Comparative Effectiveness of Noninvasive Brain Stimulation for the Treatment of Pain, Fatigue, and Sleep Quality in Fibromyalgia. A Systematic Review With Network Meta-Analysis

Objectives: There is tentative evidence to support the analgesic effects of noninvasive brain stimulation (NiBS) in fibromyalgia (FM), but a comprehensive synthesis is lacking. This systematic review with network meta-analysis (NMA) aimed to determine the relative effectiveness of different NiBS techniques, such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) in FM, and to identify the optimal stimulation location and intensity/frequency. Methods: Four databases were searched until July 9, 2023 for randomized trials (RCTs) comparing NiBS in FM. Pain was the primary outcome, while fatigue and sleep were secondary outcomes. A frequentist NMA calculated standardized-mean-differences (SMDs) for pain, with pairwise meta-analysis for fatigue and sleep. Bias was assessed with the Cochrane-risk-of-bias-tool (RoB-2.0), and evidence certainty through confidence-in-NMA. Results: Forty-three RCTs with 2120 participants were included. NMA showed that low frequency (LF)-rTMS (SMD: −1.20, 95% CI: −1.82 to −0.58), dual tDCS (SMD: −0.91, 95% CI: −1.82 to −0.58), and high frequency (HF)-rTMS (SMD: −0.58, 95% CI: −1.00 to −0.17) likely results in a reduction in pain intensity at the end of intervention compared with sham stimulation. For stimulation location, right dorsolateral prefrontal cortex (DLPFC)(SMD: −1.42, 95% CI: −2.69 to −0.15), bilateral DLPFC (SMD: −0.94, 95% CI: −1.82 to −0.05), and left primary motor cortex (M1)(SMD: −0.49, 95% CI: −0.85 to −0.14) likely results in reduction in pain intensity at the end of intervention, with DLPFC maintaining effects in short-term. LF-rTMS over DLPFC (SMD: −1.42, 95% CI: −2.69 to −0.15) and HF-rTMS over M1 (SMD: −0.78, 95% CI: −1.39 to −0.18) likely results in the reduction in pain intensity at the end of intervention, with LF-rTMS over right DLPFC maintaining effects in the short term. NiBS appears to be safe and may reduce fatigue and improve sleep quality. Discussion: Excitatory stimulation like HF-rTMS over M1 and inhibitory like LF-rTMS over DLPFC may yield better results.