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Before I went on antidepressants for four years, I was outspoken and opinionated. I lost all that. I was allowing my life to be mediocre—letting it just evolve around me. I've been off medication for the last ten months, and since then, I've returned to school so I can study law, signed up for dance classes at Arthur Murray, started traveling—even that had slacked off. I've got my drive and heated passion for life back. It's wonderful.
— Tracey Coppotelli, 43

One after another, the e-mails came in. Whether unremitting depression itself was responsible for the memory loss and apathy or whether these cognitive side effects were somehow related to the drugs was devilishly hard to say. But as I dug in, talking to many of the top experts in the field—psychologists, psychiatrists, neurologists, psychopharmacologists, government researchers, academics, and drug company representatives—it became clear that this question was a legitimate one to be asking.

To back up for a moment, it's almost impossible to adequately emphasize how valuable these drugs can be. Often whatever side effects they may produce are a small price to pay for individuals with specific types of recurring psychiatric problems, including clinical depression, anxiety, panic, and bipolar disorders. "The drugs allow people to carry on with their lives," says Peter Kramer, MD, the author of Listening to Prozac and Against Depression. Untreated depression is dangerous. Fifty to 60 percent of individuals who've had one bout of major depression will have another; for those with two episodes, there is an 80 to 90 percent chance of a third. In a recent essay, Kramer wrote, "Research shows depression to be an aggressive, destructive process. A variety of studies suggest that it is linked to progressive damage in the brain … Nor is the brain the only organ at risk. Scientists have found depression to be correlated with heart disease, bone fragility, abnormalities of endocrine glands, and changes in blood elements."

But for some of these patients, antidepressants aren't helpful. According to the largest clinical trial on depression to date, funded by the National Institute of Mental Health (NIMH), only about half of "real world" patients with major depressive disorder had a significant response after taking an antidepressant for 12 to 14 weeks. (About 30 percent achieved full remission, which is in line with other studies, and another 10 to 15 percent found their symptoms reduced by at least half.) An estimated 20 percent of people with major depression fail to improve even with multiple treatments—different medications, therapy—according to various experts, including researchers at Columbia University Medical Center.

Yet the drugs are such an effective and easy solution for milder depression, they're readily prescribed—and sometimes, experts worry, overprescribed. Joseph Glenmullen, MD, a clinical instructor in psychiatry at Harvard Medical School, believes the majority of antidepressants are handed out to people who don't need them—many suffering from distress over a specific event such as divorce, illness, or a death in the family. "Physicians have become so comfortable with using these medications," says William Prey, MD, a San Francisco neuropsychiatrist, "they're prescribing them to treat conditions that would have previously merited a stiff upper lip." As one government expert, Matthew Rudorfer, MD, acting chief of the NIMH's Adult Interventions branch, puts it, "If there is a real condition there that warrants a diagnosis, I wouldn't want to miss it. But a lot of these cases that present for treatment are common problems of everyday living, and we are labeling them as pathology."

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