Depot buprenorphine as an opioid agonist therapy in New South Wales correctional centres: a costing model.

BACKGROUND: In 2019 daily liquid methadone and sublingual buprenorphine-naloxone were primary opioid agonist treatments for correctional centres in New South Wales, Australia. However, both had significant potential for diversion to other patients, and their daily administration was resource intensive. An alternative treatment in the form of subcutaneous depot buprenorphine became a viable option following a safety trial in 2020 - the UNLOC-T study. Depot preparation demonstrated advantages over current treatments as more difficult to divert and requiring fewer administrations. This paper reports the results of economic modelling of staffing costs in medication administration comparing depot buprenorphine, methadone, and sublingual buprenorphine provision in UNLOC-T trial facilities. METHODS: The costing study adopted a micro-costing approach involving the synthesis of cost data from the UNLOC-T clinical trial as well as data collected from Justice Health and Forensic Mental Health Network records. Labour and materials data were collected during site observations and interviews. Costs were calculated from two payer perspectives: a) the New South Wales (state) government which funds custodial and health services; and b) the Australian Commonwealth government, which pays for medications. The analysis compared the monthly-per-patient cost for each of the three medications in trial-site facilities during July 2019. This was followed by simulation of depot buprenorphine implementation across the study population. Costs associated with medical assessment and reviews were excluded. RESULTS: The monthly-per-patient New South Wales government service costs of depot buprenorphine, methadone and sublingual buprenorphine were: $151, $379 and $1,529 respectively while Commonwealth government medication costs were $434, $80 and $525. The implementation simulation found that service costs of depot buprenorphine declined as patients transitioned from weekly to monthly administration. Costs of treatment using the other medications increased as patient numbers decreased alongside fixed costs. At 12 months, monthly-per-patient service costs for depot buprenorphine, methadone and sublingual buprenorphine-which would be completely phased out by month 13-were $92, $530 and $2,162 respectively. CONCLUSIONS: Depot buprenorphine was consistently the least costly of the treatment options. Future modelling could allow for dynamic patient populations and downstream impacts for participants and the state health system. TRIAL REGISTRATION: ACTRN12618000942257 . Registered 4 June 2018.

Oral THC:CBD cannabis extract for refractory chemotherapy-induced nausea and vomiting: a randomised, placebo-controlled, phase II crossover trial.

BACKGROUND: This multicentre, randomised, double-blinded, placebo-controlled, phase II/III trial aimed to evaluate an oral THC:CBD (tetrahydrocannabinol:cannabidiol) cannabis extract for prevention of refractory chemotherapy-induced nausea and vomiting (CINV). Here we report the phase II component results. PATIENTS AND METHODS: Eligible patients experienced CINV during moderate-to-high emetogenic intravenous chemotherapy despite guideline-consistent antiemetic prophylaxis. Study treatment consisted of one cycle of 1-4 self-titrated capsules of oral THC 2.5 mg/CBD 2.5 mg (TN-TC11M) three times daily, from days -1 to 5, and 1 cycle of matching placebo in a crossover design, then blinded patient preference for a third cycle. The primary end point was the proportion of participants with complete response during 0-120 h from chemotherapy. A total of 80 participants provided 80% power to detect a 20% absolute improvement with a two-sided P value of 0.1. RESULTS: A total of 81 participants were randomised; 72 completing two cycles were included in the efficacy analyses and 78 not withdrawing consent were included in safety analyses. Median age was 55 years (range 29-80 years); 78% were female. Complete response was improved with THC:CBD from 14% to 25% (relative risk 1.77, 90% confidence interval 1.12-2.79, P = 0.041), with similar effects on absence of emesis, use of rescue medications, absence of significant nausea, and summary scores for the Functional Living Index-Emesis (FLIE). Thirty-one percent experienced moderate or severe cannabinoid-related adverse events such as sedation, dizziness, or disorientation, but 83% of participants preferred cannabis to placebo. No serious adverse events were attributed to THC:CBD. CONCLUSION: The addition of oral THC:CBD to standard antiemetics was associated with less nausea and vomiting but additional side-effects. Most participants preferred THC:CBD to placebo. Based on these promising results, we plan to recruit an additional 170 participants to complete accrual for the definitive, phase III, parallel group analysis. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12616001036404; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370473&isReview=true.

