CNS SPECTRUMS CME Review Article Keeping up with the clinical advances: schizophrenia This activity is provided by the Neuroscience Education Institute. Additionally provided by the American Society for the Advancement of Pharmacotherapy. Downloaded from https://www.cambridge.org/core. IP address: 170.106.33.42, on 27 Sep 2021 at 16:43:56, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms. https://doi.org/10.1017/S109285291900124X CME Information Released: July 25, 2019 Peer Review CME credit expires: May 15, 2022 This content has been peer reviewed by an MD specializ- ing in psychiatry to ensure the scientific accuracy and Learning Objectives medical relevance of information presented and its inde- After completing this activity, you should be better able to: pendence from commercial bias. NEI takes responsibility for the content, quality, and scientific integrity of this • Differentiate the mechanisms of action of new and CME activity. emerging antipsychotics • Evaluate the latest clinical data on new and emerg- Disclosures ing antipsychotics All individuals in a position to influence or control con- tent are required to disclose financial relationships of any Accreditation and Credit Designation amount with any entity producing, marketing, re-selling, Statements or distributing health care goods or services consumed The Neuroscience Education Institute (NEI) is accred- by, or used on, patients. Although potential conflicts of ited by the Accreditation Council for Continuing interest are identified and resolved prior to the activity Medical Education (ACCME) to provide continuing being presented, it remains for the participant to deter- medical education for physicians. mine whether outside interests reflect a possible bias in NEI designates this enduring material for a maximum either the exposition or the conclusions presented. of 1.5 AMA PRA Category 1 CreditsTM. Physicians should claim only the credit commensurate with the extent of Authors their participation in the activity. A posttest score of Amanda Krogmann, BSc, is affiliated with Charité 70% or higher is required to earn CME credits. Universitätsmedizin, Department of Child and Adolescent The American Society for the Advancement of Psychiatry in Berlin, Germany. Ms Krogmann has no finan- Pharmacotherapy (ASAP), Division 55 of the American cial relationships to disclose. Psychological Association, is approved by the American Luisa Peters, BSc, is affiliated with Charité Psychological Association to sponsor continuing educa- Universitätsmedizin, Department of Child and Adolescent tion for psychologists. ASAP maintains responsibility Psychiatry in Berlin, Germany. Ms Peters has no financial for this program and its content. relationships to disclose. The American Society for the Advancement of Laura von Hardenberg, MPhil, is affiliated with Pharmacotherapy designates this program for 1.5 CE Charité Universitätsmedizin, Department of Child and credits for psychologists. Adolescent Psychiatry in Berlin, Germany. Ms von Nurses and Physician Assistants: for all of your Hardenberg has no financial relationships to disclose. CE requirements for recertification, the ANCC and Katja Bödeker, PhD, is affiliated with Charité NCCPA will accept AMA PRA Category 1 Credits™ from Universitätsmedizin, Department of Child and Adolescent organizations accredited by the ACCME. The content of Psychiatry in Berlin, Germany. Dr. Bödeker has no financial this activity pertains to pharmacology and is worth 1.5 relationships to disclose. continuing education hours of pharmacotherapeutics. Viktor B. Nöhles, MA, is affiliated with Charité Universitätsmedizin, Department of Child and Adolescent Optional Posttest and CME Credit Instructions Psychiatry in Berlin, Germany. Mr. Nöhles has no financial 1 Read the article relationships to disclose. 2 Complete the posttest, available only online at Christoph U. Correll, MD, is affiliated with Charité www.neiglobal.com/CME (under “CNS Universitätsmedizin, Department of Child and Adolescent Spectrums”) Psychiatry in Berlin, Germany; the Zucker Hillside 3 Print your certificate (passing score = 70% or Hospital, Psychiatry Research, Northwell Health in Glen higher) Oaks, New York, USA; and Zucker School of Medicine at Hofstra/Northwell, Department of Psychiatry and Questions? call 888–535–5600, or email Molecular Medicine in Hempstead, New York, USA. [email protected] Dr. Correll has been a consultant/advisor to or has received Downloaded from https://www.cambridge.org/core. IP address: 170.106.33.42, on 27 Sep 2021 at 