A preliminary study of association of genetic variants with early response to olanzapine in schizophrenia

BACKGROUND: Treatment response can be predicted in schizophrenia by DNA information in the drug metabolism pathways. This study aimed to examine clinical characteristics and genetic determinant (s) of early response to olanzapine treatment in schizophrenia using specified drug metabolizing genes. MATERIALS AND METHODS: Consenting participants (n = 33) suffering from schizophrenia were diagnosed on Diagnostic Interview for Genetic Studies. Oral olanzapine was administered in an incremental dose up to 10 mg (2 weeks) and 20 mg (6 weeks). All participants were tested on Positive and Negative Syndrome Scale, Clinical Global Impressions, and Global Assessment of Functioning at 0, 2, and 6 weeks. Side effects were also evaluated. After 2 weeks, 11 (33.33%) fulfilled criteria for early response, whereas 17 (51.52%) responded at 6 weeks. We investigated the contribution of clinical factors and five polymorphisms (rs2740574, rs2470890, rs762551, rs3892097, and rs1065852) in predicting response to olanzapine at 2 and 6 weeks of treatment with a standard dose. RESULTS: Severity of positive symptoms at baseline was associated with response at 2 weeks (P = 0.01) while higher scores on Scale for the Assessment of Negative Symptoms (SANS) at baseline was associated with response at both 2 (P = 0.04) and 6 weeks (P = 0.03). None of the five single nucleotide polymorphisms (SNPs) selected were significantly associated with response to olanzapine. CONCLUSIONS: Olanzapine is an effective and safe drug. Positive and Negative Syndrome Scale positive score and SANS score were variably associated with response at 2 and/or 6 weeks. Replicate studies with bigger sample size are warranted for conclusive results in the Indian population for genetic association.