Cognition and adaptive functioning in older people attending drug and alcohol services.

BACKGROUND: Substance use disorders in older adults are expected to increase dramatically in the coming years. Given the increased susceptibility to cognitive deficits in older substance users (defined here as aged 50+ years due to the accelerated health decline observed in this population), it is important to consider the functional correlates of cognitive impairment in these older adults. This study details the cognitive status of older individuals attending outpatient drug and alcohol (D&A) treatment services and seeks to determine of the association of cognitive impairment to self-reported daily functioning. METHODS: Ninety nine clients aged 50 years or over attending outpatient D&A treatment services in Sydney, Australia participated. Cognition was assessed using the Addenbrooke's Cognitive Examination - Revised (ACE-R). Recent substance use (Australian Treatment Outcome Profile), physical and mental health (SF12, Geriatric Depression Scale), social isolation (Lubben Social Network Scale), and activities of daily living (Bayer ADL Scale) were also assessed. RESULTS: Nearly two-thirds of participants screened positive for cognitive impairment on the ACE-R; 41% and 65% of clients met the cut-off scores for mild cognitive impairment (MCI) and more severe cognitive impairment, respectively. Self-reported seizure history was a predictor of cognitive impairment. CONCLUSIONS: The results suggest that cognitive impairment in this group is common. The assessment of cognitive status for this older group of patients should not only include the identification of cognitive impairment but also encompass mental health and social functioning. A greater understanding of the needs of this cohort will also enable better co-ordination with other health and welfare services tailored to this population.

Clinical trials of medicinal cannabis for appetite-related symptoms from advanced cancer: a survey of preferences, attitudes and beliefs among patients willing to consider participation.

BACKGROUND: Australian clinical trials are planned to evaluate medicinal cannabis in a range of clinical contexts. AIMS: To explore the preferences, attitudes and beliefs of patients eligible and willing to consider participation in a clinical trial of medicinal cannabis for poor appetite and appetite-related symptoms from advanced cancer. METHODS: A cross-sectional anonymous survey was administered from July to December 2015 online and in eight adult outpatient palliative care and/or cancer services. Respondents were eligible if they were ≥18 years, had advanced cancer and poor appetite/taste problems/weight loss and might consider participating in a medicinal cannabis trial. Survey items focused on medicinal rather than recreational cannabis use and did not specify botanical or pharmaceutical products. Items asked about previous medicinal cannabis use and preferences for delivery route and invited comments and concerns. RESULTS: There were 204 survey respondents, of whom 26 (13%) reported prior medicinal cannabis use. Tablets/capsules were the preferred delivery mode (n = 144, 71%), followed by mouth spray (n = 84, 42%) and vaporiser (n = 83, 41%). Explanations for preferences (n = 134) most commonly cited convenience (n = 66; 49%). A total of 82% (n = 168) of respondents indicated that they had no trial-related concerns, but a small number volunteered concerns about adverse effects (n = 14) or wanted more information/advice (n = 8). Six respondents volunteered a belief that cannabis might cure cancer, while two wanted assurance of efficacy before participating in a trial. CONCLUSION: Justification of modes other than tablets/capsules and variable understanding about cannabis and trials will need addressing in trial-related information to optimise recruitment and ensure that consent is properly informed.

The use of paracetamol (acetaminophen) among a community sample of people with chronic non-cancer pain prescribed opioids.

