A Placebo-Controlled Randomized Trial of Vigabatrin in the Management of Acute Alcohol Withdrawal.

OBJECTIVE: To undertake a double blinded randomised placebo-controlled trial to assess the efficacy of vigabatrin, a GABA-transaminase inhibitor, as a benzodiazepine sparing agent in the management of acute alcohol withdrawal syndrome in a residential setting. METHODS: We enrolled 120 patients with alcohol use disorder who were randomly assigned to either treatment with vigabatrin (2g/day for 4 days) or placebo. The primary outcome was defined as the number of participants in each treatment arm needing diazepam for withdrawal management. A secondary outcome prespecified was the total dose of diazepam received by participants in each treatment arm. Participants were recruited on admission to a residential withdrawal unit at St Vincent's Hospital Melbourne from December 2014 to April 2019. RESULTS: No significant difference was observed in the number of participants requiring benzodiazepines during their residential withdrawal stay with 44 participants (78.6%) in placebo arm requiring at least one dose of diazepam compared to 38 (66.7%) in vigabatrin arm (p = .156). An 18.1% difference was observed between the proportion of participants who received a total dose of >100mg of diazepam during their residential withdrawal stay in placebo arm (32.1%), compared to vigabatrin arm (14.0%, p = .022). There were higher rates of reported adverse events in placebo arm with nine (15.0%) participants reporting adverse events compared with two (3.3%) participants in vigabatrin arm (p = .027). CONCLUSION: Vigabatrin significantly reduced the number of participants requiring >100mg diazepam over the course of their alcohol withdrawal and was associated with a reduction in adverse effects when compared to placebo.

Methamphetamine-associated cardiomyopathy: an addiction medicine perspective.

Methamphetamine-associated cardiomyopathy (MaCM) is an increasingly recognised serious complication from methamphetamine (MA) use. It is characterised as the development of otherwise unexplained heart failure in the context of MA use. MaCM predominantly affects a young and vulnerable population with high morbidity and mortality. It is the second leading cause of mortality in patients with MA use disorder (MUD). Our understanding of MaCM pathogenesis is based on observational cohorts and autopsy studies. Currently, the treatment of MaCM is predicated on abstinence. Medical therapies offer some benefit to a minority of patients; however, without abstinence, medical therapies are often ineffective. Abstinence is difficult for most patients to achieve; all clinicians require an understanding of MaCM and how to educate patients on the risks of ongoing use. Where available, referral to addiction medicine specialists to assist with treatment of MUD is recommended. This review aims to: (i) explain the proposed pathologic mechanisms of MaCM; (ii) summarise recent recommendations of the screening and treatment of MaCM; and (iii) highlight the role of addiction medicine in the management of patient with MaCM.

Using Social Media Data to Investigate Public Perceptions of Cannabis as a Medicine: Narrative Review.

BACKGROUND: The use and acceptance of medicinal cannabis is on the rise across the globe. To support the interests of public health, evidence relating to its use, effects, and safety is required to match this community demand. Web-based user-generated data are often used by researchers and public health organizations for the investigation of consumer perceptions, market forces, population behaviors, and for pharmacoepidemiology. OBJECTIVE: In this review, we aimed to summarize the findings of studies that have used user-generated text as a data source to study medicinal cannabis or the use of cannabis as medicine. Our objectives were to categorize the insights provided by social media research on cannabis as medicine and describe the role of social media for consumers using medicinal cannabis. METHODS: The inclusion criteria for this review were primary research studies and reviews that reported on the analysis of web-based user-generated content on cannabis as medicine. The MEDLINE, Scopus, Web of Science, and Embase databases were searched from January 1974 to April 2022. RESULTS: We examined 42 studies published in English and found that consumers value their ability to exchange experiences on the web and tend to rely on web-based information sources. Cannabis discussions have portrayed the substance as a safe and natural medicine to help with many health conditions including cancer, sleep disorders, chronic pain, opioid use disorders, headaches, asthma, bowel disease, anxiety, depression, and posttraumatic stress disorder. These discussions provide a rich resource for researchers to investigate medicinal cannabis-related consumer sentiment and experiences, including the opportunity to monitor cannabis effects and adverse events, given the anecdotal and often biased nature of the information is properly accounted for. CONCLUSIONS: The extensive web-based presence of the cannabis industry coupled with the conversational nature of social media discourse results in rich but potentially biased information that is often not well-supported by scientific evidence. This review summarizes what social media is saying about the medicinal use of cannabis and discusses the challenges faced by health governance agencies and professionals to make use of web-based resources to both learn from medicinal cannabis users and provide factual, timely, and reliable evidence-based health information to consumers.

