Format

Send to

Choose Destination
See comment in PubMed Commons below
Biol Psychiatry. 1998 Jan 15;43(2):79-83.

Hypothesis testing: is clozapine's superior efficacy dependent on moderate D2 receptor occupancy?

Author information

  • 1Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore 21228, USA.

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.

PMID:
9474440
DOI:
10.1016/S0006-3223(98)00226-1
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center