Drug adherence: effects of decreased visit frequency on adherence to clozapine therapy

To study the effects of visit frequency on drug-adherence parameters subsequent to the change in the United States Food and Drug Administration (FDA)-mandated monitoring of white blood cell counts from weekly to every 2 weeks (biweekly) after 6 months of clozapine therapy.

Paid prescription claims records for clozapine from September 1, 1995-August 31, 2001, were extracted from the Texas Medicaid Vendor Drug Program database. Two groups of subjects were identified: subjects treated before and those treated after the FDA labeling change in monitoring frequency, which occurred on April 1, 1998. Prescription claims records for each subject were assessed for 365 days after the initial 6 months of therapy. Adherence measures included persistence, medication possession ratio (MPR), and time taking clozapine.

Subjects receiving weekly hematologic monitoring had significantly higher rates of persistence (0.79 +/- 0.35 vs 0.70 +/- 0.38, p < 0.001) and MPRs (0.75 +/- 0.36 vs 0.66 +/- 0.38, p < 0.001) and continued to take clozapine longer (p < 0.002) compared with subjects receiving biweekly monitoring. Fewer subjects in the weekly monitoring group discontinued clozapine therapy during the 1-year study period (49.4% vs 57.9%, p = 0.008). Similar results were observed when cohorts were matched according to age, sex, and index clozapine dosage.

Significant effects of visit frequency on adherence to clozapine therapy were noted. For patients inadequately adherent to therapy, an increase in visit frequency may improve adherence, and based on these results, the extra visits do not need to be with a physician or have any specific purpose other than contact with a provider.