, you see them doing good for patients and that's 16:19:38 21 probably explaining why the prescription rates are rising so 16:19:41 22 rapidly. 16:19:42 23 Q. And could you move to the second category of 16:19:44 24 recommendations from the consensus statement? 16:19:52 25 A. Now, the second category was a very interesting category 1578 16:19:59 1 and it really arose out of the idea if something doesn't 16:20:02 2 occur very often, you want thousands of patients to see 16:20:05 3 whether it happens or not. You've got to get as many 16:20:08 4 patients as you can. That's to do what we call sort of an 16:20:12 5 epidemiological kind of study. Epidemiological. Spelling 16:20:17 6 was never my forte. That looks right. 16:20:21 7 That was to go and find huge databases of patients 16:20:27 8 who were getting these medications and see if there were 16:20:29 9 patients that were running into trouble that we were missing 16:20:33 10 in the controlled clinical trials. 16:20:35 11 Well, there have been such studies, and a good 16:20:39 12 example is a study where a guy called Inman was the first 16:20:46 13 author. And he reported on data between 1991 and 1993. This 16:20:53 14 was called -- this was a prescription event monitoring 16:21:01 15 study -- and you're probably sick to death now of these 16:21:05 16 little acronyms -- PEM, but anyway, it looked at, believe it 16:21:12 17 or not, 13,000 plus patients who received Paxil. 16:21:22 18 And in these 13,000 patients that received Paxil, 16:21:25 19 they got a little bit of information about each patient to 16:21:28 20 see what's going on. About 93 percent of them were given the 16:21:34 21 Paxil for depression, so it is just the question we want to 16:21:38 22 know: What happened to 13,000 patients who got Paxil for 16:21:42 23 depression? 16:21:45 24 And they had to have received it for at least a 16:21:47 25 minimum period of time so you could actually see something, 1579 16:21:52 1 not like you took one dose. 16:21:57 2 What is interesting about this 13,000-patient study 16:22:00 3 is that there wasn't a single case of Paxil-attributed 16:22:06 4 suicidal behavior in the 13,000 patients. In fact, in the 16:22:14 5 13,000 patients there was one case, one case of aggressive 16:22:21 6 behavior not attributed to the drug. One case. 16:22:28 7 So it is also interesting, by the way, that, you 16:22:30 8 know, it is not like these people took five different other 16:22:34 9 things. 8 percent of these people got an antianxiety drug 16:22:40 10 along with the Paxil, so it is very low, 8 percent. 16:22:46 11 MR. VICKERY: Dr. Mann, would you excuse me for 16:22:48 12 interrupting you? 16:22:49 13 Your Honor, I'm sorry. I was trying as I was 16:22:51 14 listening to find this in the disclosure and I don't believe 16:22:55 15 anything about this 13,000-patient Inman study is in there. 16:22:58 16 I may have overlooked it, and if so, I apologize. 16:23:08 17 THE WITNESS: It is in the -- 16:23:09 18 THE COURT: We will let Mr. Preuss respond to this. 16:23:50 19 MR. VICKERY: Okay, Counsel pointed it out to me. 16:23:54 20 THE COURT: That's all right. We want to make 16:23:55 21 everybody stick with their designations. That's fine. 16:23:58 22 Why don't you go ahead and continue? 16:24:08 23 A. We have already discussed and I am not going to repeat the 16:24:08 24 story about the Isaacson-type study, which is the study that 16:24:11 25 looked at in Sweden and Scandinavian countries which showed 1580 16:24:15 1 there was a big rise in the prescription of the SSRIs and 25 16:24:21 2 percent drop in the national suicide rate, and the rate of 16:24:24 3 rise was proportionate to the rate of fall in suicidality. 16:24:27 4 So that's the kind of massive epidemiological study. 16:24:32 5 Isaccson also said what about the number of people 16:24:36 6 committing suicide -- 16:24:37 7 MR. VICKERY: Excuse me, Dr. Mann. 16:24:38 8 Your Honor, the report gives no indication whatsoever 16:24:41 9 of any reliance on either of these two studies. Now, there 16:24:45 10 is a list of things that might be referred to at the end, but 16:24:50 11 there's no clue in the designation that Dr. Mann was going to 16:24:54 12 come in here relying on these studies to contend that someone 16:24:57 13 lived up to the ACNP recommendations in the body of the 16:25:02 14 report itself, which is supposed to disclose the opinions and 16:25:05 15 the bases for them. 16:25:09 16 THE COURT: Mr. Preuss, would you point out in his 16:25:11 17 designation these opinions? 16:25:16 18 MR. PREUSS: His opinions are to discuss suicidality 16:25:19 19 and Paxil, and we have attached an entire list of documents, 16:25:25 20 of articles that may be referred to in his testimony. And 16:25:30 21 Mr. Vickery elected not to depose any of the experts, 16:25:33 22 including this one. 16:25:34 23 THE COURT: Whether he elected to or not, he's 16:25:36 24 relying on the designation. The designation must set forth 16:25:39 25 each and every opinion and specifically the basis of how this 1581 16:25:42 1 expert arrived at that opinion. And that's, I think, the 16:25:45 2 basis of the objection by Mr. Vickery, that he does not 16:25:48 3 believe that was disclosed and that the witness is testifying 16:25:51 4 beyond his designation. 16:25:54 5 And you just need to point out to me where in the 16:25:56 6 body of the designation these opinions are set forth. If 16:25:59 7 they're there, I will allow him to testify. If not, I will 16:26:03 8 sustain the objection. 16:26:07 9 MR. PREUSS: Your Honor, it talks in paragraph 10 16:26:09 10 that there's no controlled scientific evidence that Paxil 16:26:12 11 causes suicidal ideation or behavior or that it worsens 16:26:17 12 existing suicidal ideation or behavior, as reviewed in the 16:26:21 13 ACNP consensus statement case reports, so it discusses that 16:26:26 14 specifically. 16:26:31 15 THE COURT: And where's the reference to -- what is 16:26:33 16 this -- the Inman study? 16:26:35 17 MR. PREUSS: There is no direct reference to that 16:26:37 18 particular study in the body of the designation, and indeed, 16:26:42 19 it would make -- we added all of the articles that you rely 16:26:46 20 on to support the opinions. 16:26:48 21 The opinion itself is what he's testified to, and the 16:26:52 22 basis of it are the articles. That's the only way the expert 16:26:56 23 can testify. I think it is a full disclosure that all you 16:26:59 24 have to do is read the articles. And we notified him of the 16:27:03 25 articles and the opinions in the articles are -- the articles 1582 16:27:09 1 are always used in support of the opinions to support whether 16:27:14 2 Paxil does or does not cause suicide. 16:27:18 3 THE COURT: The basis of the opinion has to be set 16:27:20 4 out specifically, and where is that? We have the opinion. I 16:27:23 5 know that. He relies on this -- I can't remember the 16:27:28 6 letters -- ACNP or whatever it is, and that's fine. Any 16:27:35 7 other specific reference to his basis for this particular 16:27:39 8 opinion? 16:27:46 9 MR. PREUSS: Other than I've specifically stated, 16:27:47 10 there's no specific mention of it in the body of it. The 16:27:50 11 articles that he says he's going to rely on is attached. 16:27:54 12 Clearly there's no surprise as to the opinion he's rendering. 16:27:58 13 The issue is did I put this article in the paragraph, and we 16:28:00 14 attached them, chose to attach them. 16:28:18 15 THE COURT: There's literally dozens of articles we 16:28:21 16 see here. We know he reviewed these particular matters and 16:28:23 17 relied on some of them. 16:28:27 18 I think that the testimony we're hearing now places a 16:28:32 19 lot of emphasis on particular articles that have not been 16:28:35 20 disclosed as the basis of these opinions and that's the 16:28:38 21 problem, and that's the lack of thoroughness that I think all 16:28:43 22 counsel have experienced in their designations throughout 16:28:45 23 this trial and this is where it comes to haunt you. 16:28:52 24 I will let him finish on this but I don't see it here 16:28:55 25 and I don't think it covers you to just say, "Well, we listed 1583 16:28:58 1 all of these things and now he can testify in detail about 16:29:01 2 them." I don't think that's a proper designation of the 16:29:05 3 bases of his opinions. You need to be more specific than 16:29:09 4 that. 16:29:29 5 Q. (BY MR. PREUSS) Doctor, have you finished up with the 16:29:31 6 Isaccson matter? 16:29:33 7 A. Yes. 16:29:39 8 Q. Any other studies? 16:29:40 9 A. I also wanted to include a study that I also coauthored 16:29:44 10 with Dr. Kapur, and I hope it is designated in the right 16:29:54 11 place in the books because I thought I stuck them all, the 53 16:29:54 12 articles that I'm supposed to confine myself to, but okay, 16:29:56 13 live and learn. 16:29:57 14 MR. VICKERY: Excuse me, Your Honor. 16:29:59 15 MR. PREUSS: It is on -- 16:30:00 16 MR. VICKERY: May I take the witness on voir dire 16:30:02 17 with regard to the opinions disclosed in his report? 16:30:04 18 THE COURT: No, let's let this move along. I've made 16:30:08 19 my decision on this matter. It is clear and unequivocal how 16:30:12 20 I'm ruling. I'm being consistent with what I've done before. 16:30:15 21 We're going to let him go forward. If it is not in the 16:30:19 22 designation, he's not going to talk about it. He's finished 16:30:23 23 up with the matter you've objected to. I don't know what 16:30:25 24 we're getting into now and it is unclear to me. 16:30:28 25 MR. PREUSS: Actually, Your Honor, I did find 1584 16:30:30 1 Isaccson cited on paragraph 5, the end of paragraph 5 and 16:30:56 2 paragraph 6. I apologize for missing that the first time 16:31:01 3 around. 16:31:01 4 THE COURT: All right. Go ahead. 16:31:03 5 Q. (BY MR. PREUSS) We have Isaccson. Now if you would turn 16:31:06 6 your attention to Kapur, please. 