Background/Aim: The aim of the current study was to review drug harms as they occur in Australia using the Multi-criteria Decision Analysis (MCDA) methodology adopted in earlier studies in other jurisdictions. Method: A facilitated workshop with 25 experts from across Australia, was held to score 22 drugs on 16 criteria: 9 related to harms that a drug produces in the individual and 7 to harms to others. Participants were guided by facilitators through the methodology and principles of MCDA. In open discussion, each drug was scored on each criterion. The criteria were then weighted using a process of swing weighting. Scoring was captured in MCDA software tool. Results: MCDA modelling showed the most harmful substances to users were fentanyls (part score 50), heroin (part score 45) and crystal methamphetamine (part score 42). The most harmful substances to others were alcohol (part score 41), crystal methamphetamine (part score 24) and cigarettes/tobacco (part score 14). Overall, alcohol was the most harmful drug when harm to users and harm to others was combined. A supplementary analysis took into consideration the prevalence of each substance in Australia. Alcohol was again ranked the most harmful substance overall, followed by cigarettes, crystal methamphetamine, cannabis, heroin and pharmaceutical opioids. Conclusions: The results of this study make an important contribution to the emerging international picture of drug harms. They highlight the persistent and pervasive harms caused by alcohol. Policy implications and recommendations are discussed. Policies to reduce harm from alcohol and methamphetamine should be a priority.

Alcohol use disorder (AUD) is a leading cause of morbidity and mortality. 1-2 Alcohol consumption is related to approximately 4% of the global burden of disease. 1 It has been estimated that, in clinical settings and compared to the general population, the relative risk of mortality is 3.38 for male patients and 4.57 for female patients with AUD. 2 Patients who reduce their alcohol consumption may halve this increased risk of mortality compared to patients with AUD who do not. 3 However, currently the approved pharmacotherapies that may help patients with AUD to achieve abstinence and/or reduce alcohol consumption to lower drinking levels are limited in number and efficacy. 4-5 Therefore, there is an urgent need to develop more effective treatments in this area. Preclinical and human studies suggest that baclofen, a GABA B receptor agonist, might be a novel treatment for patients with moderate to severe AUD. 6 Notably, a few years after initial randomized clinical trials (RCTs) were conducted, the potential use of this medication for AUD dramatically increased in its popularity due to a French case report describing the use of very high doses of baclofen to treat alcohol craving and drinking. 7 This intriguing yet purely anecdotical case report led to significant scientific and mass media attention and to the use of baclofen (off-label) in the treatment of AUD, such that the French drugs regulatory agency became involved in evaluating the use of baclofen in AUD. However, clinical studies conducted in Europe, USA, Australia, Israel and that evaluated baclofen efficacy in AUD have yielded conflicting results with some but not all RCTs showing an effect of baclofen. 6 The three recent meta-analyses do not draw definitive conclusions on the efficacy of baclofen in the treatment of AUD. 8-10 In fact, one meta-analysis 8 found no significant superiority of baclofen over placebo on the outcomes of each study whereas the other two found that baclofen treatment significantly increased the rate of abstinent patients 9-10 and time to first lapse 9 compared to placebo. Furthermore, one meta-analysis found larger effect sizes of baclofen among heavy drinkers and studies using lower doses. 9 The other study found no significant efficacy of baclofen in reducing the severity of craving for alcohol, anxiety, and depression. 10 In addition, these two meta-analyses reported no significant efficacy of baclofen on other important outcomes such as rate of abstinence days 9-10 or rate of heavy drinking days. 10 Chiefly, all three meta-analyses found overall a small effect size and substantial heterogeneity among studies. 8-10 Following the publication of these metaanalyses, 8-10 a further RCT has been completed and data analysis is currently under way (JC Garbutt, unpublished; ClinicalTrials.gov: NCT01980706). Despite the lack of consistent evidence of efficacy, baclofen is frequently used off-label to treat AUD, especially in some European countries and Australia. However, there is significant variability in the use of baclofen for cl...