Consumer-Generated Discourse on Cannabis as a Medicine: Scoping Review of Techniques.

BACKGROUND: Medicinal cannabis is increasingly being used for a variety of physical and mental health conditions. Social media and web-based health platforms provide valuable, real-time, and cost-effective surveillance resources for gleaning insights regarding individuals who use cannabis for medicinal purposes. This is particularly important considering that the evidence for the optimal use of medicinal cannabis is still emerging. Despite the web-based marketing of medicinal cannabis to consumers, currently, there is no robust regulatory framework to measure clinical health benefits or individual experiences of adverse events. In a previous study, we conducted a systematic scoping review of studies that contained themes of the medicinal use of cannabis and used data from social media and search engine results. This study analyzed the methodological approaches and limitations of these studies. OBJECTIVE: We aimed to examine research approaches and study methodologies that use web-based user-generated text to study the use of cannabis as a medicine. METHODS: We searched MEDLINE, Scopus, Web of Science, and Embase databases for primary studies in the English language from January 1974 to April 2022. Studies were included if they aimed to understand web-based user-generated text related to health conditions where cannabis is used as a medicine or where health was mentioned in general cannabis-related conversations. RESULTS: We included 42 articles in this review. In these articles, Twitter was used 3 times more than other computer-generated sources, including Reddit, web-based forums, GoFundMe, YouTube, and Google Trends. Analytical methods included sentiment assessment, thematic analysis (manual and automatic), social network analysis, and geographic analysis. CONCLUSIONS: This study is the first to review techniques used by research on consumer-generated text for understanding cannabis as a medicine. It is increasingly evident that consumer-generated data offer opportunities for a greater understanding of individual behavior and population health outcomes. However, research using these data has some limitations that include difficulties in establishing sample representativeness and a lack of methodological best practices. To address these limitations, deidentified annotated data sources should be made publicly available, researchers should determine the origins of posts (organizations, bots, power users, or ordinary individuals), and powerful analytical techniques should be used.

New Australian guidelines for the treatment of alcohol problems: an overview of recommendations.