BACKGROUND: The regular use of simple analgesics in addition to opioids such as paracetamol (or acetaminophen) is recommended for persistent pain to enhance analgesia. Few studies have examined the frequency and doses of paracetamol among people with chronic non-cancer pain including use above the recommended maximum daily dose. AIMS: To assess (i) the prevalence of paracetamol use among people with chronic non-cancer pain prescribed opioids, (ii) assess the prevalence of paracetamol use above the recommended maximum daily dose and (iii) assess correlates of people who used paracetamol above the recommended maximum daily dose including: age, gender, income, education, pain severity and interference, use of paracetamol/opioid combination analgesics, total opioid dose, depression, anxiety, pain self-efficacy or comorbid substance use, among people prescribed opioids for chronic non-cancer pain. METHODS: This study draws on baseline data collected for the Pain and Opioids IN Treatment (POINT) study and utilises data from 962 interviews and medication diaries. The POINT study is national prospective cohort of people with chronic non-cancer pain prescribed opioids. Participants were recruited from randomly selected pharmacies across Australia. RESULTS: Sixty-three per cent of the participants had used paracetamol in the past week (95% CI = 59.7-65.8). Among the paracetamol users 22% (95% CI = 19.3-24.6) had used paracetamol/opioid combination analgesics and 4.8% (95% CI = 3.6-6.3) had used paracetamol above the recommended maximum daily dose (i.e. > 4000 mg/day). Following binomial logistic regression (χ(2) = 25.98, df = 10, p = 0.004), people who had taken above the recommended maximum daily dose were less likely to have low income (AOR = 0.52, 95% CI = 0.27-0.99), more likely to use paracetamol/opioid combination analgesics (AOR = 2.01, 95% CI = 1.02-3.98) and more likely to take a higher opioid dose (AOR = 1.00, 95% CI = 1.00-1.01). CONCLUSION: The majority of people with chronic non-cancer pain prescribed opioids report using paracetamol appropriately. High income, use of paracetamol/opioid combination analgesics and higher opioid dose were independently associated with paracetamol use above the recommended maximum daily dose.

Diagnosing and managing prescription opioid use disorder in patients prescribed opioids for chronic pain in Australian general practice settings: a qualitative study using the theory of Planned Behaviour.

BACKGROUND: Chronic pain is a debilitating and common health issue. General Practitioners (GPs) often prescribe opioids to treat chronic pain, despite limited evidence of benefit and increasing evidence of harms, including prescription Opioid Use Disorder (pOUD). Australian GPs are worried about the harms of long-term opioids, but few are involved in the treatment of pOUD. There is little research on GPs' experiences diagnosing and managing pOUD in their chronic pain patients. METHODS: This qualitative research used semi-structured interviews and a case study to investigate GPs' experiences through the lens of the Theory of Planned Behaviour (TPB). TPB describes three factors, an individual's perceived beliefs/attitudes, perceived social norms and perceived behavioural controls. Participants were interviewed via an online video conferencing platform. Interviews were transcribed verbatim and thematically analysed. RESULTS: Twenty-four GPs took part. Participants were aware of the complex presentations for chronic pain patients and concerned about long-term opioid use. Their approach was holistic, but they had limited understanding of pOUD diagnosis and suggested that pOUD had only one treatment: Opioid Agonist Treatment (OAT). Participants felt uncomfortable prescribing opioids and were fearful of difficult, conflictual conversations with patients about the possibility of pOUD. This led to avoidance and negative attitudes towards diagnosing pOUD. There were few positive social norms, few colleagues diagnosed or managed pOUD. Participants reported that their colleagues only offered positive support as this would allow them to avoid managing pOUD themselves, while patients and other staff were often unsupportive. Negative behavioural controls were common with low levels of knowledge, skill, professional supports, inadequate time and remuneration described by many participants. They felt OAT was not core general practice and required specialist management. This dichotomous approach was reflected in their views that the health system only supported treatment for chronic pain or pOUD, not both conditions. CONCLUSIONS: Negative beliefs, negative social norms and negative behavioural controls decreased individual behavioural intention for this group of GPs. Diagnosing and managing pOUD in chronic pain patients prescribed opioids was perceived as difficult and unsupported. Interventions to change behaviour must address negative perceptions in order to lead to more positive intentions to engage in the management of pOUD.

Feasibility and outcomes of a general practice and specialist alcohol and other drug collaborative care program in Sydney, Australia.

