Naltrexone efficacy in treating alcohol-use disorder in individuals with comorbid psychosis: a systematic review

Background: Psychotic illnesses, such as schizophrenia, are typically enduring and disabling conditions, impacting individual, family, and societal outcomes. Individuals with these face greater vulnerabilities in developing alcohol-use disorder (AUD). Furthermore, the nature of psychoses, often manifesting with paranoia, cognitive impairment, a lack of insight, sub-optimal treatment adherence, and stigma from others, means that they can pose unique treatment challenges when these two conditions comorbidly occur. These challenges mean that the standard literature on the effectiveness of the opioid antagonist naltrexone in AUD does not necessarily translate to this vulnerable population. Methods: Following PRISMA guidelines, we herein systematically reviewed the evidence for naltrexone in individuals with both psychosis and AUD. Overall, there is a paucity of research in this important area, with only nine reports meeting search criteria, only four of which were randomized control trials. Studies compared naltrexone with: placebo, another pharmaceutical agent, or upon changes to baseline drinking behaviour. One study evaluated the long-acting injectable formulation of this drug. Results: Most studies, including the methodologically more robust ones, supported naltrexone's effectiveness over placebo in terms of reduction in drinking days and numbers of drinks consumed on such days in this cohort. Work comparing naltrexone to other pharmaceutical interventions showed approximate equivalence with disulfiram, and modest superiority over acamprosate. Conclusions: On this limited evidence base, this review endorses the use of naltrexone as both safe and effective in those with both psychotic illnesses and AUD. Several key issues remain to be elucidated. Critically, study designs meant that they were limited to individuals with good engagement with services, and levels of adherence were attained that are unlikely to be replicated in this cohort in real-world settings. Finally, effects of specific psychosis symptomatology, not least paranoia and insight, upon naltrexone use, and the reverse directional potential of double dysphoria' from an opioid antagonist remain largely unexplored.