Dopamine D2 receptor imaging and neuroleptic drug response

Studies with positron emission tomography and single photon emission computed tomography have yielded important findings concerning the relationship between dopamine D2 receptor occupancy and neuroleptic dose, plasma neuroleptic levels, and clinical response. For "typical" neuroleptics, therapeutic response is associated with occupancy levels as low as 60%-70%, which can be achieved at lower doses than are routinely used. For these drugs, extrapyramidal side effects increase, and therapeutic response remains unchanged with higher occupancy levels. Although the mechanisms responsible for the improved clinical efficacy and tolerability of atypical neuroleptics are still poorly understood, antipsychotic efficacy has been observed at lower D2 receptor occupancy rates than with typical neuroleptics. It is unclear whether the lower incidence of extrapyramidal side effects observed with the atypical neuroleptic clozapine can be attributed to its lower D2 occupancy, its relatively specific effects on the ventral striatum, or its nondopaminergic effects. There are a number of additional unresolved issues, including the high interindividual variation in scan outcome measurements, possible effects of concomitant medication, possible effects of endogenous dopamine, and assumptions in various strategies used to model receptor densities and occupancy rates.