A Call to Action for Starting Clozapine: Increasing Clozapine Use and Safety in a Post-REMS Era

Clozapine remains the only medication approved by the U.S. Food and Drug Administration (FDA) for managing treatment-resistant schizophrenia and for reducing the risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder. Despite its known benefits, its use remains suboptimal with non-evidence-based treatments often trialed before clozapine. These delays have been shown to reduce the likelihood of clozapine response or increase the risk of early discontinuation. With the elimination of the Clozapine Risk Evaluation and Mitigation Strategy program, one barrier that had impeded clozapine use has been negated. However, barriers persist that are related to clinicians' perceptions of clozapine and knowledge related to appropriate titration, monitoring, and management of adverse drug reactions. With a growing body of evidence suggesting that current FDA-recommended hematologic monitoring is overly cautious, there is future potential that these requirements become less stringent. This marks an important time to bring forth a call to action for increased use of clozapine and focus on important clozapine-related initiation and monitoring strategies. Such strategies include slower initial titration, understanding differences in clozapine metabolism across different genetic ancestry groups, awareness of inflammatory reactions, recognition of pneumonia-related mortality, and appropriate bowel care. This review highlights best and evidence-based practices to help clinicians increase clozapine prescribing and ensure that patients have the greatest opportunity for a successful, potentially life-saving clozapine trial.