January 9, 2005
Baum - Hedlund
www.baumhedlundlaw.com
Below is the time-line presented to the jury in the Forsyth v. Eli Lilly Trial. It was presented during closing arguments by the plaintiffs. It lists Lilly's internal documents. The plaintiffs allege that it shows that Lilly knew about Prozac-induced suicidality and violence (even before Prozac was approved for marketing in the United States) and that this was withheld from the public.
1) Aug. 1978 - Team Meeting Minutes - "There have been a fairly large number of reports of adverse reactions . . . Another depressed patient developed psychosis . . . Akathisia and restlessness were reported in some patients." Exhibit 30 (2nd page, end of 2nd paragraph)
2) May 1984 - BGA Comments - "During the treatment with the preparation (Prozac) 16 suicide attempts were made, 2 of these with success. As patients with a risk of suicide were excluded from the studies, it is probable that this high proportion can be attributed to an action of the preparation (Prozac) . . ." Exhibit 42 (page 3, 6th paragraph)
3) Jan. 1985 - Lilly receives reasons why the BGA will reject Lilly registration, one of which was because of "SUICIDAL RISK." With instructions for "IMMEDIATE FOLLOW-UP ON ALL KEY OPINION LEADERS ON THE BGA COMMISSION FOR SELECTED VISITATION NEXT WEEK." Exhibit 53
4) March 29, 1985 - "Benefit/Risk Considerations" - "The incidence rate (suicide) under fluoxetine (Prozac) therefore purely mathematically is 5.6 times higher than under the other active medication imipramine." . . . "The benefits vs. risks considerations for fluoxetine (Prozac) currently does not fall clearly in favor of the benefits. Therefore, it is of the greatest importance that it be determined whether there is a particular subgroup of patients who respond better to fluoxetine (Prozac) than to imipramine, so that the higher incidence of suicide attempts may be tolerable." Exhibit 58 (pages 18 & 22)
5) June 1986 - Draft of Proposed PRECAUTIONS and ADVERSE REACTIONS Sections of the Prozac Package Insert - "Mania and psychosis may be precipitated in susceptible patients by antidepressant therapy." Exhibit 5 (1st page) (never included in actual inserts)
6) Aug. 1989 - Additional Feedback Regarding the Fluoxetine (Prozac) Review by the Commission A (Germany) - "3. The counterindication because of acute suicidality should become a warning whereby the physicians should be advised that in the absence of sedation, the risk of higher suicidality should be taken into account." Exhibit 88
7) Nov. 17, 1989 - Letter to sales representatives on article about Prozac-induced akathisia authored by Dr. Lipinski and others. "In the article the authors voice their suspicion that ‘the triad of symptoms' (anxiety, nervousness, and insomnia) reflects the syndrome of akathisia, ‘which, in their view is apparently related to fluoxetine (Prozac) therapy." But the sales people are warned: "Use of this information in product discussions may violate federal law." Exhibit 91 (1st page, 2nd paragraph and 2nd page, last sentence)
8) Jan. 1990 - PROZAC and SELF-DIRECTED VIOLENCE - "We have just received a pre-print of an article (not a letter to ed.) Which we understand is to appear in the February 1990 AMERICAN JOURNAL OF PSYCHIATRY suggesting that Prozac can induce severe, intense, obsessional suicidal ideation." . . ." Exhibit 94
9) Jan. 30, 1990 - Letter to sales representatives giving the sales people a "heads-up" on the forthcoming Teicher article regarding Prozac and Suicide and instructing them as follows: "Because these issues (suicide) are not part of our current marketing plan, you should not initiate discussions on these articles. ... "Again, because these issues are not part of our current marketing plan, discussions should not be initiated by you." Exhibit 15 (bottom of second page)
10) Feb 1990 - Teicher article published "Emergence of Intense Suicidal Preoccupation During Fluoxetine (PROZAC) Treatment" - "The purpose of this report is to suggest the surprising possibility that fluoxetine (Prozac) may induce suicidal ideation in some patients." . . . "In our experience, this side effect has occurred in 3.5% of patients receiving fluoxetine (Prozac) . . ." Exhibit 95
11) February 7, 1990 - Leigh Thompson Memo - "Anything that happens in the UK (England) can threaten this drug (Prozac) in the US and worldwide. We are now expending enormous efforts fending off attacks because of (1) relationship to murder and (2) inducing suicidal ideation." Exhibit 97
