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A Neuroanatomic and Pathophysiologic Framework for Novel Pharmacological Approaches to the Treatment of Post-traumatic Stress Disorder

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Abstract

Post-traumatic stress disorder (PTSD) is a debilitating disorder inflicting high degrees of symptomatic and socioeconomic burdens. The development of PTSD results from a cascade of events with contributions from multiple processes and the underlying pathophysiology is complex, involving neurotransmitters, neurocircuitry, and neuroanatomical pathways. Presently, only two medications are US FDA-approved for the treatment of PTSD, both selective serotonin reuptake inhibitors (SSRIs). However, the complex underlying pathophysiology suggests a number of alternative pathways and mechanisms that may be targets for potential drug development. Indeed, investigations and drug development are proceeding in a number of these alternative, non-serotonergic pathways in an effort to improve the management of PTSD. In this manuscript, the authors introduce novel and emerging treatments for PTSD, including drugs in various stages of development and clinical testing (BI 1358894, BNC-210, PRAX-114, JZP-150, LU AG06466, NYV-783, PH-94B, SRX246, TNX-102), established agents and known compounds being investigated for their utility in PTSD (brexpiprazole, cannabidiol, doxasoin, ganaxolone, intranasal neuropeptide Y, intranasal oxytocin, tianeptine oxalate, verucerfont), and emerging psychedelic interventions (ketamine, MDMA-assisted psychotherapy, psilocybin-assisted psychotherapy), with an aim to examine and integrate these agents into the underlying pathophysiological frameworks of trauma-related disorders.

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Authors and Affiliations

  1. Mental Health and Behavioral Sciences Service, James A. Haley Veterans Hospital, Tampa, FL, USA

    Michael A. Norred & Zachary D. Zuschlag

  2. Department of Psychiatry and Behavioral Neurosciences, University of South Florida, Tampa, FL, USA

    Michael A. Norred & Zachary D. Zuschlag

  3. Behavioral Health Service, Ralph H. Johnson VA Medical Center, 109 Bee Street, Charleston, SC, 29401, USA

    Mark B. Hamner

  4. Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA

    Mark B. Hamner

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This material is the result of work supported with resources and the use of facilities at VA Medical Centers. The contents of this publication do not represent the views of the Department of Veterans Affairs or the United States Government. Mark B. Hamner is a recipient of research funds from Boehinger-Ingleheim. Zachary D. Zuschlag and Michael A. Norred report no competing interests or conflicts of interest.

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Norred, M.A., Zuschlag, Z.D. & Hamner, M.B. A Neuroanatomic and Pathophysiologic Framework for Novel Pharmacological Approaches to the Treatment of Post-traumatic Stress Disorder. Drugs 84, 149–164 (2024). https://doi.org/10.1007/s40265-023-01983-5

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