Prozac and the BGA - how a killer drug was registered in Germany

The story of the SSRI antidepressants began in the eighties with the new "wonder drug" Prozac. It was aggressively marketed as more effective and safer than the old antidepressants. Prominent people like Woody Allen praised it and books were published telling the readers about its positive effects.
Soon after Prozac was registered in 1987 it was a blockbuster selling like mad. But only a few years later some doctors and scientists reported strange side effects: some patients became violent or suicidal after taking Prozac. One of the first scientific articles was by Teicher (1991). But despite these early reports Prozac was admitted by the regulatory agencies in other countries too. This is well known by now. But what is not known or some people in high places don’t want to hear is that at least in some countries the regulatory agencies had serious doubts right from the beginning. They were not convinced about the efficacy of the drug Prozac and had concerns about the side effects, especially the risk of suicide.
One case in point is Germany and the German regulatory agency, the Bundesgesundheitsamt (or BGA for short). When Eli Lilly applied for registration of Prozac in the early eighties the BGA had doubts about the efficacy of Prozac ( german name: Fluctin) and was concerned about the suicide risk. In a fax from 25th May 1984 to the headquarter in Indianapolis the BGA expressed the following concerns
(see http://www.baumhedlundlaw.com/01.pdf ) :

“…The frequency of side-effects was very high (partly more than 90%) and the side-effects resulted nearly in each study in dropouts. The frequency of side-effects depended on dose, the age and the duration of therapy. Deciding for the clinical significance of side-effects is not only the frequency of their occurrence but also their severity…”

“… In 15-20% of cases side-effects occur, which involve the central nervous system. As most of them resemble the clinical picture of the underlying disease, even from theoretical reasons one has to expect an intensification and not improvement of symptoms…”

“… During the treatment with the preparation 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 in the sense of a deterioration of the clinical condition, which reached its lowest point….

In the summary of the fax, the BGA notes:

“… Considering the benefit and the risk, we think this preparation (Prozac) totally unsuitable for the treatment of depression…”.

In June 1984 the BGA told Eli Lilly which additional data are necessary to decide about the application for registration of Prozac (see: http://www.baumhedlundlaw.com/02.pdf) :

“… As we already explained by our telex to Dr. Zerbe of June 8, 84 we need a careful analysis of suicide and suicide attempts: patient by patient, syptomatology/severity upon entry into the study and week by week until the event occurred, dose of fluoxetine, side-effects, etc.
This is a very serious issue in the opinion of the BGA. It might well be that we will have to recommend concomitant tranquilizer intake for the first 2 or 3 weeks in the package literature…”

Not surprisingly the application for registration was denied by the BGA in 1985. In a letter from Berlin to Eli Lilly in Indianapolis dated 26.02.1985 we can read the reasons (see http://www.baumhedlundlaw.com/04.pdf) :

“… 2. For the drug concerned there is according to their specific profile of adverse effects the justified suspicion, that they have unacceptable damaging effects (§ 25 par. 2 No. 5 AMG).
2.1. The use of the preparation seems objectionable, as the increase in agitation effects occurs earlier than the mood alleviating effect and therefore an increased risk of suicide exist…”

In April 1986 the BGA was still not convinced that Prozac is safe and effective (see: http://www.baumhedlundlaw.com/06.pdf ):

“… Still not resolved is the fact that suicide attempts have been observed more frequently on fluoxetine as compared to imipramine (only epidemiologic data or literature on other antidepressants may help to identify, wether it happened by chance that incidence of suicide attempts was abnormally high on fluoxetine, or abnormally low under comparators)…”


Eli Lilly has written a report in 1986 on all the data on suicide for the BGA (see: http://www.healyprozac.com/Trials/CriticalDocs/badhom030890.htm) and this report was submitted to the BGA in December 1986.

But in 1988 the application for registration of Prozac was rejected a second time by the BGA.

But then mysteriously in 1991 the BGA admitted Prozac for the treatment of depression despite all previous concerns. What has happened? Have critical people at the BGA been intimidated or fired? Or has money been paid to get Prozac registered in Germany?

I have written to our German ministry of health and to the German regulatory agency BfArM about the early doubts of the BGA about Prozac and ask them for an explanation. Why was it approved despite these early health concerns? The ministry has remained silent on that subject and I am still waiting for an answer.

To be continued...