12) February 7, 1990 - Leigh Thompson Memo - "I am concerned about reports I get re UK attitude toward Prozac safety. Leber (FDA) suggested a few minute ago we using CSM database to compare Prozac aggression and suicidal ideation with other antidepressants in UK. Although he is a fan of Prozac and believes a lot of this is garbage, he is clearly a political creature and will have to respond to pressures. I hope Patrick realizes that Lilly can go down the tubes if we lose Prozac and just one event in the UK can cost us that." Exhibit 98
13) June 1990 - Letter to Lilly by concerned doctor - "I am writing to inform Eli Lilly Company that a disturbing number of suicides or suicide attempts associated with Prozac has come to my attention over the last several months." I am concerned that the association with Prozac may be more than coincidental." . . . "There appears to be growing concern that Prozac may somehow trigger a suicidal preoccupation in a small subset of patients and that their families should be warned of this potential risk. It is certainly possible that some of the cases reported are "coincidence" in that the depressed person may have attempted suicide independently of Prozac. However, some of these cases appear to be in patients taking Prozac for reasons other than depression." Exhibit 102 (2nd page)
14) July 18, 1990 - Memo regarding call from Paul Leber at the FDA. "Paul Leber called yesterday; I contacted him at 6:15 am this morning and half-hour conversation, very, very pleasant . . ." "The call was about suicide." . . . "He asked that we FAX nothing to him unless he has agreed before hand." "Paul (Leber) is taking a position in talking with outside folks today that Lilly and FDA working together on the suicide issue and following closely the postmarketing events, but that there are no denominators and the best that can be done is to put a ‘cap' on the number of events." Exhibit 104 (top of 1st page and bottom of 2nd page)
15) August 3, 1990 - Letter to sales representatives regarding reports of suicidal ideation/behavior possibly associated with PROZAC therapy. "This information is not intended to replace our current promotional strategy but is being provided to enable you to respond to physicians when appropriate. You should not initiate discussion on these issues nor use this letter in detailing. However, if asked to comment on these issues by a health care professional, you should: 1. Reassure the health care professional that no casual relationship has been established between suicidal ideation and PROZAC therapy." Exhibit 17 (bottom of 1st page and top of 2nd page)
16) August 31, 1990 - "Dear Doctor" letter assuring them that there is no "causal relationship between Prozac and suicidality (ideation or acts)." Exhibit 22
17) September 12, 1990 - Lilly memo between Max Talbot and Leigh Thompson- Talbot says "One possible strategy if FDA presses for an additional labeling change vis-a-vis suicide is a class-wide (i.e. ALL antidepressants) cautionary note; however we should take this position only as a last resort." Thompson replies: "that report MUST move swiftly through approval and to Dr. Leber's (FDA) hands - - he is our defender." Exhibit 109
18) September 14, 1990 - Lilly memo between John Heiligenstein (Lilly) and Leigh Thompson - Heiligenstein says: "We feel caution should be exercised in a statement that "suicidality and hostile acts in patients taking Prozac reflect the patient's disorder and not a causal relationship to Prozac - - - - Postmarketing reports are increasingly fuzzy and we have assigned ‘Yes, reasonably related' on several reports.". . . "You may want to note that trials were not intended to address issue of suicidality." Exhibit 110
19) September 25, 1990 - Minutes of Lilly Meeting with FDA - discuss doing an in-hospital rechallenge of patients who met predefined criteria for suicidal acts and ideation and agrees to "analyze international data relating to suicide." Exhibit 112
20) October 2, 1990 - Memo to Lilly employee Leigh Thompson to Lilly employee Robert Zerbe regarding an upcoming Prozac symposium in which the issue of suicidality is discussed. "Then the question is what to do with the ‘big' numbers on suicidality. If the report numbers are shown next to those for nausea, they seem small." Exhibit 113 (2nd page.)
