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Experiences of buprenorphine-naloxone (BNX) sublingual film injection are not well documented or understood. We examined how people who inject BNX film seek and share information about this practice, document the methods used to prepare BNX film for injection, and report participants' experiences of this practice.Interviews were (n = 16) conducted with people who indicated that they had injected BNX film since its introduction onto the Australian market. Semistructured interviews were recorded and transcribed. NVivo10 program (QSR International) was used to analyse the data using qualitative description methodology.Participants largely reported similar BNX film preparation techniques, although the texture of BNX film during preparation to inject was reported to be unusual (gluggy), and there were many varied accounts associated with the amount of water used. Physical harms reported as associated with injecting BNX film were described (including local and systemic issues); participants reported injecting the film to enhance its immediate effects, yet generally reported that sublingual administration provided longer-lasting effects.Understanding knowledge acquisition about injecting new formulations of opioid substitution therapy is crucial in developing more effective harm-reduction strategies. Dissemination by peer networks to those who are currently or planning to inject BNX film regarding the 'gelatine like' texture when mixing, using only cold water and double filtering is important to ensure safer injecting practices. Findings from this study highlight the importance of peer networks for the dissemination of harm-reduction information. Introduction of new formulations internationally requires more qualitative studies to inform safer practices.

Few studies have described those seeking treatment for codeine dependence. This study aimed to compare patients presenting for treatment where either codeine or a strong pharmaceutical opioid (oxycodone or morphine) was the principal drug of concern to understand if codeine users may have unique treatment needs.Retrospective case review of 135 patients from three geographical areas in New South Wales, Australia. Cases where the principal drug of concern was codeine (n = 53) or a strong pharmaceutical opioid (oxycodone or morphine, n = 82) were compared. Differences in demographic characteristics, pain history, mental health, substance use history and, subsequently, the treatment that was received were examined.People whose principal drug of concern was codeine were more likely to be female (66% vs. 37%, P0.001), employed (43% vs. 22%, P0.01) and use only one pharmaceutical opioid (91% vs. 49%, P0.001). There was no difference in age between the codeine group (mean 38.6 years) and the strong opioid group (39.3 years). Opioid substitution therapy was the most common treatment received by both groups although codeine patients were more likely to be treated with buprenorphine than methadone (odds ratio = 7.7, 95% confidence interval 2.2-27.2, P0.001) and more likely to attempt withdrawal (odds ratio = 2.6, 95% confidence interval 1.2-5.3, P = 0.010).There are important differences between codeine-dependent patients and strong prescription opioid-dependent patients. Further work should explore the outcomes of withdrawal versus maintenance treatment for codeine users.

The Randomized Injectable Opioid Treatment Trial (RIOTT) compared supervised injectable heroin (SIH) and supervised injectable methadone (SIM) with optimized oral methadone (OOM) (ISRCTN0133807). Heroin addicts (previously unresponsive to treatment) made significant reductions in street heroin use at 6 months when treated with SIH. We now examine secondary outcomes.Multi-site randomized controlled trial (RCT) comparing SIH versus OOM and SIM versus OOM.Three supervised injectable opiate clinics in England.Chronic refractory heroin addicts continuing to inject street heroin virtually daily despite oral substitution treatment (n = 127), randomized to either SIH(n = 43), SIM(n = 42) or OOM(n = 42). All received high levels of medical and psychosocial support.wider drug use, crime, health and social functioning at 6 months.At 6 months, no significant differences were found between treatment groups in wider drug use (crack/cocaine, benzodiazepines, alcohol), physical and mental health (SF-36) or social functioning. Within each treatment group, significant reductions were observed in crime [SIH = odds ratio (OR) 0.05; P0.001; SIM = OR 0.11; P = 0.002; OOM = OR 0.11; P = 0.003] and money spent per week on illicit drugs (SIH = mean change £-289.43; P0.001; SIM = mean change £-183.41; P0.001; OOM = mean change £-162.80; P0.001), with SIH significantly more likely to have reduced money spent on illicit drugs versus OOM (mean difference £-92.04; P0.001). Significant improvements were seen in physical health for SIH and SIM (SIH = mean change 3.97; P = 0.008; SIM = mean change 4.73; P = 0.002) and mental health for OOM (mean change 6.04; P = 0.013).Supervised injectable heroin treatment and supervised injectable methadone treatment showed no clearly identified benefit over optimized oral methadone in terms of wider drug use, crime, physical and mental health within a 6-month period, despite reducing street heroin use to a greater extent. However, all interventions were associated with improvements in these outcomes.

