The Modernization of Clozapine A Recapitulation of the Past in the United States and the View Forward

Purpose: Although clozapine was Food and Drug Administration (FDA) approved more than 3 decades ago, major barriers and gaps in knowledge continue to prevent its effective and safe use. We review modem-day problems encountered with clozapine in the United States (US). Methods: Information surrounding current administrative, clinical, research, and technological gaps or barriers related to clozapine use in the US was reviewed. Findings: The history of how clozapine became FDA approved likely contributes to gaps in knowledge. The frequency of safety warnings added to the FDA prescribing information may add to fears about clozapine, as evidence by numerous published survey studies. The clozapine Risk Evaluation and Mitigation Strategy (REMS) program has been modified several times in the last decade, causing access and safety issues for patients, which are discussed. Evidence may suggest that the FDA REMS requirements for hematologic monitoring are too cumbersome, and there may be ability to safely loosen requirements. The COVID-19 pandemic brought forth the ability for extended interval monitoring but also greater awareness of the clozapine-inflammation interaction. Newer guidelines published describe considerations in personalizing clozapine titration based on principles of ethnopsychopharmacology. Emerging technologies to support the use of clozapine are not widely available.

Automated summary

The article reviews the problems and barriers encountered with the use of clozapine in the United States, including gaps in knowledge, concerns about safety warnings, modifications to the clozapine Risk Evaluation and Mitigation Strategy (REMS) program, issues related to the COVID-19 pandemic, and the availability of newer guidelines and emerging technologies.