Clozapine-Related Adverse Events and Managing Inadequate Response
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Expires on Jun 01, 2026
Credit Offered
1 CME Credit
1 COP Credit

The key to keeping patients on clozapine is management of adverse effects and optimizing response. This presentation provides detailed practical information about strategies to mitigate weight gain, how to distinguish benign fever from other conditions (myocarditis, nephritis), and when to suspect cardiomyopathy. There is also be a discussion of why routine seizure prophylaxis with divalproex is not necessary and might be harmful, and methods for addressing nonresponse.

Learning Objectives

  • Discuss the rationale for and dosing of prophylactic use of metformin to manage clozapine related weight gain.
  • Identify that seizures are easily managed and should never be a reason to discontinue clozapine treatment. 
  • Express the conclusions that, due to the low prevalence of seizures, prophylactic anticonvulsants should not be used as these will be unnecessary in 98% of patients.
  • Diagnose myocarditis and interstitial nephritis, and distinguish these from benign fever and benign eosinophilia
  • Recognize the need for evaluation of cardiomyopathy
  • Explain that there is a known incidence of hematologic abnormalities other than neutropenia, including leukocytosis, neutrophilia, thrombocytosis, thrombocytopenia and anemia
  • Manage inadequate clozapine response

Target Audience

Psychiatrist; Physician (non-psychiatrist)

Estimated Duration

Estimated Duration: 1.0 hour 
Program Start Date: June 1, 2020 
Program End Date: June 1, 2026

Instructional Level


How to Earn Credit

Participants who wish to earn AMA PRA Category 1 Credit™ or a certificate of participation may do so by completing all sections of the course, including the evaluation. 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 (non-physicians) showing the completion 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 event 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


  • Jonathan Meyer, MD, Clinical Professor of Psychiatry, University of California, San Diego. Disclosures - Consultant: Acadia Pharmaceuticals, Alkermes, Abbvie, Intra-Cellular Therapies, Neurocrine; Speaker Bureau: Acadia Pharmaceuticals, Alkermes, Janssen Pharmaceutica, Neurocrine, Otsuka America, Inc., Sunovion Pharmaceuticals, and Teva Pharmaceutical Industries Ltd. 


  • Tristan Gorrindo, MD, American Psychiatric Association.  Reports no financial relationships with commercial interests.
  • Teri Brister, PhD, National Alliance on Mental Illness. Reports no financial relationships with commercial interests.
  • John Torous, MD, Beth Israel Deaconess Medical Center. Dr. Torous has no relevant financial relationships to disclose. (Reviewed on 6/4/2023)
  • Teri Brister, PhD, LPC, National Alliance on Mental Illness. Reports no financial relationships with commercial interests. (Reviewed on 6/6/2023)

Accessibility for Participants with Disabilities

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Technical Requirements

This internet-based CME activity is best experienced using any of the following:

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  • Internet Explorer 11+

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Optimal System Configuration:

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  • 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)
  • Internet Connection: 1 Mbps or higher

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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