Healthy Skepticism Library item: 2009

Warning: This library includes all items relevant to health product marketing that we are aware of regardless of quality. Often we do not agree with all or part of the contents.

Publication type: news

Bourguignon R.
Problems with Prozac
1998

Full text:

Prozac (fluoxetine) is a well-known antidepressant drug, marketed worldwide by Eli Lilly & Co, of Indianapolis, USA. In 1997, Prozac sales exceeded $ 2.5 billion, generating one-third of Lilly’s revenues. The patents elapse within a few years from now.

As one of the first SSRIs (selective serotonin reuptake inhibitors), Prozac was generally considered a breakthrough in the treatment of depression, essentially because of its better tolerance profile. Intense marketing has propelled the drug onto the front of the scene. To the public, Prozac has become the “happiness pill” popularised by Peter Kramer’s book “Listening to Prozac” (1993), which spent 21 weeks on the New York Times bestseller list.

According to Lilly, 31,000,000 patients throughout the world have been prescribed Prozac, thus proving Prozac’s safety.

But is Prozac as safe as its manufacturer says? Or is there a hidden face to this success? It would seem so. By 1996, the American FDA had received some 40,000 reports of Prozac-associated adverse reactions, many of them quite serious. As early as the eighties, reports warned of Prozac’s potential dangers. In 1990, Martin Teicher et al, of Harvard Medical School, reported six cases of “intense suicidal preoccupation” in patients who had been prescribed the drug (American Journal of Psychiatry, February 1990). According to the authors, “none of these patients had ever experienced a similar state during treatment with any other psychotropic drug”. This inspired a wave of further reports and controversy in the medical literature.

In September 1991, in spite of many harrowing accounts from “Prozac survivors”, an advisory committee of the FDA cleared Prozac. Yet “suicidal ideation” and “violent behaviours” were added to the label as “reported, but not proven”.

In 1994, David Healy (then consultant to Eli Lilly) published an article entitled “The Fluoxetine and Suicide Controversy, a Review of the Evidence” (CNS Drugs, March 1994) (1) in which he opines that antidepressants, Prozac included, can indeed induce suicidal behaviour in a minority of patients.

Since 1990, an organisation set up by former Prozac users who have suffered adverse events and their relatives, the so-called “Prozac Survivors Support Group (PSSG), has been active to warn patients against the possible side-effects of Prozac.

1994 saw a major milestone in Prozac’s legal history. As the first of some 160 cases filed, The Fentress Case (popularly known as The Wesbecker Case) was tried at Louisville, Kentucky (2). Back in 1989, Jo Wesbecker had killed and wounded several of his coworkers, and thereafter committed suicide, a few weeks after starting a Prozac treatment. By a divided 9 to 3 vote (the smallest possible margin), the jury denied the plaintiffs’ claim against Lilly, but Judge John Potter’s doubts about the proceedings led him to seek to be authorised to carry out further hearings.

Ultimately, the Kentucky Supreme Court granted him the right to do so in early 1997 (3). Thus it came to light that the plaintiffs had reached a secret deal with Lilly. In spite of their original denials, both parties have now admitted the deal, but they are still refusing to divulge the details. An attorney in the know has described the amount involved as one “that boggles the mind” (see for instance John Cornwell, “The Power to Harm”, Viking, 1996) (4).

I was very vaguely aware of this background, when in September 1996 I received a “Dear Doctor” letter from Lilly Benelux cautioning against an article in a French magazine reviewing the above book by Cornwell. This gave me the idea of finding out more about the subject. I sent some 800 questionnaires to Belgian colleagues, asking them if they had ever seen Prozac associated suicidal tendencies, aggressiveness and convulsions in their patients. Eleven doctors reported such cases, but the actual surprise was Lilly’s reaction. Lilly immediately sued me to have the survey stopped and wrote to all Belgian doctors to deter them from responding to the questionnaire.

In January 1997, my findings were published in “The Lancet” (5). The matter was raised in Belgian parliament by Thierry Detienne, MP, who questioned the Minister for Public Health, Marcel Colla. It turned out that his administration had had three reports from doctors concerning Prozac-associated suicidal acts, whereas the manufacturer had not reported any. Colla acknowledged that doctors should be better informed on the subject (6).

In May 1998, a colleague sent me a letter she had received from Lilly following her inquiry about certain side effects (7). In this letter, dated May 11, 1998, Lilly acknowledged that controlled clinical trials had shown depersonalization in one in every one 100 to 1000 patients and that other psychotic effects had been recorded, but the company suggested that these symptoms may well have been caused by the underlying disease rather than by Prozac.

