Do antidepressants work better than placebo?


Do antidepressants work better than placebo?


In 2017, 17.3 million adults in the United States experienced an episode of major depression. Many people with depression take antidepressants alongside therapies such as psychotherapy. A 2011-2014 survey found that 12.7% of US individuals aged 12 or above had taken antidepressant medication in the previous month. That equals almost 1 in 8 people. Of those individuals, a quarter had been taking antidepressants for the last ten years. Although so many people use these drugs, there is still great controversy surrounding how well they work, and studies have generated conflicting results.


Why the doubt?

The factors below and more have all combined to produce a situation where scientists are still unsure whether antidepressants work better than a placebo:

  • Pharmaceutical companies are keen to market the drugs they have spent years designing and testing.
  • Doctors want to provide medication to those with a reduced quality of life.
  • Patients are keen to try anything that might improve their well-being.
  • Journals are more likely to publish studies with positive findings.


A recent study came from scientists at the Nordic Cochrane Centre in Demark. In this study, the authors concluded that the current evidence in support of antidepressents is not sufficient to prove that they work better than placebo.


Reopening the data


The authors of the study found that earlier research on the effectiveness of antidepressants did not address certain biases in the data. Authors outlined a number of issues - for instance, in an ideal study, participants are "blinded" - they do not know whether they are receiving the drug or the placebo. However, because anti-depressants have well-known side effects, it is difficult to conuct studies wherein participants are adequately blinded - participants are likely to know they are taking the drug rather than the placebo.

The scientists decided to repeat the previous research, but account for biases they believe the team missed the first time.

The team found various concerns in the original study, such as deviating from guidelines and not addressing publication bias. The authors write:

"Publication bias of antidepressant trials is pervasive and distorts the evidence base. Many industry funded antidepressant trials remain unpublished or are inadequately reported. Cipriani et al included 436 published and 86 unpublished studies, but as many as a thousand antidepressant studies may have been conducted."


The debate will go on


The researchers argue that previous studies they analysed had short durations and were not applicable to people who had taken antidepressants for years. Effect sizes were also relatively small, and although statistically significant, they may not be clinically significant.

The authors also note that in the groups that took antidepressants, there were relatively high drop out rates in several of the studies. The authors suggested that this is because the benefits of antidepressants may not outweigh the harms. Authors also claimed that the results were not transparently presented, meaning that it was not possible to work out how some of the analyses were conducted. Overall, "the evidence does not support definitive conclusions regarding the efficacy of antidepressants for depression in adults, including whether they are more efficacious than placebo for depression."

Although the authors do not claim that antidepressants do not work, they conclude that the evidence is still not strong enough, and have called for larger, longer, more rigorous studies.



Munkholm, K., Paludan-Müller, A. and Boesen, K. (2019). Considering the methodological limitations in the evidence base of antidepressants for depression: a reanalysis of a network meta-analysis. BMJ Open, 9(6), p.e024886.

Newman, T. (2019). Do antidepressants work better than placebo?. [online] Medical News Today. Available at: [Accessed 24 Jul. 2019].

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