16:31:08 7 A. Kapur, this study is not to be confused with the previous 16:31:11 8 one. It was an examination of the available data in the 16:31:14 9 United States. What the article did was to take 16:31:19 10 antidepressants that had been marketed and try and look at 16:31:23 11 the relationship between the number of prescriptions that had 16:31:26 12 been written for these antidepressants and the frequency with 16:31:32 13 which they appeared in people who took an overdose to try and 16:31:36 14 kill themselves or people who took an overdose and did kill 16:31:39 15 themselves. 16:31:41 16 And what essentially this article demonstrated was 16:31:45 17 that there weren't any more -- 16:31:49 18 MR. VICKERY: Excuse me, Dr. Mann. What we're 16:31:51 19 getting is an opinion regarding adequacy of testing and 16:31:54 20 citing of an article in support to it. I object to it. 16:31:57 21 There is nothing in the Rule 26 report that indicates this 16:32:00 22 man was going to come to this trial and say there has been 16:32:03 23 adequate testing and here are the articles that prove it. 16:32:06 24 It is just not there. It is a completely different 16:32:08 25 opinion. It isn't just that he didn't cite an article. It 1585 16:32:11 1 is that nowhere in the Rule 26 report does it say, "In my 16:32:14 2 opinion there's been adequate testing and here is what 16:32:17 3 supports it." 16:32:22 4 MR. PREUSS: Your Honor, there's about three pages as 16:32:23 5 to the safety and efficacy of Paxil which is tied into what 16:32:28 6 is done with respect to testing. That's how you establish 16:32:32 7 safety. That's what we did with Dr. Wheadon. That's what we 16:32:35 8 did with the witness the other day. That's the only way you 16:32:38 9 can do it. 16:32:39 10 THE COURT: Where in Dr. Mann's designation does he 16:32:41 11 set forth that proper testing had been done? 16:32:47 12 MR. PREUSS: What he says is -- where he talks about 16:32:50 13 the safety of SSRIs and the efficacy of them. 16:32:54 14 THE COURT: Where are you referring to, please? 16:32:55 15 MR. PREUSS: Paragraph 7, paragraph 8, paragraph 10. 16:33:29 16 MR. GORMAN: Paragraph 11. 16:34:27 17 THE COURT: Do you have something else to cite me? 16:34:29 18 MR. PREUSS: No, those are the ones I've cited you. 16:34:31 19 THE COURT: I believe with regard to those citations 16:34:33 20 that the matter has been adequately designated and the 16:34:37 21 objection is overruled. 16:34:43 22 Q. (BY MR. PREUSS) Dr. Mann, then, I think you were 16:34:44 23 interrupted on the Dr. Kapur article. If you could again 16:34:50 24 bring us back to where we were. 16:34:52 25 A. The importance of that article is that it looks at the 1586 16:34:54 1 data in the U.S.A. and it looks at antidepressants like 16:35:03 2 SSRIs, and the idea is that if people are taking these drugs 16:35:07 3 disproportionately in terms of suicide attempts compared to 16:35:12 4 other types of antidepressants like the tricyclic 16:35:15 5 antidepressants, and the answer is it found absolutely no 16:35:19 6 evidence of that at all. 16:35:20 7 It also did find evidence which other studies 16:35:23 8 previously had looked at which is what happens if you do take 16:35:27 9 the tricyclic antidepressant compared to an SSRI-type of drug 16:35:32 10 in an overdose and your chances of dying are much greater. 16:35:37 11 So we affirmed the safety of these agents in the 16:35:40 12 unfortunate event that somebody tried to kill themselves 16:35:43 13 using the agents, but it importantly added a brand-new fact 16:35:47 14 which was that people don't try to kill themselves with these 16:35:51 15 agents any more than they do with any other kind of 16:35:54 16 antidepressant. 16:35:58 17 The third type of study -- 16:36:00 18 Q. If you want to use a second page, feel free to do that, 16:36:04 19 unless you feel you can get them all on there. 16:36:08 20 A. I'm pretty close to finishing this. 16:36:11 21 The third type of study proposed that if -- and you 16:36:18 22 think this is a bit tedious, it is because doctors are in the 16:36:23 23 business of saving lives and we have to be really careful and 16:36:26 24 sometimes that's a bit boring but it is important. 16:36:36 25 You give these antidepressants not always for the 1587 16:36:36 1 treatment of depression. SSRIs are very often given -- if 16:36:36 2 you watch television, you can see, it is advertised on TV -- 16:36:39 3 social phobia, obsessive-compulsive disorder, smoking 16:36:44 4 cessation, lose weight. There are a variety of other 16:36:48 5 indications that people have been evaluated for in terms of 16:36:52 6 the usefulness of SSRIs. And the question is are those 16:36:55 7 patients developing suicidal feelings on SSRIs? 16:37:05 8 And that question was addressed, actually, in regards 16:37:08 9 to Prozac, and I just mentioned that for completeness. I 16:37:13 10 have to tell you quite honestly I have not seen the results 16:37:16 11 published with Paxil, although I believe that there was 16:37:20 12 another expert witness here, Dr. Wheadon, who may have 16:37:24 13 discussed whether Paxil administration to other types of 16:37:26 14 patients produced evidence of what we call emergent 16:37:30 15 suicidality. So that's nondepressed populations. 16:37:46 16 And finally, number four was -- the idea of that 16:37:50 17 study was take patients who make a lot of suicide attempts 16:37:55 18 and put them in a double-blind controlled placebo study and 16:37:59 19 see what happens. 16:38:01 20 Now, if you think that's a bad idea, taking suicidal 16:38:05 21 patients and putting them in a placebo controlled study, 16:38:08 22 you're not alone. Most people think that's a bad idea. And 16:38:12 23 I don't think you could get any funding from anyone. The 16:38:17 24 National Institute of Mental Health would not give you 16:38:20 25 funding to do that. 1588 16:38:21 1 But anyway, there have been -- so that's a placebo 16:38:28 2 controlled study with suicide as the outcome. And there have 16:38:32 3 actually been two studies that have been done, the one study 16:38:46 4 is Moller and Steinmeyer. They took about 200 patients, 16:38:52 5 believe it or not, and what they did was they had one group 16:39:34 6 on Paxil, one on amitriptyline. That was a tricyclic, the 16:39:34 7 number one prescribed antidepressant until the SSRIs arrived 16:39:34 8 on the scene. 16:39:34 9 And they compared the two and looked for all of the 16:39:34 10 things we wanted to know the answer for. Suicide was the big 16:39:34 11 outcome they were interested in, suicide, suicide attempt, 16:39:34 12 suicidal ideation. That's the reason they did the study. 16:39:34 13 And they found no difference between these two 16:39:34 14 groups, dead heat. Both were efficacious. Both showed a 16:39:39 15 decline in suicidality. But was one better than the other? 16:39:43 16 No, they didn't find a difference. 16:39:45 17 Now, there was another study that is relevant here 16:39:50 18 which is a study by a man who may have already been 16:39:58 19 discussed, Verkes, et al. They were a group of nondepressed 16:40:02 20 patients but ones who had made a lot of suicide attempts. 16:40:06 21 And I guess we're probably going to be talking about these 16:40:09 22 patients, but, you know, it was Paxil versus an active drug 16:40:18 23 versus a placebo and they were treated for a year. Most 16:40:29 24 people didn't make it through the study, by the way, but 16:40:31 25 essentially, if you control statistically for the number of 1589 16:40:34 1 suicide attempts that each of these patients made, Paxil 16:40:43 2 turned out to be effective, superior in terms of efficacy 16:40:48 3 over the other active antidepressant. 16:40:50 4 So these are the four categories and that's at least 16:41:00 5 some of the findings. 16:41:02 6 Q. Thank you, Doctor. 16:41:13 7 Doctor, did any of the studies you've gone through in 16:41:15 8 the last moments here indicate that Paxil causes suicidal 16:41:18 9 thoughts or acts, sir? 16:41:22 10 A. They don't. 16:41:23 11 Q. Now, Doctor, in your opinion to a reasonable degree of 16:41:27 12 scientific and medical certainty is there any scientific 16:41:30 13 evidence that you're aware of that Paxil causes suicidal 16:41:33 14 thoughts or aggression or behavior in some subpopulation of 16:41:38 15 patients that receive it? 16:41:43 16 A. In this whole collection of studies there's no evidence 16:41:47 17 that Paxil causes suicidality. Actually, on the contrary, 16:41:52 18 there's a huge amount of evidence that Paxil does patients a 16:41:56 19 lot of good. 16:41:59 20 Q. All right. Doctor, if I could, I would like to turn your 16:42:02 21 attention to labeling on Paxil as it relates to suicide, and 16:42:08 22 I would like to take you back to where we were a moment ago 16:42:12 23 or maybe an hour or so ago dealing with the FDA ad hoc 16:42:18 24 committee. 16:42:19 25 Was the issue of suicidal labeling on antidepressant 1590 16:42:24 1 drugs raised as part of that inquiry by the advisory 16:42:28 2 committee? 16:42:29 3 A. It was. 16:42:29 4 Q. All right. And what was the issue, sir? 16:42:32 5 A. The question was in light of the evidence that had been 16:42:36 6 reviewed was there reason to change the labeling of 16:42:43 7 antidepressants, and of Paxil specifically. That was the 16:42:51 8 question put to the committee. 16:42:52 9 Q. And change the labeling as it relates to suicidality? 16:42:55 10 A. Yes. 16:43:02 11 Q. Did the committee take a vote on that issue as to whether 16:43:05 12 there should or should not be a change? 16:43:07 13 A. Yes, after the committee voted on the question of the 16:43:10 14 scientific basis or evidence for a relationship between 16:43:13 15 suicidality and medications, psychotropic medications or 16:43:19 16 antidepressants in general and any specific antidepressant, 16:43:28 17 the committee then voted on that question. 