For the first time, researchers have created a detailed ranking comparing the physical side effects of 30 commonly prescribed antidepressants. The large-scale study, conducted by King’s College London and the University of Oxford, has uncovered major variations in how these medications affect patients’ weight, heart rate, and blood pressure within just eight weeks of starting treatment. The findings, published in The Lancet medical journal, could change how millions of people worldwide are prescribed antidepressants. According to the researchers, up to one in six adults in Europe and North America currently take such medication, making the implications of these results far-reaching.
Table of contents:
- Differences between agomelatine, fluvoxamine, and nortriptyline
- Research led by Oliver Howes and Toby Pillinger
- How individual conditions affect antidepressant choice
- The dominance of SSRIs and calls for change in prescriptions
- New digital tools and long-term implications
Differences between agomelatine, fluvoxamine, and nortriptyline
The study analyzed 151 clinical trials involving more than 58,500 patients, focusing on the first eight weeks of antidepressant use. Results showed significant contrasts between individual drugs:
- Agomelatine was linked to a 2.4 kg weight loss compared with maprotiline, which caused nearly 2 kg of weight gain.
- Fluvoxamine slowed heart rate, while nortriptyline increased it by up to 21 beats per minute.
- A difference of 11 mmHg in blood pressure was observed between nortriptyline and doxepin.
“Clearly no two antidepressants are built the same,” said Dr Atheeshaan Arumuham from King’s College London. He emphasized that these differences may become clinically important, potentially influencing the risk of heart attack or stroke.
Research led by Oliver Howes and Toby Pillinger
Professor Oliver Howes, one of the study’s lead researchers, highlighted the public health implications. “There are big differences between [antidepressants] and this is important not just for individual patients, but large numbers of people are taking them, so even modest changes could have a big effect across the whole population,” he said.
Dr Toby Pillinger added that the majority of the studies were short-term, covering only eight weeks, yet already demonstrated large and clinically relevant changes in physical health parameters. “The last thing I want is for this story to be scaring people,” he told BBC Radio 4’s Today programme. “I want to see this as empowering individuals to take the initiative and to engage in shared decision-making with their practitioner.”
The researchers stressed that patients should not stop taking their medication without consulting a doctor, but that antidepressant choices should be better matched to each person’s needs.
How individual conditions affect antidepressant choice
The study illustrated how different patients could benefit from personalized prescriptions. In one example, three individuals—Sarah (32), John (44), and Jane (56)—each had depression but different health priorities.
- Sarah wanted to avoid weight gain. Dr Pillinger recommended agomelatine, sertraline, or venlafaxine, avoiding amitriptyline and mirtazapine, which tend to increase weight.
- John, who already had high blood pressure, should avoid venlafaxine, amitriptyline, or nortriptyline, and could instead take citalopram, escitalopram, or paroxetine.
- Jane, with elevated cholesterol, should avoid venlafaxine, duloxetine, and paroxetine, as they raise cholesterol levels. For her, citalopram or escitalopram would be more suitable.
These examples underline the importance of individualizing treatment, rather than prescribing the same medication for everyone.
The dominance of SSRIs and calls for change in prescriptions
Currently, about 85% of antidepressant prescriptions in the UK are for just three selective serotonin reuptake inhibitors (SSRIs)—citalopram, sertraline, and fluoxetine. This trend, according to Professor Andrea Cipriani of the University of Oxford, reflects a push for generic, low-cost medications rather than personalized care.
Fluoxetine (also known as Prozac) was found to reduce weight but increase blood pressure. Despite its mixed effects, SSRIs generally had fewer physical side effects compared with older antidepressants like amitriptyline.
Professor Cipriani said it was “impossible to say how many of the millions of people being prescribed antidepressants should be on a different drug,” but he emphasized that implementing these findings could reduce the dominance of SSRIs and provide better treatment options.
New digital tools and long-term implications
The research team is developing a free online tool to help clinicians and patients choose antidepressants more accurately. However, they acknowledged that a major cultural shift within the NHS would be required for such personalization to become standard practice.
Dr Prasad Nishtala from the University of Bath, who was not involved in the study, described the findings as “novel and valuable.” He warned that in real-world settings, where patients take antidepressants for months or years, the cumulative risks could be higher, especially for those with chronic depression.
The researchers expect that the short-term changes observed over eight weeks will likely persist, though further testing is needed to confirm this.
In summary, this pioneering study from King’s College London and the University of Oxford demonstrates major physical differences between antidepressant drugs. Its findings could transform how doctors prescribe medication and how patients manage their treatment, moving toward a future where antidepressant therapy is safer, more personalized, and better aligned with individual health needs.
Source: BBC