LONDON, UK – A large new study has found that antidepressant use can lead to significant changes in body weight, heart rate, cholesterol, and blood pressure — effects that may increase the risk of heart disease and metabolic disorders over time.
The research, published in The Lancet, analysed data from 151 clinical trials and 17 U.S. Food and Drug Administration reports covering more than 58,000 patients.
It compared 30 widely prescribed antidepressants against placebos over an average treatment period of eight weeks.
The study was conducted by researchers from King’s College London’s Institute of Psychiatry, Psychology & Neuroscience (IoPPN) and the University of Oxford.
“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.
Weight and heart rate differences
The researchers found that some antidepressants were associated with an average weight gain of up to two kilograms, while others led to weight loss.
Overall, there was a four-kilogram difference in average weight change — ranging from a 2.5 kg loss with agomelatine to a 2 kg gain with maprotiline.
Nearly half of the patients taking maprotiline or amitriptyline gained weight, while over half of those on agomelatine lost weight.
“Weight gain was most evident with antidepressants that block histamine H1 and serotonin 5-HT2C receptors, such as mirtazapine and several tricyclic antidepressants,” the report noted. “This finding is consistent with their pharmacology, as H1 and 5-HT2C antagonism is associated with weight gain.”
Cardiovascular changes were also significant.
The study found a 21-beat-per-minute difference 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 1.5 kg weight gain, a 9 bpm increase in heart rate, and a 5 mmHg rise in blood pressure, signalling a heightened risk of heart disease and premature death.
Subtle risks even in “lighter” drugs
While some drugs such as paroxetine, duloxetine, desvenlafaxine, and venlafaxine were associated with slight weight loss, they also raised cholesterol and blood glucose levels — potential markers of long-term metabolic risk.
The researchers reported that serotonin–noradrenaline reuptake inhibitors (SNRIs) and tricyclic antidepressants had the strongest links to elevated blood pressure.
In contrast, selective serotonin reuptake inhibitors (SSRIs) — including sertraline and citalopram — had milder physical side effects, with slight reductions in heart rate and blood pressure.
Doctors urge closer monitoring
Health experts say the findings underscore the need for ongoing physical monitoring of patients taking antidepressants, especially those with underlying cardiovascular or metabolic conditions.
“These results emphasise the importance of shared decision-making — the collaborative process through which patients are supported by clinicians to reach a decision about their treatment, bringing together their preferences, personal circumstances, goals, values, and beliefs,” said Professor Andrea Cipriani, Director of the NIHR Oxford Health Clinical Research Facility.