16:43:31 18 Q. And what was the vote? 16:43:35 19 A. To the best of my recollection, it was six against 16:43:40 20 changing the label and three for changing it. 16:43:43 21 Q. And did the committee explain its rationale for the votes 16:43:46 22 not to change the warning? 16:43:48 23 A. They did not. 16:43:52 24 Q. And -- 16:43:53 25 A. Only three people who wanted to change the label? 1591 16:43:58 1 Q. Yes. 16:44:00 2 A. I'm not sure why they voted. It didn't make any sense, 16:44:03 3 actually, quite frankly. 16:44:05 4 Q. Did you express your views with respect to any labeling 16:44:08 5 change on the issue of suicidality? 16:44:11 6 A. Yes, my own view of the matter was that the label was 16:44:19 7 adequate. What we needed to do was send a wake-up call to 16:44:23 8 doctors about being a little bit more alert in terms of 16:44:27 9 taking care of suicidal patients. 16:44:29 10 Q. And is this the suicidal labeling that was at issue in 16:44:47 11 1991? 16:44:54 12 A. Well, of course this is the label for 1998. 16:45:00 13 Q. Right. 16:45:01 14 A. But actually, if you -- I went and had a look at the label 16:45:05 15 prior to the hearing and it had the same language. 16:45:09 16 Q. So it stayed the same? 16:45:11 17 A. As I recall, basically, yes. From the best of my 16:45:13 18 recollection, the wording remained completely unchanged 16:45:17 19 before -- from before to after the hearing. 16:45:20 20 Q. And based on your experience and your review of the 16:45:24 21 scientific literature from the time of the hearings in 1991 16:45:30 22 up to the present, is that label still satisfactory and 16:45:36 23 appropriate, from your viewpoint, sir? 16:45:39 24 A. It is appropriate from my personal viewpoint. It was 16:45:41 25 appropriate from the FDA committee's viewpoint, and the ACNP 1592 16:45:47 1 also felt the same way. 16:45:49 2 Q. Doctor, I would like to show you a proposal that 16:45:57 3 Dr. Maltsberger provided us with respect to labeling and ask 16:46:00 4 you if you could comment -- 16:46:13 5 THE COURT: Let's refer to the evidence stickers when 16:46:15 6 we talk about these. 16:46:16 7 MR. PREUSS: I'm not sure I know the number. 16:46:41 8 Plaintiff's 17. 16:46:43 9 THE COURT: Thank you. 16:46:44 10 Q. (BY MR. PREUSS) Can you see that all right, Doctor? 16:46:46 11 A. Yes, I can. I'm just reading it. I see Dr. Maltsberger 16:46:54 12 has the same regrettable handwriting style that I'm afflicted 16:46:58 13 with. 16:47:05 14 THE COURT: 17 or 16? 16:47:09 15 THE WITNESS: 16. 16:47:09 16 MR. PREUSS: I think it is Number 17, Your Honor. I 16:47:11 17 think it was 16 at the deposition. It is 17 for purposes of 16:47:14 18 trial. 16:47:15 19 THE COURT: All right, thank you. 16:47:18 20 Q. (BY MR. PREUSS) When you have completed it, let me know, 16:47:23 21 Doctor. 16:47:24 22 A. Well, I think that there are serious problems with this 16:47:29 23 recommendation. 16:47:30 24 Q. And why is that? 16:47:32 25 A. Because it states, "The physician should be aware that in 1593 16:47:39 1 rare instances SSRI compounds such as Paxil may produce acute 16:47:45 2 homicidal and suicidal states." 16:47:48 3 I think, first of all, I don't believe that there is 16:47:51 4 scientific evidence to support a relationship between Paxil 16:48:09 5 and such states, so I don't think that one can support this 16:48:09 6 statement on scientific grounds. 16:48:09 7 Moreover, the risk of putting such statements in the 16:48:11 8 information of a company's medication like Paxil is that 16:48:15 9 we've already talked a great deal about how difficult it is 16:48:18 10 to get depressed patients to pick up the phone and talk to 16:48:22 11 their doctor, how difficult it is to get them to persist with 16:48:25 12 a medication when it doesn't produce any immediate benefit, 16:48:28 13 and the illness creates a state of mind of hopelessness and 16:48:32 14 pessimism and so on and so forth. 16:48:36 15 You put a statement that has no scientific foundation 16:48:42 16 in the information that's given to the doctor and the patient 16:48:46 17 saying that it may produce an acute suicidal or homicidal 16:48:51 18 state, even if you say in rare instances, who is going to 16:48:55 19 want to take an antidepressant? 16:48:58 20 Now, the mortality due to suicide is over 30,000 a 16:49:02 21 year. That means that over 20,000 people a year are killing 16:49:04 22 themselves with depression and most of those people are not 16:49:08 23 being treated properly. This has been the subject of 16:49:15 24 personal concern from me, but also was the subject of 16:49:19 25 testimony from people like -- from other government agencies 1594 16:49:27 1 like at the FDA hearing. 16:49:29 2 We need to warn doctors about things that are 16:49:32 3 dangerous but we need to warn doctors about things that are 16:49:35 4 dangerous when we have clear evidence of that. In this case 16:49:38 5 all of the evidence we have indicates that for the majority 16:49:46 6 of patients they're going to benefit from these medications 16:49:46 7 and we cannot detect evidence that suicidality is made worse 16:49:48 8 by a medication like Paxil. 16:49:51 9 So, you know, we want people to be treated with the 16:49:54 10 safest medications we can find. And right now Paxil is one 16:49:57 11 of those medications. 16:49:59 12 Q. So in your view, would it be a mistake to use this 16:50:02 13 particular labeling? 16:50:03 14 A. Yes, I think this label has the potential of increasing 16:50:08 15 the mortality due to depression by reducing the probability 16:50:11 16 that people are going to want to take these medications. And 16:50:14 17 it is unjustified scientifically. 16:50:17 18 MR. PREUSS: Thank you, Doctor. No further questions 16:50:19 19 at this time. 16:50:56 20 Q. (BY MR. VICKERY) So are you saying that you're willing to 16:51:02 21 sacrifice the lives of the small, vulnerable minority on 16:51:09 22 whose behalf you wrote in 1991, '92 and '93 in order to spare 16:51:13 23 the lives of the majority? 16:51:21 24 A. That is your characterization of these scientific 16:51:24 25 articles. I don't see them that way. Those articles had the 1595 16:51:27 1 objective of trying to determine the safety and efficacy of 16:51:32 2 these medications. They weren't trying to discriminate 16:51:36 3 against anybody. They were trying to give every patient the 16:51:40 4 very best chance of getting better when they went to see 16:51:43 5 their doctor. 16:51:44 6 Q. Did you in 1991 in the Mann and Kapur article, sir, write 16:51:48 7 that there may be a small, vulnerable subpopulation of 16:51:53 8 patients who are at risk? Did you write that? 16:51:57 9 A. That's a very good point. Let me just draw your attention 16:52:00 10 to what I actually wrote and the context in which it was 16:52:03 11 written. 16:52:10 12 Q. You're talking about the Mann and Kapur article, right, 16:52:14 13 SBFF 51? 16:52:17 14 A. Well, I'm happy to avoid any misunderstanding. Why don't 16:52:20 15 you direct me to the very place that you're thinking of, and 16:52:22 16 I will be happy to respond. 16:52:24 17 Q. Is the Mann and Kapur article that was published in 16:52:28 18 September of 1991 the basis of your testimony here today, in 16:52:32 19 part? I mean, you've discussed it at length, haven't you? 16:52:36 20 A. What you've tried to make clear in the testimony that I've 16:52:40 21 presented is that there has certainly been an evolution of 16:52:46 22 information that has been available to us to make judgments 16:52:49 23 in answer to the kind of question you're raising. 16:52:52 24 Q. Dr. Mann, is the Mann and Kapur article of 1991 one of the 16:52:56 25 bases of your opinions today? 1596 16:52:59 1 A. It is. 16:53:00 2 Q. And did you think that it was a good summary of the 16:53:03 3 available scientific knowledge as of September of 1991? 16:53:09 4 A. Absolutely. 16:53:09 5 Q. And you think that that information would be helpful for 16:53:14 6 our jury in deciding the issues in this case? 16:53:17 7 A. Happy to respond to your question. 16:53:19 8 Q. Do you think that information contained in your article 16:53:22 9 would be helpful to the jury to decide the issues in this 16:53:26 10 case? 16:53:26 11 A. It is certainly part of the information the jury should be 16:53:28 12 aware of. Absolutely. 16:53:31 13 MR. VICKERY: Your Honor, I would at this time offer 16:53:33 14 SBFF-51, the 1991 Mann and Kapur article into evidence. 16:53:38 15 MR. PREUSS: I object on the basis it is a scientific 16:53:41 16 article, just as any other one. If we're going to start 16:53:44 17 introducing scientific articles, then where do we stop? 16:53:48 18 MR. VICKERY: Well, the ACNP statement of 1992 upon 16:53:53 19 which his opinion is also based is in evidence as a joint 16:53:56 20 exhibit. And based upon the testimony that this man has just 16:53:59 21 given, I think that this particular article is one that has 16:54:02 22 probative value for the jury and I offer it. 16:54:07 23 THE COURT: I think we need to be consistent about 16:54:10 24 these articles and it is not typically something that is 16:54:12 25 received in evidence and disseminated to the jury directly. 1597 16:54:16 1 There will be an introduction on that. I am going to sustain 16:54:18 2 the objection. 16:54:21 3 Q. (BY MR. VICKERY) What happened after 1993 to get you to 16:54:27 4 quit writing articles calling for more scientific research? 16:54:38 5 A. In what sense do you mean I quit writing articles 16:54:41 6 requiring more scientific research? That's not true. 16:54:45 7 Q. On the issue of whether there is a small, vulnerable 16:54:47 8 subpopulation of patients at risk. That's the precise issue 16:54:51 9 I'm talking about. In '91 in the Mann and Kapur article you 16:54:56 10 talked about implications for research, right? 16:55:00 11 A. Right. 16:55:01 12 Q. And did you delineate several ways that this issue could 16:55:05 13 be studied? 