PHILADELPHIA –- A study of 30 years of antidepressant-drug treatment data published today in the Journal of the American Medical Association shows that the benefit of antidepressant medication compared with placebo may be minimal or nonexistent in patients with mild or moderate symptoms. University of Pennsylvania researchers say, however, the benefit of medications is substantial for patients with very severe depression.

Ultimately, according to the study, the majority of patients who were prescribed antidepressants did not suffer from a severity of depression that would be improved by the medications.

The research team, led by psychologists at Penn, analyzed data from studies that spanned a 30-year period to gauge the benefit of antidepressant medication compared to placebo pills across a range of patients with varying degrees of depression. The team collected data from placebo-controlled trials of antidepressants approved by the U.S. Food and Drug Administration for the treatment of Major or Minor Depressive Disorder. Studies comprised adult outpatients and included a medication vs. placebo comparison for at least six weeks. Researchers calculated depression severity scores before and after treatment using the standard Hamilton Rating Scale for Depression.

The scientists learned that medication vs. placebo differences varied substantially, relative to the severity of depression suffered by patients. Those patients shown to have less severe depression experienced little to no greater improvement in their symptoms from antidepressant medication as compared to a placebo sugar pill.

The results imply that doctors who are advising treatment for patients with mild or moderate cases of depression should consider the lack of evidence for specific benefits of the medications and compare the expected costs and benefits of the medications against alternatives such as self-help, exercise or psychological therapy.

“Antidepressant medications represent the best established treatment for Major Depressive Disorder, but there is little evidence that they have a specific pharmacological effect relative to pill-placebo for patients with less severe depression,” said Robert DeRubeis, principal investigator and professor in the Department of Psychology in Penn’s School of Arts and Sciences.

Researchers concluded that the ability of antidepressant medications to reduce depressive symptoms varied considerably. For people whose depression was considered to be mild, moderate or even severe, little evidence showed that the medications yield specific benefit beyond what is provided by engagement in treatment and the resulting boost in the patient’s expectation for improvement.

“For very severe depressions, the benefits of medications are clear and substantial,” said Jay Fournier, lead author and a doctoral candidate in Penn’s Department of Psychology. “But for others, the results of this study demonstrate how important it is for persons who are suffering from depression to take an active role in their care, regardless of the severity of their symptoms. Even placebo treatments help most people, and, although we do not fully understand how placebos work, part of the benefit comes from patients taking their depressive symptoms seriously and acting on their concern about their own mental health.”

The study was supported by the National Institute of Mental Health.

Research was conducted by DeRubeis and Fournier of Penn, Jay Amsterdam of the Department of Psychiatry in Penn’s School of Medicine, Steven Hollon and Richard Shelton of Vanderbilt University, Sona Dimidjian of the University of Colorado at Boulder and Jan Fawcett of the University of New Mexico.

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