Drugs may aid only extreme depression, new study says

Some widely prescribed drugs for depression provide relief in extreme cases but are no more effective than placebo pills for most patients, according to a new analysis.

The findings could help settle a long-standing debate about antidepressants. While the study does not imply that the drugs are worthless for anyone with moderate to serious depression — many such people do seem to benefit — it does provide one likely explanation for the sharp disagreement among experts about the drugs' overall effectiveness.

Taken together, previous studies have painted a confusing picture. On one hand, industry-supported trials have generally found that the drugs sharply reduce symptoms. On the other, many studies that were not initially published, or were buried, showed no significant benefits compared with placebos.

The new report, appearing in The Journal of the American Medical Association, reviews data from previous trials on two types of drugs and finds that their effectiveness varies according to the severity of the depression being treated.

Previous analyses had found a similar pattern. But the new study is the first to analyze responses from hundreds of people being treated for more moderate symptoms, as are most people who seek care.

Setting the bar

"I think the study could dampen enthusiasm for antidepressant medications a bit, and that may be a good thing," said Dr. Erick Turner, a psychiatrist at Oregon Health & Science University. "People's expectations for the drugs won't be so high, and doctors won't be surprised if they're not curing every patient they see with medications."

But Turner added, "The findings shouldn't dampen expectations so much that people refuse to even try medication."

A team of researchers, including psychologists who favor talk therapy and doctors who consult widely with drugmakers, performed the new analysis, using government grants. The group evaluated six large drug trials, including 728 men and women, about half of them with severe depression and half with more moderate symptoms.

Three of the trials were of Paxil, from GlaxoSmithKline, a so-called selective serotonin reuptake inhibitor (SSRI), and the other three were of imipramine, an older generic drug from the class known as tricyclics.

The team, led by Jay Fournier and Robert DeRubeis of the University of Pennsylvania, found that compared with placebos, the drugs caused a much steeper reduction in symptoms of severe depression (cases scoring 25 or higher on a standard scale of severity, putting them in the top quarter of the sample). Those with scores of less than 25 got little or no added benefit from the medications.

Ranked on scale

"We were able to give an overall estimate of effectiveness for the first time in this more moderate severity range, from 14 to 20 on the scale, in which there's no question that doctors would likely consider prescribing medication," DeRubeis said.

The effects of other popular SSRIs like Lexapro and Prozac are not likely to be much different from those of Paxil, experts said.

DeRubeis and others said antidepressants' inability to outperform placebos against moderate symptoms stemmed partly from the sustained attention that patients in drug trials received from top doctors — which itself can help relieve symptoms, drug or no drug. "The message for patients with mild to moderate depression," DeRubeis said, "is, 'Look, medications are always an option, but there's little evidence that they add to other efforts to shake the depression — whether it's exercise, seeing the doctor, reading about the disorder or going for psychotherapy.' "