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 ef fects of this combination on dopamine D-2 receptor blockade, prolactin leve l, and extrapyramidal side effects. Method: At baseline and 4-8 weeks after the addition of haloperidol (4 mg/d ay) to ongoing clozapine treatment, five patients were examined for prolact in elevation, extrapyramidal side effects, drug plasma levels, and D-2 rece ptor occupancy measured with [C-11]raclopride and positron emission tomogra phy 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 extrapyramid al side effects. Conclusions: Adding a modest dose of haloperidol to clozapine results in th e high D-2 receptor occupancy and sustained prolactin elevation usually ass ociated with typical antipsychotics. These findings suggest that the lack o f prolactin elevation associated with clozapine derives mainly from tow D-2 receptor occupancy and not from the medication's effects on other receptor s.