16:55:06 14 A. In the 1991 article, yes, we did describe a research 16:55:11 15 strategy for trying to determine more information, that's 16:55:14 16 correct. 16:55:14 17 Q. Did you also come up with a hypothesis for just how this 16:55:17 18 could be happening? 16:55:18 19 A. We made a suggestion which was elaborated upon in the ACNP 16:55:23 20 article and I spent a lot of time describing four different 16:55:33 21 strategies for enhancing the amount of available information. 16:55:33 22 And to answer your question, I guess the answer is 16:55:33 23 that a great deal of data has emerged since 1991, 1992, et 16:55:39 24 cetera, addressing these very questions. 16:55:42 25 Q. Let's talk about that. Let's make sure we're clear. 1598 16:55:45 1 In '91 you outlined a hypothesis and a research 16:55:50 2 strategy, right? 16:55:52 3 A. That's correct. 16:55:52 4 Q. In 1992 on behalf of the ACNP you delineated four 16:55:57 5 different ways the issue could be tested, right? 16:56:00 6 A. That's correct. 16:56:01 7 Q. Now, there's some differences between your '91 article and 16:56:04 8 your '92 article, aren't there? 16:56:06 9 A. One year later. 16:56:08 10 Q. Well, it is more than just one year later. There's some 16:56:12 11 differences in the way you suggested to test the issue, 16:56:14 12 aren't there, Dr. Mann? 16:56:16 13 A. First of all, your characterization of the ACNP article as 16:56:21 14 my article is misleading. 16:56:26 15 Q. Okay. Were you the principal author of the article? 16:56:31 16 A. I was the first author. But as I pointed out in an 16:56:34 17 article of this type which is termed a consensus statement, 16:56:37 18 the views of the council of the college have to be 16:56:44 19 represented. 16:56:44 20 Q. Do you remember the first time I took your deposition? 16:56:47 21 A. Yes, I do. 16:56:48 22 Q. That was in the Miller versus Phizer case, wasn't it? 16:56:51 23 A. Yes. 16:56:52 24 Q. And do you remember at that time I said, "Now, if I want 16:56:57 25 to know the opinions of Dr. J. John Mann, which of these two 1599 16:57:01 1 papers should I go to?" And you remember you told me then 16:57:05 2 that the '91 article you wrote with your colleague Dr. Kapur 16:57:09 3 more accurately reflected your personal views for the very 16:57:13 4 reasons you're explaining now? 16:57:14 5 A. At that time. 16:57:16 6 Q. All right. And at that time you told me you still stand 16:57:20 7 by both of those papers, didn't you? 16:57:22 8 A. I don't think I made that statement. 16:57:50 9 Q. At that time, Dr. Mann, so that we're clear, we're talking 16:57:52 10 about a deposition that I took on March 29th, 2000, just 16:57:56 11 slightly over a year ago, right? 16:57:59 12 A. It is conceivable. I'm not sure of the exact date. 16:58:04 13 Q. You want me to show it to you or will you accept it? 16:58:07 14 A. I'm willing to accept it is probably right. 16:58:11 15 Q. Do you recall that I asked you one year ago in March on 16:58:18 16 page 117 of the Miller deposition, line 9, "Do you hold today 16:58:24 17 the views that you express in that consensus statement?" 16:58:28 18 And do you recall that your answer then was, "That 16:58:31 19 consensus statement was a consensus statement. It largely 16:58:34 20 overlaps with my view of these matters. I might differ from 16:58:38 21 it in some nuances"? 16:58:42 22 Do you recall giving that sworn testimony a year ago? 16:58:45 23 A. I'm sure the jury understands that whatever I said on that 16:58:48 24 page and on that line, you know, it would be easier if I 16:58:52 25 looked at it to refresh my memory. 1600 16:58:55 1 MR. VICKERY: May I approach? 16:58:56 2 THE COURT: Yes, you may. 16:59:10 3 Q. (BY MR. VICKERY) My question is did you give that answer 16:59:12 4 under oath on that day? 16:59:13 5 A. "It largely overlaps. My view of these matters might 16:59:17 6 differ from it in some nuances." 16:59:29 7 Q. We will look at it to put in context the Mann and Kapur 16:59:34 8 article and the ACNP paper, but in both of those you wrote, 16:59:38 9 did you not, sir, that there may be a small, vulnerable 16:59:42 10 subpopulation of patients who are at risk? 16:59:49 11 A. You know, I think I can quote it to you more precisely by 16:59:53 12 reading it, which would avoid any kind of misunderstanding. 16:59:58 13 Q. Which one you going to read from first? 17:00:01 14 A. Shall we do Mann and Kapur, 1991? 17:00:03 15 Q. That would be good. Read me a sentence about the small, 17:00:07 16 vulnerable subpopulation. 17:00:11 17 A. It begins with a statement that, "Clinicians should be 17:00:19 18 aware that emergence or intensification of suicide" -- 17:00:28 19 Q. Would you tell me the page so I can read along with you? 17:00:32 20 A. Sure. Page 1032. 17:00:35 21 Q. I'm right with you. 17:00:37 22 A. So this is the paragraph -- I would like to read the 17:00:43 23 paragraph because one sentence in the middle of the paragraph 17:00:46 24 doesn't give you the idea of what the sentence really means. 17:00:48 25 Q. I tell you what let's do. Let's put it on the screen so 1601 17:00:51 1 we can all look at it, if we may. Let's look at that page, 17:00:55 2 okay? 17:00:55 3 A. Sure. While we are waiting for this to come into focus, 17:01:24 4 implications force the clinicians -- 17:01:28 5 Q. Excuse me. What question are you answering? We have to 17:01:31 6 kind of do it on question and answer here, if that's okay 17:01:34 7 with you. At the top of that very page you see where I've 17:01:39 8 highlighted on the screen, "We've postulated that" -- would 17:01:44 9 you read the highlighted sentence? 17:01:52 10 A. "We postulate that in a subset of patients introduction of 17:01:52 11 a serotonin reuptake inhibitor increase" -- I guess everybody 17:01:56 12 can read it -- "increase in dose may result in an exaggerated 17:01:59 13 initial decrease in serotonin transmission and thus enhance 17:02:03 14 suicidality early in the treatment because of an effect on 17:02:06 15 the neurobiological regulator of suicide or aggression 17:02:13 16 threshold." 17:02:14 17 Q. You were talking about a subset of patients there, weren't 17:02:17 18 you? 17:02:17 19 A. That's correct. 17:02:18 20 Q. Now, you wanted to read the entire paragraph at the bottom 17:02:23 21 and so let's do that, if we may. You want to read the one 17:02:39 22 "Clinicians should be aware.."? 17:02:41 23 A. Did you have a question about that previous thing I read 17:02:43 24 out or you just wanted me to read it out? 17:02:46 25 Q. I just wanted you to read it out. 1602 17:02:48 1 A. Okay. "Clinicians should be aware that emergence or 17:02:55 2 intensification of suicidal ideation or behavior in patients 17:02:59 3 receiving antidepressant treatment has been reported in 17:03:01 4 patients with various psychiatric diagnoses and has not been 17:03:06 5 proven to be associated with any specific type of 17:03:09 6 antidepressant." 17:03:13 7 Q. Please read on. We're going to get to the small, 17:03:16 8 vulnerable subpopulation. 17:03:19 9 A. "Whether certainty" -- "Whether certain antidepressants 17:03:24 10 precipitate or aggravate suicidal ideation in a small, 17:03:28 11 vulnerable subpopulation of psychiatric patients who require 17:03:31 12 antidepressants is uncertain, in practice, whatever the 17:03:34 13 antidepressant medication, the clinician should always 17:03:39 14 monitor the patient to assess the severity of depression and 17:03:43 15 suicidal ideation, aggressive ideation or behavior..." 17:03:49 16 Q. Keep going. Let's finish that sentence, "...or behavior, 17:03:54 17 agitation or," something else. What does it say? 17:03:58 18 A. Agitation and akathisia. 17:04:00 19 Q. Why did you write about akathisia? 17:04:05 20 A. If you look at this article in context, it discussed all 17:04:11 21 psychotropic medications. And earlier in the article I made 17:04:15 22 a particular point of the fact that antipsychotic medications 17:04:20 23 produce akathisia pretty frequently. As a matter of fact, 17:04:24 24 estimates range from 20 to 70 percent of patients getting 17:04:27 25 antipsychotics get akathisia. 1603 17:04:29 1 And in the same context I made the point that 17:04:33 2 akathisia is reportedly associated, when it is very severe 17:04:37 3 and the patients are very desperate, with aggressive or 17:04:40 4 suicidal feelings or behavior. 17:04:42 5 So keeping an eye on patients getting antipsychotics 17:04:46 6 was the underlying thought behind this comment. 17:04:51 7 Q. Is akathisia a risk factor for violence and suicide? 17:04:57 8 A. There are case reports that purport that. 17:05:01 9 Q. Have you previously testified under oath, sir, that 17:05:03 10 akathisia is a risk factor for violence and suicide? 17:05:08 11 A. I've actually published a statement that -- a case report 17:05:14 12 indicating that I thought that or my colleagues and I thought 17:05:18 13 in a particular patient that the akathisia was of such 17:05:21 14 severity it may have contributed to the patient feeling 17:05:24 15 suicidal, which is precisely, precisely why it is listed in 17:05:31 16 this article as something for clinicians to watch out for. 17:05:35 17 Q. Dr. Mann, I'm not interested in a case report because you 17:05:39 18 denigrate the value of them. I am interested in your sworn 17:05:42 19 testimony. 17:05:43 20 And my question is have you previously testified 17:05:46 21 under oath that akathisia is a risk factor for violence and 17:05:50 22 suicide? 17:06:06 23 A. I haven't changed my view. I still think that akathisia 17:06:06 24 has the potential when it is severe of contributing to 17:06:06 25 suicidality and aggression. 1604 17:06:08 1 Q. Thank you. Let's look at the last sentence in this 17:06:10 2 article: "The clinician can then judge whether the cause is 17:06:13 3 the illness, the environment or the treatment." 