Importance There are no medications approved for treating cannabis dependence or withdrawal. The cannabis extract nabiximols (Sativex), developed as a multiple sclerosis treatment, offers a potential agonist medication for cannabis withdrawal. Objective To evaluate the safety and efficacy of nabiximols in treating cannabis withdrawal. Design, Setting, and Participants A 2-site, double-blind randomized clinical inpatient trial with a 28-day follow-up was conducted in New South Wales, Australia. Participants included 51 DSM-IV-TR cannabis-dependent treatment seekers. Interventions A 6-day regimen of nabiximols (maximum daily dose, 86.4 mg of Δ9-tetrahydrocannabinol and 80 mg of cannabidiol) or placebo with standardized psychosocial interventions during a 9-day admission. Main Outcomes and Measures Severity of cannabis withdrawal and cravings (Cannabis Withdrawal Scale), retention in withdrawal treatment, and adverse events. Secondary outcomes include postwithdrawal cannabis use, health outcomes, and psychosocial outcomes. Results Nabiximols treatment significantly reduced the overall severity of cannabis withdrawal relative to placebo ( F 8,377.97 = 2.39; P = .01), including effects on withdrawal-related irritability, depression, and cannabis cravings. Nabiximols had a more limited, but still positive, therapeutic benefit on sleep disturbance, anxiety, appetite loss, physical symptoms, and restlessness. Nabiximols patients remained in treatment longer during medication use (unadjusted hazard ratio, 3.66 [95% CI, 1.18-11.37]; P = .02), with 2.84 the number needed to treat to achieve successful retention in treatment. Participants could not reliably differentiate between nabiximols and placebo treatment (χ 2 1 = 0.79; P = .67), and those receiving nabiximols did not report greater intoxication ( F 1,6 = 0.22; P = .97). The number ( F 1,50 = 0.3; P = .59) and severity ( F 1,50 = 2.69; P = .10) of adverse events did not differ significantly between groups. Both groups showed reduced cannabis use at follow-up, with no advantage of nabiximols over placebo for self-reported cannabis use ( F 1,48 = 0.29; P = .75), cannabis-related problems ( F 1,49 = 2.33; P = .14), or cannabis dependence ( F 1,50 P = .89). Conclusions and Relevance In a treatment-seeking cohort, nabiximols attenuated cannabis withdrawal symptoms and improved patient retention in treatment. However, placebo was as effective as nabiximols in promoting long-term reductions in cannabis use following medication cessation. The data support further evaluation of nabiximols for management of cannabis dependence and withdrawal in treatment-seeking populations. Trial Registration anzctr.org.au Identifier:ACTRN12611000398909

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. Selfcomplete 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 postwithdrawal. 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.

