Antidepressants differ widely in how they affect the body, according to new research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King's College London, in collaboration with the University of Oxford.
Published in The Lancet, the large-scale study found that some antidepressants can cause clinically relevant changes in body weight, heart rate, and blood pressure within just a few weeks, while others appear largely neutral in their physical effects. Researchers are calling for antidepressant treatment guidelines to be updated to reflect these findings.
Up to 20 per cent of adults in Europe and North America are prescribed antidepressants to treat a range of conditions. While these medications are known to cause physical side effects, the degree to which these alterations occur in patients treated with different antidepressants was previously unclear.
Researchers in this study analysed the data from 151 different studies, comparing the physical health effects of 30 different antidepressants across more than 58,000 people.
"Our findings show that SSRIs, which are the most prescribed type of antidepressant, tend to have fewer physical side-effects, which is reassuring. But for others, closer physical health monitoring may be warranted."
Dr Toby Pillinger, Academic Clinical Lecturer at the IoPPN, Consultant Psychiatrist at the South London and Maudsley NHS Foundation Trust, and the study's senior author
They found notable variation between drugs, even over relatively short treatment periods - most studies involved around eight weeks of antidepressant use. For example, there was up to a 4-kilogram difference in average weight change between some drugs, equivalent to around 2.5 kg of weight loss with agomelatine compared with about 2 kg of weight gain with maprotiline.
The study also estimated that weight gain occurred in nearly half of people prescribed drugs such as maprotiline or amitriptyline, whereas over half of those taking agomelatine experienced weight loss. Similarly, there was a 21-beat-per-minute difference in heart rate between fluvoxamine and nortriptyline.
By contrast, some commonly prescribed SSRIs - the most commonly used type of antidepressant - showed little or no adverse impact on these physical health measures.
Dr Toby Pillinger, Academic Clinical Lecturer at the Institute of Psychiatry, Psychology & Neuroscience, Consultant Psychiatrist at the South London and Maudsley NHS Foundation Trust, and the study's senior author said, "Antidepressants are among the most widely used medicines in the world. While many people benefit from them, these drugs are not identical - some can lead to meaningful changes in weight, heart rate, and blood pressure in a relatively short period."
"Our findings show that SSRIs, which are the most prescribed type of antidepressant, tend to have fewer physical side-effects, which is reassuring. But for others, closer physical health monitoring may be warranted."
"The aim isn't to deter use, but to empower patients and clinicians to make informed choices and to encourage personalised care."
Professor Andrea Cipriani, Professor of Psychiatry at the University of Oxford, Director of the NIHR Oxford Health Clinical Research Facility and the study's last author said, "Most clinical decisions - especially in mental health - are still made by physicians with little input from patients."
"Our results emphasise the importance of shared decision making, the collaborative process through which patients are supported by the clinicians to reach a decision about their treatment, bringing together their preferences, personal circumstances, goals, values, and beliefs. This should the way forward in the NHS and globally."
This research was funded by the National Institute for Health and Care Research, Maudsley Charity, Wellcome Trust, and Medical Research Council.
The effects of antidepressants on cardiometabolic and other physiological parameters: a systematic review and network meta-analysis (Pillinger, Cipriani et al) (DOI10.1016/S0140-6736(25)01293-0) was published in The Lancet.
