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 (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 (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 (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.

Figure 1

Flow diagram of the selection process.

Figure 2

Forest plots of the different-term effects of rTMS on self-reported neuropathic pain in TBI.

Figure 3

Funnel plot regarding self-reported neuropathic pain in the rTMS group compared with the control group.

Figure 4

Forest plots of the effect of rTMS on depression measured by the MADRS in TBI patients. (a) Total analysis; (b) subgroup analysis of posttreatment effectiveness. DLPFC: dorsolateral prefrontal cortex; MADRS: Montgomery-Asberg Depression Rating Scale.

Figure 5

Forest plots of the effect of rTMS on depression measured by the HRSD in TBI patients. HRSD: Hamilton Rating Scale for Depression.

Figure 6

Forest plots of different-term effects of rTMS on depression measured by the PHQ-9 in TBI patients. PHQ-9: Patient Health Questionnaire-9.

Figure 7

Forest plots of different parts of rTMS on the severity of different symptoms measured by the RPQ in TBI patients: (a) the RPQ; (b) the RPQ-13; (c) the RPQ-3. RPQ: Rivermead Post-Concussion Questionnaire.

Figure 8

Forest plots of different parts of rTMS on cognition measured by the TMT-A and TMT-B in TBI patients: (a) the TMT-A; (b) the TMT-B. TMT: Trail Making Test.

Figure 9

Forest plots of different parts of rTMS on cognition measured by the SCWT in TBI patients. SCWT: Stroop Color-Word Test.