Background: Internationally, there is concern about the increased prescribing of pharmaceutical opioids for chronic non-cancer pain (CNCP). In part, this is related to limited knowledge about the long-term benefits and outcomes of opioid use for CNCP. There has also been increased injection of some pharmaceutical opioids by people who inject drugs, and for some patients, the development of problematic and/or dependent use. To date, much of the research on the use of pharmaceutical opioids among people with CNCP, have been clinical trials that have excluded patients with complex needs, and have been of limited duration (i.e. fewer than 12 weeks). The Pain and Opioids In Treatment (POINT) study is unique study that aims to: 1) examine patterns of opioid use in a cohort of patients prescribed opioids for CNCP; 2) examine demographic and clinical predictors of adverse events, including opioid abuse or dependence, medication diversion, other drug use, and overdose; and 3) identify factors predicting poor pain relief and other outcomes. Methods/Design: The POINT cohort comprises around 1,500 people across Australia prescribed pharmaceutical opioids for CNCP. Participants will be followed-up at four time points over a two year period. POINT will collect information on demographics, physical and medication use history, pain, mental health, drug and alcohol use, non-adherence, medication diversion, sleep, and quality of life. Data linkage will provide information on medications and services from Medicare (Australia’s national health care scheme). Data on those who receive opioid substitution therapy, and on mortality, will be linked. Discussion: This study will rigorously examine prescription opioid use among CNCP patients, and examine its relationship to important health outcomes. The extent to which opioids for chronic pain is associated with pain reduction, quality of life, mental and physical health, aberrant medication behavior and substance use disorders will be extensively examined. Improved understanding of the longer-term outcomes of chronic opioid therapy will direct community-based interventions and health policy in Australia and internationally. The results of this study will assist clinicians to better identify those patients who are at risk of adverse outcomes and who therefore require alternative treatment strategies.

This paper concerns pharmacists dispensing methadone to intoxicated clients, drawing on both questionnaire and focus-group data from a 1996 evaluation of the community-based methadone programme in Victoria, Australia. The questionnaire was sent to registered community methadone pharmacies in Victoria (N = 188). The response rate was 84% and 148 questionnaires were analysed. Pharmacists were asked how they would respond to clients who presented intoxicated for their methadone dose. Results indicated that 32% of pharmacists said that they would provide a client who presented intoxicated with his or her usual methadone dose. The analyses suggested that pharmacists who were male and those pharmacists whose number of methadone clients exceeded 10 were more likely to dispense methadone to an intoxicated client than female pharmacists and those pharmacists with less than 10 clients. Pharmacists who would withhold the methadone dose were more likely to inform the client's prescribing doctor at the time (74%) than...

One hundred and ninety-five metropolitan clients enrolled in the community-based methadone programme in Victoria, Australia were surveyed in order to evaluate client perspectives of methadone treatment delivered from primary health care settings. Results indicated that the average daily methadone dose was 41 mg, ranging from 7 mg to 140 mg. The majority of clients were satisfied with the programme and the services delivered by dispensing pharmacies and prescribing doctors. Most clients were found to have reduced their heroin use and criminal activity since commencing methadone. A number of concerns about the programme were identified, however, including the high proportion of weekly income spent on methadone-related activities and a high use of tranquillizers by clients on higher methadone doses. In general the community-based methadone programme was found to be an acceptable methadone of service delivery to metropolitan clients in Victoria, Australia. [Ezard N, Lintzeris N, Odgers P, Koutroulis G, Muhleisen P, Stowe A, Lanagan A. An evaluation of community methadone services in Victoria, Australia: results of a client survey. Drug Alcohol Rev 1999;18 :417 i423]

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.

