Is Naltrexone Effective and Safe for Treating Amphetamine-Type Stimulant Use Disorder? A Systematic Review and Meta-analysis.

Objectives: We conducted a systematic review and meta-analysis (PROSPERO ID: CRD42023401796) of randomized placebo-controlled trials evaluating the effectiveness and safety of naltrexone as a standalone pharmacotherapy for amphetamine-type stimulant use disorder (ATSUD).

Methods: We searched EMBASE, MEDLINE, EBM Reviews, PsycINFO, CINAHL, Google Scholar, and trial registries on April 11, 2023, and updated on September 24, 2024, to identify randomized placebo-controlled trials evaluating the effectiveness of naltrexone for the treatment of ATSUD. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines were followed for reporting the study. Risk of bias and quality of evidence were assessed with the Cochrane Risk-of-bias Assessment tool and the Grading of Recommendations, Assessment, Development, and Evaluation. Risk ratios (RRs) or Peto odds ratio were estimated for binary outcomes as appropriate. Standardized mean differences were calculated for continuous outcomes.

Results: Five studies (n = 419 participants) were eligible. We found no significant difference between naltrexone and placebo for amphetamine-type stimulant use (RR = 0.903, 95% confidence interval [CI] = 0.698 to 1.167, P = 0.44, I2 = 96.1%; 4 studies), study retention (RR = 1.055, 95% CI = 0.942 to 1.182, P = 0.35, I2 = 45.0%; 4 studies), end-of-treatment craving (standardized mean difference = 0.069, 95% CI = -0.272 to 0.410, P = 0.69, I2 = 0.0%; 2 studies), and serious adverse events (odds ratio = 1.086, 95% CI = 0.414 to 2.849, P = 0.87, I2 = 0.0%; 3 studies). The quality of evidence was low to very low.

Conclusions: The available evidence does not support the use of standalone naltrexone to treat ATSUD. Significant research efforts must be put toward to identify effective pharmacotherapies to complement psychosocial interventions for ATSUD.