Network meta-analysis of non-pharmacological interventions for psychiatric symptoms among individuals with substance...

Comorbid depression and anxiety are prevalent among individuals with substance use disorders (SUDs), complicating treatment outcomes and increasing relapse risk. Poor efficacy and safety concerns often limit pharmacological options for these psychiatric symptoms. Non-pharmacological interventions (NPIs) have gained traction, yet their relative effectiveness remains uncertain.

This study aimed to evaluate the comparative efficacy of NPIs-including cognitive-behavioral therapy (CBT), mindfulness-based approaches, exercise therapy, and neuromodulation-in reducing depression, anxiety, and substance craving among individuals with SUDs.

A systematic search of PubMed, Embase, and Cochrane Library (up to February 2025) identified 24 RCTs (1,437 participants, 901 males) with DSM/ICD-diagnosed SUDs, following PRISMA-NMA guidelines (PROSPERO: CRD420250654383). Outcomes encompassed depressive/anxiety symptoms (primary) and craving (secondary). Data were analyzed via Bayesian network meta-analysis (NMA), reported as standardized mean differences (SMDs) with 95% credible intervals (CrIs), with treatment efficacy ranked by surface under the cumulative ranking curve (SUCRA) values.

Exercise therapy ranked highest for alleviating depression (SUCRA: 90.77%; SMD -0.79, 95% CrI:-1.04 to -0.54 vs. placebo), while physical-stimulus (PS) therapy and mindfulness interventions showed robust efficacy across outcomes. Subgroup analyses identified disease-specific efficacy profiles: cognitive behavioral therapy (CBT) demonstrated superiority for opioid use disorder (OUD)-related anxiety (SUCRA: 76.83%; SMD 0.74, 95% CrI:0.26-1.25 vs. placebo).

This NMA highlights varied efficacy among PS therapy, mindfulness-based, and exercise interventions in alleviating depression, anxiety, and craving in SUD patients. Results advocate integrating neuromodulatory and behavioral therapies into comprehensive addiction care. Future research should prioritize longitudinal mechanistic studies and personalized protocols to enhance treatment durability and recovery outcomes.