Prozac discovery

A major challenge to the development of new drugs is the discovery of new therapeutic targets. For example, the phenomenal success of fluoxetine (Prozac ) has been due to the fact that it was the first selective serotonin re-uptake inhibitor approved for world market release, combined with its improved adverse drug reaction profile. However, no new classes of antidepressants have emerged in recent years. 

A breakthrough in the treatment of major depression was the discovery of fluoxetine, marketed as Prozac. Fluoxetine has a mechanism of action similar to that of imipramine with an important exception. It is a selective serotonin reuptake inhibitor, an SSRI. This strongly suggests that, in some sense, the symptoms of major depression result from a deficit in serotonin specifically. By inhibiting its reuptake from the synapse, the activity of serotonin is enhanced. Two other important drugs for major depression, sertraline (Zoloft) and paroxetine (Paxil), among several others,... 

Some naturally occurring neurotransmitters may be similar to drugs we use. For example, it is well known that the brain makes its own morphine (i.e., beta endorphin), and its own marijuana (i.e., anandamide). The brain may even make its own antidepressants, it own anxiolytics, and its own hallucinogens. Drugs often mimic the brain s natural neurotransmitters. Often, drugs are discovered prior to the natural neurotransmitter. Thus, we knew about morphine before the discovery of beta-endorphin marijuana before the discovery of cannabinoid receptors and anandamide the benzodiazepines diazepam (Valium) and alprazolam (Xanax) before the discovery of benzodiazepine receptors and the antidepressants amitriptyline (Elavil) and fluoxetine (Prozac) before the discovery of the serotonin transporter site. This un-... 

An unpublished document obtained during discovery in product liability suits against the drug company disclosed that Eli Lilly, the manufacturer of fluoxetine (Prozac), had evaluated the comparative rates of suicide attempts on fluoxetine, amitriptyline, and placebo (the documents are available from http //www.breggin.com). The data were generated during controlled clinical trials conducted for the FDA approval process for Prozac for depression. On the basis of the company s data for controlled clinical trials, patients taking fluoxetine were 12 times more... 

In materials gained through discovery in the Wesbecker case, I found in-house documents from Eli Lilly clearly demonstrating an increased rate of suicide attempts in Prozac patients compared to placebo and to tricyclic antidepressants (Breggin, 1994 available on http //www.breggin. com). This was a shocking discovery as Eli Lilly claimed, and continues to claim, that no such data exist. 

Princeton University, have shown that chronic treatment with Prozac (fluoxetine) causes new neurons to be born in the hippocampus, a region important for memory formation. This discovery is fascinating because it implies that depression may be caused by decreases in neuronal birth. 

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