Wide Variation in Antidepressant Side Effects Urge Personalized Treatment Approaches, Lancet Study Reveals

Antidepressants can differ widely in how they physically affect the body, including around a 4 kg difference in weight change between certain drugs (approximately 2.5 kg weight loss from agomelatine and 2kg weight gain from maprotiline), confirms a systematic review and meta-analysis published in The Lancet. The authors emphasise that these findings should not deter people from taking antidepressants, which remain vital and effective treatments for mental health conditions. Instead, they say the results highlight the importance of tailoring the treatment to each individual, taking into account their personal health and preferences.

This large-scale systematic review and network meta-analysis combined results from 151 clinical trials and 17 US Food and Drug Administration (FDA) reports involving over 58,000 participants to assess the effect of 30 different antidepressants on the body over an average of eight weeks course of treatment. The study found that antidepressants also differ in their effects on heart rate, with a difference of more than a 20 beats-per-minute difference in heart rate (approximately eight BPM decrease for fluvoxamine and a 14 BPM increase for nortriptyline); and blood pressure, with a difference of over 10 mmHg variation in blood pressure (approximately seven mmHg decrease for nortriptyline and a five mmHg increase for doxepin).

The study estimates that some antidepressants (e.g., maprotiline and amitriptyline) were associated with weight gain in almost half of individuals prescribed them, while other antidepressants (agomelatine) were associated with weight loss in 55% of patients. Most antidepressants did not show major effects on kidney or liver function, electrolyte levels, or heart rhythm. The authors also note that it is not known if antidepressant-induced physical effects persist or change over time, and more research is needed to understand how antidepressants affect the body over longer time periods.

The authors say their results suggest that treatment guidelines should be updated to reflect the differing physical side effects of antidepressants, and decisions about which drug to use should always be made by the doctor and patient on an individual basis. They also note that other effects of antidepressants were not covered in their study, such as sexual or emotional changes and differences in drug effectiveness, and these should also be considered alongside these results.

Reference:

Pillinger, Toby et al, The effects of antidepressants on cardiometabolic and other physiological parameters: a systematic review and network meta-analysis, The Lancet, DOI:10.1016/S0140-6736(25)01293-0