Increased dopamine D2 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. Method: 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 [C-11]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 tow D-2 receptor occupancy and not from the medication's effects on other receptors.