Background Stimulant drugs are second only to cannabis as the most widely used class of illicit drug globally, accounting for 68 million past-year consumers. Dependence on amphetamines (AMPH) or methamphetamine (MA) is a growing global concern. Yet, there is no established pharmacotherapy for AMPH/MA dependence. A comprehensive assessment of the research literature on pharmacotherapy for AMPH/MA dependence may inform treatment guidelines and future research directions. Methods We systematically reviewed the peer-reviewed literature via the electronic databases PubMed, EMBASE, CINAHL and SCOPUS for randomised controlled trials reported in the English language examining a pharmacological treatment for AMPH/MA dependence or use disorder. We included all studies published to 19 June 2019. The selected studies were evaluated for design; methodology; inclusion and exclusion criteria; sample size; pharmacological and (if included) psychosocial interventions; length of follow-up and follow-up schedules; outcome variables and measures; results; overall conclusions and risk of bias. Outcome measures were any reported impact of treatment related to AMPH/MA use. Results Our search returned 43 studies that met our criteria, collectively enrolling 4065 participants and reporting on 23 individual pharmacotherapies, alone or in combination. Disparate outcomes and measures (n = 55 for the primary outcomes) across studies did not allow for meta-analyses. Some studies demonstrated mixed or weak positive signals (often in defined populations, e.g. men who have sex with men), with some variation in efficacy signals dependent on baseline frequency of AMPH/MA use. The most consistent positive findings have been demonstrated with stimulant agonist treatment (dexamphetamine and methylphenidate), naltrexone and topiramate. Less consistent benefits have been shown with the antidepressants bupropion and mirtazapine, the glutamatergic agent riluzole and the corticotropin releasing factor (CRF-1) antagonist pexacerfont; whilst in general, antidepressant medications (e.g. selective serotonin reuptake inhibitors [SSRIs], tricyclic antidepressants [TCAs]) have not been effective in reducing AMPH/MA use. Conclusions No pharmacotherapy yielded convincing results for the treatment of AMPH/MA dependence; mostly studies were underpowered and had low treatment completion rates. However, there were positive signals from several agents that warrant further investigation in larger scale studies; agonist therapies show promise. Common outcome measures should include change in use days. Future research must address the heterogeneity of AMPH/MA dependence (e.g. coexisting conditions, severity of disorder, differences between MA and AMPH dependence) and the role of psychosocial intervention.

Issues Cessation of methamphetamine use may result in a characteristic withdrawal syndrome, no medication has been approved for this indication. This systematic review aims to assess the efficacy of pharmacotherapy for methamphetamine withdrawal, the first comprehensive meta‐analysis since 2008. Approach MEDLINE (1966–2020), CINAHL (1982–2020), PsychINFO (1806–2020) and EMBASE (1947–2020) were systematically searched. Studies were included if they were randomised controlled trials (RCT) investigating pharmacological treatments for methamphetamine withdrawal, reviewing outcomes of treatment discontinuation, mental health outcomes, withdrawal symptoms (including craving) and patient safety. The relative risk (RR) and weighted mean difference (MD) were used to meta‐analyse dichotomous and continuous data respectively, with 95% confidence intervals. Risk of bias and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessments were conducted. Key Findings Nine RCTs of six medications (n = 242 participants) met inclusion criteria, however, only six trials of four medications (n = 186) could be meta‐analysed. Mean sample size across studies was 27 participants, and 88% of participants were male. The quality of evidence in this review varies from low to very low on GRADE assessments. Amineptine may reduce discontinuation rates (RR 0.22, 95% confidence interval [CI] 0.07, 0.72, p = 0.01), and improve global state (MD −0.49, 95% CI −0.80, −0.17), compared with placebo, however, this medication is no longer approved. No other medications improved any domain when compared with placebo. Due to lack of reporting safety profiles could not be established. Conclusions There is insufficient evidence to indicate any medication is effective for the treatment of methamphetamine withdrawal. The poor quality of the evidence indicates a need for better powered, high‐quality trials.

Objective Although most unintentional opioid deaths in Australia are attributed to pharmaceutical opioids, take‐home naloxone (THN) programmes have to date predominantly targeted people using illicit opioids in drug treatment and harm reduction settings. We sought to examine the feasibility of delivering THN brief interventions (THN‐BIs) with intranasal naloxone in EDs. Methods This pilot feasibility study was conducted across three major metropolitan EDs in Sydney and Melbourne. ED staff were surveyed about their perspectives regarding THN before completing a 30‐min training programme in THN‐BI delivery. Patients presenting with opioid overdose or considered high risk for future overdose were eligible to receive the THN‐BI. Staff survey responses were compared between hospitals and provider types using one‐way analysis of variances. Patient demographic and clinical characteristics were extracted from medical records and compared between hospitals and overdose type using Fisher's exact test and one‐way analysis of variances. Results One hundred and twenty‐two ED staff completed the survey. One hundred and ten (90.2%) agreed that EDs should provide THN‐BIs, whereas 23 (19.2%) identified time constraints and 17 (12.9%) felt uncomfortable discussing overdose with patients. Fifty‐seven patients received the THN‐BI, with the majority (n = 50, 87.7%) having presented following opioid overdose. The median age was 44 years and 40 (71.4%) were men. Two‐thirds of the overdoses (n = 31, 66.0%) were attributed to heroin with one‐third (n = 16, 34%) being attributed to pharmaceutical opioids. Conclusions ED‐based delivery of THN‐BIs can reach a wide range of individuals at‐risk of overdose. The present study supports the feasibility of THN interventions in EDs and underscores the importance of addressing implementation barriers including staff training.