Individual Differences in Response to Antidepressants

Abstract

Major depressive disorder (MDD) is a common and heterogeneous mental condition characterized by emotional, cognitive, somatic, and behavioral symptoms.¹ Antidepressants are one of the first-line interventions for the treatment of depression,² but their efficacy appears to be variable. While a significant proportion of individuals experience remission of depression after 8 weeks of treatment, more than 50% of patients improve very little or their depression worsens.³ This observed variation has prompted efforts to identify moderators of antidepressant efficacy and to personalize treatments by matching specific antidepressants with the unique characteristics of individual patients.^4-6 The variability in the efficacy of psychiatric medications is typically deduced from aggregate data of randomized clinical trials (RCTs), which estimate average treatment effects.^5,6 To some degree, treatment effects in RCTs vary between individuals owing to random factors or other factors, such as placebo effects, regression to the mean, or measurement error.^6,7 The ability to personalize treatments rests on the assumption that individual differences contribute to this variability, but detecting treatment by individual interactions requires more complex study designs.⁸