King's College London

Published in Psychological Medicine, the study explored different factors that could explain why SSRIs – a common form of antidepressants – work for some people with major depressive disorder, but not others.

Researchers analysed data from UK Biobank on 19,516 participants who had tried at least one SSRI, such as citalopram, fluoxetine, paroxetine or sertraline, for at least two weeks. Participants reported whether the SSRI helped them “feel better” using a single item questionnaire with possible responses “yes, at least a little”, “no”, “do not know”, or “prefer not to answer”. This is the first detailed analysis of this large-scale study which assesses SSRIs using self-reported experiences rather than clinician-reported remission from symptoms.

Overall, 74.9 per cent felt SSRIs helped them feel better. 18.8 per cent said the prescribed drug was not helpful.

Using a range of data collected by UK Biobank, the study analysed what factors might influence whether people found SSRIs helpful.

It found that sociodemographic factors such as age, gender and household income were linked to differences in how people perceived the effectiveness of SSRIs. Those participants who were older, male, had lower incomes, and reported alcohol or illicit drug use were more likely to say that they did not find antidepressants helpful.

Participants who had experienced no mood improvement even when positive events occurred or whose worst episode of depression lasted more than two years, were also less likely to report that SSRIs were helpful. Lastly those who had a greater genetic risk for depression, calculated using polygenic risk scores, were less likely to report that SSRIs were helpful.

Professor Andrew McIntosh, Professor of Biological Psychiatry at the University of Edinburgh’s Centre for Clinical Brain Sciences and co-investigator on the study, said: "The findings from this large study show that nearly three-quarters of people in UK Biobank who were treated with antidepressants found them helpful. There is already excellent evidence from clinical trials that antidepressants work for people with depression. However those studies focus on addressing only whether they are more effective than placebos, and not why they are more effective in some people than others. We must now focus on developing a better understanding of how antidepressants work and how we can predict which people are most likely to benefit from these treatments."

Cat Sebastian, Head of Evidence for Mental Health at Wellcome, said: "Studies like this, which help us understand why antidepressants work for some people but not for others, are fundamental for developing more targeted and personalised treatments for depression."

The study offers key insights into antidepressant response, however the sample may not fully represent the general population and reliance on retrospective self-reports can lead to inaccurate recollection.

The study was funded by Wellcome and the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre. The research is part of the ‘Antidepressant Medications: Biology, Exposure & Response (AMBER)’ study, a larger programme of work led by Professor Cathryn Lewis and funded by Wellcome.

“Sociodemographic, clinical, and genetic factors associated with self-reported antidepressant response outcomes in the UK Biobank” (Michelle Kamp, Chris Wai Hang Lo, Grigorios Kokkinidis, Mimansa Chauhan, Alexandra C. Gillett, AMBER Research Team, Andrew M. McIntosh, Oliver Pain, and Cathryn M. Lewis) was published in Psychological Medicine. Doi: 10.1017/S0033291725000388

For more information, please contact Patrick O’Brien (IoPPN Media Manager).