17:06:18 4 When you wrote this article in 1991, you were trying 17:06:23 5 to send a wake-up call to the profession to say that in some 17:06:27 6 instances for a small subpopulation of patients the treatment 17:06:31 7 may actually be what is causing it; isn't that true? 17:06:38 8 A. If you read the article you will see that we discuss 17:06:40 9 specifically the concern of maprotiline which was in a 17:06:47 10 double-blind, controlled, randomized, prospective clinical 17:06:51 11 trial suggesting that even though the patient benefited from 17:06:53 12 the antidepressant effects of this drug, maprotiline, which 17:06:57 13 incidentally is not an SSRI, the rate of suicide and suicide 17:07:00 14 attempts in the patients getting maprotiline was a little 17:07:04 15 higher and that led to a point of view that may be cranking 17:07:07 16 up the level of norepinephrine in some patients may help 17:07:14 17 depression but may make them more prone to act on their 17:07:18 18 suicidal feelings. That was obviously one concern. 17:07:21 19 The second concern related to the antipsychotic 17:07:24 20 medications. All of this is openly written about in this 17:07:28 21 article, that they have a very high rate of akathisia, that 17:07:38 22 it could produce quite severe akathisia in a few patients, 17:07:38 23 maybe the patients are more vulnerable than others to getting 17:07:40 24 akathisia and some of those patients may become or feel more 17:07:43 25 suicidal as a result and the clinician should be aware of 1605 17:07:47 1 these things. 17:07:48 2 Q. Dr. Mann, my question was when you wrote this article were 17:07:51 3 you trying to send the wake-up call to the profession that 17:07:55 4 they could be part of the problem instead of part of the 17:07:57 5 cure, that something they were going to give someone for at 17:08:01 6 least a small, vulnerable subpopulation could trigger 17:08:05 7 suicide? Were you trying to alert them or not, sir? 17:08:09 8 A. This was an article which wanted to encourage better 17:08:12 9 clinical practice amongst several things, and better clinical 17:08:17 10 means being aware that you need to look at the individual 17:08:21 11 patient and adjust the dose so that they get the maximum 17:08:24 12 benefit and the least side effects. I think that's fair. 17:08:27 13 Q. When you wrote, "The clinician can then judge whether the 17:08:31 14 cause is the illness, the environment or the treatment," were 17:08:34 15 you trying to alert physicians to the notion they could be 17:08:41 16 giving a treatment that could be the cause actually of 17:08:44 17 suicidality or aggression? Either you were or you were not 17:08:47 18 trying to alert them. Which was it? 17:08:49 19 A. I thought I responded to that very specifically. Two 17:08:53 20 medications, antipsychotics and akathisia and the maprotiline 17:08:58 21 clearly warranted some thoughtfulness on the part of the 17:09:01 22 clinicians using it. 17:09:03 23 Q. Would you agree with me, Dr. Mann, that when we look at a 17:09:08 24 scientific article, one way to kind of get the gist of the 17:09:11 25 article is to look at the very first thing and the very last 1606 17:09:14 1 thing so we kind of know where the author is coming from? 17:09:21 2 A. No. 17:09:22 3 Q. You would not agree with that? 17:09:24 4 A. No, I certainly wouldn't agree with that. Scientific 17:09:27 5 articles are not an article that appears in the newspaper 17:09:31 6 with a big headline so you read the headline and you know 17:09:35 7 what's in it. Often most of the important information is on 17:09:39 8 page 2. 17:09:40 9 Q. Why do you highlight information at the beginning or at 17:09:42 10 the end of an article? Isn't it to catch the reader's 17:09:46 11 attention, to give them a wake-up call, as you say? 17:09:50 12 A. So in this article you've got a whole half page devoted to 17:09:53 13 implications for the clinician. To look at one or two 17:09:57 14 aspects of those implications without reading the whole 17:10:02 15 article I think is a poor way to read a scientific article. 17:10:05 16 Maybe it is good for a magazine, but that's not how we 17:10:08 17 practice scientific medicine. 17:10:14 18 Q. Let's look at what you started the article with, okay? 17:10:17 19 Back on the first page of it, "Making the cure" -- "From 17:11:00 20 making the cure of a disease more grievance than its 17:11:00 21 endurance, good Lord deliver us." Sir Robert Hutchinson, who 17:11:00 22 was he? 17:11:00 23 A. He was a great physician of yesteryear. 17:11:00 24 Q. The purpose of putting that quote in italics at the 17:11:00 25 beginning of the article is to tell the reader that is going 1607 17:11:00 1 to be reading this -- to get your attention that you could be 17:11:00 2 giving a treatment that is causing a problem; isn't that 17:11:00 3 true? 17:11:00 4 A. That's not correct. The goal of putting this quotation at 17:11:03 5 the beginning of this article is precisely because physicians 17:11:05 6 are always aware that when you give medication, you want to 17:11:09 7 do more good than harm. That's the whole goal of treatment, 17:11:12 8 and hopefully want to do a lot more good and very little 17:11:16 9 harm. 17:11:17 10 And it goes on in the very opening line of this 17:11:22 11 article to describe the motivation for what follows which is 17:11:27 12 "It has recently been suggested that a selective serotonin 17:11:32 13 reuptake inhibitor, fluoxetine," that's Prozac, "may trigger 17:11:38 14 suicidal ideation or acts in patients receiving this drug for 17:11:42 15 the treatment of depression." 17:11:43 16 And it goes on to say this hypothesized association 17:11:46 17 is surprising, et cetera, et cetera, because there's a huge 17:11:49 18 amount of biological data that suggests it is the exact 17:11:52 19 opposite effect of what we think should happen. 17:11:55 20 And then it goes on to analyze most of the literature 17:11:59 21 that was all we could find at that time to see whether the 17:12:04 22 answer is it does do it or it doesn't do it. 17:12:07 23 If you go to the very end of the article, you find 17:12:10 24 that the conclusions are that you cannot see this kind of 17:12:17 25 association between SSRIs and suicidality, but there are two 1608 17:12:22 1 other classes of medications that may have some potential and 17:12:25 2 we need to bear that in mind when we're treating our 17:12:27 3 patients. 17:12:28 4 Q. What does the word "iatrogenic" mean? 17:12:34 5 A. Iatrogenic is a technical term referring to the possible 17:12:41 6 causation of illness by a medical treatment. 17:12:45 7 Q. So if a doctor gave a drug and the drug caused some side 17:12:49 8 effect, then that would be an iatrogenic illness? 17:12:59 9 A. Absolutely not. 17:12:59 10 Q. It is not? 17:12:59 11 A. No. 17:12:59 12 Q. I thought iatrogenic was something from the cure. 17:13:03 13 A. Side effects are not illnesses. 17:13:05 14 Q. Would that be an iatrogenic adverse experience? 17:13:09 15 A. A better example -- no, I don't agree. I think the term 17:13:13 16 is used -- it fits better -- let's say you have cancer and 17:13:17 17 most of the cancer drugs that we have it is a balance between 17:13:22 18 how much they're killing you and how much they're killing the 17:13:25 19 cancer because they essentially work on tissues that 17:13:28 20 multiply. So we try to choose and use drugs in doses and in 17:13:32 21 ways so that they do more harm to the cancer than they do to 17:13:36 22 the patient. 17:13:37 23 But every now and then the cancer -- the anticancer 17:13:41 24 drug will shut down people's bone marrow because bone marrow 17:13:45 25 is making a lot of cells and it is very vulnerable. I guess 1609 17:13:49 1 if your bone marrow shuts down you've got an iatrogenic 17:13:53 2 illness. 17:13:54 3 Q. Iatrogenic is something that is precipitated by the cure 17:13:58 4 or attempted cure, isn't it, by the treatment? 17:14:02 5 A. Yes, in this case the bone marrow would shut down because 17:14:06 6 people were getting medication for their cancer. 17:14:08 7 Q. And do you recall when I have taken your deposition on two 17:14:13 8 occasions and I asked about this statement from Sir Robert 17:14:17 9 Hutchinson here that you indeed told me that was there 17:14:20 10 because you wanted to participate in a debate, a scientific 17:14:25 11 dialogue about iatrogenic phenomenon? 17:14:30 12 A. I don't recall using that language. 17:14:32 13 Q. All right. I will dig it out at the appropriate time and 17:14:35 14 show it to you. 17:14:36 15 Now, you did say that sometimes the most important 17:14:38 16 information is not in the first or the end, so let's look at 17:14:42 17 page 3 of this article, if we may. "Selective serotonin 17:15:02 18 reuptake inhibitors and effects on suicidality," big capital 17:15:08 19 letters here, why would you write about the selective 17:15:11 20 serotonin reuptake inhibitors as a class in conjunction with 17:15:15 21 suicidality if that's just a completely scientifically 17:15:19 22 irresponsible thing to do? 17:15:26 23 A. That would be a mystery if that were the case, I agree. 17:15:31 24 Q. And you have written about them as a class, haven't you, 17:15:34 25 on this issue? 1610 17:15:37 1 A. One way of classifying medications is to look at 17:15:43 2 particular properties -- a particular property they may have 17:15:46 3 in common. As I testified at some length earlier today, 17:15:52 4 selective serotonin reuptake inhibitors have in common that 17:15:56 5 they're SSRIs, but they differ in structure, in the rate of 17:16:02 6 metabolism, the activity of metabolites, et cetera, et 17:16:07 7 cetera. 17:16:08 8 Q. Can you tell us what is the neurological pathway for 17:16:12 9 Guillain-Barre Syndrome? 17:16:22 10 A. It happens to be a unique effect of this one drug, 17:16:25 11 zimelidine, on the brain. 17:16:27 12 Q. Is it caused by virtue of the inhibition of serotonin 17:16:30 13 reuptake? 17:16:32 14 A. It is not. 17:16:33 15 Q. What is it caused by? What neurotransmitter system caused 17:16:37 16 Guillain-Barre Syndrome? 