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.

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.

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).

Glucose patterns following alcohol and illicit drug use in young adults with type 1 diabetes: A flash glucose monitoring study.

INTRODUCTION: To assess the effects of alcohol and illicit drug use in young adults (age 18-35) with type 1 diabetes (T1D) on flash glucose monitor sensor glucose (SG) readings. METHODS: Twenty young adults with T1D were enrolled from a tertiary referral hospital outpatient department in Melbourne, Australia for a 6-week prospective observational study using flash glucose monitoring (FGM). Glucometrics comparing substance using days (SUEDs) to those without substance use (non-SUEDS) were analysed. The primary outcomes were the difference in mean SG values, its standard deviation and minutes/24-h period out of range (SG <3.9 mmol/L or >10.0 mmol/L) between matched SUEDs vs non-SUEDs. An interaction model with the primary effect of HbA1c on SG values was also performed. RESULTS: There were no differences in the primary outcome measures between SUEDS and non-SUEDs. However, there were differences in the regression coefficients for HbA1c and glucometrics between non-SUEDs and SUEDs for mean SG, time out of range and time with SG > 10 mmol/L. This difference was also identified between non-SUEDS and days of ≥40 g alcohol for mean SG. CONCLUSIONS: While there was no difference between glucometrics for SUEDs and non-SUEDs on primary outcomes, HbA1C was found to be a less reliable predictor of glucose patterns in the 24-h period following substance use than control days. Young adults with T1D need to monitor and respond to their glucose levels following substance use and engage in harm minimisation practices irrespective of baseline glucose control.

The 5-HT2C receptor as a therapeutic target for alcohol and methamphetamine use disorders: A pilot study in treatment-seeking individuals.

Alcohol use disorder (AUD) and methamphetamine use disorder (MUD) are prevalent and have high adverse impacts on both the individual and society. Current treatment strategies for these disorders are ineffective at a population level. Lorcaserin, a 5-HT2C receptor agonist, has shown potential at reducing the symptoms of substance use disorder. This pilot study (initiated prior to market withdrawal) examined feasibility and safety of lorcaserin treatment in people undergoing residential detoxification and treatment for AUD and MUD. This was an open label pilot study of lorcaserin where participants (n = 10 AUD; n = 8 MUD) received 10-mg lorcaserin daily for 4 days then twice daily for 1 month. Primary outcome measures included recruitment and retention rate, incidence of treatment-emergent events, incidence of methamphetamine or alcohol withdrawal-related events, heart rate, and blood pressure. Secondary measures included pharmacokinetic data and self-reported alcohol or methamphetamine use, craving, and psychological distress. AUD participants were recruited faster and had a greater retention rate compared with MUD participants. Lorcaserin did not alter vital signs, was well tolerated, and had a similar pharmacokinetic profile to individuals with obesity. Lorcaserin reduced self-reported alcohol and amphetamine-type substance use and craving in AUD and MUD participants, respectively. Self-reported psychological health also improved over the treatment period for all participants. Despite the pilot nature of this study, our data support the notion of 5-HT2C receptors as a therapeutic target for drug and alcohol abuse.

Alcohol and illicit drug use in people with diabetes.

As the prevalence of type 1 and type 2 diabetes increases and population-level patterns of alcohol and illicit drug use evolve, clinicians will continue to encounter people with diabetes whose substance use is affecting health outcomes. Substance use contributes substantially to the population-level prevalence of cardiovascular events, cerebrovascular events, cancers, mental health conditions, road trauma, and domestic violence. Alcohol and drug use also have a measurable effect on diabetes incidence and the development of both acute and chronic diabetes-related complications. In this Review, we examine the effect of alcohol and illicit drug use on people with type 1 or type 2 diabetes. We describe evidence for substance use as a risk factor for new-onset diabetes, prevalence of use in people with diabetes, evidence linking substance use with diabetes-related health outcomes, and evidence on the management of these co-occurring conditions.

The Australian drug harms ranking study.

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.

Experiences of young adults with type 1 diabetes while using alcohol and recreational drugs: An interpretative phenomenological analysis (IPA) of semi-structured interviews.

AIMS: Alcohol and recreational drug use is common in young adults with type 1 diabetes (T1DM) and may account for increased morbidity and mortality. This study explores the motivations and experiences unique to this population while using alcohol and recreational drugs. METHODS: Semi-structured interviews focusing on substance use were performed with 16 young adults aged 18-35 with T1DM who drink alcohol (at least 50 g, 5 Australian standard drinks, in a single session) and/or used recreational drugs. A qualitative interpretative phenomenological analysis (IPA) of the interview data was performed by three clinicians with differing expertise (a psychologist, endocrinologist and addiction medicine specialist). RESULTS: A range of motivations, experiences and harm reduction strategies regarding substance use were described specific to young adults with T1DM with most aimed at mitigating the risk of hypoglycaemia. Clinicians remained the most trusted resources, however, substance use was rarely discussed at clinical encounters. Currently available information, especially for illicit drugs, was described as inadequate. CONCLUSIONS: This analysis identified experiences unique to young adults with T1DM when using alcohol and other drugs. Understanding these experiences and how these young adults attempt to mitigate the risks of substance use may lead to improved clinical interactions and management strategies.

The Use of Baclofen as a Treatment for Alcohol Use Disorder: A Clinical Practice Perspective.

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.

Alcohol and recreational drug use in young adults with type 1 diabetes.

Alcohol and other recreational drug use reaches peak prevalence in young adulthood, including for those with chronic medical conditions such as type 1 diabetes. This review summarises the current literature on the patterns of substance use amongst young adults with type 1 diabetes and the mechanisms through which alcohol and recreational drugs may affect diabetes related health outcomes. These include the direct physical effect of intoxication, as well as the effects of alcohol and drugs on mental health and glucose metabolism. Evidence for increased associated mortality and morbidity is also presented, and current guidelines, management strategies and directions for further research are discussed.

High-dose baclofen for treatment-resistant alcohol dependence.

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.