In June 1998, Minister Colla announced in Parliament that he had ordered the Prozac label to be changed to incorporate newly reported side effects (8). This was done under the supervision of the Belgian drugs commission and approved at the end of August (9).

My letter in The Lancet led to a number of reactions, one of them from a former teacher of English and freelance publicist, Frank van Meerendonk, of Oisterwijk, Holland. A former user of Prozac himself, he had begun to look into the matter in the early nineties. In 1994, through the media he began to warm the public in a personal capacity, later he decided to become a director for PSSG, Inc. and to set up a Dutch foundation with the same name. Van Meerendonk claims to have had numerous reactions from Prozac-patients. In 1996, Lilly started a smear campaign against Van Meerendonk shortly before he was to testify in a Prozac-associated murder trial. In a letter to the media, it accused Van Meerendonk and his Dutch Prozac Survivors Support Group of being synonyms of the Scientology Church. Van Meerendonk immediately sued Lilly, asking for rectification of the letter, but to his utter amazement, he lost. Among other things, the judge opined this was a matter of freedom of speech. Several authors support Van Meerendonk in his opinion that Lilly uses the Scientology ruse as an Argumentum ad Hominem to deflect criticism.

In March 1998, I testified in a murder case at an Assizes trial in Belgium (10). A man who had shot his partner in 1995 claimed he had done so because of Prozac. This trial became a national event. Several people testified to their bad experiences with Prozac in the media.

It is quite remarkable that Lilly did not use any scientific arguments to deflect criticism: no new survey was published, although that would have been the best response to public questioning about the safety of the drug.

In 1993, William Forsyth, a retired businessman residing in Maui, Hawaii, stabbed his wife to death, then committed suicide ten days after starting Prozac. His children are suing Lilly, claiming Prozac is to blame for their father’s acts (11). Eli Lilly sought “summary judgement”, but on January 5, 1998, Judge Alan Kay decided there were sufficient grounds for the case to be tried before a federal jury in Honolulu. Having been postponed several times, this trial is now scheduled to take place in March 1999.

In July 1997, I was asked to testify at the Forsyth trial. Besides some other practitioners, also David Healy will act as an expert witness for the plaintiffs (12).

It is my opinion that Prozac can induce psychotic episodes in a small percentage of patients (5-7%), especially those with borderline or manic personalities. In a small minority of these people, psychosis manifests itself by dangerous behaviours such as self-mutilation and suicidal/homicidal ideation and acts. So far, Lilly has refused to conduct (or publish the results of) double-blind studies specifically developed to find out more about these possible side-effects. In my opinion, by refusing to do so, Lilly fails to meet normal standards in health care.

In my opinion Lilly unduly reassures doctors and patients, while neglecting doctors’ and patients’ reports by calling them “anecdotal”. It would appear that Lilly is prepared to go to great lengths to protect Prozac sales. (13).

References:

(1) David Healy, The Fluoxetine and suicide Controversy, a review of the evidence, Adis International Ltd, CNS Drug, 1994
(2) Fentress vs Eli Lilly and Co. (Cir Ct, Jefferson County, Ky) No.90-CI-06033
(3) Potter vs Eli Lilly and Co. (1996 Ky) 926 SW2d 449, 454
(4) John Cornwell, The Power to Harm, Viking, New York 1996
(5) Robert Bourguignon, Dangers of Fluoxetine, in The Lancet, vol. 349, p.214, January 18, 1997
(6) Chambre des représentants de Belgique, 49e législature, SO 1996-1997 GZ, Annales COM, 18 mars 1997
(7) Letter from Lilly Dista, Eli Lilly Benelux, dated May 11, 1998, signed Dr M. Sangeleer and Ph. Vandevelde
(8) Chambre des représentants de Belgique, 49e législature, 22 juin 1997
(9) Notice scientifique de Prozac approuvée par la Chambre pour les médicaments à usage humain, August 24, 1998
(10) Ministère public contre Maurice Hincq, Cour d’assises du Hainaut siégeant à Mons
(11) Forsyth vs Eli Lilly and Co. (DC Haw) Civ No 95-00185
(12) David Healy, Psychiatric opinion of David Healy on the apparent homicide on June Forsyth and on the apparent suicide of William Forsyth, March 1993, May 28, 1997
(13) Robert Bourguignon and Jean-Frédérick Deliège, Le Dossier Prozac, Editions Luc Pire