Stefanie Leung

Baclofen for the Treatment of Alcohol Dependence and Possible Role of Comorbid Anxiety

AIM To conduct a double-blind, placebo-controlled randomized clinical trial of baclofen in the treatment of alcohol dependence. METHODS Out of 69 participants consecutively screened, 42 alcohol-dependent patients were randomized to receive placebo, baclofen 30 mg/day or baclofen 60 mg/day for 12 weeks. All subjects were offered BRENDA, a structured psychosocial therapy for alcohol dependence that seeks to improve motivation for change, enhance strategies to prevent relapse and encourage compliance with treatment. RESULTS Intention-to-treat analyses revealed that alcohol consumption (heavy drinking days, drinks per drinking day) significantly reduced across all three groups during the treatment period. There were no statistically significant advantages to treatment on time to first heavy drinking day (relapse) (P = 0.08), nor time to first drink (lapse) (P = 0.18). A post hoc analysis stratifying according to whether there had been a comorbid anxiety disorder, revealed a beneficial effect of baclofen 30 mg/day versus placebo on time to lapse and relapse (P < 0.05). There was also a beneficial effect for baclofen 60 mg/day relative to placebo on time to relapse in this comorbid group (P < 0.05). Both doses of baclofen were well tolerated. There were no serious adverse events. CONCLUSIONS In spite of the small sample for a 3-arm clinical trial, this study suggests a specific role of baclofen in alcohol-dependent individuals with comorbid anxiety. Replication in larger, fully-powered studies is required.

A randomised controlled trial of sublingual buprenorphine-naloxone film versus tablets in the management of opioid dependence

BACKGROUND Buprenorphine-naloxone sublingual film was introduced in 2011 in Australia as an alternative to tablets. This study compared the two formulations on subjective dose effects and equivalence, trough plasma levels, adverse events, patient satisfaction, supervised dosing time, and impact upon treatment outcomes (substance use, psychosocial function). METHODS 92 buprenorphine-naloxone tablet patients were recruited to this outpatient multi-site double-blind double-dummy parallel group trial. Patients were randomised to either tablets or film, without dose changes, over a 31 day period. RESULTS No significant group differences were observed for subjective dose effects, trough plasma buprenorphine or norbuprenorphine levels, adverse events and treatment outcomes. Buprenorphine-naloxone film took significantly less time to dissolve than tablets (173±71 versus 242±141s, p=0.007, F=7.67). CONCLUSIONS The study demonstrated dose equivalence and comparable clinical outcomes between the buprenorphine-naloxone film and tablet preparations, whilst showing improved dispensing times and patient ratings of satisfaction with the film.

Benzodiazepines, Opioids and Driving: An Overview of the Experimental Research

ISSUES Road crashes contribute significantly to the total burden of injury in Australia, with the risk of injury being associated with the presence of drugs and/or alcohol in the drivers blood. Increasingly, some of the most commonly detected drugs include prescription medicines, the most notable of these being benzodiazepines and opioids. However, there is a paucity of experimental research into the effects of prescribed psychoactive drugs on driving behaviours. APPROACH This paper provides an overview of experimental studies investigating the effects of prescribed doses of benzodiazepines and opioids on driving ability, and points to future directions for research. KEY FINDINGS There is growing epidemiological evidence linking the therapeutic use of benzodiazepines and opioids to an increased crash risk. However, the current experimental literature remains unclear. Limitations to study methodologies have resulted in inconsistent findings. IMPLICATIONS Limited experimental evidence exists to inform policy and guidelines regarding fitness-to-drive for patients taking prescribed benzodiazepines and opioids. CONCLUSION Further experimental research is required to elucidate the effects of these medications on driving, under varying conditions and in different medical contexts. This will ensure that doctors prescribing benzodiazepines and opioids are well informed, and can appropriately advise patients of the risks associated with driving whilst taking these medications.

The efficacy and biobehavioural basis of baclofen in the treatment of alcoholic liver disease (BacALD): Study protocol for a randomised controlled trial

BACKGROUND Effective treatments for alcohol use disorders in those with significant liver disease are critically lacking. The primary aim of the current study is to explore the effectiveness and biobehavioural basis of low and high dose baclofen in improving treatment outcomes for alcohol dependence in people with alcoholic liver disease (The BacALD study). METHODS This double-blind, placebo-controlled study will randomize 180 participants to a 12-week regime of either baclofen (30 mg/day baclofen, 75 mg/day baclofen) or placebo. Participants must meet the ICD-10 criteria for alcohol dependence in addition to alcoholic liver disease (ALD) defined as the presence of symptoms and/or signs referable to liver disease or its complications with or without cirrhosis. Primary outcome measures will include total abstinence duration, and time to lapse and relapse. Furthermore, 60 of the ALD patients enrolled in the trial will also participate in a pharmacokinetic and cue-reactivity component, along with an additional 30 healthy volunteers matched for age and gender randomised to a 1 week regime of either 30 mg/day baclofen or 75 mg/day baclofen. At week 1, plasma levels of baclofen and β-p-chlorophenol-γ-hydroxybutric acid will be measured at 0, 1 and 4 h following baclofen administration and psychophysiological responses to alcohol-associated stimuli will be assessed in a cue reactivity paradigm. Recruitment commenced in late March 2013. CONCLUSIONS This trial will demonstrate the efficacy and safety of two doses of baclofen in patients with alcoholic liver disease and will explore the biobehavioural mechanisms of the treatment effect.

