Can Genes Predict Response to Antipsychotics?: Viewpoint
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Analysis of Gene Variants Previously Associated With Iloperidone Response in Patients With Schizophrenia Who Are Treated With Risperidone
Fijal BA, Stauffer VL, Kinon BJ, et alJ Clin Psychiatry. July 12, 2011. [Epub ahead of print]
Study Summary
Six single nucleotide polymorphisms (SNPs) previously reported to be associated with response to iloperidone therapy were tested for association with response to risperidone therapy. Data were obtained during a 12-week randomized controlled trial in patients with schizophrenia in which all participants received risperidone 2-6 mg/d for the first 2 weeks. After 2 weeks, responders to risperidone (defined as ≥ 20% improvement in the Positive and Negative Syndrome Scale [PANSS] total score) continued risperidone treatment, but nonresponders were randomly assigned to either risperidone or olanzapine treatment (10-20 mg/d) for an additional 10 weeks. Associations between change in PANSS and the 6 SNPs were examined in risperidone-treated patients (N = 145). Two 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.
Viewpoint
Regarding change in PANSS total scores, the positive and negative predictive values were 52% and 56%, respectively, for XKR4 rs9643483, and were 57% and 62%, respectively, for GRIA4 rs251326. The authors further remark that the positive predictive values for response to risperidone treatment were very similar to that found for iloperidone, but the negative predictive values were inferior by 7%-18%. They conclude that genetic models that reliably predict response to atypical antipsychotics will most likely include numerous SNPs that individually provide little predictive power but, when considered together, account for a substantial portion of variation in response. Should this be true, the ever-decreasing cost of genetic testing may perhaps soon put personalized medicine within the reach of routine clinical practice. The authors correctly point out that much larger datasets than are usually available in individual trials of patients with schizophrenia will be required. This illustrates the need for joint collaboration on this type of work among all the manufacturers of antipsychotic medications.
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