Large variation in side effects of different antidepressants, finds study

Researchers have for the first time put together a detailed comparison of the side effects associated with different antidepressants which highlights large variation in their impact on the body.

Some antidepressants lead to substantial changes in weight, blood pressure and heart rate, the large analysis by UK researchers found.

The research follows the addition of medications used to treat depression to the New Medicine Service (NMS) later this month 2025.

The ranking of the side effects reported in The Lancet should encourage more personalised prescribing based on individuals needs, the researchers from Kings College London said.

To assess the differences, the team looked at data from 151 clinical trials and 17 US Food and Drug Administration (FDA) reports involving over 58,000 participants taking 30 different antidepressants.

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They found marked variation including a 4kg difference in weight change from an approximate 2.5kg weight loss associated with agomelatine to a 2kg weight gain from maprotiline.

Overall, some antidepressants such as maprotiline and amitriptyline were associated with weight gain in almost half of individuals prescribed them, while others including agomelatine were associated with weight loss in 55% of patients.

For heart rate, the impact of the drugs varied by 20 beats-per-minute (BPM) from around an eight BPM decrease for fluvoxamine and a 14 BPM increase for nortriptyline.

When it came to blood pressure, the analysis showed a 10 mmHg variation from an approximate 7 mmHg decrease for nortriptyline to a 5 mmHg increase for doxepin.

They also reported that most antidepressants did not show major effects on kidney or liver function, electrolyte levels, or heart rhythm.

The side effects were assessed in the first eight weeks of taking the drugs and it is not known if they persist or change over time with more research is needed to understand how antidepressants affect the body over longer time periods, they explained.

But 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 concluded.

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Study leader Dr Toby Pillinger, consultant psychiatrist at the South London and Maudsley NHS Foundation Trust, said: ‘While many people benefit from antidepressants, 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.’

He added: ‘The aim isn’t to deter use, but to empower patients and clinicians to make informed choices and to encourage personalised care.’

RCGP chair Professor Kamila Hawthorne said: ‘While evidence shows that antidepressants can be a safe and effective treatment for some patients, like any medication they are not without side effects which can vary from patient to patient – and as this research lays out, these can sometimes be physical and include weight gain.’

Regular medication reviews should be done to determine whether the treatment is still optimal, whether it’s having any side-effects and whether to reduce the dosage or stop taking medication altogether, she said.

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Professor Hawthorne added: ‘These reviews are particularly important, as this study suggests, given that various factors, including lifestyle, can change how an antidepressant works.

‘This is why it’s so important that GPs have enough time with their patients to have the conversations necessary to provide holistic, follow up care.’

This article was first published in our sister publication Pulse.