What are the risks?
June 2, 2000 -- For five years, antidepressant drugs have redefined daily life for Carla, a graphic designer in Des Moines, Iowa. They've helped her pry loose from depression so powerful she could barely get out of bed in the morning. They've helped her raise three teenage sons and put an end to her occasional thoughts of suicide.
But such help has come at a price -- a price some doctors are starting to question. Twelve years after Prozac first hit the market, a growing chorus of psychiatrists claims that America is becoming an overmedicated society, reaching for prescriptions at the first sign of mild depression -- and risking potentially dangerous side effects in the process.
Like Carla, one in eight Americans have taken one of the popular new class of antidepressants called selective serotonin reuptake inhibitors, according to an ABC News survey done in April. Better known by the brand names Prozac, Paxil, Zoloft, or Luvox, these drugs are thought to boost brain levels of the chemical serotonin and to quell an array of emotional disorders, from depression to panic to anxiety. Indeed, the drugs are so popular that an estimated 28 million Americans -- one in 10 -- currently use them. To date, over 60 million prescriptions for this class of drug have been written. That's a stunningly high figure considering that the National Mental Health Association estimates that only 19 million Americans suffer from severe depression.
Stephen Crystal, PhD, a Rutgers researcher who studies prescription trends, calls it a "massive uncontrolled experiment," in which doctors are handing their patients prescriptions when they haven't even been diagnosed with a mental disorder in the first place. Equally troubling, the ABC News survey found that nearly half of people on the new antidepressants have taken the drugs for a year or more, even though these drugs haven't been tested for long-term use.
Leading the dissent is Harvard psychiatrist Joseph Glenmullen, MD, author of Prozac Backlash. Glenmullen argues that as many as 75% of patients are on antidepressants for mild -- even trivial -- conditions. For many of these people, he says, the risk-benefit ratio of taking antidepressants is simply unacceptable.
For example, some studies have shown that Prozac and its cousins cause sexual dysfunction in up to 60% of users, though the drug's manufacturer, Eli Lilly and Co., says the rate is less than half that. Glenmullen points to a Spanish study published in the Journal of Sex and Marital Therapy in 1997 as one of the best examples: It examined the effects of Prozac, Paxil, Zoloft, and Luvox in 344 patients and found that 58% experienced sexual dysfunction. Weight gain and tremors are other leading side effects.
Carla is one patient who has struggled to find an antidepressant with few side effects. After her family doctor first prescribed Paxil five years ago, Carla found herself numb to everything around her. "I sure wasn't depressed anymore," she says. "I wasn't sad, I wasn't happy, I wasn't anything." Sex with her husband lost all its appeal. "It's kind of hard to have sex when you have no physical feelings and no emotional feelings."
Alarmed, she went back to her doctor. She next tried Prozac -- that had problems too -- and finally settled on 50 milligrams of Zoloft each day. Never once has she gone to a psychiatrist or psychologist during these five years. Such expense seemed unnecessary; after all, she is taking antidepressants. Lately, though, she wonders. She's starting to feel depressed again, and her once-a-day Zoloft doesn't seem to help much. "My biggest frustration is that I wish I could enjoy sex more," Carla says.
Today, some psychiatrists question whether patients like Carla really need to take antidepressants for years, or whether a dummy pill or therapy alone might work just as well. Several recent studies indicate that many of the beneficial effects attributed to antidepressants can be explained by the "placebo effect" -- the improvement many people experience when they believe they're taking medicine.
In the April issue of the journal Archives of General Psychiatry, researchers analyzed studies of seven new antidepressants, using the Food and Drug Administration's vast database. Their conclusion? The rates of suicide and suicide attempts were just as high among patients treated with antidepressants as for those who took placebos.
"When you look at the reviews, it appears that about six out of 10 patients do achieve some level of benefit. But the issue is, how many of those six are achieving a benefit that they wouldn't achieve with a placebo or some other approach?" asks Roger Greenberg, PhD, a psychologist at SUNY Upstate Medical University at Syracuse and author of From Placebo to Panacea. "I'd say that out of the six, only about two are receiving a unique benefit from antidepressants, and even that is questionable."
Should people who feel better on Prozac shred their prescriptions? Not just yet. This debate is far from settled.
Some leading psychiatrists and mental health advocates are outraged at the views of Glenmullen and other critics. "Patients say to me, 'I feel normal for the first time in my life,' " says Harvey Ruben, MD, a clinical professor of psychiatry at the Yale School of Medicine.
Ruben calls much of Glenmullen's book "pure speculation." Yes, the antidepressants cause side effects in some patients -- every drug does. "For any drug, if you look in the Physician's Desk Reference, there are probably 150 side effects, many of them so severe that you'd probably never take the drug if you read them," he says. "Glenmullen has taken legitimate side effects, which are very rare, and some terrible case histories, and written a book that makes the uninitiated reader believe that these side effects happen to everybody."
Several psychiatrists also dispute the studies that question the clinical effectiveness of antidepressants. "If you look at all of the studies in the world literature, there are no studies in which a placebo is better than an antidepressant," says Columbia psychiatrist Frederic Quitkin, MD. "In 60% to 70% of the studies, the antidepressant performs better than a placebo. It's simply impossible for that to happen by accident."
What about the studies that seem to indicate that placebos work just as well as antidepressants? Quitkin believes that some of these results may be attributable to flaws in the way the studies were designed and conducted. If a study isn't long enough, or uses an inappropriate dose, it may show a drug is less effective than it really is.
Some experts even call Glenmullen's book dangerous because it may discourage depressed people from seeking treatment. "The truth about depression is just the opposite of what the book claims," says Mike Faenza, president of the National Mental Health Association, which receives some funding from Eli Lilly and Co. Depression isn't overdiagnosed, it's underdiagnosed and undertreated, he says, and reports of antidepressants' risks are greatly exaggerated.
Years will likely pass before psychiatrists can accurately answer the question: Are Prozac and similar drugs worth it? In the meantime, even vehement professional rivals agree on some basic advice for patients like Carla. Antidepressants are useful to a great number of people, say both Prozac critic Glenmullen and supporter Ruben. The key for both physician and patient is to be cautious and conservative with these or any drugs.
"Don't start people who don't need the drug," Ruben says. "Start at the lowest dosage and monitor usage carefully. In my office, nobody ever gets an automatic refill. If you have to call and check in, we can monitor your usage. Doctors giving nine months of refills -- that's just negligence, and that's why we try to educate people."
Gina Shaw, a Washington-based medical writer, reports regularly for WebMD.
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