Efficacy and safety of naltrexone for amphetamine and methamphetamine use disorder: a systematic review of randomized controlled trials

Abstract

Background: Methamphetamine intake has increased substantially in recent years, being the second most abused illicit substance after cannabis. However, there is currently no effective evidence‐based pharmacological treatment for amphetamine or methamphetamine use. Naltrexone, an opioid antagonist has been suggested as a possible treatment option by blocking the rewarding effects of amphetamine and methamphetamine. Objectives: To evaluate the practicality in using naltrexone as a pharmacological treatment for amphetamine and methamphetamine use disorder. Methods: We searched PubMed, EMBASE, and Cochrane Library with bibliographies of the retrieved articles screened. Studies investigating the effects of naltrexone on amphetamine or methamphetamine use were eligible for inclusion. Primary outcome was defined as attenuated subjective measures of amphetamine or methamphetamine (eg, level and frequency of drug use). Secondary outcome was rate of abstinence, compliance, adverse events and physiological changes (ie, blood pressure, heart rate). All studies were rated as low risk of bias using the Cochrane tool for risk of bias. Results: Among 591 identified studies, nine randomized controlled trials were included after eligibility assessment. In total, five studies investigated the effects of naltrexone for amphetamine and four studies for methamphetamine use disorder. Naltrexone modestly attenuated subjective effects for amphetamine users but revealed conflicting results for methamphetamine users. Two amphetamine studies showed conflicting results on abstinence rate and inconclusive results for methamphetamine after treatment. All studies reported well tolerability of naltrexone. Conclusions: Naltrexone has a modest effect on amphetamine but varying effect on methamphetamine disorder regarding attenuated subjective effects. The effects of naltrexone on the abstinence rate of amphetamine and methamphetamine remains inadequate and inconclusive. The tolerability and safety in both amphetamine and methamphetamine studies appears to be promising and in favor of naltrexone. Due to the limited large‐scale studies conducted to confirm the efficacy of naltrexone for amphetamine and methamphetamine use disorder, more high‐quality studies are warranted to further evaluate the potential use of naltrexone.