17:16:40 17 A. It is not related to a specific neurotransmitter system 17:16:44 18 effect like serotonin reuptake inhibition. 17:16:48 19 Q. Okay. But you're trying to create the impression with the 17:16:51 20 jury when you said, well, zimelidine -- it is not fair to 17:16:56 21 talk about Paxil and Prozac together because there's this 17:16:59 22 drug zimelidine and it causes something that none of the 17:17:03 23 others cause. What it causes is Guillain-Barre Syndrome, 17:17:08 24 isn't it? 17:17:09 25 A. That's exactly my point, that just because drugs share a 1611 17:17:14 1 common property like serotonin reuptake inhibition doesn't 17:17:18 2 mean that they share other properties. 17:17:22 3 Q. Right. But the Guillain-Barre Syndrome doesn't have 17:17:29 4 anything to do with the reuptake of serotonin, does it? 17:17:33 5 A. That's my point. 17:17:34 6 Q. And mine as well. When you have postulated as to how it 17:17:38 7 is that SSRI drugs as a class may or may not affect 17:17:42 8 suicidality, you have talked about the effects on the 17:17:46 9 serotonin system, haven't you? 17:17:49 10 A. That's correct. And the reason for that is that it is 17:17:52 11 paradoxical to postulate that enhancement of the serotonin 17:17:57 12 system should make suicidality worse when the hypothesis 17:18:02 13 that the biology findings in the brain suggest is that 17:18:07 14 serotonin-enhancing drugs should reduce the risk of 17:18:10 15 suicidality and, in fact, that's consistent with the results 17:18:14 16 from the double-blind placebo-controlled trials. 17:18:17 17 MR. VICKERY: If I may approach, Your Honor. 17:18:19 18 THE COURT: You may. 17:18:22 19 Q. (BY MR. VICKERY) I'm going to show you from your 17:18:24 20 deposition in the Miller case that Mr. Fitzgerald was kind 17:18:29 21 enough to find for me -- you see what date it was taken? 17:18:37 22 A. March 20th, 2000. 17:18:37 23 Q. Okay. Now, why don't we just do this? On page 73, 17:18:39 24 beginning on line 6, we're talking about this quote from Sir 17:18:42 25 Robert Hutchinson. And I'll read the questions I was asking 1612 17:18:46 1 you, then if you would be so kind as to just read the answer 17:18:50 2 that you gave. 17:18:53 3 "Did you think that he chose an appropriate quote?" 17:18:56 4 A. "I thought it of some doubt the debate that was ongoing 17:19:01 5 in the medical world at the time." 17:19:02 6 Q. "Would you read the quote for me, please?" 17:19:05 7 A. "From making the cure of the disease more grievance than 17:19:08 8 its endurance, good Lord help us." 17:19:11 9 Q. "Does that quote refer to a phenomenon that physicians 17:19:14 10 sometimes call iatrogenic?" 17:19:16 11 A. "Yes." 17:19:18 12 Q. "Want to read on?" 17:19:19 13 A. "Sure. We pronounce it a little differently." 17:19:21 14 Q. "How do you pronounce it?" 17:19:22 15 A. "Well, now you've got it right." 17:19:24 16 Q. "You taught me how to say it, didn't you? 17:19:28 17 "And what is an iatrogenic illness?" 17:19:35 18 Right there, line 21, what did you tell me? 17:19:37 19 A. We skipped a couple of lines. "That's an illness produced 17:19:40 20 by the treatment." 17:19:42 21 Q. So now do you acknowledge that under oath a year ago when 17:19:51 22 I asked about Sir Robert Hutchinson's quote that it was in 17:19:55 23 because it related to an iatrogenic phenomenon? 17:19:59 24 A. I think I said to you in that deposition exactly what I've 17:20:02 25 said here today. 1613 17:20:03 1 Q. Well, we will let these folks decide that, okay? 17:20:06 2 A. Okay. 17:20:07 3 Q. Now, let us move on to something else. 17:20:10 4 We were talking about your writings in 1991, '92 and 17:20:16 5 '93 on behalf of the small, vulnerable minority or 17:20:21 6 subpopulation of patients and we've looked at one of them, 17:20:24 7 correct, the '91 Mann and Kapur article. Let's look at the 17:20:29 8 ACNP paper. Can you find that provision? 17:21:09 9 MR. VICKERY: I believe it is 245, Your Honor. 17:21:14 10 Q. (BY MR. VICKERY) Once again, it is at the very end, isn't 17:21:16 11 it? 17:21:16 12 A. What is at the very end? 17:21:17 13 Q. Your discussion about the small, vulnerable subpopulation 17:21:21 14 of patients at risk. 17:21:42 15 Dr. Mann, let's be blunt about it. After my opening 17:21:42 16 statement in my case these lawyers told you I said lots of 17:21:42 17 things about your writings about small, vulnerable 17:21:42 18 subpopulation, didn't they? 17:21:43 19 A. I haven't had lots of conversation with these lawyers 17:21:45 20 since you made your opening statement, but -- 17:21:48 21 Q. Did they tell you that I referenced your writing about a 17:21:51 22 small, vulnerable subpopulation in my opening statement? 17:21:55 23 A. Yes, I did hear that you made quite a number of references 17:21:57 24 to my writing. I'm happy to discuss that. 17:22:01 25 Q. Let's read if we may -- just start right there where it 1614 17:22:05 1 says, "Side effects such as akathisia..." 17:22:13 2 Would you prefer I read it or would you like to? 17:22:17 3 A. I don't mind. You can read it. 17:22:20 4 Q. "Side effects such as akathisia may be associated with a 17:22:23 5 worsening psychiatric state. Patients should be warned that 17:22:27 6 suicidal ideation may occasionally worsen in the course of 17:22:30 7 treatment, as may overall depression, and that such an event 17:22:34 8 would be a reason for immediately contacting their doctor. 17:22:37 9 "Applying this standard clinical practice to all 17:22:40 10 patients would constitute a reasonable safeguard in the event 17:22:43 11 that there are, indeed, a small minority of vulnerable 17:22:47 12 patients who are at risk for emergent suicidal ideation. It 17:22:53 13 should be recognized that such emergent suicidal ideation may 17:22:57 14 be the consequence of the patient's illness, adverse changes 17:23:00 15 in the life situation, or perhaps, in a few cases, because of 17:23:04 16 an adverse effect of the antidepressant." 17:23:10 17 When you wrote this on behalf of the ACNP in 1992, 17:23:15 18 you were concerned about the small, vulnerable subpopulation 17:23:19 19 of patients for whom the suicidal ideation could be caused as 17:23:25 20 an adverse effect of the antidepressant, weren't you, sir? 17:23:30 21 A. I would make the same response as I did with the previous 17:23:33 22 article. You can't really understand this paragraph until 17:23:37 23 you read paragraph number 3 which is immediately above it. 17:23:43 24 Q. Let's do that because there's a point I wanted to bring 17:23:47 25 out about that. Why don't you read paragraph 3 for us? 1615 17:23:58 1 A. "There is no evidence that antidepressants such as the 17:24:02 2 selective serotonin reuptake inhibitors, for example, 17:24:05 3 fluoxetine, trigger emergent suicidal ideation over and above 17:24:09 4 the rates that may be associated with depression and other 17:24:12 5 antidepressants." 17:24:13 6 Q. Let me stop you right there. You're a scientific man and 17:24:17 7 a man that chooses his words very precisely; isn't that true, 17:24:26 8 sir? 17:24:26 9 A. Try to. 17:24:26 10 Q. And you did not write, "There's no evidence that 17:24:26 11 antidepressants such as the selective serotonin reuptake 17:24:29 12 inhibitors, for example, fluoxetine, trigger emergent 17:24:34 13 suicidal ideation"? You said there's no evidence they 17:24:39 14 trigger it over and above the rates that may be associated 17:24:41 15 with depression and other antidepressants, true, sir? 17:24:46 16 A. It amounts to the same thing. Do you want me to explain? 17:24:51 17 Q. No, sir, I don't. I'm sure that if counsel wants you to, 17:24:55 18 they will ask you to in their redirect. 17:24:58 19 Every time you have written about this, you have used 17:25:01 20 the phrase "over and above"; isn't that true? 17:25:08 21 A. I couldn't be that dogmatic. 17:25:10 22 Q. Isn't the reason you've used that phrase is because you 17:25:14 23 recognize that there is a small, vulnerable subpopulation of 17:25:17 24 people who get caught in the wash because these drugs do help 17:25:22 25 suicide for some people? Isn't that why you've used that 1616 17:25:28 1 phrase "over and above," Dr. Mann? 17:25:31 2 A. This is a scientific way of stating unequivocally that 17:25:36 3 there's a lot of suicidality associated with depression. 17:25:39 4 We've talked about this quite a number of times. And if you 17:25:43 5 give a patient an SSRI, you are going to reduce their 17:25:50 6 suicidality. If they don't have it when you start treatment, 17:25:54 7 they have less chance of developing it. If they have it when 17:25:56 8 you start treatment it is going to go away and probably 17:25:59 9 faster than with other types of antidepressants. That's the 17:26:03 10 bottom line. It is not complicated. 17:26:06 11 Q. Dr. Mann, was the '92 article the last time that you wrote 17:26:09 12 on behalf of the small, vulnerable subpopulation of patients 17:26:14 13 or did you speak on their behalf one more time? 17:26:21 14 A. I'm not writing articles on behalf of vulnerable 17:26:25 15 populations that are small. I'm writing articles on behalf 17:26:28 16 of a giant, vulnerable population, 11 million people who 17:26:34 17 suffer from depression each year in the United States. 17:26:37 18 Q. Did you subsequent to the ACNP paper in 1992 write again 17:26:43 19 the following year in 1993 trying to caution your colleagues 17:26:48 20 that they needed to be careful when they talked about SSRIs 17:26:52 21 and suicide because there might be a small, vulnerable 17:26:58 22 subpopulation of patients out there? Did you do that? 17:27:02 23 A. It is possible. Which article are you referring to? 17:27:05 24 Q. Do you recall that there was an article on 17:27:10 25 fluoxetine-associated side effects and suicidality in the 1617 17:27:15 1 Journal of Clinical Psychopharmacology in 1993? 