For the first time, scientists have ranked antidepressants by their physical side effects, revealing significant differences in how these drugs affect weight, blood pressure, and heart rate. The large-scale study, led by researchers at King’s College London’s Institute of Psychiatry, Psychology & Neuroscience (IoPPN) and the University of Oxford, compared 30 commonly prescribed antidepressants across more than 150 clinical trials involving over 58,000 patients. Some antidepressants caused patients to gain up to 2kg in just eight weeks, while others reduced weight or significantly altered heart rate and blood pressure. Experts say the findings could help clinicians better match treatments to individual health needs rather than relying on one-size-fits-all prescribing.
Major variations in physical side effects of antidepressasant
The study, published in The Lancet, found striking disparities between medications. For instance, agomelatine was linked to an average weight loss of 2.4kg, while maprotiline led to a 1.8kg gain. Nortriptyline, a tricyclic antidepressant, was associated with an average increase of nearly 14 beats per minute in heart rate, compared with fluvoxamine, which reduced it by about eight beats. Researchers also noted an 11 mmHg variation in blood pressure between nortriptyline and doxepin, suggesting some antidepressants could raise cardiovascular risk over time.Amitriptyline, another tricyclic antidepressant, caused an average weight gain of 1.6kg and raised both heart rate and blood pressure. In contrast, the SSRI sertraline, one of the most prescribed antidepressants in the UK, was linked to slight weight loss (0.76kg) and a small reduction in heart rate. Citalopram, another SSRI, also caused a mild drop in heart rate and systolic blood pressure while slightly increasing diastolic pressure. Researchers said these results highlight an “approximate 4kg difference in weight change” depending on the antidepressant used.
What these side effects mean for patients
Experts warn that the physical changes linked to antidepressants, while sometimes small, can have real-world health implications, especially when treatment continues for months or years. Even modest weight gain or an increase in heart rate can elevate long-term risks of heart disease, stroke, and metabolic issues. Each kilogram of additional weight, for instance, increases cardiovascular risk, and changes in blood pressure could influence a patient’s overall wellbeing.Dr Toby Pillinger, senior author of the study, said that these variations are not just academic findings but factors that could shape future prescribing decisions. “While many people benefit greatly from antidepressants, the physical effects we observed are not trivial. They can accumulate and, in some cases, lead to serious consequences if left unmonitored,” he said.The research team also emphasised that these findings highlight the importance of ongoing physical health monitoring for people taking antidepressants. Patients with pre-existing heart disease, hypertension, or obesity may need extra caution when starting or switching medications. “The goal is not to alarm patients,” Dr Pillinger added, “but to ensure they and their doctors have all the information needed to make the safest and most effective choices.”
SSRIs show fewer side effects overall
Overall, the most prescribed class of antidepressants — selective serotonin reuptake inhibitors (SSRIs) — tended to produce fewer physical side effects compared with older tricyclics. SSRIs such as citalopram, escitalopram, paroxetine, and sertraline were generally better tolerated, though still capable of causing subtle cardiovascular and metabolic changes. In contrast, drugs like amitriptyline and nortriptyline, while effective for depression and pain, increased the risk of weight gain and higher blood pressure, both of which can raise the likelihood of heart disease and stroke.Dr Pillinger explained, “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.”
Matching medication to individuals
The study underscores the need for personalised antidepressant treatment based on patients’ physical and mental health profiles. For example, patients worried about weight gain may respond better to agomelatine or sertraline, while those with hypertension could consider citalopram or escitalopram. People with high cholesterol might avoid paroxetine, duloxetine, or venlafaxine, which are more likely to elevate lipid levels.Professor Andrea Cipriani of the University of Oxford said the research should promote “shared decision-making,” where patients collaborate with doctors to select treatment options aligned with their preferences and health conditions. “Most clinical decisions in mental health are still made with little patient input. Our results emphasise the importance of involving patients in those decisions,” he said.According to NHS data, about 8.9 million people in England were prescribed antidepressants last year, amounting to 92.6 million prescriptions. Sertraline alone was prescribed to 2.9 million patients, while 2.2 million received amitriptyline and 1.4 million were given citalopram. Researchers note that these three drugs account for nearly 85 percent of antidepressant prescriptions in the UK, reflecting the healthcare system’s preference for generic, low-cost medications.Professor Cipriani said implementing the new ranking could significantly diversify antidepressant use. “If these findings are applied, the dominance of a few generic drugs would reduce dramatically, allowing more people access to treatments that better suit their physical and mental health,” he explained.
Patients urged not to stop medication suddenly
Experts stress that patients should not discontinue antidepressants without medical supervision. Rosie Weatherly of the mental health charity Mind said, “It’s so important that people receive support and treatment that considers their individual needs. Antidepressants vary in their side effects, and health professionals must weigh the benefits and risks for each person.”Dr Pillinger added, “The aim isn’t to deter use but to empower patients and clinicians to make informed choices. Our findings show that SSRIs tend to have fewer physical side effects, which is reassuring, but others may require closer health monitoring.”