New Study Reveals Major Differences Between Antidepressants

Millions of people take antidepressants to help manage their mental health, often staying on them for long periods. Most discussions focus on how these medications affect mood and emotional well-being, but their physical impact has remained far less clear.

Until recently, no one had systematically ranked antidepressants based on their side effects in a structured, comparative way. That gap has finally been addressed.

A major new study has now compared how commonly prescribed antidepressants differ when it comes to physical changes such as weight gain, heart rate, and blood pressure. Conducted by researchers from King’s College London and the University of Oxford, the study focused on the first eight weeks of treatment, a crucial phase when the body is still adapting to the medication.

The findings, published in The Lancet medical journal, offer new insight into why people can have very different physical reactions to drugs prescribed for the same condition. To build a comprehensive view, the research team analysed data from 151 studies covering 30 widely used antidepressants and more than 58,500 patients.

The results highlight that antidepressants are not physically interchangeable. In fact, the differences in side effects between medications were more significant than many might expect.

This research challenges the common assumption that all antidepressants work similarly in the body beyond their emotional effects. With this new evidence, patients and healthcare providers may be better equipped to choose treatments that align not only with emotional needs but also with physical health considerations.

Key Findings

Some of the most striking results include: patients taking agomelatine lost an average of 2.4kg compared with those on maprotiline, resulting in nearly 2kg of weight gain.

There was a difference of up to 21 beats per minute in heart rate between fluvoxamine (which slowed heart rate) and nortriptyline (which increased it). Nortriptyline was also associated with an 11 mmHg higher rise in blood pressure than doxepin.

Prof Oliver Howes, one of the researchers involved, highlighted why these differences matter:

“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.”

Dr Atheeshaan Arumuham, from King’s College London, put it simply:

“Clearly no two antidepressants are built the same.”Pexels

Changes in weight, heart rate, or blood pressure might not seem dramatic on their own, especially over just eight weeks. However, researchers warn that when these changes are sustained, they can contribute to more serious long-term health risks, including heart disease, stroke, and metabolic conditions.

Dr Toby Pillinger stressed this point during an appearance on BBC Radio 4’s Today programme:

“The majority of the studies we looked at were relatively short. We're looking at eight weeks' duration and still within that duration we were seeing large changes in physical health parameters which we would argue have clinical relevance.”

He also addressed a concern many people might have upon hearing this news:

“The last thing I want is for this story to be scaring people. I want to see this as empowering individuals to take the initiative and to engage in shared decision-making with their practitioner.”

Which Drugs Came Out Better?

The study did not label any antidepressants as “good” or “bad,” but it did observe general patterns. SSRIs - like sertraline, citalopram, escitalopram, and paroxetine - are often the first-line treatment for depression, and the study found they usually caused fewer physical side effects compared to other types.

Interestingly, fluoxetine (better known by its brand name Prozac) was linked with slight weight loss but also a rise in blood pressure. This highlights how trade-offs exist and why medication needs to be tailored to the individual.

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Professor Andrea Cipriani from the University of Oxford noted that it’s hard to estimate how many people might benefit from switching medications based on this new data.

However, he pointed out that prescribing habits may need to shift. At the moment, 85% of antidepressant prescriptions in the UK involve just three drugs, citalopram, sertraline, and fluoxetine, largely because they are cheap and widely available.

According to Cipriani, applying the findings of this research more consistently could reduce that dominance and open the door for more personalised treatment choices: “The 85% would reduce dramatically, with more people accessing better treatments.”

This study isn’t a reason to stop taking medication abruptly or second-guess treatment without medical advice. Instead, it reinforces the importance of choosing antidepressants based not only on mood-related outcomes but also on physical health, lifestyle, and individual risk factors.

If anything, it gives patients more ground to ask questions, express preferences, and work with doctors to find a medication that supports both their mental and physical well-being.