Efficacy of transcranial magnetic stimulation in the treatment of combat-related PTSD: a systematic review and meta-analysis.

Introduction: Combat-related post-traumatic stress disorder (PTSD) remains highly prevalent among military personnel and veterans and is frequently chronic, disabling, and only partially responsive to first-line pharmacological and psychotherapeutic interventions. Given the central role of fronto-limbic circuit dysfunction in PTSD, transcranial magnetic stimulation (TMS) has emerged as a biologically plausible neuromodulatory strategy, yet its protocol-level efficacy in combat-exposed populations is not well established. Clarifying whether specific TMS modalities offer clinically meaningful benefit beyond sham, and whether any protocol can be prioritized, is critical for rationally integrating TMS into veteran-focused care pathways. Methods: This systematic review and meta-analysis followed PRISMA 2020 and Cochrane Handbook recommendations and was prospectively registered in PROSPERO (CRD420251105555). We searched PubMed, SCOPUS, Embase, Web of Science, and EBSCO (March-June 2025) for clinical studies of adults with combat-related PTSD (DSM-IV, DSM-5, ICD-10, or ICD-11) receiving any TMS modality (rTMS, theta-burst stimulation, deep TMS, synchronized or accelerated TMS), compared with sham, standard care, or both. Primary outcomes were changes in PTSD severity measured with validated instruments (e.g., CAPS, PCL-5); secondary outcomes included depressive and anxiety symptoms, psychosocial functioning, acceptability, and safety. Random-effects meta-analyses (DerSimonian-Laird) were conducted for within-group pre-post change and between-group mean differences (TMS vs. control); heterogeneity was quantified with I². Risk of bias in randomized trials was assessed using the Cochrane RoB 2.0 tool. Results: From 191 records, 7 studies (n = 963) were included in the quantitative synthesis. Five studies contributed pre-post data (including one of the randomized controlled trial that presented the pre and post data of the TMS group), showing a large, clinically meaningful pooled reduction in PTSD symptoms after TMS (pooled mean change -20.39 points; 95% CI -23.94 to -16.83; p < 0.001; I² = 88.7), with the greatest improvements observed in high-frequency (10 Hz) left DLPFC rTMS protocols delivered over 20-30 sessions. In contrast, three randomized controlled trials (n = 116) comparing active TMS with sham yielded a non-significant pooled mean difference favoring TMS (MD -3.83; 95% CI -16.32 to 8.65; p = 0.098; I² = 56.9), suggesting that a substantial portion of symptom improvement may reflect non-specific or shared therapeutic factors. Subgroup analyses hinted at benefit for conventional rTMS and inconclusive effects for deep TMS, but were underpowered and did not identify any modality as clearly superior. Across studies, TMS was well tolerated: no serious adverse events were reported, dropout rates were low (~7%), and adverse effects were predominantly mild (transient headache, scalp discomfort, fatigue). Overall, the evidence indicates that TMS yields robust within-group clinical improvement and an excellent safety profile in combat-related PTSD, while the specific advantage over sham and the comparative superiority of individual TMS protocols remain uncertain, underscoring the need for larger, protocol-focused randomized trials with standardized parameters and longer follow-up. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251105555