Geographical and temporal variations in clozapine prescription for schizophrenia.

Despite its unsurpassed efficacy in treatment-resistant schizophrenia, clozapine remains underutilized. Trends in the prescription of clozapine in patients with ICD-10 F20.x schizophrenia were assessed using data from Danish national registers. Three substudies were carried out: (i) an assessment of differences in national prescription patterns between 1996 and 2007 using a cross-sectional design; (ii) a comparison of time from first schizophrenia diagnosis to first prescription of clozapine in a five-year cohort study, using the Cox regression model, of two patient groups who were first diagnosed in 1996 and in 2003; (iii) an assessment of differences in the general psychiatric hospitals' use of clozapine in 2009. The results are as follows: (i) The percentage of schizophrenia patients receiving clozapine rose from 9.0% in 1996 to 10.1% in 2007 (p<0.001). In the same period, the percentage of patients having clozapine treatment augmented with another antipsychotic increased from 43.1% to 64.2%, p<0.001. (ii) Time from diagnosis with schizophrenia until first clozapine prescription was longer for patients diagnosed in 2003 compared to those diagnosed in 1996 (HR: 0.28 CI: 0.16-0.49). (iii) In 2009 there was significant variation in clozapine administration from one hospital to the other, with percentages of patients receiving the drug ranging from 5.7% to 16.8%, with 10.2% as the national mean. Although, the percentage of schizophrenia patients receiving clozapine increased from 1996 to 2007, the time from diagnosis of schizophrenia until first prescription of clozapine increased.