Research design overview for the first pattern (UKB). Credit score: Organic Psychiatry World Open Science (2025). DOI: 10.1016/j.bpsgos.2025.100502
Switching from one selective serotonin reuptake inhibitor (SSRI) to a different antidepressant could possibly be used to measure antidepressant non-response, in keeping with new analysis from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s Faculty London.
Within the UK, present medical apply is to maneuver sufferers with main depressive dysfunction from first-line SSRI remedy to a special antidepressant if they do not reply to the remedy. Measuring antidepressant ‘switching’ harnesses this data, which might be present in digital well being data, to determine non-responders and higher perceive why antidepressants work for some individuals and never for others.
The research, revealed in Organic Psychiatry World Open Science, means that switching patterns can seize antidepressant response. Utilizing switching as a measure may enable researchers to conduct bigger research investigating the components which affect antidepressant response, fairly than counting on medical research of small pattern sizes.
The researchers analyzed information from UK Biobank and Era Scotland on greater than 40,000 individuals who had been prescribed antidepressants (5,133 SSRI “switchers” and 33,630 “non-switchers” in UK Biobank, and 498 switchers and 1,279 non-switchers in Era Scotland).
Members who switched from an SSRI to a different antidepressant inside a 90-day interval have been categorised as “switchers,” and individuals who had greater than three consecutive prescriptions of the identical SSRI have been “non-switchers.”
The traits of individuals who switched have been just like these seen in medical trials which assess the effectiveness of antidepressants, affirming that switching is an effective indication that the preliminary antidepressant did not work for that person.
“We were able to trace the switching pattern of over 5,000 UK Biobank participants, which gave us a much bigger sample size than any clinical trials normally have. Our study found that switching is a valid measure of antidepressant non-response. This provides a new way for researchers to investigate why antidepressants work for some but not others,” says Chris Lo, Ph.D. Pupil at King’s IoPPN and first writer of the research.
“Antidepressants are some of the most widely prescribed drugs, but we have little idea of who is likely to respond favorably, and to which drug. This work is a first step in using health records to define and predict SSRI drug responses. From this we can explore what factors might be instrumental in determining who antidepressants might work for,” says Professor Cathryn Lewis, Professor of Genetic Epidemiology & Statistics at King’s IoPPN and Co-Deputy Lead of the Trials, Genomics and Prediction theme on the Nationwide Institute for Well being and Care Analysis (NIHR) Maudsley Biomedical Analysis Centre and senior writer of the research.
The researchers used the switching patterns to determine components that have been linked with non-response. They discovered that individuals have been extra more likely to change if that they had a decrease annual revenue and academic degree. These with a college diploma have been round 25% much less more likely to change than those that didn’t full secondary schooling.
These with the next genetic threat of not recovering from despair, as indicated by their polygenic threat rating, have been additionally extra more likely to change. In distinction, genetic threat of growing despair was not linked with switching, suggesting that the genetics of remedy response differs from the genetics of susceptibility to despair.
These demographic and genetic components linked with switching have been additionally just like these seen in medical trials, offering additional assist for the validity of switching as a measure of non-response.
“We still don’t understand the genetics of antidepressant treatment response, in large part because the available studies are too small. This recent work provides us with a new approach to identifying people who respond to antidepressants that may result in much larger genetic studies in the future. We hope that this approach will ultimately lead to genetic tests that can help identify which antidepressant drugs work best for whom,” says Professor Andrew McIntosh, Professor of Organic Psychiatry on the College of Edinburgh and co-author on the research.
The researchers word a limitation of the research is that sufferers may change antidepressants for a wide range of causes, for instance, on account of uncomfortable side effects or availability, which is not a mirrored image of remedy non-response.
Extra data:
Chris Wai Hold Lo et al, Antidepressant switching as a proxy phenotype for drug non-response: investigating medical, demographic and genetic traits, Organic Psychiatry World Open Science (2025). DOI: 10.1016/j.bpsgos.2025.100502
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Remedy switching may measure antidepressant remedy failure (2025, Might 28)
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