Alcohol and other drug (AoD) use is an important health and community issue and may be positively affected by collaborative care programs between specialist AoD services and general practice. This paper describes the feasibility, model of care and patient outcomes of a pilot general practice and specialist AoD (GP-AoD) collaborative care program, in Sydney, Australia, based on usual care data, the minimum data set, service utilisation information and the Australian Treatment Outcome Profile (ATOP), a patient-reported outcome measure. There were 367 referrals to the collaborative care program. GPs referred 210 patients, whereas the AoD service referred 157 patients. Most GP referrals (91.9%) were for AoD problems, whereas nearly half the AoD service referrals were for other issues. The primary drugs of concern in the GP group were either opioids or non-opioids (mostly alcohol). The AoD service-referred patients were primarily using opioids. An ATOP was completed for 152 patients. At the time of referral, those in the GP-referred non-opioid group were significantly less likely to be abstinent, used their primary drug of concern more days and were more likely to be employed (all P < 0.001). A second ATOP was completed for 93 patients. These data showed a significant improvement in the number of days the primary drug of concern was used (P = 0.026) and trends towards abstinence, improved quality of life and physical and psychological well-being for patients in the program. There are few studies of GP-AoD collaborative care programs and nothing in the Australian context. This study suggests that GP-AoD collaborative care programs in Australia are feasible and improve drug use.

Effects of ascending buprenorphine doses on measures of experimental pain: A pilot study.

BACKGROUND: Buprenorphine is widely used in the treatment of opioid use disorder and pain management. Little is known about the analgesic effects of high-dose sublingual buprenorphine, particularly in doses of >8 mg. The aim of this study was to examine the effect of ascending doses of buprenorphine upon acute pain measures in patients stabilized on buprenorphine as treatment for opioid dependence. METHODS: The pilot study (n = 7) was a randomised, controlled, double-blind, double-dummy, within-subject crossover study examining cold-pressor threshold and tolerance testing under different buprenorphine dose conditions. Each participant attended three sessions to test the analgesic effect of buprenorphine in their usual dose (100%), 150% and 200% of their usual daily dose. RESULTS: No significant effects of increased dose were seen on experimental pain measures. Expected physiological effects on pupil size and pulse were observed with increasing dose. No effect of buprenorphine condition was seen on subjective ratings of drug strength, or self-reported sedation, though lower ratings drug liking were seen with 150% and 200% conditions, and lower ratings of 'bad effects' and intoxication were reported with the 200% buprenorphine dose condition. No safety concerns with the 150 and 200% buprenorphine dose condition were observed. DISCUSSION: This pilot study suggests that a ceiling effect on analgesia may be observed in people maintained on buprenorphine, though larger studies may confirm this finding. Clinical Trial Number: ACTRN12614001038684.

Cognitive, physical, and mental health outcomes between long-term cannabis and tobacco users.

INTRODUCTION: Cannabis intoxication adversely affects health, yet persistent effects following short-term abstinence in long-term cannabis users are unclear. This matched-subjects, cross-sectional study compared health outcomes of long-term cannabis and long-term tobacco-only users, relative to population norms. METHODS: Nineteen long-term (mean 32.3years of use, mean age 55.7years), abstinent (mean 15h) cannabis users and 16 long-term tobacco users (mean 37.1years of use, mean age 52.9years), matched for age, educational attainment, and lifetime tobacco consumption, were compared on measures of learning and memory, response inhibition, information-processing, sustained attention, executive control, and mental and physical health. RESULTS: Cannabis users exhibited poorer overall learning and delayed recall and greater interference and forgetting than tobacco users, and exhibited poorer recall than norms. Inhibition and executive control were similar between groups, but cannabis users had slower reaction times during information processing and sustained attention tasks. Cannabis users had superior health satisfaction and psychological, somatic, and general health than tobacco users and had similar mental and physical health to norms whilst tobacco users had greater stress, role limitations from emotional problems, and poorer health satisfaction. CONCLUSIONS: Long-term cannabis users may exhibit deficits in some cognitive domains despite short-term abstinence and may therefore benefit from interventions to improve cognitive performance. Tobacco alone may contribute to adverse mental and physical health outcomes, which requires appropriate control in future studies.