Background We compared the diversion and injection of a new formulation of buprenorphine, a buprenorphine-naloxone film product (BNX film), with buprenorphine-naloxone tablets (BNX tablets), mono-buprenorphine (BPN) and methadone (MET) in Australia. Methods Surveys were conducted with people who inject drugs regularly (PWID) (2004–2012) and opioid substitution treatment (OST) clients (2012, N = 543). Key outcome measures: the unsanctioned removal of supervised doses, diversion, injection, motivations, drug liking and street price. Levels of injection among PWID were adjusted for background availability of medication using sales data. Doses not taken as directed by OST clients were adjusted by total number of daily doses dispensed. Results Among out-of-treatment PWID, levels of injection for BNX film were comparable to those for MET and BNX tablet formulations, adjusting for background availability; BPN injecting levels were higher. Among OST clients, recent injecting of one's medication was similar among clients in all OST types; weekly or more frequent injection of prescribed doses was reported by fewer BNX film clients (3%; 95% CI: 1–6) than BPN clients (11%; 95% CI: 3–17), but at levels similar to those observed among MET and BNX tablet clients. The proportion of BNX film doses injected was lower than that for BPN and BNX tablets, and equivalent to that for MET. The majority of BNX film doses injected by OST clients were unsupervised doses, although some injection of supervised doses of BNX film did occur. The median price of all buprenorphine forms on the illicit market was the same. Conclusions Non-adherence and diversion of the BNX film formulation was similar to MET and BNX tablet formulations; BPN had higher levels of all indicators of non-adherence and diversion.

BackgroundDespite evidence of the effectiveness of injectable opioid treatment compared with oral methadone for chronic heroin addiction, the additional cost of injectable treatment is considerable, and cost-effectiveness uncertain.AimsTo compare the cost-effectiveness of supervised injectable heroin and injectable methadone with optimised oral methadone for chronic refractory heroin addiction.MethodMultisite, open-label, randomised controlled trial. Outcomes were assessed in terms of quality-adjusted life-years (QALYs). Economic perspective included health, social services and criminal justice resources.ResultsIntervention costs over 26 weeks were significantly higher for injectable heroin (mean £8995 v. £4674 injectable methadone and £2596 oral methadone; PP =n.s.) due to higher costs of criminal activity. In cost-effectiveness analysis, oral methadone was dominated by injectable heroin and injectable methadone (more expensive and less effective). At willingness to pay of £30 000 per QALY, there is a higher probability of injectable methadone being more cost-effective (80%) than injectable heroin.ConclusionsInjectable opioid treatments are more cost-effective than optimised oral methadone for chronic refractory heroin addiction. The choice between supervised injectable heroin and injectable methadone is less clear. There is currently evidence to suggest superior effectiveness of injectable heroin but at a cost that policy makers may find unacceptable. Future research should consider the use of decision analytic techniques to model expected costs and benefits of the treatments over the longer term.

There has been an increase in prescription of opioids for chronic non-cancer pain, and concern exists over possible diversion of prescription opioids to the illicit marketplace. Recent media coverage suggests that elderly patients sell their prescribed opioids for additional income. This study investigated the extent to which an Australian community sample of chronic pain patients prescribed opioids reported supplying their prescribed opioids to others.Participants living with chronic non-cancer pain and prescribed opioids for their pain (n=952) were recruited across Australia via advertisements at pharmacies. A telephone interview included questions about their pain condition and opioid medication.Participants had been living with pain for a mean of 14.2 years; most common conditions included chronic back/neck problems and arthritis/rheumatism. Around half (43%) were currently prescribed one opioid, and 55% had been prescribed 2-5 opioids; the most common was oxycodone. Forty-two participants (4%) reported ever supplying prescribed opioids to another person; one participant reported receiving payment. Participants who supplied opioids to others were younger (odds ratio 0.97, 95% confidence interval 0.95-0.99) and engaged in a greater number of aberrant behaviours relating to their opioid medication (odds ratio 1.77, 95% confidence interval 1.45-2.17), including tampering with doses, taking opioids by alternative routes, seeing doctors to obtain extra opioids and refilling prescriptions early.Few people with chronic non-cancer pain divert their opioids to others. Media reports of elderly patients selling their opioids to supplement their income may be reflective of exceptional cases. Future studies may investigate the extent to which other patient groups divert prescription opioids to the illicit marketplace.

