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Mild to severe depression might be better treated with alternatives to antidepressant drugs, which do not help patients much more than an inactive placebo, researchers said on Tuesday.

Combining data from six studies that examined the effectiveness of two commonly prescribed antidepressants - paroxetine and imipramine - found the drugs produced benefits only slightly greater than a placebo in patients with mild to severe depression.

"They would have done just as well or just about as well with a placebo," said Robert DeRubeis, a psychologist at the University of Pennsylvania, Philadelphia, who with colleagues performed the meta-analysis.

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Paroxetine is one of a popular class of drugs, selective serotonin reuptake inhibitors, and is sold under the brand name Paxil by GlaxoSmithKline. Imipramine is an older tricyclic antidepressant drug developed in the 1950s.

The so-called placebo effect is powerful in treating depression, where people believe they are helped even though they are taking an inactive sugar pill, Dr. DeRubeis said.

In the report published in the Journal of the American Medical Association involving nearly 800 patients, the drugs' impact was noticeably stronger than a placebo in people diagnosed with very severe cases of depression.

Using a scoring system for depression where a diagnosis of 24 or above indicates a very severe case, the researchers said patients treated with drugs saw their scores drop by 13 points, compared to a drop of 9 points for those given a placebo.

But for those with initial depression scores of 23 or below the drop averaged 8 points for those given antidepressants and 7 points for those given a placebo. Roughly half of those prescribed antidepressants fit into the mild to severe categories.

"Our data should give some pause" to doctors and patients weighing antidepressants, Dr. DeRubeis said in a telephone interview. "They should give some consideration to other alternatives."

Exercise has been shown to be helpful to stem depression, as does psychotherapy, and even "self-treatment" with the aid of the plethora of self-help literature, he said.

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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.

At least 27 million Americans take antidepressants, nearly double the number that did in the mid-1990s, according to a study by Columbia University and University of Pennsylvania researchers reported in the Archives of General Psychiatry.

More than 164 million prescriptions for antidepressants were written in 2008, totalling nearly $10-billion in U.S. sales, according to IMS Health. Global sales were twice that.

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