Alcohol use disorder (AUD) is a brain disorder associated with high rates of mortality and morbidity worldwide. Baclofen, a selective gamma-aminobutyric acid-B (GABA-B) receptor agonist, has emerged as a promising drug for AUD. The use of this drug remains controversial, in part due to uncertainty regarding dosing and efficacy, alongside concerns about safety. To date there have been 15 randomized controlled trials (RCTs) investigating the use of baclofen in AUD; three using doses over 100 mg/day. Two additional RCTs have been completed but have not yet been published. Most trials used fixed dosing of 30–80 mg/day. The other approach involved titration until the desired clinical effect was achieved, or unwanted effects emerged. The maintenance dose varies widely from 30 to more than 300 mg/day. Baclofen may be particularly advantageous in those with liver disease, due to its limited hepatic metabolism and safe profile in this population. Patients should be informed that the use of baclofen for AUD is as an “off-label” prescription, that no optimal fixed dose has been established, and that existing clinical evidence on efficacy is inconsistent. Baclofen therapy requires careful medical monitoring due to safety considerations, particularly at higher doses and in those with comorbid physical and/or psychiatric conditions. Baclofen is mostly used in some European countries and Australia, and in particular, for patients who have not benefitted from the currently used and approved medications for AUD.

Screening and assessment (Chapter 2): screening techniques to identify patients with alcohol problems, and subsequent assessments for clinicians to undertake before providing specific treatments or interventions.• Interventions, treatments, relapse prevention and aftercare (Chapter 3): a range of varying interventions and treatments, including brief interventions, brief e-health interventions, psychosocial interventions, alcohol withdrawal management, pharmacotherapy options, and peer support programs. In the final section of this chapter, relapse prevention, aftercare, and long term follow-up strategies are discussed.• Considerations for specific populations (Chapter 4): the management of alcohol problems and treatment considerations for specific population groups of interest in Australia -genderspecific considerations, adolescents and young people, pregnant and breastfeeding women, Aboriginal and Torres Strait Islander peoples, culturally and linguistically diverse groups, sexually diverse and gender diverse populations, older people, and cognitively impaired people.• Understanding comorbidities (Chapter 5): the importance of considering a range of comorbidities when providing treatment for alcohol problems. Polydrug use, comorbid mental disorders, and physical-related comorbidities are discussed.The content of this supplement is based on the various chapters of the full Guidelines for the Treatment of Alcohol Problems, which were based on reviews of the evidence, including well designed meta-analyses and randomised controlled trials, wherever possible. Where this evidence was not available, recommendations were based on the best available research or clinical experience. Each recommendation in the guidelines is accompanied with a level of evidence based on National Health and Medical Research Council evidence recommendations (Box 2), 21 with "A" representing the most evidence and "GPP" (good practice point) indicating a recommendation with no evidence.For more on the Guidelines for the Treatment of Alcohol Problems, visit https://alcoh oltre atmen tguid elines.com.au/. Acknowledgements:The Guidelines for the Treatment of Alcohol Problems project was funded by the Australian Government, under the Drug and Alcohol Program. We would like to express our gratitude to members of the Guidelines Steering Committee for providing invaluable guidance and advice on this project. We thank Daniel Winter, Sophia Little, Brennan Geiger and James Pham for providing research and administrative support, and Joshua Watt for providing clinical support, across sections of this supplement. Finally, we thank Donna Ah Chee, Kylie Lee, Teagan Weatherall, Craig Holloway and Martin Nean for conversations and work which informed the Aboriginal and Torres Strait Islander peoples section in the guidelines and Chapter 4 of this supplement.Competing interests: Paul Haber has been funded by the Lambert Initiative for Cannabinoid Therapeutics at the University of Sydney to undertake clinical trials of cannabinoid treatment for alcohol withdra...

Alcohol dependence is associated with a wide array of physical and psychiatric complications and is a major cause of morbidity and mortality worldwide. Recent randomized trials of baclofen, with a total daily dose 30 mg administered in 3 divided doses, have supported its efficacy in reducing craving and promoting abstinence from alcohol. Individual case studies support a possible increased effect at higher doses for treatment-resistant patients. Here, we report on 4 alcohol-dependent patients resistant to standard treatments who responded to higher doses of baclofen ranging from 75 to 125 mg daily. Further research into the use of high-dose baclofen for treatment-resistant alcohol dependence is warranted.

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