16:43:56, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms. https://doi.org/10.1017/S109285291900124X honoraria from: Alkermes, Allergan, Angelini, Boehringer- The Content Editor, an NEI Peer Reviewer, and the Ingelheim, Gedeon Richter, Gerson Lehrman Group, Planning Committee have no financial relationships Indivior, IntraCellular Therapies, Janssen/J&J, LB to disclose. Pharma, Lundbeck, MedAvante-ProPhase, Medscape, Merck, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Disclosure of Off-Label Use Rovi, Servier, Sumitomo Dainippon, Sunovion, Supernus, This educational activity may include discussion of unla- Takeda, and Teva. He has provided expert testimony for beled and/or investigational uses of agents that are not Bristol-Myers Squibb, Janssen, and Otsuka. He served on currently labeled for such use by the FDA. Please consult a Data Safety Monitoring Board for Boehringer- the product prescribing information for full disclosure of Ingelheim, Lundbeck, Rovi, Supernus, and Teva. He labeled uses. received royalties from UpToDate and grant support from Janssen and Takeda, and is also a shareholder of LB Pharma. Cultural and Linguistic Competency No writing assistance was utilized in the production of this article. A variety of resources addressing cultural and linguistic competency can be found at this link: www.neiglobal. CNS Spectrums Peer Review com/go/cmeregs All CME articles are peer reviewed in accordance with the strict standards of CNS Spectrums and in accordance with Providers requirements and recommendations of the International This activity is provided by NEI. Additionally provided by Committee of Medical Journal Editors. The Editorial pol- the ASAP. icies of the journal CNS Spectrums and peer review of all articles that appear in the journal is managed independ- Support ently by Cambridge University Press and no financial relationship exists between the CME provider and This activity is supported by an unrestricted educational Cambridge for this service. grant from Indivior. Downloaded from https://www.cambridge.org/core. IP address: 170.106.33.42, on 27 Sep 2021 at 16:43:56, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms. https://doi.org/10.1017/S109285291900124X CNS Spectrums (2019), 24,41–68. © The Author(s) 2020. Published by Cambridge University Press. This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which per- mits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited. doi:10.1017/S109285291900124X REVIEW ARTICLE Keeping up with the therapeutic advances in schizophrenia: a review of novel and emerging pharmacological entities Amanda Krogmann,1,† Luisa Peters,1,† Laura von Hardenberg,1 Katja Bödeker,1 Viktor B. Nöhles,1 and Christoph U. Correll1,2,3* 1 Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany 2 Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, New York, USA 3 Department of Psychiatry and Molecular Medicine, Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA Schizophrenia remains one of the most severe medical diseases. Current dopamine modulating first-generation and second-generation anti- psychotics target mainly positive symptoms, but not/inadequately negative and cognitive symptoms. Additional challenges include non- adherence and adverse effects, especially cardiometabolic dysregulation. This review evaluates new/emerging pharmacological treatments for schizophrenia. Therapies targeting total symptoms include cannabidiol, D3 antagonist/5-HT1A partial agonist F17464, lumateperone (ITI-007), phosphodiesterase 10A (PDE10A) inhibitors MK-8189 and TAK-063, sodium nitroprusside, and trace amine-associated recep- tor-1 (TAAR1) agonist RO5263397 and SEP-363856. Treatments targeting negative symptoms include the PDE10A inhibitor LuAF-11167, 5-HT2A inverse agonist pimavanserin, sigma-2/5-HT2A antagonist roluperidone (MIN-101), and d-amino acid oxidase (DAAO) inhibitor TAK-831. Agents targeting primarily cognitive dysfunction are the glycine transporter-1 inhibitor BI-425809 and cannabidiol. Therapies targeting residual positive symptoms/treatment-resistant schizophrenia include pimavanserin, dopamine D1/D2 antagonist LuAF-35700, and DAAO inhibitor sodium benzoate. Two new long-acting injectable antipsychotic formulations, Aripiprazole Lauroxil NanoCrystal® and the first subcutaneous injectable LAI Perseris (RBP-7000), were recently approved by U.S. Food and Drug Administration, and positive results were announced for Risperidone ISM®, each achieving therapeutic levels within 24 hours, without need for initial oral cotreatment/ loading injection-strategies. Paliperidone palmitate 6-monthly intramuscularly injectable