Keeping Up with Clozapine REMS: A Guide to Navigating the November 15 Changes
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Expires on Sep 30, 2024
Credit Offered
1 CME Credit
1 COP Credit

Clozapine is the only medication approved by the FDA for treatment resistant schizophrenia, and is widely underutilized in the US (Olfson et al. 2016). One serious possible side effect of clozapine is severe neutropenia, which is defined as an absolute neutrophil count of <500/µL.  A recent meta-analysis found the incidence of clozapine-induced severe neutropenia was 0.9%, with 1/7700 people exposed to clozapine dying from severe neutropenia (Myles et al. 2018).  To help manage the risk of neutropenia, clozapine has a Risk Evaluation and Mitigation Strategy (REMS) mandated by the FDA.  Currently there are 61 available REMS programs (U.S. Food and Drug Administration), and changes or updates to REMS systems can have important implications.  For example, after the FDA approved a new benign ethnic neutropenia treatment algorithm (Clozapine REMS 2014), a study found that patients with schizophrenia on clozapine would be less likely to need treatment interruption after the new guidelines were released (Sultan et al. 2017).  Effective November 15, 2021, a new clozapine REMS system will replace the existing system.  The new system will require all prescribers and pharmacists to re-certify, and additionally, all patients must be re-enrolled.  Failure to re-enroll or re-certify may lead to clozapine interruption, which could result in significant consequences and negative outcomes for individuals stabilized on clozapine.  This webinar will provide an update on clozapine-induced neutropenia, an overview of the changes coming to clozapine REMS (from the prescriber and pharmacist perspectives), and will discuss strategies for how prescribers may navigate these changes successfully.  The presenters will also have an open discussion with participants to listen to their concerns and brainstorm potential solutions on the new program. 


Recorded webinar, non-interactive, self-paced distance learning activity with post-test.

This presentation was recorded on September 29, 2021.

Learning Objectives

  • Review hypothesized mechanisms, risk factors, and team-based management strategies for severe neutropenia due to clozapine  
  • Assess the function of a REMS system and review examples of REMS used for medications commonly prescribed in psychiatry  
  • Summarize the changes for prescribers and pharmacists with the changes in clozapine REMS.

Target Audience

Nurse/Nurse PractitionerPharmacistPhysician (Non-psychiatrist)Physician AssistantPsychiatrist

Instructional Level

Introductory, Intermediate, Advanced

Estimate Time to Complete

Estimated Duration: 1.0 hour
Program Start Date: September 302021
Program End Date: September 302024

How to Earn Credit

Participants who wish to earn AMA PRA Category 1 Credit™, CE credit for psychologists, CE credit for social workers, nursing continuing professional development contact hours (NCPD, formerly CNE).After evaluating the program, course participants will be provided with an opportunity to claim hours of participation and print an official CME certificate (physicians) or certificate of participation (other disciplines) showing the event date and hours earned.  

Continuing Education Credit


The American Psychiatric Association (APA) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The APA designates this enduring activity for a maximum of 1.0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. 

Faculty and Planner Disclosures

All financial relationships relevant to this activity have been mitigated.


