Lancet

Antidepressants show wide variation in cardiometabolic effects: Meta-analysis

November 4, 2025

Study details: This systematic review and network meta-analysis included 151 randomized trials and 17 FDA reports, encompassing >58,000 participants. Thirty antidepressants were compared to placebo over a median treatment duration of 8 weeks. The study assessed changes in weight, heart rate, blood pressure, cholesterol, glucose, liver enzymes, and renal parameters.

Results: Antidepressants differed substantially in their cardiometabolic and physiological effects. Weight change varied by up to 4 kg between agents, and heart rate and systolic BP differences exceeded 21 bpm and 11 mmHg, respectively. Paroxetine, duloxetine, desvenlafaxine, and venlafaxine increased total cholesterol; duloxetine also raised glucose. Duloxetine, desvenlafaxine, and levomilnacipran increased liver enzymes, but not to clinically significant levels. No strong evidence was found for clinically significant changes in QTc, electrolytes, or renal markers. Higher baseline weight and age predicted greater metabolic changes. Changes in depressive symptoms weren’t associated with metabolic disturbance.

Clinical impact: These findings highlight the importance of tailoring antidepressant choice to individual patient profiles, especially in those with cardiometabolic risk.

Source:

Pillinger T, et al. (2025, November 1). Lancet. The effects of antidepressants on cardiometabolic and other physiological parameters: a systematic review and network meta-analysis. https://pubmed.ncbi.nlm.nih.gov/41135546/