Time-to-First Discontinuation, Adherence and Persistence in New Users of Second-Generation Antipsychotics

Consensus guidelines which are applicable in New Zealand and worldwide recommend that the duration of exposure to antipsychotics not exceed 12 weeks, unless justified for mental illnesses like schizophrenia and severe psychotic symptoms which require longer treatment. There has been limited information on time-to-first discontinuation (TTFD) for second-generation antipsychotics (SGAs) in a real world population setting in older people. The study objective was to compare TTFD, adherence, and persistence for individual SGA new users among people 65 years and older. A cohort of 30,297 SGA new users was followed up for antipsychotic discontinuation from January 1, 2006, to December 31, 2012. Data for oral formulations were extracted using health care databases from the New Zealand Ministry of Health. The TTFD, adherence, and persistence were defined using (dispensing gap ≥ 91 days, variable medication possession ratio ≥ 0.8, and gap duration < 91 days between refills), respectively. Kaplan-Meier curves and Cox regression analysis were used to estimate and adjust for outcomes. The overall TTFD in SGA new users was 192.3 days (95% confidence interval [CI], 177.6-206.9), mean age at dispensing was 80.9 years (SD, 8.1 years), and 60.3% were women. The TTFD for was shortest for risperidone, 101.3 days (95% CI, 85.0-117.7; P = 0.03) compared with clozapine, 68.3 days (95% CI: 43.7, 92.9). The adjusted all-cause TTFD risk for risperidone, olanzapine, quetiapine, or ziprasidone (hazard ratios, 0.54, 0.29, 0.22, and 0.08, respectively) was significantly lower than clozapine. The TTFD risk in the nonadherent compared with the adherent group was more than 3 times.