Composition and Use of Cannabis Extracts for Childhood Epilepsy in the Australian Community.

Recent surveys suggest that many parents are using illicit cannabis extracts in the hope of managing seizures in their children with epilepsy. In the current Australian study we conducted semi-structured interviews with families of children with diverse forms of epilepsy to explore their attitudes towards and experiences with using cannabis extracts. This included current or previous users of cannabis extracts to treat their child's seizures (n = 41 families), and families who had never used (n = 24 families). For those using cannabis, extracts were analysed for cannabinoid content, with specific comparison of samples rated by families as "effective" versus those rated "ineffective". Results showed that children given cannabis extracts tended to have more severe epilepsy historically and had trialled more anticonvulsants than those who had never received cannabis extracts. There was high variability in the cannabinoid content and profile of cannabis extracts rated as "effective", with no clear differences between extracts perceived as "effective" and "ineffective". Contrary to family's expectations, most samples contained low concentrations of cannabidiol, while Δ9-tetrahydrocannabinol was present in nearly every sample. These findings highlight profound variation in the illicit cannabis extracts being currently used in Australia and warrant further investigations into the therapeutic value of cannabinoids in epilepsy.

Author Correction: Composition and Use of Cannabis Extracts for Childhood Epilepsy in the Australian Community.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

A cost-effectiveness analysis of heroin detoxification methods in the Australian National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD).

This economic evaluation was part of the Australian National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD) project. Data from four trials of heroin detoxification methods, involving 365 participants, were pooled to enable a comprehensive comparison of the cost-effectiveness of five inpatient and outpatient detoxification methods. This study took the perspective of the treatment provider in assessing resource use and costs. Two short-term outcome measures were used-achievement of an initial 7-day period of abstinence, and entry into ongoing post-detoxification treatment. The mean costs of the various detoxification methods ranged widely, from AUD 491 dollars(buprenorphine-based outpatient); to AUD 605 dollars for conventional outpatient; AUD 1404 dollars for conventional inpatient; AUD 1990 dollars for rapid detoxification under sedation; and to AUD 2689 dollars for anaesthesia per episode. An incremental cost-effectiveness analysis was carried out using conventional outpatient detoxification as the base comparator. The buprenorphine-based outpatient detoxification method was found to be the most cost-effective method overall, and rapid opioid detoxification under sedation was the most cost-effective inpatient method.

Validation of techniques to detect illicit heroin use in patients prescribed pharmaceutical heroin for the management of opioid dependence.

BACKGROUND: The clinical implementation and evaluation of heroin substitution programmes have been confounded by the lack of objective and validated biomarkers for illicit heroin use in patients prescribed pharmaceutical heroin. This study examined the capacity to detect illicit heroin use by gas chromatography-mass spectrometry (GC-MS) analysis of urine samples for the presence of opium impurities common to illicit, but not pharmaceutical heroin. AIMS: To characterize the diagnostic properties of the metabolites of noscapine and papaverine in comparison to morphine as a gold-standard marker of illicit heroin use; and to examine the relationships between the self-reported time since most recent heroin use and the detection of these opioids in urine. DESIGN: A cross-sectional study of 52 opioid-dependent patients in treatment (not prescribed heroin), who self-reported illicit heroin use within the preceding 2 weeks. Self-report data regarding recent drug use and a urine sample were collected. GC-MS analyses of urines were conducted and reported by laboratory staff blinded to self-report data. FINDINGS: The metabolites of papaverine (hydroxypapaverine and dihydroxypapeverine) were found to have high sensitivity, specificity and negative predictive values as markers for illicit heroin use compared to the 'gold-standard' morphine. Other opioids, including 6-mono-acetylmorphine (6-MAM), codeine and noscapine metabolites (e.g. meconine) were less adequate in detecting heroin use. CONCLUSIONS: GC-MS detection of papaverine metabolites in urine appears to be suitable method of identifying illicit heroin use for clinical and research purposes.

