Largest Analysis Yet Offers New Data on Heart, Weight, and Cholesterol Risks
A sweeping new study from King’s College London has compared the physical side effects of 30 common antidepressants, offering the most comprehensive look yet at how these medications impact the body. Published this week in The Lancet, the analysis combines data from more than 150 clinical trials involving over 58,000 patients.
The findings quantify, for the first time, the effects of different antidepressants on weight, heart rate, blood pressure, and cholesterol. “It’s never been done at this scale before,” said lead author Dr. Toby Pillinger, a psychiatrist at King’s College London. “No one’s ever put specific numbers to the amount of weight you’ll put on or how much your cholesterol might go up.”
SSRIs Show Fewer Physical Effects
The research found that selective serotonin reuptake inhibitors (SSRIs)—such as Zoloft and Prozac, the most prescribed antidepressants in the U.S.—tend to have fewer physical side effects compared with older drug classes.
By contrast, some tricyclic antidepressants were linked to more pronounced impacts. For example, nortriptyline users experienced average heart rate increases up to 20 beats higher than those taking the SSRI fluvoxamine. In terms of weight, changes ranged from losses to gains of around four pounds depending on the medication.
Dr. Pillinger emphasized that no single antidepressant is universally “best” or “worst.” “One drug that’s problematic for one person might work perfectly for another,” he said. “The goal is to match treatment to each individual’s health profile and preferences.”
Tools to Personalize Treatment
To help with that, Pillinger’s team created a free digital tool for clinicians that organizes antidepressants by side-effect profiles. The platform allows doctors and patients to build a “menu” of treatment options based on existing health conditions and which side effects are most important to avoid.
Dr. Nina Kraguljac, a psychiatrist at Ohio State University and chair of the American Psychiatric Association’s Council on Research, called the study “well-done and largely reassuring.” She noted that “side effects alone should not guide treatment decisions,” since the findings reflect population averages rather than individual experiences.
Limitations and Context
The study’s data came primarily from eight-week trials, even though most antidepressant users stay on medication for months or years. It also excluded some key side effects, including sexual dysfunction, digestive issues, and “emotional blunting,” which often influence whether patients continue treatment.
Dr. David Hellerstein, a psychiatry professor at Columbia University, said the results reinforce that “most of these drugs seem quite safe on a lot of physical parameters, especially the newer ones like SSRIs and SNRIs.” However, he cautioned that side effects can still be important for certain patients and might shape which medication is prescribed.
Hellerstein added that side effects can sometimes be beneficial, depending on the patient’s condition. “If someone lost a lot of weight due to depression, an antidepressant that increases weight could actually be helpful,” he said. “That’s not a side effect—that’s a therapeutic effect.”
Overall, experts agree the study provides valuable data to help doctors personalize antidepressant treatment, balancing mental health benefits with physical well-being.