Is clozapine-related agranulocytosis the result of the medication itself or due to an as yet unconfirmed report of a contaminant in the medication which has now been removed by the drug's manufacturers? To determine the answer to this question, the proposed research will compare incidence of precipitant agranulocytosis in a sample of 50 patients beginning clozapine treatment (all with a past history of clozapine-related agranulocytosis which is now cured).
To place the proposed research in the context of the existing work in the field, this section of the proposal presents a comprehensive review of the literature. The first section of the review presents a general discussion of clozapine-induced agranulocytosis with an emphasis upon defining terms and providing basic facts about the condition.
The second section of the presented review describes and discusses studies supporting the notion that the medication itself produces agranulocytosis while the third section presents a brief review of studies suggesting factors responsible for clozapine-induced agranulocytosis. The final section of the review provides at least preliminary data supporting the speculation that the development of agranulocytosis may not be clozapine-related, but may be actually due to a contaminant in the drug which the manufacture has presumably now removed.
Among the psychotropic drugs, neuroleptics such as chlorpromazine or haloperidol are very effective treatments for schizophrenia. These compounds have one property in common, their ability to antagonize the action of dopamine at post-synaptic dopamine D2 receptors, which has been correlated with their antipsychotic activity.
Unfortunately, this blockade in the central nervous system (CNS) is associated with two major side effects: abnormal movements or extrapyramidal side effects and hyperprolactinemia. Unlike those agents, clozapine, a dibenzodiazepine derivative, is very active aga...