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Researchers at the University of Tartu Institute of Genomics have gained a deeper understanding of why some people are more prone to experiencing side effects when taking antidepressants.
Analysing data from over 13,000 gene donors who had used antidepressants, the team studied 25 common side effects across 16 frequently prescribed antidepressants in Estonia, such as nausea, weight gain, sleepiness, headaches, and heart palpitations. The study was published in the European Journal of Human Genetics.
According to the study’s author, Hanna Maria Kariis, the focus was on the CYP2C19 gene, which, together with other factors, affects how quickly the body can metabolise certain antidepressants. “Understanding the basic genetic mechanisms underlying side effects helps identify people who belong to a risk group for developing side effects, which can improve treatment outcomes,” said Kariis, highlighting the significance of the study.
It was found that, compared to normal metabolizers, slow metabolizers (people with a genetic variant causing the medication to break down more slowly in the body) were 49% more likely to experience side effects. In comparison, ultra-rapid metabolizers had a 17% lower likelihood. “This means that the same medication may affect individuals very differently depending on their genetic profile, and depending on how quickly the drug is metabolised, a doctor may recommend a dosage adjustment or the use of a different antidepressant,” explained Kariis. All gene donors can check their CYP2C19 gene activity on the Minu Geenivaramu (“My Genome”) portal.
For the first time, the study also analysed a CYP2C19 deletion found in over 3% of Estonians, where a large portion of the gene is missing. “This mutation has not been described in other populations before, so its effects on people have not been studied. It is an important discovery for Estonia,” Kariis noted. The results revealed that the deletion strongly impacted the development of side effects, and the genetic variant should therefore be added to the pharmacogenetic tests available in Estonia. “By doing so, we could reduce the risk of side effects among people in Estonia who take antidepressants,” Kariis added.
Researchers further explored whether genetic predispositions to psychiatric disorders influence side effect occurrence. Genetic predisposition for schizophrenia or depression was associated with more side effects across multiple antidepressant classes. Likewise, individuals with a genetic predisposition for higher BMI were more likely to experience weight gain from antidepressants.
A meta-analysis comparing the results with an Australian study confirmed strong links between polygenic risk for higher BMI and antidepressant-induced weight gain. People with a genetic predisposition to headaches also reported more headaches when taking sertraline-based drugs.
To arrive at these conclusions, the scientists used anonymised responses from mental health and adverse effects questionnaires as well as medical records, employing data mining and natural language processing (NLP) methods to detect mentions of side effects in clinical notes.
The study underscores the potential of genetic data to personalise antidepressant treatment, improving treatment outcomes and minimising therapy discontinuation due to adverse effects.
Read more: https://www.nature.com/articles/s41431-025-01894-x.
This article was originally published on the EurekAlert webpage, sent to us by University of Tartu.
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