The measurement of clinical outcomes is an important, but lacking, component of drug and alcohol treatment in Australia. This study aimed to psychometrically validate the Treatment Outcomes Profile under Australian conditions, examining implementation and feasibility issues in three public opioid treatment program clinics in NSW.The Treatment Outcomes Profile was modified to reflect Australian conditions and re-named the Australian Treatment Outcomes Profile (ATOP). The ATOP was introduced into the participating clinics and administered by clinic staff at 3-month intervals as part of routine clinical practice. Participants completed a research interview, consisting of the ATOP and a suite of 'gold standard' instruments assessing substance use and related health and welfare domains, in the 72 h following completion of a routine clinical ATOP. The researcher- and clinician-administered ATOPs were compared to assess interrater reliability, and the researcher-administered ATOP and 'gold standard' instruments were compared to assess concurrent validity. Implementation and feasibility issues were assessed using questionnaires and focus groups with clinician and clients.The ATOP demonstrated acceptable concurrent validity and interrater reliability. It was well received by clients and clinicians, particularly for its ease of use, applicability and brevity.The ATOP is a psychometrically valid instrument for the measurement of treatment outcomes in Australian opioid treatment populations and can feasibly be implemented as part of routine clinical practice in specialist opioid treatment program clinics. The role of the ATOP to measure outcomes in other drug and alcohol treatment modalities requires exploration.

Introduction. Few general practitioners (GP) prescribe opioid substitution therapy.Our aim was to analyse their previously identified motivating factors by describing their frequency and demographic associations. Methods. An anonymous, cross- sectional questionnaire-based survey on opioid prescribing in pain and dependency was distributed across five New South Wales Divisions of GPs. Questions elicited opinions on 11 barriers and five facilitators previously described in qualitative literature. Data were analysed against demographic variables, including opioid substitution therapy prescriber (OSTP) status and postgraduate training status.'Profiles'of non-OSTPs were then constructed using latent class analysis. Results. Of the 1735 surveys posted,there were 404 responses (23.3%),with 16% respondents being OSTPs.Frequently reported barriers included: 'negative experiences with the opioid dependent' (72%),'heavy workload' (60%) and 'lack of specialist support' (58%), with most barriers less frequent among OSTPs. Facilitating factors included: 'more accessible specialist support' (75%), 'more accessible training' (67%) and 'better evidence of safety and efficacy' (64%), with the latter two significantly less frequently among OSTPs. Latent class analysis of the non-OSTPs revealed three distinct clusters.The smallest ('class 3') had the least barriers and resembled OSTPs demographically. Discussion and Conclusions. The pattern of motivating factors towards the psychological, social and behavioural challenges of the management of dependency has a predominantly negative bias. However, this lessens with postgraduate training and OSTP experience. Structural and logistical options are identified to promote OSTP recruitment and retention. GPs resembling class 3 may be more amenable to becoming OSTPs and may be worth targeting for recruitment. (Holliday S, Magin P, Oldmeadow C, Dunbabin J, Henry J-M, Lintzeris N,Attia J, Goode S, Dunlop A. An examination of the influences on New South Wales general practitioners regarding the provision of opioid substitution therapy. Drug Alcohol Rev 2013)

Introduction and Aims: The limited literature on pain in opioid-treatment samples indicates that it is highly prevalent. Understanding the implications of pain on treatment outcomes is important, particularly in light of ageing opioid-treatment cohorts. This study explores correlates of pain, including aberrant behaviours related to prescribed opioids. Our hypothesis is that pain may increase aberrant opioid-related behaviours, including illicit substance use, among opioid-dependent people. Design and Methods: We examined pain in methadone or buprenorphine patients (n = 141) from three treatment services. Measures included basic demographics, Brief Pain Inventory, general mental health, physical health and quality of life measures, pain history and treatments, and an aberrant opioid-related behaviour scale. Univariate and multivariate analyses were used to examine correlates of pain. Results: Forty percent reported current pain, measured with the first question of the Brief Pain Inventory. Correlates of pain were depression ratings [adjusted odds ratio (OR) 2.24, 95% confidence interval (CI) 1.04, 4.83], anxiety ratings (adjusted OR 4.29, 95% CI 1.88, 9.80) and self-reported health ratings (adjusted OR 0.35, 95% CI 0.16, 0.76). Contrary to our hypothesis, pain was not associated with greater use of illicit opioids, nor any aberrant opioid-related behaviours. Pain was comparable among methadone and buprenorphine patients. Discussion and Conclusions: The lack of association with pain and aberrant behaviours suggest that it should not be assumed that those in opioid treatment misuse medications in response to pain. The high prevalence of depression/anxiety symptoms indicates a need for further work with larger samples to explore pain and co-morbidity among opioid-dependent people.

