Supplementary Material for: Antidepressants and Social Functioning in Patients with Major Depressive Disorder – Systematic Review and Meta-analysis of Double-blind, Placebo-controlled RCTs

Introduction: Social functioning (SF) is the ability to fullfill one’s social obligations and a key outcome in treatment. Objective: To estimate the effects of antidepressants on SF in patients with MDD. Methods: This meta-analysis and its reporting are based on Cochrane Collaboration’s Handbook of Systematic Reviews and Meta-Analyses and PRISMA guidelines (protocol registration at OSF). We systematically searched CENTRAL, Medline, PubMed Central, and PsycINFO for double-blind RCTs comparing antidepressants with placebo and reporting on SF. We computed standardized mean differences (SMD) with 95%-CIs and prediction intervals. Results: We selected 40 RCTs out of 1188 records screened, including 16.586 patients (age 46.75 years, 64.2% women). In 27 studies investigating patients with major depressive disorder (primary depression), antidepressants resulted in a SMD of 0.25 compared to placebo ([95%-CI: 0.21; 0.30] I2: 39%). In 13 trials with patients suffering from major depressive disorder comorbid with physical conditions or disorders the summary estimate was 0.24 ([0.10; 0.37] I2 : 75%). In comorbid depression, studies with high/uncertain risk of bias had higher SMDs than low risk studies: 0.29 [0.13; 0.44] vs. 0.04 [-0.16; 0.24]; no such effect was evident in primary depression. There was no indication of sizeable reporting bias. SF efficacy correlates with efficacy on depression scores, Spearman’s rho 0.67 (p<0.001), and QoL, 0.63 (p<0.001). Conclusions: The effect of antidepressants on social functioning is small, similar to its effect on depressive symptoms in primary major depressive disorder and doubtful in comorbid depression. Strong correlations with both antidepressive and QoL effects suggest overlap among domains.