Persistence of haloperidol in human brain tissue

Objective: After discontinuation of neuroleptic drugs, their antipsychotic and antiparkinsonian effects are still present for a prolonged period. It i s not known whether the extended effects of neuroleptic drugs in humans are due to the continued presence of drug in brain tissue or to long-lasting d rug-induced physiologic changes. The aim of this study was to directly exam ine haloperidol concentrations in human brain tissue in relation to drug-fr ee time, Method: Haloperidol concentrations were measured in five regions ( temporal cortex, cingulate gyrus, caudate nucleus, dentate nucleus, corpus callosum) of the postmortem brains of 11 patients previously treated with h aloperidol. Haloperidol was analyzed by means of high-performance liquid ch romatography with ultraviolet detection. The half-life in brain tissue was estimated by a population kinetic analysis. Results: Haloperidol concentrat ions in the human brain tissue were 10-30 times higher than optimal serum c oncentrations used in the treatment of schizophrenia. Haloperidol concentra tions appeared to be homogeneously distributed across different brain areas within a single patient. There was no apparent relation between duration o f treatment and mean haloperidol concentration. Higher doses of haloperidol seemed to be related to higher concentrations in brain tissue. The elimina tion half-life from brain tissue was calculated to be 6.8 days, Conclusions : The results may have implications for clinical treatment decisions and th e design of clinical research protocols. Patients exposed to haloperidol ca nnot be considered to be free of residual effects of the drug for a number of weeks after withdrawal.