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.
Journal
The Lancet
Method of Research
Meta-analysis
Subject of Research
People
Article Title
The effects of antidepressants on cardiometabolic and other physiological parameters: a systematic review and network meta-analysis
Article Publication Date
21-Oct-2025
COI Statement
TP has received speaker or consultancy fees from Boehringer Ingelheim, Recordati, Lundbeck, Otsuka, Janssen, CNX Therapeutics, Sunovion, ROVI Biotech, Schwabe Pharma, and Lecturing Minds Stockholm AB; he receives book royalties from Wiley Blackwell; and he co-directs a company that designs digital resources to support treatment of mental illness. RAM has participated in advisory and speaker meetings organised by Otsuka, Karuna, Boehringer Ingelheim, and Janssen. GB has participated in speaker meetings organised by Pfizer. SJ has participated in educational speaker meetings organised by Lundbeck, Otsuka, Sunovion, Janssen, and Boehringer Ingelheim. ODH has received investigator-initiated research funding from or participated in advisory and speaker meetings organised by Angelini, Autifony, Biogen, Boehringer Ingelheim, Eli Lilly, Heptares, Global Medical Education, Invicro, Janssen, Lundbeck, Neurocrine, Otsuka, Sunovion, Rand, Recordati, Roche, and Viatris–Mylan. AHY has delivered paid lectures and advisory boards for the following companies with drugs used in affective and related disorders: AstraZenaca, Boehringer Ingelheim, Eli Lilly, LivaNova, Lundbeck, Sunovion, Servier, Janssen, Allergan, Bionomics, Sumitomo Dainippon Pharma, COMPASS, Sage, Novartis, and Neurocentrx. AC has received research, educational, and consultancy fees from the Italian Network for Paediatric Trials, CARIPLO Foundation, Lundbeck, and Angelini Pharma outside the submitted work. TAF reports personal fees from Boehringer Ingelheim, Daiichi Sankyo, DT Axis, Micron, Shionogi, SONY, and UpToDate, and a grant from DT Axis and Shionogi, outside the submitted work. TAF has a patent (7448125) and a pending patent (2022–082495), and has licensed intellectual properties for Kokoro-app to DT Axis. ED’A received lecture fees from Lundbeck. DMT has received investigator-initiated research grants and spoken at events for AstraZeneca, Eli Lilly, Janssen, Lundbeck, Otsuka, Viatris, and Recordati, and has shares in Myogenes, Saladax, and 428-Pharma. AT has received research, educational, and consultancy fees from Angelini Pharma and lecture fees from Takeda outside the submitted work. CM has participated in educational speaker meetings organized by AbbVie, Dr Falk, Ferring, Lilly, and Takeda. All other authors declare no competing interests.