Background: Patterns of discontinuation of atypical antipsychotic drugs, Including the return to therapy after an Interruption, have not been examined longitudinally. Objective: This study was conducted to describe discontinuation patterns of atypical antipsychotic drugs across a spectrum Of Outpatients in the province of Quebec. Methods: This retrospective, Inception cohort Study employed data from the Quebec health insurance board databases and the Quebec hospitalization registry on Quebec Drug Plan beneficiaries between the ages of 20 and 64 years who first filled a prescription for any antipsychotic drug between January 1, 2000, and December 3 1, 2007. Five subcohorts were Constructed according to the initial antipsychotic received: either I of the 4 atypical antipsychotics covered by the Quebec drug plan at the time of the study-olanzapine, quetiapine, risperidone, and clozapine-or polytherapy (>1 atypical antipsychotic, or I atypical and I typical antipsychotic). Discontinuation was defined as a failure to refill the initial prescription within 2 times the days' supply of the preceding claim. In individuals who discontinued initial drug treatment, a new course of treatment was defined as initiation of treatment with any antipsychotic drug after a first treatment discontinuation. Discoutinuation of a second Course of treatment was defined as failure to refill a prescription for the second drug within 2 times the days' supply of the preceding claim. Patients were followed from initiation to December 31, 2004, ineligibility for the drug plan, or death, whichever came first. Kaplan-Meier curves and Cox regression models were used to compare discontinuations and new courses of treatment by initial atypical antipsychotic. Results: The overall cohort consisted of 46,074 drug plan beneficiaries who had initiated antipsychotic treatment during the specified period. The majority of individuals were female (54.6%) and lived in urban areas (79.2%); the median age ranged from 40 to 44 Nears. The mean (SD) duration of follow-up was 2.67 (1.91) years. Compared with Individuals whose initial therapy was olanzapine, those whose initial therapy was quetiapine had a significantly higher likelihood of discontinuing initial treatment (adjusted hazard ratio [AHR] = 1.06; 95%, CI, 1.04-1.09; P < 0.001). The likelihood of discontinuing initial treatment was significantly lower among those whose Initial therapy was risperidone (AHR = 0.93; 95% CI, 0.90-0.95; P < 0.001), clozapine (AHR = 0.56; 95% CI, 0.46-0.68; P < 0.001), or polytherapy (AHI = 0.69; 95%, CI, 0.64-0.741 P < 0.00.1). Those whose Initial therapy was quetiapine were significantly less likely than those whose initial therapy was olanzapine to begin a second Course of treatment (AHR = 0.95; 95% CI, 0.90-0.99; P = 0.02). Compared with individuals who initiated a second Course of treatment with olanzapine, those who initiated a second Course with quetiapine were more likely to discontinue again (AHR = 1.09; 95% CI, 1.04-1.14; P < 0.001), whereas those who initiated a second Course with risperidone were less likely to discontinue again (AHR = 0.95; 95% CI, 0.90-1.00; P = 0.04). Conclusions: This study population had a high risk of discontinuing initial atypical antipsychotic therapy within 1 year. Those who discontinued had a low likelihood of returning to treatment, and those who did return to treatment had a high likelihood of discontinuing again. These patterns of use may have serious consequences for patients' health and for the utilization of health services. (Clin Ther. 2010;32[Suppl A]: S21-S31) (C) 2010 Excerpta Medica Inc.