Repetitive Transcranial Magnetic Stimulation for Neuropathic Pain and Neuropsychiatric Symptoms in Traumatic Brain Injury: A Systematic Review and Meta-Analysis

Abstract

Neuropathic pain and neuropsychiatric symptoms are common complications reported by the traumatic brain injury (TBI) population. Although a growing body of research has indicated the effectiveness of repetitive transcranial magnetic stimulation (rTMS) for the management of neurological and psychiatric disorders, little evidence has been presented to support the effects of rTMS on neuropathic pain and neuropsychiatric symptoms in patients with TBI in all age groups. In addition, a better understanding of the potential factors that might influence the therapeutic effect of rTMS is necessary. The objective of this preregistered systematic review and meta-analysis was to quantify the effects of rTMS on physical and psychological symptoms in individuals with TBI. We systematically searched six databases for randomized controlled trials (RCTs) of rTMS in TBI patients reporting pain and neuropsychiatric outcomes published until March 20, 2022. The mean difference (MD) with 95% confidence intervals (CIs) was estimated separately for outcomes to understand the mean effect size. Twelve RCTs with 276 TBI patients were ultimately selected from 1605 records for systematic review, and 11 of the studies were included in the meta-analysis. Overall, five of the included studies showed a low risk of bias. The effects of rTMS on neuropathic pain were statistically significant ( $\text{MD}=-1.00$ , 95% CI -1.76 to -0.25, $P=0.009$ ), with high heterogeneity ( $I^2=76\%$ ). A significant advantage of 1 Hz rTMS over the right dorsolateral prefrontal cortex (DLPFC) in improving depression ( $\text{MD}=-6.52$ , 95% CI -11.58 to -1.46, $P=0.01$ ) was shown, and a significant improvement was noted in the Rivermead Post-Concussion Symptoms Questionnaire-13 (RPQ-13) scores of mild TBI patients after rTMS ( $\text{MD}=-5.87$ , 95% CI -10.63 to -1.11, $P=0.02$ ). However, no significance was found in cognition measurement. No major adverse events related to rTMS were reported. Moderate evidence suggests that rTMS can effectively and safely improve neuropathic pain, while its effectiveness on depression, postconcussion symptoms, and cognition is limited. More trials with a larger number of participants are needed to draw firm conclusions. This trial is registered with PROSPERO (PROSPERO registration number: CRD42021242364.