Is specialized integrated treatment for comorbid anxiety, depression and alcohol dependence better than treatment as usual in a public hospital setting?

AIM To assess the effectiveness of a 12 week specialized, integrated intervention for alcohol dependence with comorbid anxiety and/or mood disorder using a randomized design in an outpatient hospital setting. METHODS Out of 86 patients meeting the inclusion criteria for alcohol dependence with suspicion of comorbid anxiety and/or depressive disorder, 57 completed a 3-week stabilization period (abstinence or significantly reduced consumption). Of these patients, 37 (65%) met a formal diagnostic assessment of an anxiety and/or depressive disorder and were randomized to either (a) integrated intervention (cognitive behavioural therapy) for alcohol, anxiety and/or depression, or (b) usual counselling care for alcohol problems. RESULTS Intention-to-treat analyses revealed a beneficial treatment effect of integrated treatment relative to usual counselling care for the number of days to relapse (χ(2) = 6.42, P < 0.05) and lapse (χ(2) = 10.73, P < 0.01). In addition, there was a significant interaction effect of treatment and time for percentage days of abstinence (P < 0.05). For heavy drinking days, the treatment effect was mediated by changes in DASS anxiety (P < 0.05). There were no significant treatment interaction effects for DASS depression or anxiety symptoms. CONCLUSIONS These results provide support for integrated care in improving drinking outcomes for patients with alcohol dependence and comorbid depression/anxiety disorder. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01941693.

Alprazolam use and related harm among opioid substitution treatment clients – 12 months follow up after regulatory rescheduling

BACKGROUND Alprazolam, has been associated with disproportionate harms compared to other benzodiazepines, especially among people in opioid substitution treatment (OST). We examine the effect of the rescheduling of alprazolam in Australia, from Schedule 4 to Schedule 8 in February 2014 amongst a high-risk population of clients in OST. METHODS OST participants who reported recent (last month) alprazolam use were recruited from three Sydney clinics. Participants (n=57) were interviewed immediately prior to rescheduling and again three months and 12 months after rescheduling. We examined self-reported patterns of drug use, drug availability, mental and physical health. A linear mixed models approach was used to analyse changes in alprazolam and other benzodiazepine use. RESULTS Mean days of alprazolam use in the past 28 days decreased from 13.7 to 7.1 days, and mean weekly alprazolam dose decreased from 15.1mg to 6.1mg at 12 months follow-up (p=0.001). Total weekly benzodiazepine use also reduced from a mean of 222mg diazepam equivalent to 157mg (p=0.044). Other substance use did not change significantly. Reported mode of cost price of street alprazolam doubled from

Substance use, health status and service utilisation of older clients attending specialist drug and alcohol services

5 to

Knowledge, advice and attitudes toward women driving a car after caesarean section or hysterectomy: A survey of obstetrician/gynaecologists and midwives.

10 over the 12-month period. CONCLUSION Alprazolam rescheduling resulted in an overall reduction in alprazolam and total benzodiazepine use, without substitution with other drugs, in the short term. Unintended harms were not observed. Rescheduling appears to have been effective in reducing alprazolam use in this high-risk population.

Reversal of central sleep apnoea with change from methadone to buprenorphine-naloxone: a case report.

INTRODUCTION AND AIMS The number of older clients attending drug and alcohol (D&A) services is increasing, although there is insufficient knowledge regarding service needs for this group. The aim of this study was to document the patterns of substance use, health status, cognition, social conditions, and health service utilisation of older clients in D&A treatment. DESIGN AND METHODS A cross-sectional observational study of 99 clients aged ≥50 years (M = 55, SD = 4.5; 77% male) attending specialist D&A services (N = 30 alcohol treatment, N = 69 opioid treatment) in Sydney, Australia. Participants completed a confidential research interview. Findings were compared to aggregated data from younger opioid substitution treatment (OST) clients attending the same services (N = 214). RESULTS Alcohol (46%), benzodiazepines (40%) and cannabis (38%) were the most commonly reported substances used in the past 4 weeks; 23% reported no recent substance use, and 17% reported using three or more drugs. Participants reported high levels of physical and mental health problems, social isolation, low levels of employment, and a third reported difficulties with daily living activities. Forty percent had been injured in a fall in the past 12 months. The mean Addenbrookes Cognitive Examination-R score was 82.4 ± 9.6, with 40% performing at a level consistent with severe cognitive impairment. A significantly higher proportion of older participants used alcohol and benzodiazepines than younger clients, and older participants had significantly poorer psychological health, physical health and quality of life. DISCUSSION AND CONCLUSIONS D&A services will require strategies to address the complex physical, mental, cognitive and social problems of older clients.

Maternal car driving capacity after birth: a pilot prospective study randomizing postnatal women to early verses late driving in a driving simulator

Women are given variable information about when to recommence driving after surgery.