Monitoring plasma concentrations of neuroleptics

Among the neuroleptics chlorpromazine has been the most extensively studied despite its complex metabolic pathways. Several metabolites, in particular 7-hydroxychlorpromazine, are psychotropically active. Oral phenothiazines are extensively metabolised "first-pass" through the liver. The relationship between clinical response and plasma concentrations of neuroleptics is tenous. The reasons for the lack of correlation include spontaneous remission in some patients, problems with flexible dosage schedules, the type of patient studied, differences in metabolic patterns, induction of metabolism in the liver, interactions with other drugs, and variations in plasma protein binding. Alternative research strategies might be to study metabolically less complex drugs such as haloperidol or to relate clinical response to autonomic, extrapyramidal, EEG, biochemical or endocrine measures.