Analysis of Gene Variants Previously Associated With Iloperidone Response in Patients With Schizophrenia Who Are Treated With Risperidone

Objective: We examined 6 single nucleotide polymorphisms (SNPs) previously reported to be associated with response to iloperidone therapy for association with response to risperidone therapy.

Method: Patients with schizophrenia (DSM-IV) were assessed during 2006 and 2007 for response/nonresponse (defined as ≥ 20%/ = 145). Genotype frequencies and improvement in PANSS total scores were analyzed for those SNPs significantly associated with change in PANSS total score.

Results: The SNPs XKR4 rs9643483 and GRIA4 rs2513265 were significantly associated with change in PANSS total response (adjusted P < .05 for both), with the same direction of effect as reported for iloperidone. For patients with nonresponsive genotypes for these SNPs, mean improvement in PANSS total score for African Americans was two-thirds that seen for whites (XKR4: −13.9 versus −21.4; GRIA4: −12.5 versus −20.9).

Conclusions: In this retrospective pharmacogenomic analysis, we found that 2 SNPs previously linked to iloperidone response were also associated with response to risperidone.

Trial Registration: clinicaltrials.gov Identifier: NCT00337662

J Clin Psychiatry

Submitted: August 18, 2010; accepted December 21, 2010.

Online ahead of print: July 12, 2011 (doi:10.4088/JCP.10m06507).

Corresponding author: John P. Houston, MD, PhD, Lilly USA, LLC, Lilly Corporate Center, Drop Code 4133, Indianapolis, IN 46285 ([email protected]).