For the first time, scientists have ranked the side effects of different antidepressants, revealing a patchwork of significant differences that could reshape how millions of people are treated for depression. The landmark findings, published in The Lancet on October 21, 2025, stem from a sweeping analysis conducted by researchers at King’s College London and the University of Oxford. Their work, which synthesized data from 151 clinical trials and 17 FDA reports covering over 58,000 participants and 30 antidepressant medications, upends the long-held notion that these drugs have similar impacts on physical health.
According to the BBC, the study examined the effects of antidepressants on patients during the first eight weeks of treatment—a critical period when side effects can determine whether a patient sticks with their medication or gives up in frustration. The results are eye-opening: some drugs caused patients to gain up to 2 kilograms (about 4.4 pounds), while others actually triggered weight loss of a similar magnitude. Heart rate changes varied by as much as 21 beats per minute between medications, and blood pressure differences exceeded 10 millimeters of mercury (mmHg) in some cases. These are not trivial shifts; they can spell the difference between improved well-being and dangerous complications like heart attacks or strokes, especially for people with preexisting health problems.
Professor Oliver Howes, one of the lead researchers, told the BBC, “There are large differences between antidepressants, and this is important not only for individual patients—millions of people take them, so even small differences can have a substantial effect at the population level.” His colleague Dr. Atishan Arumugham added, “It’s clear that no antidepressant is the same as another.”
The data show, for example, that agomelatine, a melatonergic antidepressant, was associated with an average weight loss of about 2.4 to 2.5 kilograms, while maprotiline, a tetracyclic antidepressant, led to nearly 2 kilograms of weight gain. That’s a roughly 4-kilogram swing depending on which medication a patient receives. The study also found that maprotiline and amitriptyline could provoke weight gain in nearly half of patients, while agomelatine was linked to weight loss in about 55% of cases. These differences go beyond cosmetic concerns—weight changes can affect self-esteem, physical health, and a patient’s willingness to continue treatment.
Cardiovascular effects were equally varied. Fluvoxamine was found to slow the heart by an average of 8 beats per minute, while nortriptyline sped it up by about 14 beats per minute—a 21-beat difference when comparing the two drugs. Blood pressure shifts were also notable: nortriptyline was associated with a reduction of roughly 7 mmHg, while doxepin tended to raise blood pressure by around 5 mmHg. These findings, reported in both The Lancet and BGNES, have real implications for patients with hypertension or existing cardiovascular risk.
Dr. Toby Pillinger, who helped illustrate the study’s findings for the BBC, offered hypothetical scenarios to show how these differences could matter in the real world. For instance, Sarah, a 32-year-old worried about weight gain, would be steered toward agomelatine, sertraline, or venlafaxine, and away from amitriptyline or mirtazapine. John, 44, with high blood pressure, should avoid venlafaxine, amitriptyline, or nortriptyline, and might do better with citalopram, escitalopram, or paroxetine. Jane, 56, who has raised cholesterol, would be advised to avoid venlafaxine, duloxetine, and paroxetine, and instead consider citalopram or escitalopram, which are more neutral regarding cholesterol.
The study’s authors and outside experts alike stress that these findings should not prompt anyone to stop their medication without consulting a doctor. Instead, they call for a more nuanced, personalized approach to prescribing. “It means even people with the same diagnosis could be better suited to different antidepressants depending on their own preferences and other health conditions,” Dr. Arumugham told the BBC. Dr. Prasad Nishtala, a pharmacologist at the University of Bath not involved in the research, described the findings as “novel and valuable,” pointing out that in real-world settings, where patients often take antidepressants for months or years, the cumulative risks are likely to be higher—especially for those with chronic depression.
Interestingly, the most commonly prescribed class of antidepressants, selective serotonin reuptake inhibitors (SSRIs) like citalopram, sertraline, and fluoxetine, tended to have fewer physical side effects. That’s likely one reason why 85% of antidepressant prescriptions in the UK are for just three SSRIs, according to Professor Andrea Cipriani of the University of Oxford. However, he noted that a push for generic, cheap medications has contributed to this concentration, and that implementing the findings of this new research could “see the 85% reduce dramatically” as more people gain access to treatments better matched to their individual needs.
From a scientific standpoint, the study’s authors suggest that the differences in side effects stem from the unique ways each drug interacts with neurotransmitter systems and metabolic pathways. These pharmacological quirks influence appetite, energy balance, autonomic regulation, and vascular tone, which in turn affect weight, heart rate, and blood pressure. Yet, the researchers also acknowledge that their analysis did not cover other important side effects, such as sexual dysfunction or emotional blunting, nor did it compare the drugs’ effectiveness in treating depression itself. These gaps highlight the complexity of antidepressant prescribing and the need for ongoing research.
One area of uncertainty remains: the long-term effects of these medications. The current analysis focused on the first eight weeks of treatment, and while Dr. Pillinger told the BBC that “complimentary data” suggest these short-term changes may persist, this still needs to be properly tested. The authors of the Lancet study echoed this caution, noting that it’s unclear whether the observed physiological effects stabilize, worsen, or improve with prolonged use.
To help clinicians and patients navigate this complex landscape, the research team is developing a free online tool that will allow for more personalized antidepressant selection. However, as Professor Cipriani pointed out, making such individualized prescribing a reality would require a significant cultural shift within the healthcare system—especially in places like the NHS, where generic prescribing is the norm.
For now, the message is clear: antidepressants are not one-size-fits-all. With millions relying on these medications worldwide, even modest improvements in how they are prescribed could have profound effects on public health, patient satisfaction, and the overall success of depression treatment.
