Related Experiment Video
Updated: Apr 15, 2026
12:21
Thermostabilization, Expression, Purification, and Crystallization of the Human Serotonin Transporter Bound to S-citalopram
Published on: November 27, 2016
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CYP2C19 Genotype is Associated with Citalopram Treatment Outcomes in a Real-World Setting
Yoomi Park1,2, Yitian Zhou1, Volker M Lauschke1,3,4,5
1Department of Physiology and Pharmacology and Center for Molecular Medicine, Karolinska Institutet and University Hospital, Stockholm, Sweden.
Clinical Pharmacology and Therapeutics
|April 14, 2026
Summary
CYP2C19 genetic variants impact citalopram response, with ultrarapid metabolizers more likely to experience treatment failure. This study highlights CYP2C19 and BMP2K as key genetic factors influencing antidepressant outcomes.
Area of Science:
- Pharmacogenomics
- Psychiatry
- Genetics
Background:
- CYP2C19 genetic variants influence the metabolism of selective serotonin reuptake inhibitors (SSRIs).
- The impact of CYP2C19 variability on citalopram response remained unclear.
- Real-world data is crucial for understanding pharmacogenetic associations in unguided treatment settings.
Purpose of the Study:
- To evaluate the association between CYP2C19 genotypes and citalopram treatment outcomes.
- To identify novel genetic factors, beyond CYP2C19, associated with SSRI response.
- To leverage UK Biobank data for advancing precision psychiatry.
Main Methods:
- Analysis of CYP2C19 genotypes and citalopram prescription data from 11,079 UK Biobank participants.
- Evaluation of associations between CYP2C19 metabolizer status and therapeutic failure, treatment resistance, maintenance dose, and time to dose escalation.
- Rare variant analyses to identify novel candidate genes, including BMP2K, for SSRI response.
Main Results:
- CYP2C19 ultrarapid metabolizers showed increased likelihood of therapeutic failure (OR 2.03) and treatment resistance (OR 1.74).
- CYP2C19 poor metabolizers also exhibited increased treatment resistance (OR 1.85).
- A U-shaped association was observed between CYP2C19 metabolizer status and citalopram outcomes, with dose adjustments correlating significantly with genotype.
- BMP2K variants were significantly associated with citalopram therapeutic failure (P = 5.49 × 10⁻⁶) and replicated in escitalopram users (P = 0.042).
- Higher BMP2K variant burden correlated with lower citalopram maintenance dose.
Conclusions:
- CYP2C19 genotype significantly influences citalopram outcomes in a real-world, unguided treatment setting.
- BMP2K is identified as a novel candidate gene contributing to interindividual differences in citalopram response.
- These findings support the value of large-scale biobank data for pharmacogenetic research and precision psychiatry.
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