Lead writer: Walter Armstrong
August 21, 2008

prozac-mood-brightenerAre drugs like Prozac less effective than we think?(DYSTHYMIA.COM)"Antidepressants' Benefits May Be Exaggerated." "Antidepressants Under Scrutiny Over Efficacy." "End of the Prozac Nation?" In early 2008, a pair of studies questioning the track record of antidepressants spawned a rash of headlines like these and led depression patients to wonder if their antidepressants were doing any good.

The first salvo against antidepressants came from a study led by Erick Turner, MD, a psychiatrist at Oregon Health & Science University. After reviewing the entire mass of drug-company studies submitted to the FDA (where he once worked as a reviewer) in the approval process for 12 antidepressants, Dr. Turner and his fellow researchers reported that 94% of the studies with positive results were later published, while only 14% with negative or ambiguous results found their way into print.

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This so-called "file-drawer effect" has made antidepressants appear more effective than they actually are, at least to physicians and the public. "There is a view that these drugs are effective all the time," Dr. Turner told The Wall Street Journal. When he would tell other doctors that antidepressants work only 40% to 50% of the time, they would protest, "What are you talking about? I have never seen a negative study."

The second study, led by Irving Kirsch, a professor of psychology at the University of Hull, in Britain, arrived at a similar conclusion. Kirsch found that when he factored in unpublished data, four widely prescribed antidepressants—all but one of which belonged to the popular class known as SSRIs (selective serotonin-reuptake inhibitors)—worked only marginally better in clinical trials than sugar pills. And even then, the only clinically significant efficacy was observed in severely depressed patients (who are less apt to respond to the placebo effect). "It is time for a change of emphasis to nondrug treatments and [to] reserve these drugs for very severely depressed patients," Kirsch said when the study was released.

Next Page: In clinical practice, antidepressants work [ pagebreak ]In clinical practice, antidepressants work
In response to these studies and the ensuing publicity, many psychiatrists and other doctors were quick to vouch for the real-world benefits of antidepressants. "Most clinicians see them working extremely well for some people—and thats where I am," says Michael Hirsch, MD, director of psychopharmacology at Bostons Beth Israel Deaconess Medical Center and an instructor in psychiatry at Harvard Medical School. "I am convinced that they are not just placebos. In fact, when they work, they can have very profound effects." Dr. Hirschs caseload averages 300 patients; "a lot" are on SSRIs, he says.

Convincing evidence of the effectiveness of antidepressants that jibes with Dr. Hirschs firsthand experience has been reported in recent years. The most notable example was a federally funded study dubbed STAR*D, or Sequenced Treatment Alternatives to Relieve Depression, the largest (4,000 patients) and longest (seven years) analysis of antidepressants ever.

This study was designed to measure the overall rates of remission induced by a first-line antidepressant treatment, which was replaced, if necessary, by a second, third, and fourth antidepressant (for those whose symptoms persisted); it's a fair facsimile of how doctors deploy the drugs in practice. Two-thirds of the people who stuck with the study saw their symptoms go into remission, although only 37% and 31% got that result on their first and second treatment, respectively. And more than a third of those who achieved remission relapsed within a year. While it may have been somewhat inflated by the carefully monitored treatment given to participants (compared to an occasional visit with a primary care physician, for instance), a remission rate of 67% doesnt exactly spell the "End of Prozac Nation."

Next Page: Antidepressant backlash? [ pagebreak ]Antidepressant backlash?
To some extent, antidepressants may be a victim of their own success. Prozac, the first of the SSRIs, was approved by the FDA in 1987, and within three years, nearly 4.5 million Americans had tried it. By 2002, the number of Americans who had received a prescription for an SSRI had soared to 67.5 million by some estimates, and more than 7.5 million had become long-term users. By 2005, the number of antidepressant prescriptions filled in the United States was up to 170 million.

As these statistics suggest, over the past two decades a good portion of the population has been diagnosed with depression or a related condition and treated with antidepressants. Such eye-popping numbers, not to mention Big Pharmas massive marketing effort, have inevitably raised allegations of overprescribing. SSRIs are being prescribed for a wide range of medical conditions far beyond depression, from social anxiety to premenstrual syndrome to compulsions of all kinds—shopping, eating, gambling, and sex. Children are taking antidepressants for attention deficit hyperactivity disorder (ADHD), as are the elderly for dementia. Even dogs are having the pills forced down their throats.

As the media and blogosphere clamor that SSRIs are ineffective, overprescribed, and even dangerous (concern that the drugs may lead to an increase in suicidality among young people prompted the FDA to add a "black box" warning to all antidepressants), the people who could benefit from the drugs but dont access them are often overlooked.

The National Institute of Mental Health (NIMH) estimates that as many as two-thirds of Americans with depression dont get appropriate treatment, and as Kirschs study illustrated, antidepressants have shown to be most effective in those who are most depressed.

"These drugs are both overprescribed for people who dont need them and underprescribed for people who do need them," says Dr. Hirsch.

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