Why Is Clozapine Uniquely Effective in Treatment-Resistant Schizophrenia? A Review and Proposal

Abstract

A great deal is known about the use, benefits, and side effects of clozapine in treatment-resistant schizophrenia (TRS). However, why clozapine is more effective than other antipsychotics in TRS remains unclear. In this article, we address this question. Patients with TRS show glutamate abnormalities, and clozapine has widespread effects on glutamate. However, these actions have not been proven to be different from those of other antipsychotics. Immune dysfunction is also reported in TRS, and clozapine has anti-inflammatory actions, but these have not been correlated with clinical improvement. Currently, there is a great deal of interest in muscarinic abnormalities in psychosis. Unlike most ..