Understanding the Variability in Antidepressant Side Effects: A Path to Personalized Prescribing

A recent meta-analysis finds antidepressants vary markedly in physical side effects — weight trajectories and cardiometabolic signals differ across agents, a clinically meaningful consideration for patients with cardiometabolic risk.

The review, pooling 151 randomized trials and more than 58,000 participants, quantifies distinct weight trajectories across drugs: some agents (for example, maprotiline and amitriptyline) trend toward weight gain, others (notably agomelatine) trend toward weight loss, and many appear largely weight-neutral. Data pooled across arms produce roughly a 4 kg span between these extremes (about 2.5 kg loss with agomelatine versus about 2 kg gain with maprotiline), though measurable heterogeneity and limited follow-up reduce certainty about longer-term persistence.

Beyond weight, the analysis highlights differences in heart rate and blood pressure across agents that may shift short-term physiological profiles. These cardiometabolic signals—small average shifts in resting heart rate and systolic blood pressure reported across comparisons—are most relevant for patients with hypertension, arrhythmia risk, or other cardiovascular vulnerability and may affect monitoring thresholds and co-management strategies.

How might this change individualized prescribing? The analysis supports using baseline weight and cardiometabolic risk to inform agent selection: favoring weight-neutral or weight-loss–associated drugs for patients with elevated metabolic risk, while balancing these tolerability signals against efficacy and other adverse-effect domains not covered in the review. Clinicians may incorporate routine weight and cardiometabolic monitoring when initiating or switching antidepressants.