COVER

Questioning Prozac

MARK NICHOLS May 23 1994
COVER

Questioning Prozac

MARK NICHOLS May 23 1994

Questioning Prozac

COVER

MARK NICHOLS

With more than 11 million mostly satisfied customers around the globe, it is one of the most rapidly successful drugs in history. An antidote to clinical depression, the green-and-yellow capsule, introduced six years ago, has also been extolled by some enthusiasts as just the thing to help frazzled parents cope with their kids or to make chronic loners stop fearing rejection. Prozac—brand name for the chemical fluoxetine hydrochloride—has entered pop culture, as well, becoming the stuff of cartoons and stand-up comedy routines. And it has summoned the vision of an era of so-called cosmetic psychopharmacology, in which a society of pill-poppers, seeking relief from everything from shyness to fear of crowds, will have to look no further than the nearest medicine cabinet. That day may yet come. But it raises serious medical and philosophical questions—and the first wave of them is descending upon Prozac itself. Is Prozac—non-addictive and, according to some doctors, capable of transforming personalities for the better—a nearly perfect pill? Well, not quite.

There are some problems. Many medical experts worry that some doctors may be overprescribing Prozac and using it to treat relatively trivial personality disorders. As a result, far too many people—including some of the estimated 200,000 Canadians currently taking Prozac—may be using a drug whose long-term effects might not be known for decades. As well, there have been reports—contradicted by manufacturer Eli Lilly and Co. of Indianapolis and U.S. health officials—suggesting that a small number of Prozac patients may become violent or prone to suicidal thinking. Even more worrisome, Dr. Lome Brandes, a Winnipeg cancer researcher, claims to have evidence that Prozac and some other widely used drugs may promote

the growth of cancerous tumors. “I’m very concerned about Prozac,” says Brandes, who reported in 1992 that rats and mice with artificially induced cancer showed an increased rate of tumor growth when they were given Prozac and another antidepressant. Brandes’s findings alarmed some cancer researchers and prompted federal scientists to launch a similar study (page 40).

And although Prozac has fewer side-effects than earlier antidepressants, it does have some. Users may experience nausea, nervousness and insomnia and their sex life can suffer: a U.S. study, published in The Journal of Clinical Psychiatry in April, found that among 160 patients taking Prozac, 54 reported that sexual desire or response diminished after they began using the drug. And even proponents wonder about the social implications of a medicine that promises to abolish angst—what would happen to the world’s art and culture if future Vincent van Goghs and F. Scott Fitzgeralds were prescribed Prozac? Peter D. Kramer, a psychiatrist from Providence, R.I., who paints a largely favorable portrait of the pill in his best-selling book Listening to Prozac, allows: ‘We cannot escape entirely the fear that a drug that makes people optimistic and confident will rob them of the morally beneficial effects of melancholy and angst.”

In defence of Prozac, which grossed $1.7 billion in worldwide sales last year, Eli Lilly officials say that it is one of the most thoroughly tested medications in history: more than 32,000 people took part in Prozac’s clinical trials, and scientists have conducted at least 3,000 separate studies. “Nothing alarming has shown up,” says Cameron Battley, corporate affairs manager for Eli Lilly Canada Inc. in Scarborough, Ont. Battley also insists that, despite reports of the drug being used to treat people who do not really need an antidepressant, “there is absolutely no indication of any inappropriate use of Prozac in Canada.” Maybe, but there are signs that Eli Lilly suspects something is amiss. In an advertisement that began appearing recently in North American medical publications, the company deplores the “unprecedented amount of media attention” given to Prozac and stresses that the drug is intended for use “only where a clear medical need exists.”

Are too many people popping a pill to treat clinical depression?

While there are concerns about Prozac, there is also unstinting praise from doctors and patients for an antidepressant that has made it easier to treat a debilitating illness. The side-effects of older antidepressantsincluding a parched mouth, difficulty urinating and feelings of psychological detachment—made them hard to take. “There were serious problems involved in getting patients to tolerate those drugs in therapeutic doses,” says Dr. James Brooks, a Toronto general practitioner. ‘With Prozac, you don’t have this. I’m really pleased with Prozac.”

