Only people with very severe depression appear to derive clear and substantial benefits from taking antidepressant medication, an analysis of published studies released today shows.

For people who are mildly to moderately depressed, taking an antidepressant like Paxil (paroxetine) may do little to improve mood, the analysis found.

“The ability of antidepressant medications to reduce depressive symptoms varies considerably depending on the severity of the symptoms when treatment is initiated,” Jay C. Fournier, of the University of Pennsylvania, Philadelphia, who was involved in the study, told Reuters Health by email.

“For people whose depression is considered to be mild, moderate, or even severe, there is little evidence 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,” the researcher added.

“Prescribers, policy makers, and consumers may not be aware that the efficacy of medications largely has been established on the basis of studies that have included only those individuals with more severe forms of depression,” the researchers point out in the January 6 issue of the Journal of the American Medical Association. And this fact is often neglected in marketing messages aimed at doctors and the public.

For their research, Fournier and colleagues pooled data from six large trials pitting the antidepressant medication Paxil or Tofranil (imipramine) against placebo, or dummy pills, in a total of 718 depressed adults. They found that only patients with very severe depression seemed to benefit from antidepressant therapy.

True drug effects (an advantage of antidepressants over placebo) were “nonexistent to negligible” among depressed patients having mild, moderate, or even severe symptoms at the outset, whereas they were “large” for patients with very severe symptoms, they report.

“As has been found repeatedly in tests of antidepressants, we documented that among those patients with very severe depression, the medications provide a large specific benefit,” Fournier said. “However, by available estimates, this degree of severity is above that experienced by the majority of patients who are diagnosed with depression.”

A spokeswoman for GlaxoSmithKline said the report “contributes to the extensive research” into antidepressants, noting that Paxil received U.S. government approval in 1992 and has helped “millions of people battling mental illness.”

“The studies used for the analysis in the JAMA paper differ methodologically from studies used to support the approval of paroxetine for major depressive disorder, so it is difficult to make direct comparisons between the results,” spokeswoman Sarah Alspach said.

Fournier told Reuters Health, “It is important 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.”

SOURCE: JAMA/Journal of the American Medical Association, January 6, 2010.