17:27:22 2 A. You will have to show me the article. I'm not sure which 17:27:25 3 one you're referring to. 17:27:26 4 Q. Sure. It is by Drs. Morton, Sohn and Lidier at the 17:27:44 5 University of South Carolina. Do you remember them 17:27:49 6 publishing that article? 17:28:09 7 A. Give me a moment while I look at it. 17:28:11 8 Q. I will be glad to. 17:28:12 9 A. I've realized now this isn't an article that I wrote, but 17:28:15 10 I assume you're referring to the response I wrote to this 17:28:18 11 article. 17:28:20 12 Q. That's exactly. You remember it, don't you? Do you 17:28:23 13 remember the response you wrote to that article, sir? 17:28:25 14 A. Not too clearly, but if you've got a copy, I would be 17:28:28 15 happy to refresh my memory. 17:29:29 16 Q. I don't want to rush you, Dr. Mann, but I'm more 17:29:31 17 interested in your response than the article. 17:29:34 18 A. Okay. This is a little difficult because this is a long 17:29:37 19 article with a lot of stuff in it, but what's the question? 17:29:40 20 Q. What these people had done is they had conducted a chart 17:29:43 21 review. The Teicher and Cole article came out. Everybody 17:29:46 22 was talking about whether Prozac causes suicide for some 17:29:49 23 patients and these people went through and looked at their 17:29:52 24 charts and they said, "Gosh, we don't see any evidence that 17:29:57 25 it does. It looks like Prozac is pretty good to us." 1618 17:30:01 1 And you were so upset about them just saying that 17:30:04 2 blithely based on a retrospective review of their charts you 17:30:09 3 sat down and wrote a letter to the editor, didn't you? It is 17:30:13 4 right there on your screen. You want to read it? 17:31:59 5 I will read it for us: "Although our studies and 17:31:59 6 review of the literature indicate that fluoxetine does not 17:31:59 7 appear to have any different risk for emergent suicidal 17:31:59 8 ideation or behavior compared with other types of 17:31:59 9 antidepressant drugs, the study by Morton and colleagues does 17:31:59 10 not contribute very much to the evidence relevant for our 17:31:59 11 conclusion. 17:31:59 12 "Their study is methodologically limited by the use 17:31:59 13 of a chart review method for determining the presence of 17:31:59 14 suicidality in patients seeking treatment of depression. The 17:31:59 15 low rate of suicidality detected by the chart review method 17:31:59 16 raises the question as to its sensitivity. It may therefore 17:31:59 17 be equally insensitive in terms of detecting emergent 17:31:59 18 suicidality during treatment. 17:31:59 19 "This study highlights the need for better controlled 17:31:59 20 research, with the methodology of controlled studies and 17:31:59 21 blind assessment, to determine whether specific 17:31:59 22 antidepressant drugs are associated with emergent suicidality 17:31:59 23 in a subpopulation of depressed patients." 17:31:59 24 Were you concerned about a subpopulation then or a 17:31:59 25 whole bunch of people that aren't going to take Paxil if 1619 17:31:59 1 there's an adequate warning on it for the doctor? 17:31:59 2 A. I think this actually illustrates a very good point. I 17:31:59 3 certainly stand by it. I think the letter makes a critical 17:31:59 4 point because here is a study that says it is not a problem, 17:31:59 5 but it is poorly designed. You cannot rely on this study to 17:32:09 6 say it is safe to use this medication. You've got to go to 17:32:09 7 other types of well-designed studies. 17:32:11 8 I was really in this letter trying to make an appeal 17:32:13 9 to the field to place more reliance on better quality studies 17:32:19 10 and less reliance on case reports. It is true, I do not 17:32:25 11 value case reports terribly highly and these kinds of 17:32:30 12 retrospective chart reviews because you don't know how 17:32:34 13 attentive -- a lot of the people filling out these charts 17:32:38 14 were residents, how attentive they may have been to recording 17:32:41 15 all of the effects that were present in their patients. 17:32:44 16 Q. Now, Dr. Mann, answer me this direct question, if you 17:32:46 17 would, sir. Were you concerned when you wrote that letter to 17:32:49 18 the editor about emergent suicidality in a subpopulation of 17:32:54 19 depressed patients? That one is a yes or no if you would, 17:33:00 20 please, sir. 17:33:01 21 A. I was certainly concerned that the scientific evidence 17:33:04 22 used to address this question, which was very much alive in 17:33:07 23 the medical community at that time, be as good as possible. 17:33:12 24 And I didn't think this was a helpful contribution. 17:33:14 25 Q. Let me try one more time. 1620 17:33:16 1 Were you concerned when you wrote this letter to the 17:33:19 2 editor about a subpopulation of patients who were at risk? 17:33:25 3 A. I was concerned about the whole population, the 17:33:27 4 subpopulation, and their families. 17:33:33 5 Q. What happened since 1993, December of 1993, when this 17:33:35 6 letter to the editor was written? 17:33:41 7 A. Could you be a little more specific? 17:33:44 8 Q. Nowhere that I've been able to find in all of your 200 17:33:48 9 articles since December of 1993 is there anything in which 17:33:53 10 you express any concern for the small, vulnerable minority, 17:34:00 11 the subpopulation of patients, or indeed in which you call 17:34:04 12 for further scientific research and evidence on this very 17:34:07 13 important question of SSRI-induced suicide. 17:34:11 14 Now, maybe I've overlooked it, but can you point me 17:34:14 15 to anything you've written since December of 1993 that says, 17:34:19 16 "We need to study this issue and we particularly need to 17:34:23 17 focus on a subpopulation of patients"? 17:34:27 18 A. I certainly haven't lost interest or deviated in any way 17:34:35 19 from my major concern that we do the very best we can to 17:34:41 20 reduce suicide rates in the U.S. and overseas. And as a 17:34:46 21 matter of fact, I'm sorry to have disappointed you by not 17:34:50 22 having written on this very specific subject in the way you 17:34:53 23 would have liked me to, but I can assure you on two points. 17:34:59 24 I'm in the middle of working on a paper reviewing the 17:35:02 25 U.S. data on this very question all over again, and the 1621 17:35:05 1 results of that review are going to be appearing not only in 17:35:10 2 scientific articles but I have the responsibility of writing 17:35:13 3 the section on the safety of these medications for this 17:35:16 4 Institute of Medicine committee that I described before. 17:35:19 5 Q. Who is funding that effort? 17:35:21 6 A. I think I mentioned that previously. I did mention it 17:35:23 7 previously. It is the Surgeon General's office, it is the 17:35:29 8 Centers for Disease Control, the National Institute of Mental 17:35:33 9 Health, the National Institute of Drug Abuse and the National 17:35:39 10 Institute on Alcoholism and Alcohol Abuse. 17:35:42 11 So there will be an opportunity to read in writing a 17:35:44 12 more thorough and up-to-date-review. I thought in the sort 17:35:51 13 of special -- under the special rules of evidence that apply 17:35:55 14 in a court of law today that I gave the jury a brief summary 17:35:59 15 of a lot of the controlled clinical data that applied 17:36:04 16 particularly to Paxil which is the subject of our discussion 17:36:07 17 indicating that there's now a lot of powerful evidence ruling 17:36:12 18 out this so-called vulnerable minority and ruling in a very 17:36:17 19 clear and profound beneficial effect of Paxil. 17:36:21 20 Q. Well, one of the things you said -- the many articles that 17:36:25 21 you said you would be prepared to discuss here, one of them 17:36:27 22 is an article in 1993 by Dr. Teicher and Nurse Glod and 17:36:36 23 Dr. Jonathan Cole, right? 17:36:36 24 A. Yes. 17:36:36 25 Q. And you have previously testified, as others have, that 1622 17:36:39 1 Jonathan Cole is a pioneer in the field of 17:36:42 2 psychopharmacology, correct? 17:36:44 3 A. He is. 17:36:44 4 Q. A man of incredible reputation and unimpeachable 17:36:50 5 integrity, correct? 17:36:52 6 A. He is certainly a man of unimpeachable integrity, yes. 17:36:57 7 Q. What he wrote in 1993 along with his colleagues is that 17:37:01 8 the real concern was that the risk is being redistributed, 17:37:04 9 that some people are getting better because the drug helps 17:37:08 10 them, but there are others that are getting worse? You 17:37:11 11 recall reading that in his '93 article, don't you? 17:37:16 12 A. I don't recall that specific wording. 17:37:18 13 Q. I'm sure Ms. Hawkins will find it momentarily and I'll 17:37:21 14 show it to you. 17:37:22 15 In December of 1993 when you last wrote on behalf of 17:37:26 16 the small, vulnerable subpopulation, you were in Pittsburgh, 17:37:30 17 right? 17:37:31 18 A. Yes. 17:37:31 19 Q. And then when did you move to New York? 17:37:33 20 A. In '94. 17:37:35 21 Q. '94? Now, since that time you have done work as a 17:37:41 22 consultant and as an expert witness for Phizer with respect 17:37:45 23 to Zoloft, correct? 17:37:50 24 A. That's very recent, as you know, since you're trying the 17:37:55 25 case. 1623 17:37:56 1 Q. A couple of -- you got on a couple years ago in that case, 17:38:01 2 right? 17:38:01 3 A. The deposition was, as you indicated, last -- 2000. 17:38:06 4 Q. Since that time you have signed on with SmithKline Beecham 17:38:09 5 as an expert with them in this case, right? 17:38:12 6 A. That's correct. 17:38:12 7 Q. Now, before that time actually you had been a principal 17:38:15 8 investigator for Eli Lilly, hadn't you? 17:38:19 9 A. When was that? 17:38:21 10 Q. 1988 to 1990. 17:38:24 11 A. I persuaded Eli Lilly to fund a small study that I was 17:38:29 12 doing and that I designed looking at the mechanism of 17:38:32 13 antidepressants, and I was interested in whether the 17:38:35 14 biological mechanism of action of norepinephrine reuptake 17:38:41 15 inhibitors or serotonin reuptake inhibitors was the same or 17:38:46 16 different. I was also looking at the safety of these 17:38:49 17 medications. 