A recent study led by researchers from King”s College London has highlighted the varying side effects of antidepressants, particularly during the first eight weeks of treatment. The investigation involved 58,534 participants from over 150 studies comparing 30 different antidepressants to a placebo.
The findings, published in The Lancet, indicate marked differences in weight changes, heart rate, and blood pressure among the medications. The researchers aim to inform and empower patients regarding their treatment options, while encouraging discussions with healthcare professionals about any concerns they may have.
In the period of 2024/25, approximately 92.6 million prescriptions for antidepressants were issued to an estimated 8.89 million patients in England. Notably, the antidepressant sertraline, known commonly as Lustral, was prescribed to around 2.9 million patients last year. This medication was associated with an average weight loss of 0.76 kilograms and a decrease in heart rate by two beats per minute. However, it was also linked to slight elevations in both systolic and diastolic blood pressure.
Another significant medication, amitriptyline, was prescribed to 2.2 million patients in the same timeframe. This tricyclic antidepressant showed an average weight gain of 1.6 kilograms and an increase in heart rate by nine beats per minute, along with rises in both systolic and diastolic blood pressure. It is worth noting that amitriptyline is not typically recommended as a first-line treatment for depression; selective serotonin reuptake inhibitors (SSRIs) like sertraline are preferred.
Last year, 1.4 million individuals were prescribed citalopram, another SSRI. This drug was found to result in an average weight loss of 0.65 kilograms and decreases in heart rate and systolic blood pressure, although it did result in a slight increase in diastolic blood pressure.
Overall, researchers observed an approximate 4-kilogram difference in weight changes based on the prescribed antidepressants. For instance, patients taking agomelatine lost an average of 2.44 kilograms, while those given maprotiline, which is not commonly prescribed in the UK, experienced an average weight gain of 1.82 kilograms. In heart rate changes, there was a notable difference of more than 21 beats per minute between fluvoxamine, which reduced heart rate by eight beats per minute, and nortriptyline, which increased it by an average of 13.8 beats per minute.
The researchers emphasize that each kilogram of weight gain can heighten a patient”s risk for heart-related issues, and increases in blood pressure elevate the risk of stroke. However, they also acknowledge a key limitation of the study: the focus on the initial eight weeks of treatment. They assert that further research is necessary to evaluate the long-term side effects of these medications.
Dr. Toby Pillinger, the senior author of the study, noted, “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. Our findings show that SSRIs, which are the most prescribed type of antidepressant, tend to have fewer physical side effects, which is reassuring. But for others, closer physical health monitoring may be warranted.”
Andrea Cipriani, a professor of psychiatry at the University of Oxford, emphasized the necessity for shared decision-making in treatment plans, stating, “Most clinical decisions – especially in mental health – are still made by physicians with little input from patients. Our results emphasize the importance of shared decision making, the collaborative process through which patients are supported by the clinicians to reach a decision about their treatment.”
In response to the findings, Rosie Weatherly from the mental health charity Mind said, “It”s so important that people receive mental health support and treatment that considers their individual needs and preferences. As this study highlights, antidepressants vary in their side effects, and health professionals need to carefully consider the benefits and risks of different medications for different people.”
Professor Azeem Majeed from Imperial College London underscored the importance of routine physical health checks for patients on antidepressants, stating, “Moreover, awareness of these side effects is essential to support shared decision-making about the risks and benefits of treatment with antidepressants.”
Dr. Lade Smith, president of the Royal College of Psychiatrists, reiterated the critical role of antidepressants in treating severe depression, noting their effectiveness, especially when combined with talking therapies. He welcomed the study for enhancing understanding of the physical side effects associated with various antidepressants.
Professor Kamila Hawthorne, chair of the Royal College of GPs, added that patients are prescribed antidepressants only when warranted, and that GPs typically follow up with patients two to three weeks after initiating a new prescription to monitor for side effects, along with regular medication reviews thereafter.
