CYP1A2*1F polymorphism decreases clinical response to clozapine in patients with schizophrenia

Introduction: Genetic polymorphisms of cytochrome P450 (CYP) may predict the treatment response or occurrence of side effects of antipsychotic drugs. Aim: We studied the association of response to clozapine treatment in schizophrenic patients in relation to polymorphisms in the CYP1A2 gene. Methods: The degree of psychosis of the patients (n=55) was assessed using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS) and routine biochemistry. The patients were monitored for 18 weeks and the scales were applied before starting the treatment and at the end of the follow up period. Clozapine was used at doses of 200 to 600 mg/day. A positive response was defined as a 20% decrease in pre-and posttreatment scores of one of the BPRS, SANS, or SAPS scores. In addition, 45 patients, who were already on clozapine treatment, were assessed retrospectively. Results: As assessed at the 18th week after start of therapy, lack of response to clozapine treatment was 2.4 fold higher in the patients carrying the CYP1A2*1F*1F genotype (p=0.02) compared to patients carrying at least one wild type allele (i.e. *1/*1 or *1/*1F). Smoking decreased the response rate by about 15% (p=0.014). Conclusion: The results of our study suggest that the CYP1A2*1F/*1F genotype may be a risk factor for lack of response to clozapine treatment in psychotic patients, especially in cigarette smokers