Combining Ketamine Infusions and Written Exposure Therapy for Chronic PTSD: An Open-Label Trial.
| Title: | Combining Ketamine Infusions and Written Exposure Therapy for Chronic PTSD: An Open-Label Trial. |
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| Authors: | Feder A; Department of Psychiatry, Depression and Anxiety Center for Discovery and Treatment, Icahn School of Medicine at Mount Sinai, New York, New York.; Corresponding Author: Adriana Feder, MD, Department of Psychiatry, Depression and Anxiety Center for Discovery and Treatment, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Pl, Box 1230, New York, NY 10029 (adriana.feder@mssm.edu).; Brown O; Department of Psychiatry, Depression and Anxiety Center for Discovery and Treatment, Icahn School of Medicine at Mount Sinai, New York, New York.; Rutter SB; Department of Psychiatry, Depression and Anxiety Center for Discovery and Treatment, Icahn School of Medicine at Mount Sinai, New York, New York.; Cahn L; Department of Psychiatry, Depression and Anxiety Center for Discovery and Treatment, Icahn School of Medicine at Mount Sinai, New York, New York.; Overbey JR; Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York.; Seeley SH; Department of Psychiatry, Depression and Anxiety Center for Discovery and Treatment, Icahn School of Medicine at Mount Sinai, New York, New York.; Yu A; Department of Anesthesiology, Icahn School of Medicine at Mount Sinai, New York, New York.; Bonanno PA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.; Fremont RA; Department of Psychiatry, Depression and Anxiety Center for Discovery and Treatment, Icahn School of Medicine at Mount Sinai, New York, New York.; Delgado AA; Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York.; Jha MK; Department of Psychiatry, Depression and Anxiety Center for Discovery and Treatment, Icahn School of Medicine at Mount Sinai, New York, New York.; Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas, Texas.; Costi S; Department of Psychiatry, Depression and Anxiety Center for Discovery and Treatment, Icahn School of Medicine at Mount Sinai, New York, New York.; Psychopharmacology and Emotion Research Laboratory, Department of Psychiatry, University of Oxford, Oxford, UK.; Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK.; Yehuda R; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York.; Department of Psychiatry, James J. Peters Veterans Affairs Medical Center, Bronx, New York.; Schiller D; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York.; Pietrzak RH; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.; Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, VA Connecticut Health Care System, West Haven, Connecticut.; Charney DS; Department of Psychiatry, Depression and Anxiety Center for Discovery and Treatment, Icahn School of Medicine at Mount Sinai, New York, New York.; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York.; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.; Sloan DM; Department of Psychiatry, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts.; Behavioral Science Division, Department of Veterans Affairs National Center for PTSD, Boston Health Care System, Boston, Massachusetts.; Murrough JW; Department of Psychiatry, Depression and Anxiety Center for Discovery and Treatment, Icahn School of Medicine at Mount Sinai, New York, New York.; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York. |
| Source: | The Journal of clinical psychiatry [J Clin Psychiatry] 2025 Apr 02; Vol. 86 (2). Date of Electronic Publication: 2025 Apr 02. |
| Publication Type: | Journal Article; Clinical Trial |
| Language: | English |
| Journal Info: | Publisher: Physicians Postgraduate Press Country of Publication: United States NLM ID: 7801243 Publication Model: Electronic Cited Medium: Internet ISSN: 1555-2101 (Electronic) Linking ISSN: 01606689 NLM ISO Abbreviation: J Clin Psychiatry Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Memphis, Tenn., Physicians Postgraduate Press. |
| MeSH Terms: | Stress Disorders, Post-Traumatic*/therapy ; Ketamine*/administration & dosage ; Implosive Therapy*/methods; Humans ; Male ; Female ; Middle Aged ; Adult ; Chronic Disease ; Combined Modality Therapy ; Infusions, Intravenous ; Treatment Outcome |
