(84) Meta-analysis of the Therapeutic Role of TMS and tDCS in Opioid Disorder

Background & Introduction: Opioid use disorder (OUD) is a significant public health challenge, affecting over 16 million people worldwide. Despite the availability of effective treatments, high rates of treatment discontinuation and relapse remain a challenge. New therapeutic options are necessary. Emerging evidence suggests that neuromodulation techniques, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), could be a promising treatment for OUD. These non-invasive therapies offer the advantage of complementing medications for opioid use disorder (MOUD) without the risk of drug-drug interactions.
Additionally, both treatments have shown broad tolerability, and because they are already widely available, they could be rapidly scaled and integrated into addiction clinical practices. Both tDCS and rTMS may be efficacious in treating OUD by altering brain function in key regions of the reward pathway, including the ventral tegmental area (VTA) and the nucleus accumbens (NAc). The objective of this systematic review and meta-analysis is to investigate the effectiveness of rTMS and tDCs in reducing cravings and relapse rates among individuals with OUD.

Methods: A systematic review was conducted from inception to January 2025, using PubMed, PsycINFO, Embase, and Cochrane Library, to evaluate the effectiveness of rTMS and tDCS in reducing cravings and relapse rates in individuals with OUD. Only randomized controlled trials comparing rTMS or tDCS to a placebo were included in this review. The risk of bias was assessed using the Cochrane Risk of Bias Tool. Statistical analyses were conducted using Review Manager (RevMan). The primary outcome of the study was a change in cravings for opioids. Random-effects modeling was utilized for meta-analyses, with results expressed as standardized mean differences (SMDs) and 95% confidence intervals (CIs). Heterogeneity was assessed using I2 statistics.

Results: Eighteen studies met the inclusion criteria, involving 877 participants (776 male). 8 studies investigated rTMS (n = 492; mean age: 35.9 years; 91% male), while ten studies focused on tDCS (n = 385; mean age: 34.6 years; 85% male).
Craving reduction was the most commonly assessed primary outcome, with active rTMS and tDCS both demonstrating significant effects compared to sham interventions. The effect size for craving reduction was SMD = 0.80 (95% CI: -1.03, -0.58), with a p-value of < 0.00001, indicating a significant effect. There was also considerable heterogeneity across studies (I² = 89%). rTMS, targeting the left dorsolateral prefrontal cortex (DLPFC), showed consistent reductions in craving across studies, as measured by scales such as the Obsessive Compulsive Drug Use Scale (OCDUS), Desire for Drug Questionnaire (DDQ), and Visual Analog Scale (VAS). tDCS also reduced craving, with additional benefits in cognitive flexibility, decision-making, and mood regulation.
Secondary outcomes included improved mental health (reduced depression and anxiety). They enhanced cognitive function, with heterogeneity in assessment tools such as the Beck Depression Inventory-II (BDI-II), Self-Rating Depression Scale (SDS), and Trail Making Test (TMT). Variability in scales and methodologies, including stimulation parameters and follow-up durations, limited direct comparison across studies. Few studies examined relapse rates or long-term outcomes, highlighting a need for further research to establish sustained efficacy. For mood disorders, the effect size was SMD = 1.14 (95% CI: -1.65, -0.63), with a p-value of < 0.0001, indicating a significant effect and moderate heterogeneity (I² = 61%).
The heterogeneity was attributed to the inclusion of studies with diverse methodologies and participant characteristics. Analysis of funnel plots revealed a wide dispersion of study results, further highlighting the variability across the included trials. Leave-one-out sensitivity analyses confirmed that the high degree of heterogeneity persisted even when individual studies were removed, underscoring the impact of methodological differences among the studies.

Conclusion & Discussion: Neuromodulation techniques, particularly rTMS and tDCS, show promise as non-invasive treatments for OUD. rTMS effectively reduces cravings by targeting the DLPFC, while tDCS provides additional cognitive and mood benefits. However, variability in study protocols and limited relapse data for tDCS highlight the need for standardized research. Further studies should refine methodologies and assess long-term efficacy. Despite these limitations, rTMS and tDCS represent innovative and accessible tools to enhance OUD treatment outcomes.

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