Novel Pharmacologic and Other Somatic Treatment Approaches for Posttraumatic Stress Disorder in Adults: State of the Evidence.

Posttraumatic stress disorder (PTSD) is a highly prevalent psychiatric disorder that can become chronic and debilitating when left untreated. The most commonly recommended first-line treatments for PTSD among adults are individual trauma-focused psychotherapies. Other evidence-based treatments include specific antidepressant medications and non-trauma-focused psychotherapies. Despite the effectiveness of these available treatments, many patients' symptoms do not remit. This has led to the search for novel treatments for PTSD. In this review, the authors critically evaluate the data supporting several emerging pharmacological and other somatic interventions in the categories of medication-assisted psychotherapy, novel medication monotherapy strategies, and neuromodulation, selected because of the salience of their mechanisms of action to the pathophysiology of PTSD (e.g., MDMA-assisted psychotherapy, ketamine, cannabidiol, transcranial magnetic stimulation). The authors also evaluate the evidence for treatments that are the focus of increasing scientific or public interest (i.e., hyperbaric oxygen therapy, stellate ganglion block, neurofeedback). To date, the evidence supporting most novel pharmacological and somatic treatments for PTSD is preliminary and highly variable; however, the data for several specific treatments, such as transcranial magnetic stimulation, are encouraging.
Competing Interests: Dr. Kelmendi is a Co-founder, consultant, and has equity in Transcend Therapeutics, and is also a consultant for Ceruvia Lifesciences. Dr. Alpert reports royalties from Cambridge University Press, Honoraria from Belvoir Publishing and MGH Psychiatry Academy. Dr. Carpenter discloses consulting income in the past three years from Neuronetics, Neurolief, Magnus Medical, Motif Neurotech, Sage Therapeutics, Otsuka, MAPS Public Benefit Corporation, and Change Healthcare. She has clinical trials contracts with Neuronetics, Neurolief, and Janssen and research device loans from Neuronetics and Nexstim. Her effort was supported in part by the National Institute of General Medical Sciences (P20GM130452) funded COBRE Center for Neuromodulation at Butler Hospital. Dr. Grzenda discloses income from consulting to the American Psychiatric Association. Dr. Kraguljac has served on an advisory board for Neurocrine Biosciences Inc. and is a member of the American Board of Psychiatry and Neurology Article Based Continuing Certification committee. Dr. McDonald is compensated as the chair of the DSMB for an NIA sponsored multicenter study. He is on the Board of Skyland Trail and 3Keys. He is a paid consultant for Signant and Sage Therapeutics. He receives a stipend as a deputy editor of the American Journal of Psychiatry. Dr. Rodriguez has, in the last three years, been a consultant for Biohaven Inc., Osmind, and Biogen; received research grant support from Biohaven Inc.; received royalties from American Psychiatric Association Publishing; and received a stipend from APA Publishing for her role as Deputy Editor at The American Journal of Psychiatry. Dr. Rodriguez’s effort was supported in part by the VA Office of Research and Development Clinical Science Research & Development Service, US, Department of Veterans Affairs (1I01CX001789-01A2). Dr. Widge discloses device donations from Medtronic, consulting income from Dandelion Science, and multiple unlicensed patents in the area of brain stimulation for psychiatric illness. Dr. Nemeroff serves as a paid consultant to AbbVie, ANeuroTech (division of Anima BV), Signant Health, Magstim, Inc., Intra-Cellular Therapies, Inc., EMA Wellness, Sage, Silo Pharma, Engrail Therapeutics, Pasithea Therapeutic Corp., EcoR1, GoodCap Pharmaceuticals, Inc., Senseye, Clexio, Ninnion Therapeutics, AncoraBio, and SynapseBio. Dr. Nemeroff is a stockholder with the following: Seattle Genetics, Antares, Inc., Corcept Therapeutics Pharmaceuticals Company, EMA Wellness, and Naki Health. He serves on the scientific advisory boards of ANeuroTech (division of Anima BV), Brain and Behavior Research Foundation (BBRF), Anxiety and Depression Association of America (ADAA), Skyland Trail, Signant Health, Laureate Institute for Brain Research (LIBR), Inc., Heading Health, Pasithea Therapeutic Corp., and Sage and on the board of directors for Gratitude America, ADAA, Lucy Scientific Discovery, Inc. His patents are as follows: “Method and devices for transdermal delivery of lithium (US 6,375,990B1)” and “Method of assessing antidepressant drug therapy via transport inhibition of monoamine neurotransmitters by ex vivo assay (US 7,148,027B2).” Dr. Holtzheimer receives royalties from Oxford University Press and UpToDate. Drs. Sippel, Hamblen, and Schnurr report no financial relationships with commercial interests.