New study reveals physical health risks linked to common antidepressants

Antidepressants are medications widely used to treat mental health conditions such as depression, anxiety, post-traumatic stress disorder (PTSD), sleep problems, and chronic pain or eating disorders. They work by stimulating neurotransmitters — the brain chemicals that influence mood and behaviour.

The study, led by researchers from King’s College London’s Institute of Psychiatry, Psychology & Neuroscience (IoPPN) and the University of Oxford, found clinically significant changes in body weight, heart rate, cholesterol levels, and blood pressure among patients taking antidepressants.

“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,” said Dr Toby Pillinger, the study’s senior author.

Published in The Lancet, the research analysed 151 studies and 17 U.S. Food and Drug Administration reports involving more than 58,500 patients, comparing 30 commonly used antidepressants with placebos over a treatment period of around eight weeks.

According to the findings, some antidepressants were linked to weight gain of up to two kilograms, while others led to noticeable weight loss. The study found an approximate four-kilogram difference in average weight change, from a 2.5-kilogram loss with agomelatine to a 2-kilogram gain with maprotiline.

Nearly half of the patients taking maprotiline or amitriptyline experienced weight gain, while over half of those on agomelatine lost weight.

“Weight gain was most evident with antidepressants that antagonise histamine H1 and serotonin 5-HT2C receptors, such as mirtazapine and several tricyclic antidepressants,” the research noted.

“This finding is consistent with their pharmacology, as H1 and 5-HT2C antagonism is associated with weight gain.”

The research also revealed significant cardiovascular risk differences between medications — showing over a 21-beat-per-minute variation in heart rate between fluvoxamine and nortriptyline, and an 11 mmHg difference in blood pressure between nortriptyline and doxepin.

Amitriptyline, a tricyclic antidepressant, was linked to an average weight gain of 1.5 kilograms, along with an increase of 9 bpm in heart rate and 5 mmHg in blood pressure, indicating a higher risk of cardiovascular disease and mortality.

Although some drugs such as paroxetine, duloxetine, desvenlafaxine, and venlafaxine were associated with slight weight loss, they were linked to increases in cholesterol and glucose levels.

Experts caution that even modest weight gain or elevated heart rate can increase the long-term risk of heart disease, stroke, and metabolic disorders.

“We found strong evidence of clinically relevant increases in blood pressure with the serotonin–noradrenaline reuptake inhibitors (SNRIs) duloxetine, desvenlafaxine, venlafaxine, and levomilnacipran, and the tricyclic antidepressants imipramine, maprotiline, and amitriptyline,” the study stated.

By contrast, selective serotonin reuptake inhibitors (SSRIs) — the most commonly prescribed class of antidepressants — showed milder impacts on physical health. Sertraline, for instance, was linked to slight weight loss of 0.76 kilograms and a slight drop in heart rate, while citalopram caused a minor decrease in heart rate and systolic blood pressure.

Health experts emphasised the importance of ongoing physical health monitoring for anyone taking antidepressants, particularly patients with heart disease, hypertension, or obesity.