OF RECOMMENDATIONS AND LEVELS OF EVIDENCE: Chapter 2: Screening and assessment for unhealthy alcohol use Screening Screening for unhealthy alcohol use and appropriate interventions should be implemented in general practice (Level A), hospitals (Level B), emergency departments and community health and welfare settings (Level C). Quantity-frequency measures can detect consumption that exceeds levels in the current Australian guidelines (Level B). The Alcohol Use Disorders Identification Test (AUDIT) is the most effective screening tool and is recommended for use in primary care and hospital settings. For screening in the general community, the AUDIT-C is a suitable alternative (Level A). Indirect biological markers should be used as an adjunct to screening (Level A), and direct measures of alcohol in breath and/or blood can be useful markers of recent use (Level B). Assessment Assessment should include evaluation of alcohol use and its effects, physical examination, clinical investigations and collateral history taking (Level C). Assessment for alcohol-related physical problems, mental health problems and social support should be undertaken routinely (GPP). Where there are concerns regarding the safety of the patient or others, specialist consultation is recommended (Level C). Assessment should lead to a clear, mutually acceptable treatment plan which specifies interventions to meet the patient's needs (Level D). Sustained abstinence is the optimal outcome for most patients with alcohol dependence (Level C). Chapter 3: Caring for and managing patients with alcohol problems: interventions, treatments, relapse prevention, aftercare, and long term follow-up Brief interventions Brief motivational interviewing interventions are more effective than no treatment for people who consume alcohol at risky levels (Level A). Their effectiveness compared with standard care or alternative psychosocial interventions varies by treatment setting. They are most effective in primary care settings (Level A). Psychosocial interventions Cognitive behaviour therapy should be a first-line psychosocial intervention for alcohol dependence. Its clinical benefit is enhanced when it is combined with pharmacotherapy for alcohol dependence or an additional psychosocial intervention (eg, motivational interviewing) (Level A). Motivational interviewing is effective in the short term and in patients with less severe alcohol dependence (Level A). Residential rehabilitation may be of benefit to patients who have moderate-to-severe alcohol dependence and require a structured residential treatment setting (Level D). Alcohol withdrawal management Most cases of withdrawal can be managed in an ambulatory setting with appropriate support (Level B). Tapering diazepam regimens (Level A) with daily staged supply from a pharmacy or clinic are recommended (GPP). Pharmacotherapies for alcohol dependence Acamprosate is recommended to help maintain abstinence from alcohol (Level A). Naltrexone is recommended for prevention of relapse to heavy drinking (Level A). Disulfiram is only recommended in close supervision settings where patients are motivated for abstinence (Level A). Some evidence for off-label therapies baclofen and topiramate exists, but their side effect profiles are complex and neither should be a first-line medication (Level B). Peer support programs Peer-led support programs such as Alcoholics Anonymous and SMART Recovery are effective at maintaining abstinence or reductions in drinking (Level A). Relapse prevention, aftercare and long-term follow-up Return to problematic drinking is common and aftercare should focus on addressing factors that contribute to relapse (GPP). A harm-minimisation approach should be considered for patients who are unable to reduce their drinking (GPP). Chapter 4: Providing appropriate treatment and care to people with alcohol problems: a summary for key specific populations Gender-specific issues Screen women and men for domestic abuse (Level C). Consider child protection assessments for caregivers with alcohol use disorder (GPP). Explore contraceptive options with women of reproductive age who regularly consume alcohol (Level B). Pregnant and breastfeeding women Advise pregnant and breastfeeding women that there is no safe level of alcohol consumption (Level B). Pregnant women who are alcohol dependent should be admitted to hospital for treatment in an appropriate maternity unit that has an addiction specialist (GPP). Young people Perform a comprehensive HEEADSSS assessment for young people with alcohol problems (Level B). Treatment should focus on tangible benefits of reducing drinking through psychotherapy and engagement of family and peer networks (Level B). Aboriginal and Torres Strait Islander peoples Collaborate with Aboriginal or Torres Strait Islander health workers, organisations and communities, and seek guidance on patient engagement approaches (GPP). Use validated screening tools and consider integrated mainstream and Aboriginal or Torres Strait Islander-specific approaches to care (Level B). Culturally and linguistically diverse groups Use an appropriate method, such as the "teach-back" technique, to assess the need for language and health literacy support (Level C). Engage with culture-specific agencies as this can improve treatment access and success (Level C). Sexually diverse and gender diverse populations Be mindful that sexually diverse and gender diverse populations experience lower levels of satisfaction, connection and treatment completion (Level C). Seek to incorporate LGBTQ-specific treatment and agencies (Level C). Older people All new patients aged over 50 years should be screened for harmful alcohol use (Level D). Consider alcohol as a possible cause for older patients presenting with unexplained physical or psychological symptoms (Level D). Consider shorter acting benzodiazepines for withdrawal management (Level D). Cognitive impairment Cognitive impairment may impair engagement with treatment (Level A). Perform cognitive screening for patients who have alcohol problems and refer them for neuropsychological assessment if significant impairment is suspected (Level A). SUMMARY OF KEY RECOMMENDATIONS AND LEVELS OF EVIDENCE: Chapter 5: Understanding and managing comorbidities for people with alcohol problems: polydrug use and dependence, co-occurring mental disorders, and physical comorbidities Polydrug use and dependence Active alcohol use disorder, including dependence, significantly increases the risk of overdose associated with the administration of opioid drugs. Specialist advice is recommended before treatment of people dependent on both alcohol and opioid drugs (GPP). Older patients requiring management of alcohol withdrawal should have their use of pharmaceutical medications reviewed, given the prevalence of polypharmacy in this age group (GPP). Smoking cessation can be undertaken in patients with alcohol dependence and/or polydrug use problems; some evidence suggests varenicline may help support reduction of both tobacco and alcohol consumption (Level C). Co-occurring mental disorders More intensive interventions are needed for people with comorbid conditions, as this population tends to have more severe problems and carries a worse prognosis than those with single pathology (GPP). The Kessler Psychological Distress Scale (K10 or K6) is recommended for screening for comorbid mental disorders in people presenting for alcohol use disorders (Level A). People with alcohol use disorder and comorbid mental disorders should be offered treatment for both disorders; care should be taken to coordinate intervention (Level C). Physical comorbidities Patients should be advised that alcohol use has no beneficial health effects. There is no clear risk-free threshold for alcohol intake. The safe dose for alcohol intake is dependent on many factors such as underlying liver disease, comorbidities, age and sex (Level A). In patients with alcohol use disorder, early recognition of the risk for liver cirrhosis is critical. Patients with cirrhosis should abstain from alcohol and should be offered referral to a hepatologist for liver disease management and to an addiction physician for management of alcohol use disorder (Level A). Alcohol abstinence reduces the risk of cancer and improves outcomes after a diagnosis of cancer (Level A).

