Increased dopamine d(2) receptor occupancy and elevated prolactin level associated with addition of haloperidol to clozapine.
OBJECTIVE
The authors added haloperidol, a potent D(2) blocker, to ongoing treatment with clozapine in patients with schizophrenia to determine the effects of this combination on dopamine D(2) receptor blockade, prolactin level, and extrapyramidal side effects.


METHODS
At baseline and 4-8 weeks after the addition of haloperidol (4 mg/day) to ongoing clozapine treatment, five patients were examined for prolactin elevation, extrapyramidal side effects, drug plasma levels, and D(2) receptor occupancy measured with [(11)C]raclopride and positron emission tomography imaging.


RESULTS
Adding haloperidol significantly increased D(2) receptor occupancy, from a mean of 55% to 79%, and significantly increased the prolactin level. One patient developed akathisia, and another manifested mild extrapyramidal side effects.


CONCLUSIONS
Adding a modest dose of haloperidol to clozapine results in the high D(2) receptor occupancy and sustained prolactin elevation usually associated with typical antipsychotics. These findings suggest that the lack of prolactin elevation associated with clozapine derives mainly from low D(2) receptor occupancy and not from the medication's effects on other receptors.
Kapur
S
S
PET Centre, Clarke Division, CAMH, Toronto, Ont. Canada. skapur@camhpet.on.ca
Roy
P
P
Daskalakis
J
J
Remington
G
G
Zipursky
R
R
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000453:epidemiology; D003024:Clozapine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004359:Drug Therapy, Combination; D006220:Haloperidol / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D011388:Prolactin / Q000097:blood*; D020891:Raclopride; D017448:Receptors, Dopamine D2 / 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; D020891:Raclopride; D011388:Prolactin; D003024:Clozapine; D006220:Haloperidol