Time to discontinuation of atypical versus typical antipsychotics in the naturalistic treatment of schizophrenia

Abstract

Background: There is an ongoing debate over whether atypical antipsychotics are more effective than typical antipsychotics in the treatment of schizophrenia. This naturalistic study compares atypical and typical antipsychotics on time to all-cause medication discontinuation, a recognized index of medication effectiveness in the treatment of schizophrenia.

Methods: We used data from a large, 3-year, observational, non-randomized, multisite study of schizophrenia, conducted in the U.S. between 7/1997 and 9/2003. Patients who were initiated on oral atypical antipsychotics (clozapine, olanzapine, risperidone, quetiapine, or ziprasidone) or oral typical antipsychotics (low, medium, or high potency) were compared on time to all-cause medication discontinuation for 1 year following initiation. Treatment group comparisons were based on treatment episodes using 3 statistical approaches (Kaplan-Meier survival analysis, Cox Proportional Hazards regression model, and propensity score-adjusted bootstrap resampling methods). To further assess the robustness of the findings, sensitivity analyses were performed, including the use of (a) only 1 medication episode for each patient, the one with which the patient was treated first, and (b) all medication episodes, including those simultaneously initiated on more than 1 antipsychotic.

Results: Mean time to all-cause medication discontinuation was longer on atypical (N = 1132, 256.3 days) compared to typical antipsychotics (N = 534, 197.2 days; p < .01), and longer on atypicals compared to typicals of high potency (N = 320, 187.5 days; p < .01), medium potency (N = 140, 213.5 days; p < .01), and low potency (N = 74, 208.7 days; p < .01). Among the atypicals, only clozapine, olanzapine, and risperidone had significantly longer time to all-cause medication discontinuation compared to typicals, regardless of potency level, and compared to haloperidol with prophylactic anticholinergic treatment. When compared to perphenazine, a medium-potency typical antipsychotic, only clozapine and olanzapine had a consistently and significantly longer time to all-cause medication discontinuation. Results were confirmed by sensitivity analyses.

Conclusion: In the usual care of schizophrenia patients, time to medication discontinuation for any cause appears significantly longer for atypical than typical antipsychotics regardless of the typical antipsychotic potency level. Findings were primarily driven by clozapine and olanzapine, and to a lesser extent by risperidone. Furthermore, only clozapine and olanzapine therapy showed consistently and significantly longer treatment duration compared to perphenazine, a medium-potency typical antipsychotic.

Figure 1

Treatment-episodes approach. Abbreviations: RIS, risperidone; OLZ, olanzapine; HAL, haloperidol. Using the treatment episode approach, a patient may have initiated several treatment episodes over the course of this 3-year study. This figure shows an example of the treatment pattern of a patient with 3 treatment episodes. Patients were administered study measures at the end of each 6-month assessment period.

Figure 2

Mean time to all-cause medication discontinuation for atypical and typical antipsychotics. Abbreviations: CLZ, clozapine; OLZ, olanzapine; RIS, risperidone; QUE, quetiapine; ZIP, ziprasidone; PER, perphenazine; HAL+AC, haloperidol with prophylactic anticholinergic agents; High, high-potency typical antipsychotics; Med, medium-potency typical antipsychotics; Low, low-potency typical antipsychotics. Error bars represent standard deviations. Significant differences (p < .05) between high-potency typicals and CLZ, OLZ, RIS, QUE; between medium-potency typicals and CLZ, OLZ, RIS; between low-potency typicals and CLZ, OLZ, RIS; between perphenazine and CLZ, OLZ, RIS; and between haloperidol with prophylactic anticholinergics and CLZ, OLZ, and RIS. Comparisons made with Cox Proportional Hazards regression model adjusted for patients and prior treatment characteristics.

Figure 3

Survival rates: time to all-cause medication discontinuation for atypicals versus typicals of different potency levels. Abbreviation: HAL+AC, haloperidol with prophylactic anticholinergics. Significant differences (p < .05) between the combined atypicals versus typicals of high, medium, and low potency, and versus haloperidol with prophylactic anticholinergics, using Cox Proportional Hazards regression model adjusted for patients and prior treatment characteristics.

Figure 4

Survival rates: time to all-cause medication discontinuation for clozapine, olanzapine, risperidone, quetiapine, ziprasidone versus typicals. Abbreviations: CLZ, clozapine; OLZ, olanzapine; RIS, risperidone; QUE, quetiapine; ZIP, ziprasidone. Significant differences between CLZ, OLZ, and RIS versus the combined typicals at p < .05 using the Cox Proportional Hazards regression model adjusted for patients and prior treatment characteristics.

Figure 5

Survival rates: time to all-cause medication discontinuation for clozapine, olanzapine, risperidone, quetiapine, ziprasidone versus perphenazine. Abbreviations: CLZ, clozapine; OLZ, olanzapine; RIS, risperidone; QUE, quetiapine; ZIP, ziprasidone; PER, perphenazine. Significant treatment group differences between CLZ, OLZ, and RIS versus perphenazine at p < .05, using Cox Proportional Hazards regression model adjusted for patients and prior treatment characteristics.