Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment.
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.


METHODS
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.
Clinical Research Service, John Umstead Hospital, 1003 12th St., Bldg. 32, Butner, NC 27705, USA. jpmcevoy@duke.edu
Joseph P
JP
McEvoy
Jeffrey A
JA
Lieberman
T Scott
TS
Stroup
Sonia M
SM
Davis
Herbert Y
HY
Meltzer
Robert A
RA
Rosenheck
Marvin S
MS
Swartz
Diana O
DO
Perkins
Richard S E
RS
Keefe
Clarence E
CE
Davis
Joanne
J
Severe
John K
JK
Hsiao
D000328:Adult; D000380:Agranulocytosis / Q000139:chemically induced; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use; D002908:Chronic Disease; D003024:Clozapine / Q000009:adverse effects* / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003987:Dibenzothiazepines / Q000627:therapeutic use; D016903:Drug Monitoring; D004351:Drug Resistance; D004802:Eosinophilia / Q000139:chemically induced; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D000077152:Olanzapine; D010879:Piperazines / Q000627:therapeutic use; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D000069348:Quetiapine Fumarate; D018967:Risperidone / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D013844:Thiazoles / Q000627:therapeutic use; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D010879:Piperazines; D013844:Thiazoles; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; C092292:ziprasidone; D003024:Clozapine; D018967:Risperidone; D000077152:Olanzapine