Recently, there has been much debate regarding the efficacy of antidepressants in the treatment of adults with major depressive disorder (MDD) due to the often-high levels of response to placebo in many clinical trials. Relatedly, the argument has been made that perceived efficacy of antidepressants in treating MDD may be due to a "breaking-the-blind" effect whereby patients enrolled in placebo-controlled trials who experience an adverse event realize that they are in the active drug arm of the trial and, consequently, experience a greater relief of depressive symptoms than can actually be attributed to pharmacological actions of medication itself. In this "mega-analysis" investigating over 3,000 patients taking paroxetine, citalopram, or placebo, Hieronymus and colleagues sought to investigate the possibility and extent of the placebo-breaking-the-blind hypothesis. The authors found that the presence of antidepressant-related adverse effects was not required in order to see improvement in symptoms of depression (over placebo) and that severity of adverse effects did not correlate with degree of symptom improvement. These data indicate that antidepressants (at least the selective serotonin reuptake inhibitors (SSRIs; paroxetine and citalopram) are effective in the treatment of adult MDD and that the superiority of SSRIs over placebo in clinical trials is not due to a breaking-the-blind effect.
Hieronymus F, Lisinski A, Nilsson S et al. Efficacy of serotonin reuptake inhibitors in the absence of side effects: a mega-analysis of citalopram and paroxetine in adult depression. Mol Psychiatry 2017; Epub ahead of print.