Cardiometabolic Effects of Pharmacologic Treatments for Major Depressive Disorder: A Systematic Review and Network Meta-Analysis of Antidepressants and Antipsychotics
Objective: Pharmacologic treatments for major depressive disorder (MDD), including antidepressants and adjunctive antipsychotics, are associated with varying degrees of cardiometabolic risk. Adverse effects such as weight gain, increased body mass index (BMI), and elevated blood pressure may compromise long-term health and reduce treatment adherence. This study sought to identify and compare pharmacologic treatments associated with the most adverse cardiometabolic outcomes in adults with MDD.
Methods: A systematic literature review was conducted following Cochrane Handbook guidelines to identify randomized control trials (RCTs) that reported outcomes related to weight, BMI, and blood pressure in adults with MDD prescribed an antidepressant or antipsychotic. A frequentist network meta-analysis was performed in R using random-effects models. Results were reported as mean differences or odds ratios with 95% confidence intervals; treatment rankings were based on Surface Under the Cumulative Ranking Curve (SUCRA) scores.
Results: Overall, 136 RCTs met eligibility criteria. Among the antipsychotics analyzed, brexpiprazole, aripiprazole, cariprazine, and quetiapine XR were associated with greater weight gain compared to placebo. Brexpiprazole was associated with the highest mean weight gain (SUCRA = 0.067). For the outcome of ≥7% weight gain, aripiprazole ranked among the least favorable, with a higher likelihood of this event occurring (SUCRA = 0.1710). Among the antidepressants analyzed, amitriptyline and mirtazapine were consistently identified as having the highest cardiometabolic burden, including weight gain, increased adiposity, and metabolic disturbances.
Conclusions: Both antidepressants and antipsychotics are associated with increased cardiometabolic risk, highlighting the need for MDD treatments that are both efficacious and that cause little-to-no cardiometabolic risk.
