Prozac

/proh"zak/, Pharm., Trademark.

a brand of fluoxetine hydrochloride.

[1988]

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First of the class of antidepressant drugs called selective serotonin reuptake inhibitors (SSRIs), generic name fluoxetine hydrochloride.

Introduced in 1986 as a treatment for clinical depression, Prozac is also used to treat a variety of other psychiatric disorders, including obsessive-compulsive disorder and bulimia nervosa. The drug, taken as a pill, apparently achieves its therapeutic effect by interfering with the reabsorption of the neurotransmitter serotonin within the brain.

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▪ 1995

Introduction

by Richard M. Restak

      Prozac is at once a drug treatment for depression and a bellwether of contemporary attitudes toward the place of psychoactive chemicals in society. Since its introduction in the U.S. in 1987, this drug has revolutionized psychiatry's approach to the management of depression, inspired cover articles in countless newspapers and magazines, and prompted spirited discussions and debates on radio and television talk shows. So popular has Prozac become that many people who take it show no more reluctance to talk about the experience than they would to talk about taking medicines aimed at controlling blood pressure or other traditionally less stigmatizing illnesses.

      Chemically, Prozac belongs to a class of antidepressants referred to as the selective serotonin reuptake inhibitors (SSRIs). Serotonin is one of the brain's neurotransmitters, chemical messengers that convey information from one neuron (nerve cell) to the other. This communication takes place by means of the release of a neurotransmitter from one neuron, the passage of the neurotransmitter across the synapse (the junction between neurons), and the attachment of the neurotransmitter to a specific receptor on the receiving neuron. This match between a neurotransmitter and a specific receptor is often compared to the fit of a key in a lock. Starting in the 1960s, researchers developed a series of antidepressant drugs that altered the dynamics of various neurotransmitters within the synapse. In all instances the drugs acted by increasing the amount of neurotransmitter in the synapse or prolonging its actions.

      For reasons still not fully understood, increased availability of neurotransmitters within the synapse exerts an antidepressant effect on some depressed persons. Not all patients improve on these drugs, however; about 30% of sufferers fail to respond to any antidepressant drugs. The variability of response of different patients to the main classes of antidepressants—the SSRIs, tricyclics, and monoamine oxidase inhibitors—accounts for the large number of such drugs presently on the market.

A different kind of drug.

      Until the advent of Prozac, all of the available antidepressants influenced several neurotransmitters in a general, nonspecific manner. Prozac, synthesized by scientists at Eli Lilly & Co. in 1972 and marketed some 15 years later by Dista Products Co., a division of Eli Lilly, is different from the others in that it influences only the neurotransmitter serotonin. Prozac does not cause the characteristic side effects that made the earlier antidepressant drugs unacceptable to so many patients—dry mouth, blurred vision, daytime sleepiness, constipation, and weight gain, among the most troublesome. Prozac is generally considered safe and free of serious side effects if properly prescribed and monitored by a physician. An alleged association between the drug and an increased incidence of suicide did not hold up under careful scrutiny. Suicide rates are higher among depressed people, treated or otherwise, than among those who are not depressed, and the incidence among patients taking Prozac did not appear to be any greater than that in individuals taking other antidepressants.

      While Prozac has brought relief of symptoms to hundreds of thousands of depressed people, neither it nor any other antidepressant should be considered a "cure" for depression. Rather, as with hypertension, diabetes, or a host of other chronic medical conditions, the tendency toward depression often extends over a lifetime and requires continued or periodic use of a medication such as Prozac that helps control major symptoms. (In 1994 Prozac was also approved for use in obsessive-compulsive disorder.)

      Since no one can be certain what neurochemical factors may turn out to be most important in explaining depression, the development of new classes of antidepressants remains a thriving industry. This should not be surprising. Depression is not a unitary illness with a single cause but the subjective and behavioral expression of varied neurochemical abnormalities. It is likely that different types of depression result from disturbances in different neurotransmitters acting alone or in concert.

Appropriate versus inappropriate uses.

      Recently the use of Prozac and other mood-altering drugs has been expanded beyond their traditional application to definable mental illnesses. Shyness, various forms of social inhibition, and a general feeling of dissatisfaction with one's life have been suggested as appropriate targets for psychopharmacological modification. In what may foreshadow a more liberal use of these agents, in 1994 Prozac (under the trade name Lovan) was under review by the U.S. Food and Drug Administration (FDA) for the treatment of obesity. Since obese persons are not necessarily depressed, some measure of concern seems appropriate in regard to employing a drug for weight loss that is known to exert a powerful influence on mood.

      Many questions have been raised about the use, and potential overuse, of Prozac. What attitude should physicians take when patients request Prozac to relieve irritability, mild reclusiveness, hypersensitivity, or nothing more definable than a lack of contentment with their life and accomplishments? Such uses blur the distinctions between treatment and "personality engineering." And what does it portend when neuroscientists' ability to produce specific brain-altering drugs is far in advance of their understanding of how the brain works?

      Such questions take on a special urgency in light of the favourable response to the drug shown by people afflicted with troubling personality traits (tactlessness, resentfulness, etc.) rather than depression. Indeed, every physician prescribing the drug has one or more stories of individuals "borrowing" some Prozac from a spouse or friend and reporting a generally increased sense of well-being. (Needless to say, such unorthodox uses of drugs do not meet with FDA approval.) Do such individuals represent cases of undiagnosed depression? Or are their experiences a measure of the drug's capacity to establish in those not suffering from an identifiable emotional illness what philosophers and seers have recommended for centuries: the achievement of a sense of detachment coupled with acceptance of the world as it is and one's place in it? Although the latter possibility is initially appealing, the long-term consequences of a chemically oriented approach to the emotions have yet to be carefully weighed. It is possible that the use of Prozac and other similar drugs for anything other than unequivocal depression may carry with it the danger of impairing one of the human species' most precious mental assets: the ability to employ inner feelings, especially the more uncomfortable ones, to stimulate efforts to effect positive changes in oneself and the world.

Richard M. Restak is clinical professor of neurology, George Washington University School of Medicine and Health Sciences, Washington, D.C. He is the author of numerous books, including Receptors (1994) and The Modular Brain (1994).

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▪ drug

      trade name of fluoxetine hydrochloride, first of the class of antidepressant medications called selective serotonin reuptake inhibitors (SSRIs). It was introduced by Eli Lilly pharmaceutical company as a treatment for clinical depression in 1986. Prozac is also used to treat a variety of other psychiatric disorders, including obsessive-compulsive disorder and bulimia nervosa. The drug apparently achieves its therapeutic effect by interfering with the reabsorption of the neurotransmitter serotonin within the brain. Because SSRIs only inhibit the reuptake of serotonin, they have fewer, less-serious side effects than other antidepressants, which interfere with several neurotransmitter systems. Side effects include decreased sexual drive or ability, diarrhea, insomnia, headache, and nausea. The full therapeutic effect of Prozac may not be achieved until the drug has been taken for several weeks. Most physicians prescribe Prozac for at least six months to prevent a patient's symptoms from recurring.

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