Psychiatry should not become hostage to placebo: An alternative interpretation of antidepressant-placebo differences in the treatment response in depression

Abstract

BACKGROUND: It is widely believed that in randomized controlled trials of antidepressants the difference between drug and placebo response rates is rather small (around 20%), leading to a common perception that antidepressants have limited efficacy. AIM: The aim of the present paper was to present an alternative calculation and interpretation of antidepressant-placebo difference in the treatment response to antidepressant in drug trials which may shed a new light on the efficacy of antidepressants. ISSUES: We have previously highlighted several controversial points concerning the calculation of antidepressant and placebo response rates in randomised controlled trials, which may influence views concerning the efficacy of drugs, and demonstrated several factors which may lead to overestimation of the placebo effect and underestimation of antidepressant efficacy. The traditional interpretation of antidepressant-placebo difference in randomized controlled trials on major depression has been also challenged previously from at least five points of view but all leading to a conclusion that currently prevailing opinions concerning relative placebo and antidepressant response rates overestimate placebo response, and thereby underestimate efficacy of antidepressant drugs. In our present paper we propose another method for calculating placebo and antidepressant response rates which may shed new light on an overlooked aspect of the efficacy of these drugs. CONCLUSIONS: We contend that opinions on the effectiveness of antidepressants should be reconsidered, and comparisons with placebo should be more carefully applied. Interpretation of the placebo response is of crucial importance for establishing the efficacy of antidepressive medications, and psychiatry should not become the hostage of placebo.