Many patients are equally enthusiastic. Three years ago, William Pringle, Vancouver special events organizer, was flattened by a major depression. His doctor

put him on Prozac. “I fell into this dark pit” says Pringle. “Prozac pulled me out and got me relaunched on my life.” Pringle, 36, stopped using Prozac a year ago and says that he is still feeling fine. Maria Theresa Spagnuolo of Toronto began taking it in 1989, after three automobile accidents left her with chronic pain throughout her body—and serious depression. Married and the mother of a young son, Spagnuolo found that she “was crying about everything—spilled milk was a catastrophe.” Prozac, adds the 38-year-old Spagnuolo, “gave me energy and changed my outlook so that I can cope with life. I don’t think I could function without it”

Interestingly, many doctors report that the majority of their Prozac patients are women. William Ashdown, a Prozac user who is executive director of the Winnipeg-based Society for Depression and Manic-Depression of Manitoba, says that “it is more acceptable for a woman to seek help for an emotional disorder. Most men are culturally pressured into other avenues of self-medication, alcohol being a common one.”

Spurred by Prozac’s success, competing drug companies have begun producing similar antidepressants, including Paxil (made by Britain’s SmithKline Beecham PLC) and Zoloft (by New York Citybased Pfizer Inc.). All the drugs tinker with the same delicate mechanism—the brain’s chemical communication system. Over the past decade, scientists have made important strides in understanding how the brain works—and how to affect the intricate chemical activity that makes some people chipper and outgoing while leaving others habitually despondent. Among the key determinants are a group of chemicals known as neurotransmitters— they include serotonin, dopamine and norepinephrine—that help to flash signals among the brain’s 50 billion cells. Discharged by one cell, the neurotransmitters lock onto the receptors of neighboring cells. In this chemical interplay, serotonin plays a powerful role in modifying mood and emotion—but some people apparently don’t have enough of it.

To remedy that, Prozac and similar drugs—known collectively by scientists as selective serotonin re-uptake inhibitors (SSRIs)—

prevent brain cells from reabsorbing used serotonin. That leaves a pool of serotonin available for further use, which can lighten the mood and thinking of depressed people. Rose Rancourt, a 42-year-old Vancouverite, began using Paxil last fall after battling severe depressions from the age of 16. A former computer information systems supervisor, Rancourt now devotes herself to working with other depressed people. Thanks to Paxil, she says, “I feel good. I feel fine. I have peace of mind.”

Despite its success in blazing the way for other SSRIs, Prozac has been embroiled in controversy almost from the start. After taking about 15 years to develop the drug, Eli Lilly began marketing Prozac in the United States in 1988 and in Canada the following year. Then, in February, 1990, Dr. Martin Teicher, a psychiatrist at the highly regarded McLean Hospital in Belmont, Mass., and two of his colleagues reported that six depressed patients began to have suicidal thoughts after using Prozac. Writing in The American Journal of Psychiatry, Teicher said that when they began taking the drug, none of the patients were suicidal and all were “hopeful and optimistic” about their treatment. After that, a spate of anecdotal reports told of violence and suicide among Prozac users. And the drug acquired a tenacious enemy in the Los Angeles-based Citizens Commission on Human Rights, which has ties to the Church of Scientology, a movement that, among other things, opposes some aspects of psychiatry and drug therapy.

The Scientologists claim that by Sept. 16,1993, no fewer than 1,089 suicides had been recorded among patients taking the capsule. If that figure is correct, it works out to about .01 per cent of the 11 million people who have used the drug. Eli Lilly’s Battley denies that Prozac is to blame. “Sadly,” he added, “it is impossible to eradicate the possibility of depressed people committing suicide, even if they are receiving medication.” Hearings by the U.S. Food and Drug Administration exonerated Prozac, but the bad publicity cut into its sales and produced a flood of lawsuits against Eli Lilly. So far, U.S. courts have rejected 80 claims against the company, many alleging that Prozac caused violent or suicidal tendencies; another 170 lawsuits are pending. In Canada, five lawsuits—at least one involving violence—are pending against the company.

Prozac weathered the bad notices and soon began getting good ones. Kramer’s book, published last year, describes personalities transformed by Prozac and patients made "better than well.” According to Kramer, the effect Prozac will have on a patient can never be accurately predicted. Sometimes, he writes, “you take Prozac to treat a symptom, and it transforms your

sense of self.” The pill seems “to give social

confidence to the habitually timid, to make the sensitive brash, to lend the introvert the social skills of a salesman.”

