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Am J Psychiatry 1995; 152:173-178
Copyright © 1995 by American Psychiatric Association
D2 dopamine receptor occupancy during low-dose treatment with haloperidol decanoate
S Nyberg, L Farde, C Halldin, ML Dahl and L Bertilsson
Department of Clinical Neuroscience, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden.
OBJECTIVE: The aim of this study was to examine the relationships among
clinical effects, central D2 dopamine receptor occupancy, and plasma
concentrations of haloperidol in eight clinically stabilized schizophrenic
outpatients who were responding to treatment with low doses of haloperidol
decanoate. METHOD: During a 4-week interval of haloperidol decanoate dosage
(dose range = 30-50 mg), the patients' D2 receptor occupancy was determined
with positron emission tomography on two occasions. Plasma concentrations
of haloperidol were determined with a sensitive high-performance liquid
chromatography method. RESULTS: One week after injection of haloperidol
decanoate, the mean D2 receptor occupancy was 73% (range = 60%-82%), and
the mean plasma concentration of haloperidol was 4.6 nmol/liter (range =
2.9-9.7). After 4 weeks, the mean D2 receptor occupancy had decreased to
52% (range = 20%-74%), and the mean haloperidol concentration to 2.3
nmol/liter (range = 1.0-4.4). CONCLUSIONS: The D2 receptor occupancy 1 week
after injection was high and comparable to that previously found in
patients responding to acute treatment with classic neuroleptics.
Prevention of relapse was maintained despite low D2 receptor occupancy
during the latter part of the treatment interval. These observations
indicate that continuously high D2 receptor occupancy may not be necessary
to prevent schizophrenic relapses. The results emphasize the need for
systematic clinical evaluation of intermittent low-dose treatment
strategies.
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