Family clues could help predict how we react to antidepressants

The researchers found that people were almost five times more likely to have a genetic difference affecting how they process antidepressants if both they and a parent had stopped taking the same medication early. 

Published in Nature Communications Medicine, the study looked at 600 British Bangladeshi and Pakistani families from the Genes and Health Project – one of the world’s largest community genetics studies.  

The team wanted to know if family health history could be used to predict disease risk and medication response. They focused on amitriptyline, a common antidepressant that is also prescribed for pain and migraines. Among the 600 families studied, 96 families had both a parent and an adult child prescribed amitriptyline.  

About half of the children and a quarter of the parents stopped taking the drug within three months, suggesting it wasn’t working for them or caused unpleasant side effects. 

Dr Gabriel Marengo, Bioinformatician/Data Scientist at Queen Mary and Co-first author of the study, said: “If both parents and their child have had trouble tolerating the same medicine, that could be a red flag that genetics are involved. Checking family experiences with medicines might help guide genetic testing and safer prescribing. This study is proof of concept. It shows that our families’ experiences with medicine can tell us something important about our own.” 

The genetic link 

When the team checked genetic data, the found that in families where both generations stopped the medicine early, the younger generation was significantly more likely to carry a gene variant (CYP2C19) that slows down the body’s ability to break down amitriptyline. 

The ‘slow metaboliser’ status can lead to stronger side effects or lower tolerance to the drug. 

However, a parent’s early discontinuation alone didn’t predict their child’s reaction, it was the two-generation pattern that made the difference. 

What it means for patients and doctors  

The findings suggest that family medication history – not just disease history – could be a powerful and practical tool for doctors. 

The study also highlights how genetic testing could be targeted to patients most likely to benefit, particularly in communities where such testing isn’t routine.  

While the research focused on one antidepressant and a specific group of families, the authors believe the same principle could apply to many other drugs.