Risk of discontinuation of atypical antipsychotic agents in the treatment of schizophrenia.
OBJECTIVE
To compare discontinuation rates of atypical antipsychotic agents in patients with schizophrenia.


METHODS
Adult Maryland Medicaid patients with schizophrenia were categorized based on initial atypical antipsychotic drug received: aripiprazole (n=446); olanzapine (n=1705); quetiapine (n=1467); risperidone (n=1580); and ziprasidone (n=700). Discontinuation was measured using refill patterns, allowing 14-day gaps between refill dates. Using olanzapine as the reference drug, the hazard of discontinuation within the first year of follow-up was compared across atypicals using Cox proportional hazard models adjusted for demographic and clinical covariates. Sensitivity analysis tested the robustness of results by using different definitions of the index date.


RESULTS
At one-year follow-up, most patients discontinued their antipsychotic medication (90.4% adjusted mean discontinuation). The hazard ratio (HR) for discontinuing therapy in patients starting treatment on aripiprazole, risperidone, or ziprasidone was not significantly different from olanzapine [HR 1.047, 0.973 and 0.990, respectively]. Quetiapine was associated with significantly higher hazard of discontinuation [HR 1.130] than olanzapine. Covariates associated with significantly lower discontinuation were being male [HR 0.899], older age [HR 0.997] and being on concurrent medication when initiating therapy [HR 0.225]; having a previous hospitalization was associated with significantly higher discontinuation hazard [HR 1.276]. Results were robust in the sensitivity analysis.


CONCLUSIONS
Discontinuation rates were high at one-year follow-up and did not differ significantly for patients on aripiprazole, olanzapine, risperidone, or ziprasidone. The higher hazard of discontinuation associated with quetiapine when compared to olanzapine is consistent with that observed in Phase I of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE).
Mullins
C Daniel
CD
University of Maryland School of Pharmacy, 220 Arch Street, Baltimore, MD 21201, United States. dmullins@rx.umaryland.edu
Obeidat
Nour A
NA
Cuffel
Brian J
BJ
Naradzay
John
J
Loebel
Antony D
AD
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D000068180:Aripiprazole; D003987:Dibenzothiazepines / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010359:Patient Readmission / Q000706:statistics & numerical data; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use; D016016:Proportional Hazards Models; D000069348:Quetiapine Fumarate; D015363:Quinolones / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D012307:Risk Factors; D018967:Risperidone / Q000009:adverse effects / Q000627:therapeutic use; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012563:Schizophrenia, Paranoid / Q000175:diagnosis / Q000188:drug therapy / Q000523:psychology; D012565:Schizophrenic Psychology; D012680:Sensitivity and Specificity; D013375:Substance Withdrawal Syndrome / Q000453:epidemiology* / Q000209:etiology / Q000523:psychology; D015996:Survival Rate; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D010879:Piperazines; D015363:Quinolones; D013844:Thiazoles; D000069348:Quetiapine Fumarate; C092292:ziprasidone; D000068180:Aripiprazole; D018967:Risperidone