Non-invasive brain stimulation for posttraumatic stress disorder: a systematic review and meta-analysis

Abstract

Approximately 7-9% of people develop posttraumatic stress disorder in their lifetime, but standard pharmacological treatment or psychotherapy shows a considerable individual variation in their effectiveness. Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) hold promise for the treatment of posttraumatic stress disorder. The objective of this meta-analysis was to summarize the existing evidence on the therapeutic effects of these brain stimulation treatments on posttraumatic core symptoms. We systematically retrieved articles published between 1st January 2000 and 1st January 2020 comparing the effects of active with sham stimulation or no intervention in posttraumatic patients from eight databases. Random-effects model was used for meta-analysis. Meta-regression and subgroup meta-analysis was performed to investigate the influence of stimulation dose and different stimulation protocols, respectively. 20 studies were included in this review, where of 11 randomized controlled trials were subjected to quantitative analysis. Active stimulation demonstrated significant reductions of core posttraumatic symptoms with a large effect size (Hedge's g = -0.975). Subgroup analysis showed that both excitatory and inhibitory rTMS of the right dorsolateral prefrontal cortex led to symptom reductions with a large (Hedges' g = -1.161, 95% CI, -1.823 to -0.499; p = 0.015) and medium effect size (Hedges' g = -0.680, 95% CI: -0.139 to -0.322; p ≤ 0.001) respectively. Results further indicated significant durability of symptom-reducing effects of treatments during a two to four weeks period post stimulation (Hedges' g = -0.909, 95% CI: -1.611 to -0.207; p = 0.011). rTMS of the right dorsolateral prefrontal cortex appears to have a positive effect in reducing core symptoms in patients with posttraumatic stress disorder.

Fig. 1. PRISMA flowchart.

Process of literature search.

Fig. 2. Effects of NIBS in PTSD.

a Forest plot depicting studies comparing active with sham stimulation, summarizing to an effect size of −0.975. b The corresponding funnel plot comparing active with sham stimulation shows no publication bias; the Egger’s test is non-significant (p = 0.180).

Fig. 3. Effects of excitatory and inhibitory stimulation protocols in PTSD.

a A forest plot showing studies that compared excitatory stimulation with sham stimulation. b A forest plot showing studies comparing inhibitory stimulation with sham stimulation.

Fig. 4. Effects of different NIBS protocols in PTSD.

a Forest plot showing studies that compared high frequency with low frequency rTMS. b Forest plot showing studies using rTMS as an augmentation therapy or not. c Forest plot showing studies that investigated the effects of NIBS during follow-up examinations.