For decades, millions of people around the world have relied on antidepressants to manage depression, anxiety, and a range of related disorders. But until now, little was known about how these medications stack up against each other when it comes to their effects on the body. That changed this week, as an unprecedented study led by researchers at King’s College London and the University of Oxford provided the first comprehensive ranking of 30 commonly prescribed antidepressants based on their physical side effects. The findings, published in The Lancet and echoed by outlets like CBS News and HCPLive, reveal striking differences in how these drugs can impact weight, blood pressure, heart rate, and even cholesterol.
The scale of the research is nothing short of impressive: over 58,000 patients participated in more than 150 randomized controlled trials, with additional data drawn from 17 FDA reports. The average treatment period was eight weeks—long enough, it turns out, for some medications to cause patients to gain or lose several kilograms, or to see significant swings in their cardiovascular markers.
So, what did the study find? For starters, not all antidepressants are created equal when it comes to side effects. According to the King’s College London team, there was an “approximate 4kg difference in weight change” depending on the drug prescribed. Agomelatine, for example, was linked to an average weight loss of 2.4 kg, while maprotiline led to a 1.8 kg gain. The story was similar with other medications: amitriptyline, a tricyclic antidepressant, caused patients to gain an average of 1.6 kg, while sertraline—a widely used SSRI—was linked to a modest weight loss of 0.76 kg.
But weight wasn’t the only parameter affected. The study found that nortriptyline, another tricyclic, was associated with an average increase of nearly 14 beats per minute in heart rate, compared with fluvoxamine, which actually reduced heart rate by about eight beats per minute. There was also an 11 mmHg variation in blood pressure between nortriptyline and doxepin. To put that into perspective, even small increases in blood pressure or heart rate can elevate the risk of heart disease and stroke over time—especially if treatment continues for months or years, as it so often does.
“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,” said Dr Toby Pillinger, senior author of the study, in a statement quoted by HCPLive. The research team emphasized that these findings highlight the importance of ongoing physical health monitoring for people taking antidepressants, especially those with pre-existing conditions like heart disease, hypertension, or obesity.
SSRIs (selective serotonin reuptake inhibitors) such as sertraline, citalopram, escitalopram, and paroxetine—which are among the most prescribed antidepressants in the UK and US—generally produced fewer physical side effects compared with older tricyclics. Still, even these newer drugs were not entirely free from subtle cardiovascular or metabolic changes. For example, citalopram caused a mild drop in heart rate and systolic blood pressure, while slightly increasing diastolic pressure. It’s a reminder that even the most “well-tolerated” drugs can have physiological effects that are worth considering.
Meanwhile, other medications stood out for their strong associations with particular side effects. According to the study, weight gain was most pronounced with maprotiline, amitriptyline, milnacipran, mianserin, fluvoxamine, and mirtazapine. Weight loss, on the other hand, was seen with agomelatine, moclobemide, fluoxetine, levomilnacipran, sertraline, venlafaxine, duloxetine, citalopram, desvenlafaxine, and paroxetine. Increased cholesterol was linked to desvenlafaxine, venlafaxine, and duloxetine, while duloxetine was also associated with higher glucose concentrations.
Interestingly, the study also found that kidney and liver function, electrolyte levels, and heart rhythm were not significantly affected by most antidepressants—a reassuring note for patients and clinicians alike. However, some drugs did cause increases in liver enzymes (AST and ALT), though these changes were not deemed clinically significant. There was also no strong evidence of any antidepressant significantly affecting the corrected QT interval or concentrations of sodium, potassium, urea, or creatinine.
As Dr. Sue Varma, a psychiatrist not involved in the study, told CBS News, “We do know that these medications are life-saving and life-changing, but they can have variation from person to person depending on a person’s metabolism, their age, [and] what other medications they’re on.” She also pointed out that untreated depression itself can cause many of the same side effects explored in the study, such as weight gain or loss, making it essential to “weigh the risks and the benefits” of any medication.
One of the most important takeaways from the research is the need for personalized, patient-centered care. Professor Andrea Cipriani of the University of Oxford, a co-author of the study, urged clinicians to embrace “shared decision-making,” where patients collaborate with doctors to select treatments that align with their health profiles and preferences. “Most clinical decisions in mental health are still made with little patient input. Our results emphasize the importance of involving patients in those decisions,” he said.
The practical implications of this new ranking are significant. In England alone, NHS data shows that about 8.9 million people were prescribed antidepressants last year, with sertraline, amitriptyline, and citalopram accounting for nearly 85 percent of prescriptions. If the findings are applied in practice, the dominance of a few generic drugs could wane, allowing more people access to treatments that better suit their physical and mental health needs. “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,” explained Professor Cipriani.
Of course, experts stress that patients should not stop taking their medication without medical supervision. Rosie Weatherly of the mental health charity Mind cautioned, “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 echoed this sentiment, noting, “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.”
Ultimately, this landmark study arms both patients and clinicians with the information needed to make safer, more effective choices. While antidepressants remain a cornerstone of mental health treatment, it’s clear that a one-size-fits-all approach no longer makes sense. With careful monitoring and a focus on individual needs, the hope is that more people can find relief from depression—without unnecessary risks to their physical health.
