Acupuncture for Combat-Related Posttraumatic Stress Disorder: A Randomized Clinical Trial Author: Michael Hollifield1,2, An-Fu Hsiao1,3, Tyler Smith4, Teresa Calloway1,5, Tanja Jovanovic6, Besa Smith4, Kala Carrick1, Seth D Norrholm6, Andrea Munoz1, Ruth Alpert1, Brianna Caicedo1, Nikki Frousakis1, Karen Cocozza7 Affiliation: <sup>1</sup> Tibor Rubin VA Medical Center, Long Beach, California. <sup>2</sup> Department of Psychiatry and Behavioral Sciences, George Washington School of Medicine &amp; Health Sciences, Washington, DC. <sup>3</sup> Department of Medicine, Health Policy Research Institute and General Internal Medicine, University of California, Irvine. <sup>4</sup> Analydata, San Diego, California. <sup>5</sup> Yo San University of Traditional Chinese Medicine, Los Angeles, California. <sup>6</sup> Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan. <sup>7</sup> Susan Samueli Integrative Health Institute, University of California, Irvine. Conference/Journal: JAMA Psychiatry Date published: 2024 Feb 21 Other: Special Notes: doi: 10.1001/jamapsychiatry.2023.5651. , Word Count: 395 Importance: Current interventions for posttraumatic stress disorder (PTSD) are efficacious, yet effectiveness may be limited by adverse effects and high withdrawal rates. Acupuncture is an emerging intervention with positive preliminary data for PTSD. Objective: To compare verum acupuncture with sham acupuncture (minimal needling) on clinical and physiological outcomes. Design, setting, and participants: This was a 2-arm, parallel-group, prospective blinded randomized clinical trial hypothesizing superiority of verum to sham acupuncture. The study was conducted at a single outpatient-based site, the Tibor Rubin VA Medical Center in Long Beach, California, with recruitment from April 2018 to May 2022, followed by a 15-week treatment period. Following exclusion for characteristics that are known PTSD treatment confounds, might affect biological assessment, indicate past nonadherence or treatment resistance, or indicate risk of harm, 93 treatment-seeking combat veterans with PTSD aged 18 to 55 years were allocated to group by adaptive randomization and 71 participants completed the intervention protocols. Interventions: Verum and sham were provided as 1-hour sessions, twice weekly, and participants were given 15 weeks to complete up to 24 sessions. Main outcomes and measures: The primary outcome was pretreatment to posttreatment change in PTSD symptom severity on the Clinician-Administered PTSD Scale-5 (CAPS-5). The secondary outcome was pretreatment to posttreatment change in fear-conditioned extinction, assessed by fear-potentiated startle response. Outcomes were assessed at pretreatment, midtreatment, and posttreatment. General linear models comparing within- and between-group were analyzed in both intention-to-treat (ITT) and treatment-completed models. Results: A total of 85 male and 8 female veterans (mean [SD] age, 39.2 [8.5] years) were randomized. There was a large treatment effect of verum (Cohen d, 1.17), a moderate effect of sham (d, 0.67), and a moderate between-group effect favoring verum (mean [SD] Δ, 7.1 [11.8]; t90 = 2.87, d, 0.63; P = .005) in the intention-to-treat analysis. The effect pattern was similar in the treatment-completed analysis: verum d, 1.53; sham d, 0.86; between-group mean (SD) Δ, 7.4 (11.7); t69 = 2.64; d, 0.63; P = .01). There was a significant pretreatment to posttreatment reduction of fear-potentiated startle during extinction (ie, better fear extinction) in the verum but not the sham group and a significant correlation (r = 0.31) between symptom reduction and fear extinction. Withdrawal rates were low. Conclusions and relevance: The acupuncture intervention used in this study was clinically efficacious and favorably affected the psychobiology of PTSD in combat veterans. These data build on extant literature and suggest that clinical implementation of acupuncture for PTSD, along with further research about comparative efficacy, durability, and mechanisms of effects, is warranted. Trial registration: ClinicalTrials.gov Identifier: NCT02869646. PMID: 38381417 DOI: 10.1001/jamapsychiatry.2023.5651