Antidepressants vs Placebos

An estimated 350 million people worldwide have depression. There has been great debate over the years of how best to treat depression, are non-medication based therapies best? Or do antidepressants actually work?

The meta-analysis published recently in The Lancet, looked at over 500 trials including over 116,000 patients with major depressive disorder. This analysis included both placebo-controlled trials and head-to-head trials, where antidepressants were compared with other antidepressants.

During the trials, researchers found that all 21 of the most common antidepressants (that they looked at in the study) were more effective than placebo for treating acute depression in the first eight weeks of treatment.

Agomelatine and fluoxetine showed the greatest acceptability, with patients 16% and 12% less likely respectively to stop taking their medication compared to placebo. Clomipramine had the worst acceptability, with patients 30% more likely to stop taking it than placebo.

Although this paper seems to be conclusive, it by no means will the debate end. In 2008 Irving Kirsch, Associate director of the Program in Placebo Studies at Harvard Medical School, published his own meta-analysis showing antidepressants are no more effective than placebos, which included data sent by pharmaceutical companies to the Food and Drug Administration to approve various antidepressants—which Kirsch obtained through the Freedom of Information Act.

Scientists on both sides of the debate have published various meta-analyses claiming to conclusively show that antidepressants are or are not more effective than placebo—and neither accepts the other’s evidence. There have been findings that counter Kirsch’s work show antidepressants are truly effective, which Kirsch in turn rejected through his own research. The FDA demands pharmaceutical companies provide data on all the clinical trials they sponsor—including unpublished trials. “This turned out to be very important,” wrote Kirsch in a 2014 paper. “Almost half of the clinical trials sponsored by the drug companies have not been published.”

There is also the issue of longevity. The recent meta-analysis only looks at the first eight weeks and whilst this shows that antidepressants produce strong results in the short-term. Studies have shown that non-medication based treatment options have a better effect in the longer-term.

RCGP chair Professor Helen Stokes-Lampard said: ‘This research should reassure patients who are taking or are contemplating commencing antidepressants, and the doctors that prescribe them, that they are an effective treatment for depression in the short-term.

‘Although antidepressants are of proven benefit – as this study shows – no doctor wants their patients to become reliant on medication so where possible, GPs will explore alternative treatments, such as talking therapies or CBT, which can be of great benefit for some patients.’