Boosted by Kramer’s best-seller, Prozac took off in 1993, recording a 15-per-cent increase in North American sales over the previous year—and prompting concern that doctors now may be dispensing the drug too

liberally. In Canada and the United States, Prozac has been approved for use in treating clinical depression, bulimia (habitual purging to lose weight) and obsessive-compulsive disorder (persistent irrational thoughts and actions). But many doctors have effectively expanded the definition of what constitutes clinical depression to include dysthymia— chronic low-grade depression—and in some cases have prescribed Prozac to otherwise healthy patients suffering from low self-esteem or gnawing anxieties. Hubert Van Toi, an associate professor of psychiatry and pharmacology at the University of Toronto, says: “If it’s a question of someone who isn’t feeling so hot, or maybe a man who’s nervous about addressing meetings—that’s not what the drug was designed for.”

As well, some psychiatrists argue that it is dangerous for Prozac or similar drugs to be used without accompanying psychotherapy sessions, which enable doctors to monitor the drug’s effects. Some experts worry that general practitioners, who write the majority of Prozac prescriptions and see scores of patients a day, do not have time to do that. Others argue that far from being overprescribed, the drug has just begun to realize its potential. “In terms of sheer numbers,” author Kramer told Maclean’s, “you could probably double or triple the number of people using antidepressants, because depression is so underdiagnosed.” Adds Kramer: “Prozac is not an enjoyable drug to use. It doesn’t give you a high. With people who have problems but are less than clinically depressed, we would have no compunction about treating them with psychotherapy. So I don’t see why we can’t also treat them with a chemical that will ease their symptoms.”

As compelling as that argument sounds, critics respond by insisting that

any relatively new drug may have unforeseen consequences. Sidney Wolfe, director of the Public Citizen Health Research Group, a Washington-based consumer advocacy organization, compares Prozac to Valium, the popular tranquillizer that was on the market for more than 10 years before doctors discovered its highly addictive properties during the mid-1970s. “Prozac,” declares Wolfe, “has become the Valium of the 1990s.” Asks Dr. David Bakish, associate professor of psychiatry at the University of Ottawa: “Is there a chance that with Prozac some problem could show up in 15 or 20 years? Yes, it could happen.”

Some doctors say they have seen disturbing reactions in Prozac patients. Dr. Shiva Sishta, a Fredericton psychiatrist who prescribes Prozac for people suffering from obsessive-compulsive disorders, says that one married woman who was on a fairly high dosage “became rather promiscuous—she recognized that she was not behaving properly.” Sishta took her off the drug, then resumed it later at a lower dosage with encouraging results. Dr. Randolph Catlin, a psychiatrist who is chief of the mental health service at

Harvard University in Cambridge, Mass., says that “two or three” students he treated with Prozac reported “feeling split off from themselves. They feel as though they’re not there any more.” Adds Catlin: “One wonders if these reports that you hear about people acting aggressively with Prozac might be cases where patients who are out of touch with their feelings act on their impulses, without having any feeling of guilt or concern.”

While controversy swirls around Prozac and the other SSRIs, a new generation of drugs—with an even greater potential for brightening moods and dispelling disruptive emotions—is fast coming of age. Within a few months, New York City’s Bristol-Myers Squibb Co. expects to introduce Serzone, a more finely tuned serotonin-related drug designed to help people with depression and panic disorders while causing even fewer side-effects than the current SSRIs. Effexor, a new drug produced by Philadelphia-based WyethAyerst Laboratories Co. and already on the market in the United States, controls levels of serotonin and norepinephrine to help people suffering from depression; the company claims it has even fewer side-effects than Prozac.

Early in the 21st century, the next stage of drug development may give doctors more sophisticated tools for treating mental illnesses and correcting minor personality disorders— happy pills for every occasion. Because chemical imbalances in the brain are often the result of an inherited defect, says Rémi Quirion, director of the neuroscience division at the Douglas Hospital Research Centre in Montreal, “I think in 10 years’ time we will be able to look at a patient’s genetic background and choose the drug to use accordingly.” Quirion thinks that eventually it will be possible for doctors to administer just the right mix of drugs “to fine-tune the behavior of a given person. We may be able to almost modulate personality.” At that point, says the University of Toronto’s Van Tol, society “will face an ethical question: do we think it’s right to use drugs that change our behavior in a certain direction that we want it to go in? I don’t know the answer.” It is a question that society already has begun to grapple with as it struggles to come to terms with the unanswered questions about Prozac and the dawning of the age of cosmetic psychopharmacology. □