A LARGE international study comparing more than two dozen antidepressants has revealed striking differences in their effects on the body’s physiology, including weight, blood pressure, cholesterol, and liver function. The findings highlight the importance of monitoring physical health during treatment and suggest that the choice of antidepressant should be personalised to minimise physiological side effects.
Researchers reviewed data from 151 clinical trials and 17 US Food and Drug Administration (FDA) reports, encompassing over 58,000 participants who had received one of 30 antidepressant drugs or placebo. The trials included people treated for a range of psychiatric conditions and were typically 8 weeks long. Using a network meta-analysis, the team ranked antidepressants based on their effects on 13 physiological measures, including metabolic, cardiovascular, and liver-related parameters.
Metabolic and Cardiovascular Changes Vary Across Antidepressants
The analysis found that some antidepressants caused notable metabolic and cardiovascular alterations. For instance, there was roughly a four-kilogram difference in average weight change between agomelatine, which was associated with the least weight gain, and maprotiline, which was linked to the most. Heart rate varied by more than 20 beats per minute between different drugs, with fluvoxamine producing smaller increases than nortriptyline. Similarly, systolic blood pressure differed by up to 11 mmHg between nortriptyline and doxepin.
Several commonly used antidepressants, including paroxetine, duloxetine, desvenlafaxine, and venlafaxine, were associated with raised cholesterol levels, while duloxetine also increased blood glucose. Duloxetine, desvenlafaxine, and levomilnacipran slightly elevated liver enzyme levels, though these changes were not considered clinically significant. No meaningful effects were observed on kidney function or heart rhythm (QT interval).
Tailoring Antidepressant Choice to Minimise Physiological Side Effects
The researchers also found that individuals with higher baseline bodyweight experienced greater increases in blood pressure and liver enzyme levels, while older adults were more likely to have rises in glucose. However, there was no link between improvements in depressive symptoms and changes in metabolic health, suggesting that physiological side effects occur independently of antidepressant efficacy.
According to the authors, the study underscores the need to update treatment guidelines to account for these differences and to prioritise a personalised approach. Clinicians are encouraged to weigh the potential physiological risks of each medication, alongside a patient’s overall health, when prescribing antidepressants.
Reference
Pillinger T et al. The effects of antidepressants on cardiometabolic and other physiological parameters: a systematic review and network meta-analysis. Lancet. 2025; DOI:10.1016/S0140-6736(25)01293-0.
