Patterns of discontinuation of atypical antipsychotics in the province of Québec: A retrospective prescription claims database analysis.
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 Québec.


METHODS
This retrospective, inception cohort study employed data from the Québec health insurance board databases and the Québec hospitalization registry on Québec 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 31, 2007. Five subcohorts were constructed according to the initial antipsychotic received: either 1 of the 4 atypical antipsychotics covered by the Québec drug plan at the time of the study-olanzapine, quetiapine, risperidone, and clozapine-or polytherapy (>1 atypical antipsychotic, or 1 atypical and 1 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. Discontinuation 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 years. 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 (AHR = 0.69; 95% CI, 0.64-0.74; P < 0.001). 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.
Moisan
Jocelyne
J
Université Laval, Québec, Canada. jocelyne.moisan@pha.ulaval.ca
Grégoire
Jean-Pierre
JP
D000328:Adult; D017677:Age Distribution; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use; D003024:Clozapine / Q000627:therapeutic use; D015331:Cohort Studies; D016208:Databases, Factual / Q000706:statistics & numerical data*; D003987:Dibenzothiazepines / Q000627:therapeutic use; D011307:Drug Prescriptions / Q000706:statistics & numerical data*; D004359:Drug Therapy, Combination / Q000706:statistics & numerical data; D004363:Drug Utilization / Q000706:statistics & numerical data; D017723:Drug Utilization Review / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy*; D008875:Middle Aged; D000077152:Olanzapine; D010349:Patient Compliance / Q000706:statistics & numerical data*; D011792:Quebec; D000069348:Quetiapine Fumarate; D012042:Registries / Q000706:statistics & numerical data; D012189:Retrospective Studies; D018967:Risperidone / Q000627:therapeutic use; D017678:Sex Distribution; D055815:Young Adult
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D003024:Clozapine; D018967:Risperidone; D000077152:Olanzapine