Individual response to antidepressants for depression in adults – a simulation study and meta-analysis

Background. The observation that some patients appear to respond better to antidepressants for depression than others encourages the assumption that the effect of antidepressants differs between individuals and that treatment can be personalized. To test this assumption, we compared the outcome variance in the group of patients receiving antidepressants with the outcome variance of the group of patients receiving placebo in randomized controlled trials (RCTs) of adults with major depressive disorder (MDD). An increased variance in the antidepressant group would indicate individual differences in response to antidepressants. In addition, we illustrate in a simulation study why attempts to personalize antidepressant treatment using RCTs might be misguided.Methods. We first illustrated the variance components of trials by simulating RCTs and crossover trials of antidepressants versus placebo. Second, we analyzed data of a large meta-analysis of antidepressants for depression, including a total of 222 placebo-controlled studies from the dataset that reported outcomes on the 17 or 21 item Hamilton Depression Rating Scale or the Montgomery-Åsberg Depression Rating Scale. We performed inverse variance, random-effects meta-analyses of the variability ratio (VR) between the antidepressant and placebo groups. Outcomes. The meta-analyses of the VR comprised 345 comparisons of 19 different antidepressants with placebo in a total of 61144 adults with an MDD diagnosis. Across all comparisons, we found no evidence for a larger variance in the antidepressant group compared with placebo overall (VR = 1.00, 95% CI: 0.98; 1.01, I2 = 0%) or for any individual antidepressant. Interpretation. Our findings did not provide empirical support for individual differences in response to antidepressants.