Abstract：
BACKGROUND:How clozapine exerts superior antipsychotic efficacy in treatment-resistant schizophrenia is not known. Moderate (rather than "full") occupancy of D2 postsynaptic receptors may be crucial, perhaps by achieving a more effective D1/D2 or serotonin-2a/D2 ratio. The objective of this study was to test the moderate occupancy hypothesis of clozapine's superior efficacy. METHODS:Data from the New York effectiveness of clozapine study were used to compare 6-week clozapine treatment results in patients discontinuing oral neuroleptic medication with similar patients discontinuing long-acting depot neuroleptic. The latter group is assured "full" D2 occupancy during the 6-week clozapine treatment. RESULTS:If moderate occupancy is crucial for superior efficacy, the oral discontinuation group should manifest more improvement. Both groups showed the 6-week improvement expected with clozapine therapeutics [31% and 29% reduction in Brief Psychiatric Rating Scale (BPRS) scores in the depot and oral groups, respectively]. An analysis of covariance (for baseline BPRS) revealed no difference in change scores (df = 1,100; F = 0.17; p = ns). CONCLUSIONS:The reduced D2 occupancy hypothesis is rejected.
journal_name
Biol Psychiatryjournal_title
Biological psychiatryauthors
Carpenter WT Jr,Zito JM,Vitrai J,Volavka Jdoi
10.1016/S0006-3223(98)00226-1subject
Has Abstractpub_date
1998-01-15 00:00:00pages
79-83issue
2eissn
0006-3223issn
1873-2402pii
S0006-3223(98)00226-1journal_volume
43pub_type
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