Medicinal psychedelics for mental health and addiction: Advancing research of an emerging paradigm.

The medical use of psychedelic substances (e.g. psilocybin, ayahuasca, lysergic acid diethylamide and 3,4-methylenedioxymethamphetamine) is attracting renewed interest, driven by a pressing need for research and development of novel therapies for psychiatric disorders, as well as promising results of contemporary studies. In this Viewpoint, we reflect upon the 'Clinical Memorandum on Psychedelics' recently released by the Royal Australian and New Zealand College of Psychiatrists and note subsequent developments including the application for down-scheduling of psilocybin and 3,4-methylenedioxymethamphetamine presently being considered by the Therapeutic Goods Administration and approvals for access via the Special Access Scheme. We suggest that this field is worthy of rigorous research to assess potential benefits, address safety parameters and clarify therapeutic mechanisms. To this end, we outline recent research findings, provide an overview of current knowledge relating to mechanisms of action and discuss salient aspects of the psychedelic-assisted psychotherapy treatment model. The sum of this research points towards medicinal psychedelics as a potential new class of psychiatric treatments when used within a medically supervised framework with integrated psychotherapeutic support. However, before widespread translation into clinical use can occur, appropriately designed and sufficiently powered trials are required to detect both potential positive and negative outcomes. Unique safety and regulatory challenges also need to be addressed. As for any new medical therapy, psychedelic research needs to be conducted in a rigorous manner, through the dispassionate lens of scientific enquiry. Carte blanche availability to practitioners, without specific protocols and appropriate training, would be potentially harmful to individuals and detrimental to the field.

The fentanyls: pharmacological and clinical aspects relevant to Australia.

OBJECTIVE: North American and other jurisdictions have seen an alarming rise in the abuse of the fentanyls, with related overdose deaths. We sought to review this group of drugs to alert Australian psychiatrists and drug and alcohol clinicians to their clinical effects and potential harms. CONCLUSIONS: The extreme potency of the fentanyls underlie their lethality. Vigilance and investment from both policy makers and health care providers are required to mitigate harm from a possible future Australian fentanyl epidemic.

The fentanyls: a 'future threat' for Australia?

OBJECTIVE: The fentanyls have emerged as a significant public health threat in North America but much less so in Australia. We sought to identify reasons for this discrepancy and highlight harm reduction approaches that may mitigate a future Australian fentanyl epidemic. CONCLUSIONS: Differences in drug use 'culture' and a supply of cheap high-quality methamphetamine in Australia may be reasons for the observed difference in fentanyl-related harm. More worryingly, it is possible that Australia is following North American trends and that the fentanyl epidemic is still to come.

Clinical issues in cannabis use.

Cannabis is the most commonly used illicit substance worldwide and the prevalence of users continues to increase. Over the last 2 decades, the world has seen significant changes regarding cannabis for recreational use as well as application in its use as a therapeutic medicine. This is likely to have influenced the decreasing perception of risks associated with the use of cannabis. Cannabis, however, is not benign and, depending on the pattern of its use, can incur a range of harmful effects, which have implications when prescribing medicinal cannabinoids for individuals. Based on research evidence from recreational use of cannabis as well as the emerging data from trials of medicinal cannabis, we propose some clinical domains that will need specific considerations when prescribing medicinal cannabis.