Changes in non-opioid substitution treatment episodes for pharmaceutical opioids and heroin from 2002 to 2011.

BACKGROUND: There has been a well-documented increase in the non-medical use of pharmaceutical opioids (PO) worldwide. However, there has been little detailed examination of treatment demand, or the characteristics of those presenting for treatment, particularly for treatments other than opioid substitution. METHODS: Data from closed drug and alcohol treatment episodes from the Alcohol and Other Drug Treatment Services National Minimum Data Set (AODTS-NMDS, representing non-opioid substitution treatment) in Australia for 2002-2003 to 2010-2011 were examined. In the four jurisdictions where detailed data were available, episodes where heroin was the principal drug of concern were compared to episodes for the four most frequently reported pharmaceutical opioids (morphine, codeine, fentanyl and oxycodone). RESULTS: In 2002-2003, most (93%) opioid treatment was related to heroin with seven percent of all opioid treatment episodes reporting a PO as the principal drug of concern. In 2010-2011, 20% of all opioid treatment episodes were attributed to POs. Distinct changes over time were observed for different opioids. There was an increase in the average age at the start of treatment for heroin and oxycodone episodes, and a reduction in the proportion of females for codeine episodes, with 67% in 2002-2003 compared with 44% in 2010-2011. Codeine and oxycodone episodes had the lowest current or past injection rates. CONCLUSIONS: Clear differences were observed over time and between different opioids. Monitoring these emerging patterns will be important to inform treatment needs, particularly in light of different patterns of poly drug use, different routes of administration and changing demographic characteristics.

Cannabinoid replacement therapy (CRT): Nabiximols (Sativex) as a novel treatment for cannabis withdrawal.

Cannabis is a common recreational drug that is generally considered to have low addictive potential. However, an increasing number of cannabis users are seeking treatment for dependence on the drug. There is interest in using agonist (substitution) pharmacotherapies to treat cannabis dependence and here we outline a novel approach involving a buccal spray (nabiximols) that contains tetrahydrocannabinol (THC) and cannabidiol (CBD). We review recent research with nabiximols and highlight findings relevant to clinical practice.

Methadone injecting in Australia: a tale of two cities.

AIMS: The injection of methadone syrup designed for oral consumption is potentially associated with increased morbidity and mortality. Previous reports from Sydney, Australia have suggested a high prevalence of methadone injecting by clients in methadone programmes and by heroin users not in methadone treatment. This study sought to estimate the prevalence of methadone injecting by clients in community based methadone programmes in Melbourne, Australia, which operate under different take away policies. DESIGN: The study used a cross-sectional survey of methadone clients using a self-complete questionnaire. Subjects were recruited from randomly selected methadone dispensing pharmacies across Melbourne. Participation was voluntary. PARTICIPANTS: One hundred and sixty-eight methadone clients were recruited to the study. The mean age was 34.2 years; 59% were male. FINDINGS: Two of 168 methadone clients reported having injected methadone within the preceding 6-month period. CONCLUSIONS: The lower prevalence of methadone injecting in Melbourne (compared to Sydney) is thought to be due to the less liberal take-away policy, and the mandatory dilution of methadone take-aways to 200 ml of liquid. Implications for methadone take-away policies and procedures are discussed.

LAAM maintenance vs methadone maintenance for heroin dependence.

