Antidepressant treatment outcomes in patients with and without comorbid physical or psychiatric disorders: A systematic review and meta-analysis

•Patients with major depressive disorder and comorbidities have worse antidepressant outcomes.•Studies examining comorbid conditions in major depression are highly heterogeneous.•Few studies performed direct comparisons between patients with and without comorbidities. Many patients with major depressive disorder (MDD) experience substantial impairment despite the availability of efficacious treatments. We performed a systematic review and meta-analysis to compare antidepressant outcomes in MDD with or without physical or psychiatric comorbidities. Pubmed, EMBASE, and PsycInfo were searched up to May 14th, 2020 using keywords including MDD, antidepressant, medication, and comorbid. 1915 studies were reviewed. Studies that performed a direct and quantitative comparison of antidepressant effect in patients with MDD with or without comorbidities were included. Study characteristics and primary outcomes were extracted. Continuous and dichotomous variables were considered using standardized mean difference (SMD). Heterogeneity was measured using χ2 and I2 tests. Risk of bias was assessed using Cochrane Risk of Bias tool and NIH Quality Assessment Tool. 26 studies met selection criteria. Studies of physical (6 studies; I2 = 57.69%, p = 0.04) and psychiatric comorbidities (20 studies; I2 = 75.75%, p < 0.001) were heterogeneous. When compared to patients with MDD without comorbidities, those with physical (SMD = -0.19, 95% CI: -0.30 to -0.08, p = 0.001; 1910 and 2905 patients with or without comorbidities) or psychiatric comorbidities (SMD = -0.20, 95% CI: -0.31 to -0.095, p < 0.001; 4308 and 6867 patients with or without comorbidities) had worse antidepressant outcomes. Our limitations included aggregating the comorbidities into physical and psychiatric comorbidities and the high heterogeneity of the studies. Our review provides updated evidence demonstrating that patients with MDD and physical or psychiatric comorbidities experience worse antidepressant outcomes.