Not all antidepressants are alike: New study ranks side effects for first time
Up to 21-beat swings in heart rate and 2kg weight gain within 8 weeks of treatment
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Dubai: For the first time, scientists have ranked the physical side effects of major antidepressants — revealing striking differences between the drugs widely prescribed to millions of people.
Researchers analysed data from 151 clinical trials and 17 US FDA reports, covering nearly 59,000 patients treated for depression over eight weeks.
Also Read: An antidepressant’s grim side-effect
The study, published in The Lancet medical journal, compared 30 antidepressants, including common SSRIs such as sertraline, escitalopram, and fluoxetine, as well as older medications like amitriptyline and mirtazapine.
Wide gap in side effects
The findings showed “clinically significant differences” in how these drugs affect the body. Some antidepressants caused patients to gain up to 2kg in weight or experience swings of 21 beats per minute in heart rate, the study found.
Key findings from The Lancet study
Researchers analysed 151 clinical trials and 17 FDA reports covering nearly 59,000 patients.
Compared 30 antidepressants, including SSRIs, tricyclics, and atypical drugs.
Found “clinically significant differences” in physical side effects across medications.
Weight change: Up to 4 kg difference between agomelatine and maprotiline.
Heart rate variation: As much as 21 beats per minute between fluvoxamine and nortriptyline.
Weight gain risk: Nearly half of users on maprotiline or amitriptyline experienced “clinically important” weight gain.
SSRIs (e.g., sertraline, fluoxetine, escitalopram) were found to be “relatively benign” compared to older drugs.
Side effects like weight gain or heart changes can lead some patients to stop treatment early.
Researchers urge personalised prescribing and routine physical health checks for those on antidepressants.
For instance, there was a 4kg difference in weight change between agomelatine and maprotiline, and a 21 bpm difference in heart rate between fluvoxamine and nortriptyline.
“Not all antidepressants are built the same when it comes to their physical side effects,” said Dr Toby Pillinger, clinical lecturer at King’s College London and co-author of the study.
SSRIs seen as relatively mild
The researchers found that selective serotonin reuptake inhibitors (SSRIs) were “relatively benign” compared with other classes of antidepressants.
Drugs such as maprotiline and amitriptyline, however, caused “clinically important” weight gain in almost half of the patients prescribed them.
These side effects, the study warned, can prompt people to stop taking their medication, undermining recovery.
“Better tolerability means longer treatment duration and better outcomes,” said Dr Andrea Cipriani, psychiatry professor at the University of Oxford and a co-author of the research.
Implications for treatment
Experts, according to news reports, say the results could help doctors tailor prescriptions more precisely to a patient’s health profile, particularly for those with heart disease, diabetes, or metabolic risks.
“The findings underscore the need for routine physical health checks in people treated with antidepressants,” said Dr Azeem Majeed of Imperial College London.
However, others cautioned that the study may underestimate long-term risks, since most patients remain on antidepressants for months or years. “In real-world settings, the cumulative side effects are likely to be higher,” said Dr Prasad Nishtala of the University of Bath.
Key takeaway
While experts stressed that no one should stop treatment without medical advice, the research highlights a critical message: Not all antidepressants are the same — and choosing the right one could make a major difference to both mental and physical health.
What are antidepressants?
Purpose: Medications used to treat depression, anxiety disorders, panic attacks, obsessive-compulsive disorder (OCD), and sometimes chronic pain or insomnia.
How they work: They balance brain chemicals — mainly serotonin, dopamine, and noradrenaline — that affect mood and emotions.
Main types:
SSRIs – e.g., sertraline, fluoxetine, escitalopram (most commonly prescribed).
SNRIs – e.g., venlafaxine, duloxetine.
Tricyclics – e.g., amitriptyline, nortriptyline (older drugs, more side effects).
Atypical antidepressants – e.g., mirtazapine, bupropion, agomelatine.
Typical benefits: Improve mood, sleep, appetite, and concentration; reduce anxiety and negative thoughts.
Onset: Usually take 2–6 weeks to start working.
Important note: Should always be taken under medical supervision and not stopped suddenly without consulting a doctor.
Who generally takes them
People diagnosed with major depressive disorder or generalised anxiety.
Those experiencing post-traumatic stress disorder (PTSD) or obsessive-compulsive disorder (OCD).
Patients with persistent pain, sleep disorders, or menopausal symptoms (under specialist care).
In the UK, around 8 million people are prescribed antidepressants — nearly 1 in 6 adults.
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