When should the driver with a history of substance misuse be allowed to return to the wheel? A review of the substance misuse section of the Australian national guidelines.

Assessing fitness to drive in applicants with a historical or current substance use disorder presents a specific clinical challenge. The Australian guidelines require evidence of remission and absence of cognitive change when considering applications for re-licensing driver or individuals applying to reengage in safety-sensitive work. This paper reviews some of the clinical and biochemical indicators that determine whether a particular person is in 'remission' and meets the criteria for return to driving or other safety-sensitive occupation. It provides an overview of the challenges in establishing an evidence-based approach to determining fitness for safety critical activities. There is no internationally accepted definition of 'remission'. Review of the literature and examination of assessment protocols from other national jurisdictions are available for alcohol and the more important drugs of interest in road safety. Assessing fitness to drive when there is a history of substance misuse and/or substance use disorders is a complex issue that requires assessment of biomarkers, clinical findings and clinical assessment before the person returns to driving. We propose that hair testing provides a reliable and reproducible way to demonstrate remission and provide cost-effective monitoring. Standardised psychological tests could provide a reproducible assessment of the cognitive effects of drug use and suitability to resume driving. We recommend that AustRoads amend the national guidelines to reflect an evidence-based approach to assessing fitness to drive after conviction for offences related to alcohol and drug use.

Managing opioid overdose in pregnancy with take-home naloxone.

Programs have recently been established in Australia and internationally to allow wider access to naloxone to people at risk of opioid overdose yet there are no guidelines relating to the administration of naloxone to pregnant women, particularly regarding dose requirements and resuscitative measures peculiar to pregnancy. This paper provides practical guidelines to health workers in relation to any complications that may arise during opioid overdose response (including the administration of naloxone) for pregnant women and the follow up required ensuring best possible outcomes for mother and baby.

Prescription opioid use in pregnancy.

Prescription medications, including opioid analgesics, are increasingly prescribed in Australia and internationally. More women are presenting in pregnancy with prescription opioid use which can potentially cause harm to the mother and fetus. This article outlines the different types of prescription opioids, defines how prescription opioid use disorder presents clinically and suggests a rational clinical approach to assess and manage patients in the context of pregnancy and their infants.

Role of physicians in the management of substance use disorders.

Alcohol, tobacco and other drugs are responsible for significant contribution to the global burden of disease and injury. There are several contributions that the physician can make to reduce the burden that substance use contributes to the community, not only clinically but also through leadership and contribution to community dialogue and public policy.

Managing attention deficit hyperactivity disorder in adults using illicit psychostimulants: A systematic review.

CONTEXT: Attention deficit hyperactivity disorder and stimulant use disorder commonly co-exist, and appropriate treatments have not been well established. OBJECTIVE: To provide guidance for treatment of co-existing attention deficit hyperactivity disorder and stimulant use disorder. DATA SOURCES: A systematic review of published English articles using MEDLINE, EMBASE, CINAHL, PsycINFO and Cochrane, utilising consistent search terms. STUDY SELECTION: Randomised controlled trials, comparing any treatment arm with a control group, for participants meeting Diagnostic and Statistical Manual of Mental Disorders or equivalent criteria for both attention deficit hyperactivity disorder and stimulant use disorder. RESULTS: Eight trials were identified for inclusion in this review. Four of eight studies showed improvement in attention deficit hyperactivity disorder outcome measures compared with placebo. Two of six studies that reported substance use outcomes showed improvement in treatment arms compared with placebo. Studies to show effect tended to be those with the highest treatment dosage. CONCLUSION: Evidence for the efficacy of treatment of patients with comorbid stimulant use disorder and attention deficit hyperactivity disorder is limited. Promising outcomes need replication in further studies utilising higher treatment dosage.

A case of severe and prolonged γ-hydroxybutyrate (GHB) withdrawal syndrome successfully managed with a slow benzodiazepine and baclofen taper.

