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Evoking Change Through Acceptance and Awareness: A Sysematic Review of Third-Wave Therapies for Substance Use
Andrea Calderone1, Desirèe Latella1, Antonino Todaro1
1IRCCS Centro Neurolesi Bonino-Pulejo, Messina, Italy.
Background:
Substance use disorders (SUDs) are a major global health burden, and third-wave therapies that target transdiagnostic processes such as psychological flexibility and mindfulness have emerged as promising options. This systematic review synthesized evidence on third-wave interventions for adults with diagnostic and statistical manual of mental disorder (DSM)-defined SUDs.
Methods:
A comprehensive search of seven databases (2014-2025) identified randomized and non-randomized studies of acceptance and commitment therapy (ACT), related mindfulness-based programs, and dialectical behavioral therapy skills training. Two reviewers screened records, extracted data, assessed risk of bias with Risk of Bias 2 (RoB 2) and risk of bias in non-randomized studies of interventions (ROBINS-I), and synthesized findings using SWiM-consistent narrative methods. The review was prospectively registered in PROSPERO (CRD420251028610).
Results:
Forty-seven studies (35 randomized, 12 non-randomized) met inclusion criteria. Across modalities, third-wave interventions yielded small-to-moderate benefits on abstinence, craving, and substance use outcomes compared with control conditions, with larger and more consistent gains in psychological flexibility, emotion regulation, and mindfulness. Effect sizes varied and most trials showed some concerns or serious risk of bias, resulting in generally low-to-moderate certainty of evidence.
Conclusions:
Third-wave interventions may serve as adjunctive or alternative SUD treatments by engaging targeted mechanisms, enhancing psychological functioning, and producing modest but clinically relevant substance-use benefits. More rigorous, adequately powered mechanism-focused trials are needed to clarify comparative efficacy and guide process-based personalization and implementation in routine addiction services.
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