N acetylcysteine in the treatment of alcohol use disorder: a randomized, double-blind, placebo-controlled trial.

N-acetyl cysteine (NAC) is a potent antioxidant that modulates glutamatergic signalling which is thought to play a role in alcohol use disorder (AUD). There have been no clinical trials investigating NAC for AUD. We aimed to conduct a 28 day double-blind, placebo-controlled (PL) randomized trial of NAC in the treatment of AUD (NCT03879759). A total of 42 participants with AUD (56% alcohol-related liver disease) were randomized to receive placebo or NAC 2400 mg/day. Feasibility outcomes included treatment retention and adverse events. Primary clinical outcomes included alcohol consumption (heavy drinking days, standard drinks per drinking day). Secondary clinical outcome measures included craving, liver tests, and psychological outcomes. There were no significant differences in overall retention between treatment groups (χ2(1) = 0.14, P = 0.71: 86% vs 76% for placebo and NAC, respectively). The most commonly reported adverse event in NAC-treated individuals included headache (14%). For standard drinks per drinking day, there was a significant overall effect of time (F = 9.18, P < 0.001), no significant effect of treatment (F = 0.75, P = 0.79), and a significant time x treatment (NAC vs PL) effect (F = 2.73, P < 0.05). For number of heavy drinks per day, there was a significant overall effect of time (F = 3.16, P < 0.05) but no significant effect of treatment or time x treatment (P = 0.17). There were no significant NAC vs PL effects on secondary clinical outcome measures. In the first trial of NAC for the management of AUD, NAC appears to be feasible and safe. Although there was a significant effect of NAC vs placebo on some alcohol measures such as drinks per drinking day, there does appear to be a variable pattern of effect across time suggesting that a larger trial incorporating a longer treatment duration is now required to determine efficacy.

Australian treatment outcome study: protocol for the 18-20-year follow-up of a prospective longitudinal cohort examining the natural history of heroin dependence and associated mortality, psychiatric and physical health, and health service use.

INTRODUCTION: Opioid dependence is a global health priority, currently making the biggest contribution to drug-related deaths. The chronic, long-term persistence of heroin dependence over the life course requires investigation in prospective longitudinal studies, to better understand patterns and predictors of remission and relapse, as well as the impact of changes in substance use on a range of physical and mental health outcomes. Such knowledge is critical in order to identify modifiable risk factors that can be targeted for intervention. Crucial unanswered questions include the following: What are the long-term rates of mortality? What are the long-term patterns and predictors of heroin use, remission, psychiatric health and health service use? What are the long-term physical health consequences of heroin use? METHODS AND ANALYSIS: The 18-20-year follow-up of the Australian Treatment Outcome Study (ATOS) cohort will examine the natural history of heroin dependence of an existing cohort of 615 people with heroin dependence, who were recruited into the study in 2001-2002. Five waves of follow-up interviews have since been completed, at 3-month, 1-year, 2-year, 3-year and 10-11-year post-baseline. At the 18-20-year follow-up, the ATOS cohort is (on average) approaching their 50s and an average of 30 years have passed since they first used heroin. The 18-20-year follow-up will consist of: (1) a structured interview; (2) physical health assessment; and (3) data linkage. The results of this follow-up will improve our understanding and management of age-related disorders in this population, which if not addressed in the immediate future, has the capacity to overwhelm treatment centres and aged care facilities. ETHICS AND DISSEMINATION: Ethical approval has been granted for the study (Sydney Local Health District Royal Prince Alfred Zone, Human Research Ethics Committee X18-0512 & HREC/18/RPAH/733). The results of the study will be disseminated through published manuscripts, bulletins and technical reports, as well as conference, seminars, webinar and workshop presentations.