Lilly knew about Prozac-induced suicidality and violence (even before Prozac was approved

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Sun, 27 Nov 2005 20:06:23 -0500

[sSRI-Research] Archive: 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.

 

 

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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.

 

http://ethics.ucsd.edu/seminars/2004/february.htm

 

 

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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. "

 

 

 

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