  • Robert O. Cotes, MD, is an Associate Professor at Emory University School of Medicine in the Department of Psychiatry and Behavioral Sciences. He serves as Co-Director of the PSTAR Clinic (Persistent Symptoms: Treatment, Assessment and Recovery), Director of Project ARROW (Achieving Recovery through Resilience, Optimism, and Wellness) and Co-Director of Open Dialogue Atlanta at Grady's Outpatient Behavioral Health Clinic. The PSTAR Clinic provides evidence-based, recovery-oriented care for individuals with persistent symptoms of psychosis, specializing in the use of clozapine. Project ARROW is a coordinated specialty care team for people experiencing first episode psychosis, offering comprehensive, person-centered care using a multidisciplinary approach. He is a member of the Clinical Expert Team for SMI Adviser. SMI Adviser is a joint initiative of American Psychiatric Association and Substance Abuse and Mental Health Services Administration that provides evidence-based resources to clinicians, individuals with serious mental illness, and their families. Dr. Cotes is an investigator for multiple research studies focused on treatment options for psychosis. His research focuses on clozapine, mitigating cardiometabolic side effects of antipsychotic medications, and first episode psychosis. Dr. Cotes reports no financial relationships with commercial interests. 
  • Donna Rolin, PhD, APRN is Clinical Associate Professor and the Director of the Psychiatric Mental Health Nurse Practitioner program at the University of Texas with 21 years of experience in psychiatric nursing. She is co-leading inter-disciplinary graduate training initiatives with Schools of Nursing, Medicine, Educational Psychology, Social Work, and Pharmacy with funding from the Health Resources and Services Administration and the Texas Higher Education Coordinating Board aiming to expand a culturally diverse workforce for underserved populations. She serves as the Co-Director of the Institute for Domestic Violence and Sexual Assault (IDVSA), working alongside Schools of Social Work, Law and Bureau of Business Research. Dr. Rolin’s current research focuses on wellness self-management for mental health promotion and the integration of telepresence robots in healthcare education. Dr. Rolin reports no financial relationships with commercial interests. 
  • Jonathan Meyer, MD is a Clinical Professor of Psychiatry at UC San Diego, and a Distinguished Fellow of the American Psychiatric Association. Dr. Meyer has teaching duties at UC San Diego and the Balboa Naval Medical Center in San Diego, and is a psychopharmacology consultant to the California Department of State Hospitals.  Dr. Meyer has lectured and published extensively on psychopharmacology. Along with Dr. Stephen Stahl he is co-author of the Clozapine Handbook published by Cambridge University Press in May 2019, and the recently published book The Clinical Use of Antipsychotic Plasma Levels released in September 2021 by Cambridge University Press. Dr. Meyer reports no financial relationships with commercial interests. 
  • Raymond C. Love, PharmD, BCPP, FASHP is a Professor at the University of Maryland School of Pharmacy and Department of Psychiatry (secondary appointment).  Dr. Love directs the State of Maryland Clozapine Authorization and Monitoring Program.  He has been a co-investigator on NIH funded grants entitled Biomarker and Safety Study of Clozapine in Benign Ethnic Neutropenia and A Randomized Controlled Trial of a Telementoring Program, Project ECHO, to Increase Clozapine Prescribing.  He is also a co-investigator on the University of Maryland Center of Excellence in Regulatory Science and Innovation/FDA grant Evaluation of the REMS Programs for Psychiatric Medications. Dr. Love reports no financial relationships with commercial interests. 


  • Teri Brister, PhD, LPC, National Alliance on Mental Illness. Reports no financial relationships with commercial interests.
  • John Torous, MDBeth Israel Deaconess Medical Center. Reports no financial relationships with commercial interests.

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Technical Requirements

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  • Internet Explorer 11+

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Optimal System Configuration:

  • Browser: Google Chrome (latest and 2nd latest version), Safari (latest and 2nd latest version), Internet Explorer 11.0+, Firefox (latest and 2nd latest version), or Microsoft Edge (latest and 2nd latest version)
  • Operating System: Windows versions 8.1+, Mac OS X 10.5 (Leopard) +, Android (latest and 2nd latest version), or iOS/iPad OS (latest and 2nd latest version)
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Minimum Requirements:

  • Windows PC: Windows 8.1 or higher; 1 GB (for 32-bit)/2 GB (for 64-bit) or higher RAM; Microsoft DirectX 9 graphics device with WDDM driver; audio playback with speakers for programs with video content
  • Macintosh: Mac OS X 10.5 or higher with latest updates installed; Intel, PowerPC G5, or PowerPC G4 (867MHz or faster) processor; 512 MB or higher RAM; audio playback with speakers for programs with video content

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Funding for SMI Adviser was made possible by Grant No. SM080818 from SAMHSA of the U.S. Department of Health and Human Services (HHS). The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement by, SAMHSA/HHS or the U.S. Government.
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