Effectiveness of Clozapine Versus Olanzapine, Quetiapine, and Risperidone in Patients With Chronic Schizophrenia Who Did Not Respond to Prior Atypical Antipsychotic Treatment
Joseph P. McEvoy, M.D., Jeffrey A. Lieberman, M.D., T. Scott Stroup, M.D., M.P.H., Sonia M. Davis, Dr.P.H., Herbert Y. Meltzer, M.D., Robert A. Rosenheck, M.D., Marvin S. Swartz, M.D., Diana O. Perkins, M.D., M.P.H., Richard S.E. Keefe, Ph.D., Clarence E. Davis, Ph.D., Joanne Severe, M.S., John K. Hsiao, M.D. for the CATIE Investigators
American Journal of Psychiatry 163:600-610, April 2006
doi: 10.1176/appi.ajp.163.4.600
© 2006 American Psychiatric Association
Abstract
OBJECTIVE: When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug, it is unclear what other antipsychotic to switch to and when to use clozapine. In this study, the authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness (CATIE) investigation. METHOD: Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone in phase 1 or 1B of the trials, primarily because of inadequate efficacy, were randomly assigned to open-label treatment with clozapine (N=49) or blinded treatment with another newer atypical antipsychotic not previously received in the trial (olanzapine [N=19], quetiapine [N=15], or risperidone [N=16]). RESULTS: Time until treatment discontinuation for any reason was significantly longer for clozapine (median=10.5 months) than for quetiapine (median=3.3), or risperidone (median=2.8), but not for olanzapine (median=2.7). Time to discontinuation because of inadequate therapeutic effect was significantly longer for clozapine than for olanzapine, quetiapine, or risperidone. At 3-month assessments, Positive and Negative Syndrome Scale total scores had decreased more in patients treated with clozapine than in patients treated with quetiapine or risperidone but not olanzapine. One patient treated with clozapine developed agranulocytosis, and another developed eosinophilia; both required treatment discontinuation. CONCLUSIONS: For these patients with schizophrenia who prospectively failed to improve with an atypical antipsychotic, clozapine was more effective than switching to another newer atypical antipsychotic. Safety monitoring is necessary to detect and manage clozapine’s serious side effects.
Related Articles:
Practical Treatment Information for Schizophrenia
Tamminga
Am J Psychiatry 2006 163: 563-565.
The disclosures suppliment includes
Dr. Meltzer reports having received research funding from Janssen Pharmaceutica
Products, Solvay and Acadia; and consulting and educational fees from AstraZeneca Pharmaceuticals LP, Janssen Pharmaceutica Products, Novartis, Pfizer Inc., and Solvay. He holds stock in Acadia and is on the advisory board of Janssen, Merck, Pfizer Inc and Eli Lilly and Co.
--------------------------------------------------------
Effectiveness of Olanzapine, Quetiapine, Risperidone, and Ziprasidone in Patients With Chronic Schizophrenia Following Discontinuation of a Previous Atypical Antipsychotic
T. Scott Stroup, M.D., M.P.H., Jeffrey A. Lieberman, M.D., Joseph P. McEvoy, M.D., Marvin S. Swartz, M.D., Sonia M. Davis, Dr.P.H., Robert A. Rosenheck, M.D., Diana O. Perkins, M.D., M.P.H., Richard S.E. Keefe, Ph.D., Clarence E. Davis, Ph.D., Joanne Severe, M.S., John K. Hsiao, M.D. for the CATIE Investigators
American Journal of Psychiatry 163:611-622, April 2006
doi: 10.1176/appi.ajp.163.4.611
© 2006 American Psychiatric Association
Abstract
Background: In the treatment of schizophrenia, changing antipsychotics is common when one treatment is suboptimally effective, but the relative effectiveness of drugs used in this strategy is unknown. This randomized, double-blind study compared olanzapine, quetiapine, risperidone, and ziprasidone in patients who had just discontinued a different atypical antipsychotic. METHOD: Subjects with schizophrenia (N=444) who had discontinued the atypical antipsychotic randomly assigned during phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) investigation were randomly reassigned to double-blind treatment with a different antipsychotic (olanzapine, 7.5–30 mg/day [N=66]; quetiapine, 200–800 mg/day [N=63]; risperidone, 1.5–6.0 mg/day [N=69]; or ziprasidone, 40–160 mg/day [N=135]). The primary aim was to determine if there were differences between these four treatments in effectiveness measured by time until discontinuation for any reason. RESULTS: The time to treatment discontinuation was longer for patients treated with risperidone (median: 7.0 months) and olanzapine (6.3 months) than with quetiapine (4.0 months) and ziprasidone (2.8 months). Among patients who discontinued their previous antipsychotic because of inefficacy (N=184), olanzapine was more effective than quetiapine and ziprasidone, and risperidone was more effective than quetiapine. There were no significant differences between antipsychotics among those who discontinued their previous treatment because of intolerability (N=168). CONCLUSIONS: Among this group of patients with chronic schizophrenia who had just discontinued treatment with an atypical antipsychotic, risperidone and olanzapine were more effective than quetiapine and ziprasidone as reflected by longer time until discontinuation for any reason.
Related Articles:
Practical Treatment Information for Schizophrenia
Tamminga
Am J Psychiatry 2006 163: 563-565.
--------------------------------------------------------
In This Issue
American Journal of Psychiatry 163:50A, April 2006
doi: 10.1176/appi.ajp.163.4.A50
© 2006 American Psychiatric Association
Antipsychotics in Practice: CATIE Phase 2
Real-world treatment of schizophrenia is being scrutinized in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). In phase 1, a conventional antipsychotic and several newer, "atypical," antipsychotics all had high rates of treatment discontinuation. Simulating clinical practice, phase 2 switched these patients to a different antipsychotic, one of several atypicals. Two 18-month trials were undertaken, targeting patients who discontinued treatment because of intolerable side effects and those who quit because of inefficacy. Discontinuation rates were again high, but there were noteworthy differences between drugs. Clozapine was included in one of the two trials, described by McEvoy et al. (p. 600). As expected, it produced less discontinuation (56% versus 71%–93%) and more time in treatment (10.5 months versus 2.7–3.3 months). Agranulocytosis and eosinophilia each developed in one of the 45 patients, confirming the need for safety monitoring. In a trial that excluded clozapine, reported by Stroup et al. (p. 611), discontinuation rates were 64%-84%, but olanzapine and risperidone produced longer median times to discontinuation (6.3 and 7.0 months) than quetiapine and ziprasidone (4.0 and 2.8 months) (see figure above). Ziprasidone had the highest rate of serious adverse events. The results for olanzapne illustrate the need to tailor treatment to the individual-in phases 1 and 2 it produced longer treatment continuation, but the effects on weight, cholesterol, and triglycerides rule it out for certain patients. An editorial by Carol Tamminga on treatment of schizophrenia is on p. 563.
--------------------------------------------------------
If anyone wants PDFs of the abstracted articles, PM me.
Jason |
