A major UK study finds huge variations in antidepressant side effects, from weight to heart health

A major UK study has revealed striking differences in how various antidepressants affect the body, with some causing significant weight gain while others lead to weight loss — even within just two months of starting treatment.

The research, led by teams at King’s College London and the University of Oxford, analysed data from 151 clinical trials involving more than 58,000 people taking 30 different antidepressants. The findings expose wide disparities in side effects such as changes in weight, heart rate, and blood pressure — challenging the idea that antidepressants have broadly similar physical impacts.

According to the researchers, patients on certain medications could gain up to 2kg (4.5lb) within eight weeks, while others could lose a comparable amount. For example, users of maprotiline and amitriptyline were most likely to gain weight, while those taking agomelatine typically experienced weight loss. The average difference in weight change between the drugs was about 4kg, or nearly 9lb.

The study also highlighted significant cardiovascular variations. People on nortriptyline, an older tricyclic antidepressant, had heart rates up to 21 beats per minute higher than those on fluvoxamine, while an 11 mmHg gap in blood pressure was found between nortriptyline and doxepin.

Lead researcher Dr Toby Pillinger, a clinical lecturer at King’s College London, said the findings underscore the need for closer physical monitoring of patients on certain medications.

“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,” he said.

He added that the goal was not to discourage antidepressant use, but to ensure patients and clinicians have the information they need to make informed, personalised choices.

“Our findings show that SSRIs, the most commonly prescribed antidepressants, tend to have fewer physical side effects, which is reassuring,” Dr Pillinger noted. “But for other types, closer health monitoring may be warranted. The aim isn’t to deter use but to empower patients and encourage personalised care.”

The study comes amid ongoing debates about the long-term use of antidepressants, which are typically recommended for up to two years in most treatment plans for conditions such as depression and anxiety. While they can be life-changing for many patients, the side effects often determine whether individuals stay on or abandon treatment.

Professor Andrea Cipriani, a psychiatrist at the University of Oxford and co-author of the study, said the findings highlight the importance of collaborative care between doctors and patients.

“Our results emphasise the importance of shared decision-making — where patients and clinicians work together, considering the individual’s circumstances, preferences, and beliefs,” he said. “This should be the way forward, both in the NHS and internationally.”

The researchers are now urging that UK treatment guidelines be updated to reflect the differences between antidepressants. They argue that clearer information about potential side effects could improve patient outcomes, reduce premature treatment dropouts, and make mental health care more transparent.

Experts believe the findings could help reshape conversations about antidepressants — shifting focus from whether to take them, to which one might be most suitable for each individual.

The study’s authors hope that future prescribing will take both mental and physical health impacts into account. For patients struggling with unwanted side effects, the research provides a crucial reminder: no two antidepressants are alike — and finding the right one could make all the difference.