Newer Antidepressants, Including SSRIs, No Better Treating Mild Depression Than Placebo, Researcher Claims

A prominent researcher is challenging the conventional wisdom that selective serotonin reuptake antidepressants (SSRI), a class of drugs which includes the brand name medications Paxil, Prozac, Celexa, Lexapro and Zoloft, do anything at all to treat mild to moderate depression. Appearing on the CBS News program, 60 Minutes, earlier this month, Dr. Irving Kirsch, Harvard Medical School’s Director of Placebo Studies, asserted that newer-generation antidepressants that regulate serotonin in the brain, including SSRIs, work no better than sugar pills.

“People get better when they take the drug. But it’s not the chemical ingredients of the drug that are making them better. It’s largely the placebo effect,” Kirsch, who’s been study the effect of placebos for 30 years, told Leslie Stahl during the interview, which aired February 12.

In 2008, Kirsch, along with researchers in the U.K., published a meta-analysis of clincial trials submitted to the U.S. Food & Drug Administration (FDA) for four newer-generation antidepressants -the SSRIs Paxil and Prozac, as well as Effexor and nefazodone, both serotonin-norepinephrine reuptake inhibitors. Kirsch and his colleagues concluded that, “compared with placebo, the new-generation antidepressants do not produce clinically significant improvements in depression in patients who initially have moderate or even very severe depression”. While some benefits were seen among patients with the most severe forms of depression, the study maintained that this was “due to decreased responsiveness to placebo, rather than increased responsiveness to medication”.

According to the 60 Minutes report, Kirsch’s assertions about antidepressants have prompted a counter attack from his critics, mainly from psychiatrists, who defend the use of antidepressants. However, the report also pointed out that at least one prominent Kirsch critic, Dr. Michael Thase, a professor of psychiatry at the University of Pennsylvania School of Medicine, who was also interviewed by Stahl, is a paid consultant for many drug companies.

Ironically, however, Thase even agreed that antidepressants do have a “substantial placebo effect,” but insisted to Stahl that his own research had found “convincingly that this is a large and meaningful effect for a subset of the patients in these studies.”

Dr. Walter Brown, a clinical professor of psychiatry at Brown University’s Medical School who worked on two studies that corroborated Kirsh’s findings, told Stahl that he believed patients with mild depression were getting virtually no benefit from the chemicals in the pills. According to Brown, many experts now believe the theory behind drugs like Paxil, Prozac and Zoloft – that depression is cause by a deficiency of serotonin in the brain – is a “gross oversimplification and probably is not correct.”

According to the 60 Minutes report, questions about the efficacy of antidepressants prompted regulators in the U.K. to order a review of the drugs’ clinical trials. According to Dr. Tim Kendall, a practicing psychiatrist who co-chaired the commission that conducted the review, they also concluded that the drugs were of little use to people with mild to moderate depression. The review resulted in the U.K. reforming guidelines for the use of antidepressants, which now only designate the drugs as a first-line treatment for the severely depressed.

Kendall also told Stahl that findings of the drug companies’ unpublished studies – those not ultimately submitted to the FDA as part of a medication’s approval application – were shocking: “With the published evidence, it significantly overestimated the effectiveness of these drugs and it underestimated the side effects,” Kane said.

He also refuted the idea that the additional trials his committee reviewed were unpublished because of flaws in the way they were conducted.

“This is a multibillion dollar industry. I doubt that they are spending $10 million per trial to come up with a poor methodology. What characterizes the unpublished is that they’re negative.” Kane said. “Now I don’t think it’s that their method is somehow wrong; it’s that their outcome is not suitable from the company’s point of view.”

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