BACKGROUND: LAAM and methadone are both full mu opiate agonists and have been shown to reduce dependence on heroin when given continuously under supervised dosing conditions. LAAM has a long duration of action requiring dosing every two or three days compared to methadone which requires daily dosing. LAAM is not as widely available internationally as methadone, and may be withdrawn from the market following ten cases of life-threatening cardiac arrhythmias and an association with QT prolongation. OBJECTIVES: To compare the efficacy and acceptability of LAAM maintenance with methadone maintenance in the treatment of heroin dependence. SEARCH STRATEGY: We searched MEDLINE (January 1966 to August 2000), PsycINFO (1887 to August 2000), EMBASE (January 1985 to August 2000), and the Cochrane Controlled Trials Register (Issue 2 2000). In addition we hand searched NIDA monographs until August 2000 and searched reference lists of articles. SELECTION CRITERIA: All randomised controlled trials, controlled clinical trials and controlled prospective studies comparing LAAM and methadone maintenance for the treatment of heroin dependence and measuring outcomes of efficacy or acceptability were included. DATA COLLECTION AND ANALYSIS: Data on retention in treatment, heroin use, side-effects and mortality were collected by two reviewers independently. A meta-analysis was performed using RevMan. Discrepancies were resolved by consensus. MAIN RESULTS: Eighteen studies, (15 RCTs, 3 Controlled prospective studies) met the inclusion criteria for the review. Three were excluded from the meta-analysis due to lack of data on retention, heroin use or mortality. Cessation of allocated medication (11 studies, 1473 participants) was greater with LAAM than with methadone, (RR 1.36, 95%CI 1.07-1.73, p=0.001, NNT=7.7 (or 8)). Non-abstinence was less with LAAM (5 studies, 983 participants; RR 0.81, 95%CI 0.72-0.91, p=0.0003, NNT=9.1 (or 10)). In 10 studies (1441 participants) there were 6 deaths from a range of causes, 5 in participants assigned to LAAM (RR 2.28 (95%CI 0.59-8.9, p=0.2). other relevant outcomes, such as quality of life and criminal activity could not be analysed because of lack of information in the primary studies. REVIEWER'S CONCLUSIONS: LAAM appears more effective than methadone at reducing heroin use. More LAAM patients than methadone ceased their allocated medication during the studies, but many transferred to methadone and so the significance of this is unclear. There was no difference in safety observed, although there was not enough evidence to comment on uncommon adverse events.

Withdrawal from methadone maintenance treatment: prognosis and participant perspectives.

OBJECTIVE: To determine the proportion of clients engaged in methadone maintenance treatment who have favourable prognosis for withdrawal, and to examine client perceptions and expectations of withdrawal. METHODS: A broad cross-section of 856 methadone clients was sampled across Melbourne, Sydney and Brisbane. Self-complete surveys were developed for the clients, their clinic staff or pharmacists, and methadone prescribers. The client survey examined aspects of the clients' perspectives of withdrawal, and the surveys for the service providers collected information about each client's current treatment episode. Informed consent was provided by clients to obtain information from their clinic staff member or pharmacist, and their methadone prescriber. RESULTS: Most clients (70%) were at least very interested in methadone withdrawal. Clients were also more optimistic about their own post-withdrawal outcomes (in terms of opioid use) than both their clinic staff and prescribing doctors. Clinical criteria indicated that 31% of clients had a reasonable prognosis for withdrawal. However, when considering all factors, 17% had good withdrawal prognosis, were interested in methadone withdrawal, and believed it was very likely they would remain opioid-free for three months post-withdrawal. CONCLUSIONS: Despite the likely continued increase in client numbers in substitution maintenance treatment, the majority of methadone clients have a poor prognosis for withdrawal and should not be encouraged to cease treatment. IMPLICATIONS: Clients who do not meet key clinical criteria are likely to have poor clinical outcomes regardless of how withdrawal is attempted.

Addressing dependent amphetamine use: a place for prescription.

Amphetamines are among the most widely used of illicit drugs in Australia, and evidence documenting the occurrence of amphetamine-related harms, particularly among chronic regular users, is increasing, A review of contemporary Australian treatment approaches suggests that conventional modalities are unlikely to address the needs of a large proportion of dependent amphetamine users. This has prompted clinicians in Australia and the United Kingdom to commence treatment programmes incorporating substitution therapy. Despite the positive impressions of clinicians involved in these programmes, further research is required to establish the role and efficacy of such treatment approaches. Issues to be addressed in the establishment of a controlled study are examined.

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.