Editor's Note

Antidepressant Drug Effects and Depression Severity: A Patient-Level Meta-analysis

February 8, 2010

Editor, Primary Psychiatry and Psychiatry Weekly, Professor of Psychiatry, Interim Chairman, Department of Psychiatry, New York University

First published in Psychiatry Weekly, Volume 5, Issue 3, on February 8, 2010

Whenever a new study presenting findings about antidepressant efficacy or safety is published, the first place most of us see the results is in a newspaper or online. When I returned from my holiday vacation recently, I saw the following headline in The New York Times: “Popular Drugs May Help Only Severe Depression.”¹ Even more sensationalist pronouncements could be found on cable news websites. The average reader’s impression, quite possibly, is that here is further evidence that antidepressant medication is less effective than psychiatrists and pharmaceutical companies contend.

With respect to this study, however, published in JAMA,² what stands out in this instance is that it actually affirmed that antidepressant drugs work very well for those who need it most—those who are most severely depressed. Fournier and colleagues report that “medication vs placebo differences varied substantially as a function of baseline severity.” They explain that, among patients with low depression rating scores (HHDRS scores <23), there was little difference between medication and placebo. On the other hand, patients with baseline depression severity that crossed the threshold defined by the National Institute for Clinical Excellence for a clinically significant depression (HDRS <25) demonstrated greater response to medication over placebo. The investigators conclude: “The magnitude of benefit of antidepressant medication compared with placebo increases with severity of depression symptoms and may be minimal or nonexistent, on average, in patients with mild or moderate symptoms. For patients with very severe depression, the benefit of medications over placebo is substantial.”²

The study authors address another aspect of depression treatment that would seem to be contradicted by their findings. It involves the diagnosis of dysthymia. If antidepressants don’t seem to work well in mildly depressed patients, why are there numerous studies that have demonstrated that medication is superior to placebo in dysthymia, a condition partly defined by lower symptom levels? The authors speculate that this may explained by the fact that dysthymia is a chronic condition, and chronicity is known to be associated with poor response to placebo.

One lesson we can draw from this study, and the way it has been reported, is that it is important for anyone who treats depressed patients to read the actual study before changing prescribing practices. Judith Warner did a wonderful follow-up op-ed in the Times³ providing some perspective on how these results fit into therapeutic interpretation. The real problem with American health care, she wrote “is not that the drugs don’t work; it’s that the care is not very good.” The problem is not that “perfectly healthy people [are] popping pills for no reason, but people with real illnesses [are] lacking access to care.”

References

1. Carey B. Popular Drugs May Benefit Only Severe Depression, New Study Says. New York Times. January 6, 2010: A12.

2. Fournier JC, DeRubeis RJ, Hollon SD, et al. Antidepressant drug effects and depression severity: a patient-level meta-analysis. JAMA. 2010;303(1):47-53.

3. Warner J. The Wrong Story About Depression. New York Times. January 8, 2010: A19.

Disclosure: Dr. Sussman reports no affiliations with, or financial interests in, any organization that may pose a conflict of interest.