Diverse therapeutic developments for post-traumatic stress disorder (PTSD) indicate common mechanisms of memory modulation

Raut, Sanket B., Marathe, Padma A., van Eijk, Liza, Eri, Rajaraman, Ravindran, Manoj, Benedek, David M., Ursano, Robert J., Canales, Juan J., and Johnson, Luke R. (2022) Diverse therapeutic developments for post-traumatic stress disorder (PTSD) indicate common mechanisms of memory modulation. Pharmacology & Therapeutics, 239. 108195.

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Post-traumatic stress disorder (PTSD), characterized by abnormally persistent and distressing memories, is a chronic debilitating condition in need of new treatment options. Current treatment guidelines recommend psychotherapy as first line management with only two drugs, sertraline and paroxetine, approved by U.S. Food and Drug Administration (FDA) for treatment of PTSD. These drugs have limited efficacy as they only reduce symptoms related to depression and anxietywithout producing permanent remission. PTSD remains a significant public health problem with high morbidity and mortality requiring major advances in therapeutics. Early evidence has emerged for the beneficial effects of psychedelics particularly in combination with psychotherapy for management of PTSD, including psilocybin,MDMA, LSD, cannabinoids, ayahuasca and ketamine. MDMA and psilocybin reduce barrier to therapy by increasing trust between therapist and patient, thus allowing for modification of trauma related memories. Furthermore, research into the memory reconsolidation mechanisms has allowed for identification of various pharmacological targets to disrupt abnormally persistent memories. A number of preclinical and clinical studies have investigated novel and re-purposed pharmacological agents to disrupt fear memory in PTSD. Novel therapeutic approaches like neuropeptide Y, oxytocin, cannabinoids and neuroactive steroids have also shown potential for PTSD treatment. Here,we focus on the role of fear memory in the pathophysiology of PTSD and propose that many of these newtherapeutic strategies produce benefits through the effect on fear memory. Evaluation of recent research findings suggests that while a number of drugs have shown promising results in preclinical studies and pilot clinical trials, the evidence from large scale clinical trials would be needed for these drugs to be incorporated in clinical practice.

Item ID: 73718
Item Type: Article (Research - C1)
ISSN: 1879-016X
Keywords: Psychedelics, MDMA, Psilocybin, Reconsolidation, Fear, Ketamine
Copyright Information: © 2022 Elsevier Inc. All rights reserved.
Date Deposited: 24 May 2022 01:00
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3209 Neurosciences > 320999 Neurosciences not elsewhere classified @ 70%
42 HEALTH SCIENCES > 4299 Other health sciences > 429999 Other health sciences not elsewhere classified @ 30%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200102 Efficacy of medications @ 20%
28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280112 Expanding knowledge in the health sciences @ 80%
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