TY - JOUR
T1 - The Modernization of Clozapine
T2 - A Recapitulation of the Past in the United States and the View Forward
AU - Leung, Jonathan G.
AU - De Leon, Jose
AU - Frye, Mark A.
AU - Singh, Balwinder
AU - Cotes, Robert O.
AU - McElroy, Susan L.
N1 - Publisher Copyright:
© Wolters Kluwer Health, Inc. All rights reserved.
PY - 2022/11/1
Y1 - 2022/11/1
N2 - 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 modern-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. Implications Clozapine is a unique life-saving drug but it is underused in the US, despite its established efficacy. The 2021 REMS changes led to significant difficulties for providers and patients. We highlight the importance of the clozapine-inflammation interaction, therapeutic drug monitoring, and the ability for individual care based on patient-specific factors. There is an urgent need for advancing technology used for clozapine monitoring, evaluating barriers created by REMS, and establishing consistent practices throughout the US.
AB - 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 modern-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. Implications Clozapine is a unique life-saving drug but it is underused in the US, despite its established efficacy. The 2021 REMS changes led to significant difficulties for providers and patients. We highlight the importance of the clozapine-inflammation interaction, therapeutic drug monitoring, and the ability for individual care based on patient-specific factors. There is an urgent need for advancing technology used for clozapine monitoring, evaluating barriers created by REMS, and establishing consistent practices throughout the US.
KW - clozapine
KW - clozapine REMS
KW - ethnopsychopharmacology
KW - infection
KW - inflammation
KW - neutropenia, COVID-19
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U2 - 10.1097/JCP.0000000000001606
DO - 10.1097/JCP.0000000000001606
M3 - Review article
C2 - 36170148
AN - SCOPUS:85141892084
SN - 0271-0749
VL - 42
SP - 565
EP - 580
JO - Journal of Clinical Psychopharmacology
JF - Journal of Clinical Psychopharmacology
IS - 6
M1 - 6
ER -