Safety and efficacy of ketamine for the treatment of patients with alcohol use disorder: a systematic review

<i>Background:</i> Alcohol use disorder (AUD) remains a major global health challenge with limited effective treatments. Ketamine, an NMDA receptor antagonist with rapid anti-craving and neuroplastic effects, has emerged as a promising novel therapy for AUD. <i>Objective:</i> To review the literature examining the safety and efficacy of ketamine for treating AUD. <i>Methods:</i> PubMed and Embase were searched to identify eligible studies published until December 2024. Studies were screened as per the eligibility criteria. Appropriate Joanna Briggs Institute tool was used for risk of bias assessment. A narrative synthesis of findings from the included studies was done. The review protocol was pre-registered in PROSPERO (CRD42022318120). <i>Results:</i> Six studies comprising a total of 605 patients (528 male) from three different countries (USA, UK, Russia) were reviewed. Five of them reported favorable effects of adjunctive ketamine treatment on a range of different alcohol-related outcomes such as abstinence rates or period, alcohol-related craving, and number of heavy drinking days. However, methodological differences including variations in ketamine dosing strategies (route: oral, IV, IM; dose/session: 0.5 mg/kg IV to 2.5 mg/kg IM; number of sessions: 1–3), treatment duration, sample characteristics, and method used for measuring study outcomes led to significant heterogeneity and limited comparability of results. No study reported any serious adverse event or ketamine misuse following ketamine treatment. <i>Conclusion:</i> This review underscored ketamine’s potential as an adjunctive treatment for AUD. While promising, considerable variability in dosing, therapeutic approaches, and study designs limits the certainty of evidence. Future research examining the long-term safety and efficacy of ketamine is needed.