D2 dopamine receptor occupancy during low-dose treatment with haloperidol decanoate.
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.


METHODS
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.
Department of Clinical Neuroscience, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden.
S
S
Nyberg
L
L
Farde
C
C
Halldin
M L
ML
Dahl
L
L
Bertilsson
D000328:Adult; D000553:Ambulatory Care; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006220:Haloperidol / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D017448:Receptors, Dopamine D2 / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D014055:Tomography, Emission-Computed
D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; C033563:haloperidol decanoate; D006220:Haloperidol