CYP2C19 and CYP2D6 variation and serotonin reuptake inhibitor outcomes in obsessive-compulsive disorder: a systematic review.

BACKGROUND

Serotonin reuptake inhibitors are widely used in the pharmacological management of obsessive-compulsive disorder (OCD), yet patients differ substantially in therapeutic response and tolerability. Variation in CYP2C19 and CYP2D6 can influence antidepressant exposure, but much of the available evidence comes from depression or mixed psychiatric cohorts.

OBJECTIVE

To examine OCD-specific evidence on associations of CYP2C19 or CYP2D6 genotype or metabolizer phenotype with serotonin reuptake inhibitor exposure, clinical response, and tolerability.

METHODS

We searched MEDLINE through PubMed, Scopus, Web of Science, PsycINFO, and the Obsessive-Compulsive Disorder Database from inception to 31 October 2025. Eligible primary studies had to report OCD-specific CYP2C19 or CYP2D6 data together with a relevant treatment outcome. Reviews, guidelines, case reports, and studies without separately extractable OCD data were excluded. Findings were synthesized narratively; risk of bias and certainty were assessed at study and outcome levels, respectively.

RESULTS

Three studies met the eligibility criteria: one included 91 patients with OCD, one included 74 participants of whom 39 had OCD, and one included 184 patients with OCD. CYP2D6 variation affected antidepressant blood concentrations but did not consistently predict clinical response. One retrospective study associated non-extensive CYP2D6 metabolism with more failed medication trials and venlafaxine-related adverse effects. Associations of CYP2C19 with sertraline response and CYP2D6 with fluoxetine response were not statistically significant. Overall certainty was very low because of observational designs, heterogeneity, imprecision, multiple testing, and lack of independent replication.

CONCLUSIONS

CYP2C19 and CYP2D6 genotypes have pharmacokinetic relevance for selected antidepressants, but available evidence does not establish that they predict or improve OCD-specific outcomes. Pharmacogenomic information may assist selected drug-specific decisions but cannot currently support a validated treatment algorithm for OCD.