INTRODUCTION: γ-hydroxybutyrate (GHB) is a GABA-B agonist that rapidly produces effects that are likened to both alcohol and MDMA/ecstasy. GHB use can lead to neuroadaptation with a characteristic withdrawal syndrome. There is currently a paucity of data on the progression of GHB withdrawal, however, due to the drug's short half-life it is generally considered to be typically 5-7 days, although some cases can be severe and complicated by life threatening delirium. Here, we present a case of severe GHB withdrawal, which recurred on multiple occasions over 56 days, despite initial clinical stabilisation on each occasion and toxicological evidence of abstinence from GHB between episodes. CASE PRESENTATION: A male patient in his 30s presented with agitated delirium on a background of severe GHB use disorder with a 15-year history of daily high dose GHB use. Following 3 hospital admissions over 8 weeks, all requiring intravenous sedation and tracheal intubation, the patient's withdrawal delirium was successfully treated with a slow benzodiazepine and baclofen wean over a period of 6 months. Relapse to GHB use between hospitalisations was excluded toxicologically via blood analysis performed at an institute of forensic pathology. DISCUSSION AND CONCLUSIONS: This case highlights that GHB withdrawal can be more prolonged than previously reported in the literature and in some cases may require slow and prolonged tapering of treatment to prevent re-emergence of delirium. Similar to previous case reports, benzodiazepines and GABA-B receptor agonists appear to be appropriate drug classes to manage GHB withdrawal.

Overview of global monitoring systems for the side effects and adverse events associated with medicinal cannabis use: a scoping review using a systematic approach.

OBJECTIVES: The use of cannabis-based medicine (CBM) as a therapeutic has surged in Australia over the past 5 years. Historically, the United Nations Single Convention on Narcotic Drugs (1961) prohibited cannabis use in Europe, the USA, the UK and Australia, leading to legislative resistance and limited preclinical data on CBM. Existing safety monitoring systems for CBM are poorly structured and do not integrate well into the workflows of busy health professionals. As a result, postmarketing surveillance is inconsistent. This review aims to evaluate international systems for monitoring CBM side effects and adverse events. DESIGN: To undertake a scoping review with a systematic approach, we used the Population, Intervention, Comparison, Outcome (PICO) framework to develop keyword elements, and two search queries to maximise search sensitivity and specificity. DATA SOURCES: Search queries were entered into Embase and Scopus for peer-reviewed literature, and additional searches for grey literature were conducted on 23 June 2023. ELIGIBILITY CRITERIA: We included 54 full-text articles in the review: 39 from peer-reviewed searches, 8 from grey literature and 7 from citations of relevant texts. DATA EXTRACTION AND SYNTHESIS: Our search yielded two main forms of monitoring systems: databases and registries. Out of the 24 monitoring systems identified, there were 10 databases and 14 registries, with databases often created by regulatory authorities. Systems differed in methods of causality assessment, level of detail collected, terminology and affiliations. RESULTS: Within the monitoring systems with enough published data for analysis, all except one remain active at the time of this review. VigiBase is the largest centralised monitoring system, receiving international case reports, however data heterogeneity persists. CONCLUSIONS: Our study emphasises the need for a centralised, consistent and accessible system for the postmarketing surveillance of side effects and adverse events associated with medicinal cannabis use.

The dual orexin receptor antagonist suvorexant in alcohol use disorder and comorbid insomnia: A case report.

Key Clinical Message: This case suggests using dual orexin receptor antagonists to treat alcohol use disorder and comorbid sleep disorders may be effective, commencing treatment in withdrawal and continuing it to prevent relapse. Abstract: Effective medications for the treatment of alcohol use disorder are limited. This is partially due to the heterogenous nature of the symptomatology associated with alcohol use disorder and the abundance of presenting comorbidities. One common, and often overlooked, symptom that occurs during withdrawal of alcohol use is sleep disruption. Here, we report a case study of a participant with comorbid alcohol use disorder and insomnia. This participant was treated with a dual orexin receptor antagonist, suvorexant (Belsomra®), currently approved to treat insomnia. We demonstrate improvements in alcohol cravings, physical and psychological health, and sleep outcomes with treatment. These data support abundant preclinical and emerging clinical data in this space. The findings from this case report highlight the potential for suvorexant to treat comorbid alcohol use disorder and insomnia with fully powered, randomized controlled trials moving forward.