17:38:50 18 So I designed a very small study that looked at the 17:38:54 19 biology and they gave me some funding to pay for that study, 17:38:59 20 but it wasn't an efficacy study, it was a mechanism study. I 17:39:04 21 needed a drug that affected only the norepinephrine system 17:39:09 22 and only the serotonin system. 17:39:10 23 And the drug available in the United States, the only 17:39:15 24 one that was marketed it was so selective was Prozac, so I 17:39:18 25 had to do business with them. 1624 17:39:20 1 Q. Since 1993 have you done any other business with Eli 17:39:25 2 Lilly? 17:39:26 3 A. When the original concern arose over whether Prozac 17:39:29 4 potentially caused suicidality, they asked me for my opinion 17:39:34 5 and whether I would provide them with consulting services. I 17:39:38 6 agreed but only on the condition that they didn't pay me 17:39:41 7 because I didn't want anybody to think that my opinion was 17:39:45 8 influenced by payment by a drug company. 17:39:52 9 Q. That was in 1990, right? 17:39:54 10 A. Approximately. 17:39:55 11 Q. How about since 1993? Have you gotten any payments from 17:39:59 12 Eli Lilly since then? 17:40:01 13 A. Not that I'm aware of. As a matter of fact, I have 17:40:16 14 trouble getting money from any drug company. So you can add 17:40:20 15 every other drug company to the Eli Lilly list. 17:40:22 16 Q. I'm going to talk to you in just a minute about your grant 17:40:25 17 monies, okay? 17:40:26 18 A. Very good. 17:40:27 19 Q. We have found the '93 Teicher and Cole article and if you 17:40:35 20 will look at the bottom of the page here with me, you see 17:40:53 21 where they wrote that, "We are particularly concerned with 17:40:56 22 the possibility that antidepressant drugs may redistribute 17:41:00 23 suicidal risk, diminishing it in some patients who respond 17:41:04 24 very favorably to the medication, while possibly enhancing it 17:41:08 25 in other patients who respond more poorly"? Does that 1625 17:41:13 1 refresh your recollection about what Teicher and Cole wrote 17:41:16 2 about in 1993? 17:41:17 3 A. Yes, certainly. 17:41:19 4 Q. Now, this is the same period of time when you're writing 17:41:21 5 the letter to the editor saying, "Hey, you need to have 17:41:25 6 better designed studies, better control studies," right? 17:41:33 7 This is 1993, true? 17:41:41 8 A. I'll take your word for it. I'm looking at a piece of one 17:41:44 9 page. 17:41:44 10 Q. You see where they say, "Very sophisticated studies will 17:41:47 11 need to be conducted to ascertain whether this is true if on 17:41:50 12 balance the antidepressant produces an overall incident rate 17:41:54 13 similar to placebo"? 17:41:57 14 A. Absolutely. And that's precisely what we've been talking 17:42:00 15 about all day. 17:42:01 16 Q. It is hard to tease it out -- tease out the experience of 17:42:04 17 the small, vulnerable subpopulation if it helps more people 17:42:09 18 than it hurts, isn't it? 17:42:16 19 A. It is, but there are ways of addressing that point and I 17:42:25 20 think we've just looked at four types of ways of trying to 17:42:25 21 get at that and said studies that have all endeavored to look 17:42:27 22 at that, particularly related to Paxil, and they've all been 17:42:30 23 able to show that Paxil doesn't do harm but it does good. 17:42:34 24 Q. Now, Dr. Mann, since you mentioned your research grants 17:42:38 25 why don't we have our discussion about those right now. 1626 17:42:41 1 A. Sure. 17:42:45 2 Q. Information about your research grants, who they come from 17:42:48 3 and how much money is funded, is something that you share on 17:42:52 4 your curriculum vita, your CV, true? 17:42:57 5 A. Yes. 17:42:57 6 Q. And we've looked at it just straight from your CV from 17:43:02 7 1990 or '91 to the present, and it looks like the total 17:43:07 8 amount of grants was 31,520,124. Does that sound about 17:43:15 9 right? 17:43:15 10 A. I've never added it up. 17:43:20 11 Q. Sound like the right ballpark, over $30 million? 17:43:25 12 A. It is possible. 17:43:25 13 Q. And is that one of the important ways whereby you as a 17:43:29 14 person in academic medicine maintain an income that's 17:43:34 15 compatible with your colleagues and contemporaries like 17:43:39 16 Dr. Wheadon that work in industry? 17:43:42 17 A. These grants -- and I want to be very, very clear about 17:43:46 18 this because I want to be sure I understand your question -- 17:43:49 19 have nothing to do with my salary. 17:45:09 20 Q. Did anyone tell you that Dr. Wheadon testified last week 17:45:09 21 that the way that guys like you could make as much money as 17:45:09 22 guys like him make is by going out and getting grants that 17:45:09 23 would help pay your salary? 17:45:09 24 MR. PREUSS: Objection, that's mischaracterizing 17:45:09 25 Dr. Wheadon's testimony. 1627 17:45:09 1 THE COURT: Why don't you rephrase the question? I'm 17:45:09 2 not sure he testified like that. 17:45:09 3 MR. VICKERY: I'm sure he didn't use those words, 17:45:09 4 Judge. 17:45:09 5 Q. (BY MR. VICKERY) Let me ask it to you real straight up, 17:45:09 6 Dr. Mann. Did anyone suggest to you after 1993 that if you 17:45:09 7 kept crying out in the published literature to have refined 17:45:09 8 studies that would figure out whether the SSRI drugs really 17:45:09 9 posed a risk for a small, vulnerable subpopulation of 17:45:09 10 patients, that some of your grant funding may dry up? 17:45:09 11 A. It is an excellent question, given the situation we're 17:45:09 12 discussing. 17:45:09 13 The answer is nobody told me to stop writing. If 17:45:09 14 anybody told me to stop writing the stuff, it would have no 17:45:09 15 effect. My grants are almost entirely from the federal 17:45:09 16 government and they have no financial interest in the 17:45:15 17 situation. And my salary is completely unrelated to the 17:45:15 18 grants. It is set by the hospital and the university 17:45:18 19 according to guidelines that have nothing to do with the 17:45:22 20 amount of grant money I'm bringing in. 17:45:25 21 Q. Why do you list it on your CV then? 17:45:27 22 A. It is pretty simple. The university has a very set format 17:45:33 23 for CVs. They tell you what to list and how to list it. One 17:46:20 24 of the things they require you to list on the CV -- this is 17:46:20 25 Columbia. It might be different at other universities -- are 1628 17:46:20 1 the grants that you've gotten, so I'm listing the grants that 17:46:20 2 I've gotten. 17:46:20 3 Q. You're chairman of the department at Columbia? 17:46:20 4 A. I'm chief of the Department of Neuroscience. 17:46:20 5 Q. You said you were head of another department at an 17:46:20 6 institution, right? 17:46:20 7 A. Well, the chief of the Department of Neuroscience at New 17:46:20 8 York State Psychiatric Institute. 17:46:20 9 Q. Please tell us whether your departments of which you're 17:46:20 10 the chief or chair receive funding or support monies either 17:46:20 11 from SmithKline Beecham or the other SSRI manufacturers. 17:46:24 12 A. Whether other investigators receive money from SmithKline 17:46:24 13 Beecham? 17:46:24 14 Q. Whether your department receives money from SmithKline 17:46:27 15 Beecham. 17:46:27 16 A. Yes, I'm thinking. I'm thinking hard. To the best of my 17:46:36 17 knowledge, right now there is no one in my department getting 17:46:39 18 any grant money from SmithKline Beecham. 17:46:41 19 Q. Well, how about money for things like, you know, for your 17:46:44 20 students, for meals and educational things for students that 17:46:48 21 are in your programs under your tutelage, some of these 150 17:46:52 22 people you mentioned? 17:46:55 23 A. None of them -- I'm not -- those 150 people are all 17:46:59 24 clinicians and researchers. None of them are medical 17:47:02 25 students. 1629 17:47:03 1 Q. Does anyone under your sphere of influence get anything of 17:47:10 2 value from SmithKline Beecham? 17:47:14 3 A. As I said before, not to my knowledge. You're talking to 17:47:17 4 the wrong guy. I don't like meeting with people from drug 17:47:20 5 reps who are giving out free samples. There are no pens and 17:47:24 6 stuff like that lying around on my desk, no clocks, no tennis 17:47:28 7 ball, no golf balls. I'm not into that. I don't go give 17:47:32 8 talks at fancy dinners in fancy restaurants. I'm not into 17:47:36 9 that. I'm too busy. 17:47:39 10 THE COURT: Mr. Vickery, it doesn't appear that we're 17:47:41 11 going to anytime soon finish with this witness since we have 17:47:45 12 redirect, so I think we've held everyone long enough. Maybe 17:47:54 13 we ought to go ahead and quit for the evening. We will do 17:48:04 14 so. 17:48:08 15 Ladies and gentlemen of the jury, we will retire for 17:48:10 16 the evening and the court will resume at 9:00 a.m. tomorrow 17:48:14 17 morning. Once again, please remember the admonition of the 17:48:17 18 Court not to discuss this among yourselves or with anyone 17:48:20 19 else and to, of course, avoid any exposure to media 17:48:25 20 information regarding these matters. 17:48:32 21 There being nothing further, court will stand in 17:48:37 22 recess until 9:00 a.m. tomorrow. 17:48:40 23 (Trial proceedings recessed 17:48:42 24 5:45 p.m., May 31, 2001.) 25 1630 1 C E R T I F I C A T E 2 3 I, JANET DEW-HARRIS, a Registered Professional 4 Reporter, and Federal Certified Realtime Reporter, do hereby 5 certify that I reported by machine shorthand the trial 6 proceedings, Volume VIII, contained herein, and that the 7 foregoing 160 pages constitute a full, true and correct 8 transcript. 9 Dated this 13th day of August, 2001. 10 11 12 JANET DEW-HARRIS Registered Professional Reporter 13 Federal Certified Realtime Reporter 14 15 16 17 18 19 20 21 22 23 24 25