Antidepressants Vary Significantly in Cardiometabolic Effects

TUESDAY, Oct. 28, 2025 (HealthDay News) — Antidepressants induce cardiometabolic and other physiological alterations, which vary between medications, according to a study published online Oct. 21 in The Lancet.

Toby Pillinger, Ph.D., from King”s College London, and colleagues compared and ranked antidepressants based on physiological side effects using data from randomized controlled trials. A total of 151 studies and 17 U.S. Food and Drug Administration reports met the inclusion criteria. Overall, 58,534 participants were included and 30 antidepressants were compared to placebo.

The researchers found that in terms of metabolic and hemodynamic effects, there were clinically significant differences between antidepressants, including an approximate difference of 4 kg in weight change between agomelatine and maprotiline, a difference of more than 21 beats per minute in change in heart rate between fluvoxamine and nortriptyline, and a difference of more than 11 mmHg in systolic blood pressure between nortriptyline and doxepin. Increases in total cholesterol were seen in association with paroxetine, duloxetine, desvenlafaxine, and venlafaxine; duloxetine was associated with increased glucose concentrations, despite reductions in body weight with all drugs. No strong evidence was found for any antidepressant affecting QTc or concentrations of sodium, potassium, urea, or creatinine to a clinically significant extent.

“We found strong evidence that antidepressants differ markedly in their physiological effects, particularly for cardiometabolic parameters,” the authors write. “Treatment guidelines should be updated to reflect differences in physiological risk, but choice of antidepressant should be made on an individual basis, considering clinical presentation and preferences of patients, carers, and clinicians.”

Several authors disclosed ties to the biopharmaceutical industry.

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