Risk of discontinuation of atypical antipsychotic agents in the treatment of schizophrenia.

OBJECTIVES: To compare discontinuation rates of atypical antipsychotic agents in patients with schizophrenia. METHOD: 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).

Effect of initial ziprasidone dose on treatment persistence in schizophrenia.

OBJECTIVE: To determine the relationship between ziprasidone initial dose and treatment persistence among patients diagnosed with schizophrenia. METHOD: Adult Medicaid recipients (N=1096) diagnosed with schizophrenia who had ziprasidone prescription claims between July 1, 2001 and September 30, 2003, were categorized by initial dose: low (20-60 mg per day, n=464), medium (61-119 mg per day, n=320) and high dose (120-160 mg per day, n=312). Treatment persistence up to 365 days was measured using refill patterns, allowing 15-day gaps between expected refill dates. Multivariate survival analysis explored the simultaneous impact of age, gender, race, previous hospitalization, and concomitant medication usage, in addition to initial dose of ziprasidone. Sensitivity analysis tested the robustness of results with different definitions for persistence and allowable gaps between refills. RESULTS: Discontinuation rates across the observation period (maximum, 12 months per individual) were lower for patients initiated with high-dose than low-dose ziprasidone (P=0.001). Other factors significantly associated with greater discontinuation of medication were monotherapy (versus combination therapy) and hospitalization within the 6 months prior to the index date of therapy. Black race was associated with greater discontinuation, although this was not consistent across sensitivity analyses. CONCLUSIONS: Patients with schizophrenia started on high doses of ziprasidone have lower discontinuation rates in a retrospective Medicaid database than patients started on low doses. These results were robust across various sensitivity analyses.