Are we Ready to Embrace “Third-Generation” Treatments for Schizophrenia? Beyond Postsynaptic Dopamine-2 (D2) Blockade: Broader Efficacy of New Drugs Against Psychosis Without Distressing Side Effects

Course Description

Thorazine was discovered in the 1950s with the understanding that dopamine antagonism was needed for antipsychotic action. This medication and the many first- and second-generation antipsychotics that followed are effective in reducing psychotic symptoms but most approved to date have relatively high binding affinity (60-80%) to the dopamine 2 (D2) receptor thought to be needed for their efficacy.

Antagonizing these post synaptic dopamine receptors often produces distressing adverse events including extrapyramidal side effects (EPS), akathisia and hyperprolactinemia. Many newer second-generation agents have reduced these neurologic side effects by adding serotonin type 2A (5-HT2A)–receptor antagonism to D2-receptor antagonism. While lower rates of these D2 related adverse effects are seen, these adverse effects remain variable among agents. These adverse effects have contributed to early discontinuation, nonadherence, rehospitalizations and medical comorbidities.

Recently approved and emerging antipsychotic medications that have low post synaptic D2 binding or without direct dopamine modulation have lower side effect burdens than older medications. This may introduce a new generation to treatments for schizophrenia where patients may never experience some of the severe adverse events. There is a great need to provide better efficacy and side effect burdens for our patients requiring that we understand these new mechanisms and consider these "third-generation" treatments early in the course of illness in order to prevent the adverse consequences.

During this activity participants will review the pharmacologic mechanisms and adverse effects related to receptor binding of antipsychotics, understand the role of D2 related adverse effects such as extrapyramidal side effects, akathisia, and hyperprolactinemia on patient outcomes, and learn the weight related side effect liabilities of existing agents. Lastly, participants will be able to discuss the novel pharmacological properties of newer, emerging and pipeline “third-generation” antipsychotics and the benefits of these medications in avoiding or minimizing adverse effects.

Learning Objectives

  1. Review the pharmacologic history, mechanisms, and adverse effects related to receptor binding of antipsychotics and the evolving history of the dopamine hypothesis for psychosis treatment.
  2. Understand the role of D2 related adverse effects such as extrapyramidal side effects, akathisia and hyperprolactinemia on patient nonadherence, discontinuation, and outcomes. Consider weight related side effect liabilities of these agents.
  3. Discuss the novel pharmacological properties of newer, emerging and pipeline "third-generation" antipsychotics and the benefits of these medications in avoiding or minimizing adverse effects and novel mechanisms beyond post-synaptic D2 blockade.

Target Audience

If you are a pharmacist, nurse practitioner, or other health care professional involved in the comprehensive medication management of individuals living with mental health and/or substance use disorders, we invite you to participate in this online course.

Faculty

Christoph U. Correll, MD
Austin R. Campbell, PharmD, BCPP
View biographical information

Christoph U. Correll, MD
Professor of Psychiatry and Molecular Medicine
The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, USA
Professor and Chair, Child and Adolescent Psychiatry
Charité – Universitätsmedizin, Berlin, Germany

Austin R. Campbell, PharmD, BCPP 

Clinical Pharmacy Specialist – Psychiatry
University of Missouri Health Care, Columbia, MO

Faculty Disclosures

Grant/Research Support: Christoph U. Correll: Janssen, Takeda

Consultant: Christoph U. Correll: AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Axsome, Damitsa, Gedeon Richter, Hikma, IntraCellular Therapies, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Medscape, Merck, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Servier, Sumitomo Dainippon, Sunovion, Supernus, Takeda, Teva, and Viatris

Austin Campbell: Otsuka Pharmaceutical Co. Ltd. (served on PsychU National Forum panel, October 2020)

Speakers Bureau/Educational Services: Austin Campbell: Sunovion Pharmacueticals Inc.

Financial: Austin Campbell: UpToDate (author royalties)

Presentation will include discussion of off-label, experimental, and/or investigational use of drugs or devices: Christoph U. Correll: My presentation will include discussion of off-label, experimental, and /or investigational use of drugs or devices: SEP856, Pimavanserin for schizophrenia, Xanomeline + Trospium for schizophrenia, TAK-831 for schizophrenia, deutetrabenazine and valbenazine for schizophrenia, lumateperone for bipolar depression

Course Requirements

To receive ACPE credit for this session, you must:

  • Register for this course.
  • Complete the pre-test (if applicable) before starting the activity.
  • Review the full content of the activity and reflect upon its teachings.
  • Complete the post-test at the end of the activity no later than the closing activity date.
  • Complete the evaluation at the end of the activity.
  • If necessary, complete the post-test retest no later than the closing activity date.
  • Receive a passing grade (70%).
  • Provide the necessary details in your profile to ensure correct reporting by AAPP to CPE Monitor.

Continuing Education Credit and Disclosures

Webinar Date: 08/24/2021 1:00PM central
Activity Dates: 08/24/2021 - 08/24/2024
ACPE Contact Hours: 1
ACPE Number: 0284-0000-21-060-H01-P (Knowledge)
Nursing Credit Reminder: Note that ACPE credit is accepted for ANCC Certification Renewal and AANPCB advanced practice provider content. For specific questions related to your organization's acceptance of ACPE continuing education units, please contact your organization directly.

ACPEThe College of Psychiatric and Neurologic Pharmacists is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

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View disclaimer and disclosure of off-label use

Off-Label Use: This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA (see faculty information). The opinions expressed in the educational activity do not necessarily represent the views of AAPP and any educational partners. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.

Disclaimer: Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications on dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.

Presentation-Specific Disclosure: Christoph U. Correll: My presentation will include discussion of off-label, experimental, and /or investigational use of drugs or devices: SEP856, Pimavanserin for schizophrenia, Xanomeline + Trospium for schizophrenia, TAK-831 for schizophrenia, deutetrabenazine and valbenazine for schizophrenia, lumateperone for bipolar depression

View fair balance and integrity statement

It is the policy of AAPP to ensure independence, balance, objectivity, scientific rigor, and integrity in continuing education activities. Those involved in the development of this continuing education activity have made all reasonable efforts to ensure that information contained herein is accurate in accordance with the latest available scientific knowledge at the time of accreditation of this continuing education activity. Information regarding drugs (e.g., their administration, dosages, contraindications, adverse reactions, interactions, special warnings, and precautions) and drug delivery systems is subject to change, however, and the reader is advised to check the manufacturer’s package insert for information concerning recommended dosage and potential problems or cautions prior to dispensing or administering the drug or using the drug delivery systems.

Fair balance is achieved through ongoing and thorough review of all materials produced by faculty, and all educational and advertising materials produced by supporting organizations, prior to educational offerings. Approval of credit for this continuing education activity does not imply endorsement by AAPP for any product or manufacturer identified.

This activity is supported by an educational grant from Intra-Cellular Therapies Inc.