| Abstract: | Objective: This open-label clinical trial examined the preliminary efficacy of combining a course of 6 ketamine infusions with a brief, evidence-based exposure-based psychotherapy-written exposure therapy (WET)-in patients with chronic posttraumatic stress disorder (PTSD).; Methods: The trial was conducted between June 2021 and October 2023. Patients with chronic PTSD and high-moderate to severe symptom levels received 6 intravenous ketamine infusions (0.5 mg/kg), 3 times a week for 2 consecutive weeks, plus 5 WET sessions over 2 weeks, beginning after the first 4 infusions and administered on different days than infusion days. The primary outcome was change in the Clinician Administered PTSD Scale for DSM-5 (CAPS-5) scores from baseline (before the first infusion) to 12 weeks from start of WET ("Week 12").; Results: Fourteen eligible patients began treatment, and 13 completed all infusions and WET. The combined treatment was associated with large-magnitude improvement in PTSD symptom severity from baseline (mean CAPS 5 = 41.6 [SD = 6.2]) to Week 12 (CAPS 5 = 20.8 [14.8], Cohen d [95% CI] = 1.9 [1.0-2.8], P < .001). Nine (69%) patients were treatment responders (≥30% improvement on the CAPS-5). Response was rapid and also durable in 8 (61.5%) patients, assessed up to 6 months from baseline.; Conclusions: Preliminary findings from this open-label clinical trial suggest that the combined treatment may yield large magnitude and durable reductions in PTSD symptoms for patients with more severe chronic PTSD. Large-scale randomized controlled trials are needed to determine the efficacy and potential synergistic effect of this promising combined treatment in this patient population.; Trial Registration: ClinicalTrials.gov identifier: NCT04889664.; (© Copyright 2025 Physicians Postgraduate Press, Inc.) |
| References: | JAMA Psychiatry. 2023 Nov 1;80(11):1093-1100. (PMID: 37610727); Front Pharmacol. 2022 Mar 17;13:759626. (PMID: 35370690); Neuropsychopharmacology. 2016 Mar;41(4):1156-65. (PMID: 26289143); Pharmacol Biochem Behav. 2020 Jan;188:172837. (PMID: 31830487); Am J Psychiatry. 2021 Feb 1;178(2):193-202. (PMID: 33397139); J Consult Clin Psychol. 2004 Apr;72(2):165-75. (PMID: 15065952); Expert Rev Neurother. 2024 Jun;24(6):575-584. (PMID: 38771657); Am J Psychiatry. 2015 May;172(5):430-40. (PMID: 25677355); Am J Psychiatry. 2016 Dec 1;173(12):1205-1212. (PMID: 27418378); Neurobiol Dis. 2017 Apr;100:1-8. (PMID: 28043916); JAMA Psychiatry. 2014 Jun;71(6):681-8. (PMID: 24740528); Biol Psychiatry. 2017 Oct 1;82(7):e51-e59. (PMID: 28454621); Biol Psychiatry. 2011 Apr 15;69(8):754-61. (PMID: 21292242); Behav Ther. 2016 Jan;47(1):66-74. (PMID: 26763498); J Clin Psychiatry. 2020 Nov 10;81(6):. (PMID: 33176074); Neuroimage Clin. 2016 Oct 10;12:715-723. (PMID: 27761402); Depress Anxiety. 2018 Oct;35(10):985-991. (PMID: 30144228); Behav Res Ther. 2012 Oct;50(10):627-35. (PMID: 22863540); Neuropsychopharmacology. 2023 Oct;48(11):1648-1658. (PMID: 37270621); JAMA. 2015 Aug 4;314(5):489-500. (PMID: 26241600); Trends Cogn Sci. 2021 Feb;25(2):151-171. (PMID: 33384214); Br J Psychiatry. 1979 Apr;134:382-9. (PMID: 444788); JAMA Netw Open. 2022 Jan 4;5(1):e2140911. (PMID: 35015065); Science. 2010 Aug 20;329(5994):959-64. (PMID: 20724638); Am J Psychiatry. 2018 Jun 1;175(6):508-516. (PMID: 29869547); Curr Treat Options Psychiatry. 2019 Jun;6(2):99-106. (PMID: 31245252); Front Behav Neurosci. 2018 Nov 20;12:281. (PMID: 30515086); Nat Neurosci. 2019 Mar;22(3):470-476. (PMID: 30664770); Front Cell Neurosci. 2017 Apr 20;11:100. (PMID: 28473755); Psychol Assess. 2018 Mar;30(3):383-395. (PMID: 28493729); Int Clin Psychopharmacol. 1996 Jun;11 Suppl 3:89-95. (PMID: 8923116); Neuropsychopharmacology. 2021 Dec;46(13):2266-2277. (PMID: 34333555); Psychol Trauma. 2024 Dec;16(Suppl 3):S620-S626. (PMID: 38358724); Depress Res Treat. 2012;2012:393251. (PMID: 22611490); Focus (Am Psychiatr Publ). 2023 Jul;21(3):257-265. (PMID: 37404968); Front Psychol. 2022 Mar 25;13:868103. (PMID: 35401323); Am J Psychiatry. 2017 Jul 1;174(7):695-696. (PMID: 28669202); JAMA Psychiatry. 2018 Mar 1;75(3):233-239. (PMID: 29344631); Curr Psychiatry Rep. 2017 Aug 26;19(10):74. (PMID: 28844076); J Clin Psychiatry. 2023 Feb 6;84(2):. (PMID: 36752752); Am J Psychiatry. 2017 Dec 1;174(12):1163-1174. (PMID: 28715908) |
| Grant Information: | United Kingdom WT_ Wellcome Trust; T32 MH122394 United States MH NIMH NIH HHS; UL1 TR004419 United States TR NCATS NIH HHS |
| Molecular Sequence: | ClinicalTrials.gov NCT04889664 |
| Substance Nomenclature: | 690G0D6V8H (Ketamine) |
| Entry Date(s): | Date Created: 20250411 Date Completed: 20250411 Latest Revision: 20251128 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC12645454 |
| DOI: | 10.4088/JCP.24m15622 |
| PMID: | 40215385 |
| Database: | MEDLINE |
Journal Article; Clinical Trial