Neuroleptic Concentrations and Clinical Response

The clinical effectiveness of antipsychotic chemotherapy has been proven worldwide, yet a multitude of problems remain concerning that significant percent of the target population who do not benefit from such chemotherapy. Since the introduction of chlorpromazine in the early 1950s, other phe­ nothiazines, the butyrophenones, the thioxanthenes, the dihydroindolones, and the dibenzoxazepines have been introduced and have proven therapeutically effective with varying degrees of potency and side effects( 1). Non-responders to chlorpromazine have responded to some of the newer drugs, but the param­ eters of safe and effective dosage remain to be set. In the many uncontrolled and controlled clinical trials and anecdotal case reports, drug dosing has been mainly empirical, based on pushing doses to toxic levels or on a trial-and-error titration of dose and clinical effect. The lack of therapeutic guidelines in the clinical use of the antipsychotic drugs has moved interested groups to attack the problem of wide variability in drug dosage and clinical response among psychiatric patients. The introduction of sensitive antipsychotic drug assays in biologic fluids (2) revolutionized phannacokinetic and pharmacodynamic knowledge about the various antipsychotic drugs used in different types of clinical disorders. It