Large-scale analysis demonstrates the influence of CYP2C19 genotype on specific SSRI side effects.

Authors

Chris Eijsbouts, Yunxuan Jiang, James R Ashenhurst, Julie M Granka, 23andMe Research Team, Steven Pitts, Adam Auton, Noura S Abul-Husn, Alison Chubb, R Ryanne Wu

Published in

The pharmacogenomics journal. Volume 26. Issue 4. Aug 05, 2026. Epub Aug 05, 2026.

Abstract

We evaluated the effect of CYP2C19 genotype on SSRI response in 114,627 research participants. We graded metabolizer status (0 for ultrarapid metabolizers to 4 for poor metabolizers), and regressed drug response outcomes on these grades. Among participants taking escitalopram or citalopram, slower metabolizers experienced side effects significantly more often than faster metabolizers (OR = 1.04 per grade, 95%CI = [1.02-1.06] and OR = 1.05 per grade, 95%CI = [1.02-1.07]) and were more likely to discontinue treatment due to side effects (OR = 1.05, 95%CI = [1.03-1.08], e.g. 29.7% of poor vs. 21.6% of ultrarapid metabolizers, and OR = 1.07, 95%CI = [1.04-1.11], e.g. 25.7% vs. 20.2%). Slower metabolizers taking escitalopram were more likely to suffer from sleep problems and sexual problems. Slower metabolizers taking sertraline reported tremor more often than faster metabolizers. Overall, we find substantial differences in side effect risk with different CYP2C19 genotypes, supporting the notion that individuals seeking depression treatment may benefit from pharmacogenetic-guided treatment selection to minimize side effects and reduce discontinuations.

PMID:
42552300
Bibliographic data and abstract were imported from PubMed on 05 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.