Not all antidepressants affect the body in the same way, according to new research that suggests some commonly prescribed drugs can cause significant physical changes such as weight gain, altered heart rate, and shifts in blood pressure — while others are comparatively mild.
The findings, published in The Lancet medical journal, could help doctors make more informed prescribing decisions for millions of people living with depression. Researchers said their study is the first large-scale analysis to directly compare physical side effects among individual antidepressants.
“Not all antidepressants are built the same when it comes to their physical side effects,” said Dr Toby Pillinger, academic clinical lecturer at King’s College London and one of the study’s lead authors. “It would be nice to know which antidepressants are better or worse for different physical side effects to guide personalised prescribing. Up until now, we haven’t had that comparative data available.”
The research team analysed data from 151 clinical trials and 17 reports submitted to the US Food and Drug Administration (FDA), covering nearly 59,000 participants who received either an antidepressant or a placebo for a median of eight weeks. The study assessed 30 antidepressant drugs, including widely used selective serotonin reuptake inhibitors (SSRIs) such as sertraline, escitalopram, and fluoxetine, as well as other types like mirtazapine and amitriptyline.
The results showed clear differences between drugs. For instance, there was a four-kilogram difference in weight change between agomelatine and maprotiline, while heart rate changes varied by more than 21 beats per minute between fluvoxamine and nortriptyline. Some drugs, including maprotiline and amitriptyline, were linked to “clinically important” weight gain in nearly half of those taking them. By contrast, SSRIs were generally found to be “relatively benign” in their physical impact.
According to Dr Andrea Cipriani, a psychiatry professor at the University of Oxford and co-author of the study, tolerability plays a critical role in treatment success. “Better tolerability — fewer side effects — means patients are more likely to continue their medication, and the longer they stay on it, the better their outcomes,” he said.
Independent experts said the research reinforces the need for more personalised approaches to treating depression, especially for patients with existing health conditions such as heart disease or diabetes.
Dr Azeem Majeed, chair of primary care and public health at Imperial College London, said the findings “underscore the need for routine physical health checks in those treated with antidepressants.”
However, Prasad Nishtala, a pharmacy and epidemiology specialist at the University of Bath, cautioned that the study may underestimate long-term risks. “In real-world settings, where patients take antidepressants for months or years, the cumulative risks are likely to be higher — particularly among those with chronic depression or metabolic disorders,” he said.
With up to 17 per cent of adults in Europe and North America taking antidepressants, researchers say the new evidence could lead to more tailored and tolerable treatments for patients struggling with depression.
