Efficacy and Safety of Noninvasive Electrical Neuromodulation for Treatment of Functional Constipation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Functional constipation (FC) is a prevalent disorder with large disease burden and high associated cost. Noninvasive electrical neuromodulation (NEN) has been studied for treatment of FC, but its overall efficacy and safety remain unclear. This meta-analysis evaluates the efficacy and safety of NEN for treatment of FC. Materials and Methods: A search of PubMed, Cochrane Library, Embase, and Web of Science data bases was completed for randomized controlled studies assessing the efficacy and safety of NEN in patients with FC through June 2024. We performed a metaanalysis using risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, with 95% CIs. Results: The analysis included eight randomized controlled trials with 1465 participants. Compared with sham interventions, NEN significantly increased the proportion of patients having >= three spontaneous bowel movements per week (RR [95% CI1 = 2.47 [1.79, 3.401, p < 0.00001), decreased the number of patients using laxative for FC (RR [95% CI1 = 0.81 [0.69, 0.951, p = 0.01), decreased the overall constipation severity (MD [95% CI1 = -0.58 [-0.81, -0.351, p < 0.00001), and improved the constipationspecific quality of life (MD [95% CI1 = -0.24 [-0.32, -0.161, p < 0.00001). There was no significant difference in the frequency of adverse events between NEN and sham interventions (RR [95% CI1 = 1.30 [0.77, 2.191, p = 0.32), and participant drop-out rate with NEN was lower (RR [95% CI1 = 0.38 [0.17, 0.841, p = 0.02). Mechanistically, NEN was found to modulate the autonomic function (p < 0.00001) and improve the rectal sensation (p = 0.03). Conclusions: NEN relieves constipation symptoms, improves quality of life, and reduces use of pharmacologic remedies in adults with FC. These effects seem to be modulated through improved autonomic function and rectal sensation. NEN is safe, welltolerated, and has a high level of patient compliance.