21) November 7, 1990 - Leigh Thompson memo - "I'd suggest that priorities are: (1) protect Prozac" . . . Exhibit 116
22) November 13, 1990 - Memo from Claude Bouchy (Lilly Germany) to Leigh Thompson Re: Adverse Drug Event Reporting - Suicide Fluoxetine - In response to Lilly's request that he (Bouchy) change the event "suicidal ideation" to "depression," Bouchy writes: "Hans (another Lilly employee in Germany) has medical problems with these directions and I have great concerns about it. I do not think I could explain to the BGA, a judge, to a reporter or even to my family why we would do this especially on the sensitive issue of suicide and suicidal ideation." Exhibit 117
23) November 14, 1990 - Second memo from Claude Bouchy (Lilly Germany) to Leigh Thompson Re: Adverse Drug Event Reporting - Suicide Fluoxetine in which he states: "I personally wonder whether we are really helping the credibility of an excellent ADE system by calling overdose what a physician reports as suicide attempt and by calling depression what a physician is reporting as suicide ideation." Exhibit 118
24) April 15, 1991 - Memo to Leigh Thompson called "Upcoming TV appearance" Section I. "MESSAGE GOALS - Whatever questions you are asked or direction the interview take, the three points we want to establish are: 2. ‘It's in the disease, not the drug.'; Section III ‘If pressed, or as a postscript to the above, then make the point that absolutely no evidence indicates that PROZAC as a cause of such behavior (violence and suicide).', and ‘Prozac defense . . . There is simply no medical or scientific merit to the argument." Exhibit 123
25) April 23, 1991 - Leigh Thompson Memo re 20/20 Show in which he admits that on the issue of suicidality "I did NOT share the European data AT ALL." and "She attacked on us hiding data by dividing up reports by many COSTART terms. She had numbers for suicide, overdose, intentional overdose, unintentional overdose and said they came to 1200 (or 1400) total suicides - - so we went around on OD not necessarily being suicide and COSTART, etc." Exhibit 124 (bottom of 1st page and 4th paragraph of 2nd page)
26) May 15, 1991 - FDA Meeting to Discuss Fluoxetine Rechallenge Protocol - "we agreed to have the rechallenge protocol ready to go by September 1, 1991 Exhibit 125
27) August 1991 - Dr. David Healy's Article "Antidepressant Induced Suicidal Ideation" - "These two cases suggest that the emergence of suicidal ideation on antidepressants cannot always be attributed to a lifting of psychomotor retardation but rather that the ideas may in some instances be produced by antidepressants." Exhibit 126
28) October 29, 1991 - Lilly prepared draft for Dr. Beasley entitled "Suggested Reply Points to Oswald, Healy & Creaney" in which he acknowledges that item 3 of the HAMD is an insensitive measure of suicidality and states:"There was no specific rating scale for akathisia included in the trial designs for the studies reported, so the only source of data would be adverse event reports. Akathisia is a subjective phenomenon and hence would rely on patients volunteering information." Exhibit 130 (2nd page)
29) December 1991 - Dr. Rothschild's Article "Re-exposure to Fluoxetine After Serious Suicide Attempts by Three Patients: The Role of Akathisia" - "This is the first report, to our knowledge, of patients restarted on fluoxetine (Prozac) after a previous suicide attempt during fluoxetine treatment." . . ."When re-exposed to fluoxetine, the patients again developed akathisia and suicidal ideation. The suicidal feelings abated when the akathisia was treated by the discontinuation of the fluoxetine (Prozac) or the addition of propranolol." Exhibit 131 (Cross-examination)
30) January 23, 1992 - Lilly memo regarding upcoming meeting with Taiwanese doctors (Drs. Lu and Ko) to discuss the report on their study results entitled "suicidal attempts and fluoxetine (Prozac) treatment." Exhibit 133
31) April 8, 1992 - Weinstein (Lilly employee) Report - "Mission Accomplished. Professor Lu will not present or publish his fluoxetine (Prozac) vs. maprotiline suicidality data." Exhibit 144
32) March 3, 1993 - Forsyth's deaths
33) 1994 - Dr. David Healy's Article "The Fluoxetine and Suicide Controversy" - Dr. Healy concludes: "In the opinion of this author, the volume of case reports and other studies is sufficient to demonstrate that antidepressants and antipsychotics may induce suicidal ideation in certain individuals under certain conditions." Exhibit 153
34) 1995 - Dr. Jick's Study "Antidepressants and Suicide" - "The results indicate that only fluoxetine (Prozac) has a rate that seems to be substantially higher than that of the other antidepressants." Exhibit 155
35) June 1998 - Dr. Roger Lane's article "SSRI-Induced Extrapyramidal Side-Effects and Akathisia; Implications for Treatment" appears in the Journal of Psychopharmacology. "SSRI-induced akathisia is a relatively rare but is frequently unrecognized when it does occur." . . . "The precise definition of akathisia is a matter of controversy, as is the relative importance of the objective and subjective aspects of the disorder. Is akathisia a movement disorder or an intense and uncomfortable mental state . . ." "It may be less of a question of patients experiencing fluoxetine (Prozac)-induced suicidal ideation, than patients feeling that ‘death is a welcome result' when the acutely discomforting symptoms of akathisia are experienced on top of already distressing disorders."
