A systematic review and meta-analysis exploring the recruitment hurdles and nonparticipation rate in noninvasive brain stimulation for addictive disorders.

Abstract

Background: Substance use disorders (SUDs) are a growing public health concern with high relapse rates. Noninvasive brain stimulation techniques are emerging as potential adjunctive therapies; however, recruitment challenges persist in related clinical trials. To use systematic review and meta-analysis to determine the rate and reasons for nonparticipation in randomized controlled trials (RCTs) involving noninvasive brain stimulation for substance-related and addictive disorders.

Materials and methods: Major databases (PubMed, CENTRAL, and Google Scholar) were searched from inception to January 2025 for RCTs of noninvasive brain stimulation and SUD. Of 3589 abstracts searched, 55 RCTs met the inclusion criteria. Eligible studies were peer-reviewed, published in English and examined any form of noninvasive brain stimulation in individuals with substance-related or behavioral addictions. Studies were required to report the number of individuals screened and ultimately randomized. Non-randomized studies, those involving invasive brain stimulation, were excluded.Following PRISMA guidelines, data were extracted independently by two reviewers, with discrepancies resolved by a third. Risk of bias (RoB) was assessed using the Cochrane RoB tool. Random-effects model was used for meta-analysis.

Results: A total of 55 randomized trials were included which involved diverse SUDs and behavioral addictions. The pooled nonparticipation rate was 55.9% (95% CI: 45.9-65.8%; I² = 99.56%, p < 0.001). Majority of the studies reported craving as an outcome measure. Key reasons included failure to meet inclusion criteria (reported in over 25 studies), refusal to participate due to anxiety or lack of motivation (≥15 studies), and logistical barriers such as travel or session frequency (≥10 studies).

Conclusion: Nonparticipation in noninvasive brain stimulation trials for SUD are high, largely due to stringent eligibility criteria, procedural apprehension, and practical burdens faced by participants. Addressing these barriers through broader inclusion criteria, participant education, incentives, and flexible scheduling is essential to enhance recruitment, trial generalizability, and future clinical applicability of NIBS in addiction treatment.