Objective. Our objective was to evaluate the quality of opioid analgesia prescribing in chronic nonmalignant pain (CNMP) by general practitioners (GPs, family physicians). Design. An anonymous, cross-sectional questionnaire-based survey. Setting. The setting was five Australian divisions of general practice (geographically based associations of GPs). Methods. A questionnaire was mailed to all division members. Outcome measures were adherence to individual recommendations of locally derived CNMP practice guidelines. Results. We received 404 responses (response rate 23.3%). In the previous fortnight, GPs prescribed long-term continuous opioids for CNMP for a median of 4 and a mean of 7.1 (±8.7) patients with CNMP. Guideline concordance (GLC) was poor, with no GP always compliant with all guideline items, and only 31% GPs usually employing most items. GLC was highest for the avoidance of high dosages or fast-acting formulations. It was lowest for strategies minimizing individual and public health harms, such as the initiation of opioids on a time-limited trial basis, use of contracts, and the preclusion or management of aberrant behaviors. GLC was positively associated with relevant training or qualifications, registration with the Australian Prescription Drug Monitoring Programme, being an opioid substitution therapy prescriber, and female gender. Conclusions. In this study, long-term opioids were frequently initiated for CNMP without a quality use-of-medicine approach. Potential sequelae are inadequate treatment of pain and escalating opioid-related harms. These data suggest a need for improved resourcing and training in opioid management across pain and addictions.

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.

Der Einsatz von Opioiden bei chronischen Schmerzen wird wegen Nebenwirkungen, problematischer Medikamentenennahme und Abhangigkeitsrisiko bei Nichttumorpatienten zunehmend kritisch gesehen. Nur wenige Studien haben bisher Wirksamkeit und Vertraglichkeit in der Langzeittherapie untersucht, dennoch steigt die Anzahl der Verschreibungen. Mehr Klarheit uber Verschreibungsmuster und Nebenwirkungsprofil verspricht man sich von der australischen Kohortenstudie Pain and Opioid IN Treatment (POINT).

The study investigates patients' pre-treatment expectations of, and post-treatment satisfaction with, supervised injectable opiate treatment delivered within UK's first such clinics within the Randomised Injectable Opiate Treatment Trial (RIOTT) (ISRCTN0133807).Data were collected from 127 chronic heroin addicts recruited to RIOTT and randomised to receive supervised injectable (heroin or methadone) treatment or optimised oral maintenance treatment at supervised injectable maintenance clinics in London, Darlington and Brighton.Of 127 RIOTT patients, 113 (89%) provided responses to structured enquiry about treatment expectations, and 94 (74%) subsequent responses about treatment satisfaction (at six months). Patients were hoping that injectable heroin treatment would: reduce substance misuse (81%); help achieve normality, routine and structure (16%); and increase education and work prospects (15%). At six months, an area of treatment satisfaction most commonly reported by all three trial groups was reduced substance misuse (supervised injectable heroin 59%, supervised injectable methadone 56%, optimised oral methadone 54%). Most found supervision acceptable, but some desired modifications were also identified.Patients previously considered non-responsive to treatment appear to have similar treatment expectations and aspirations as other drug users in treatment. Supervised injectable opioid treatment patients consistently reported treatment satisfaction but also that more could be done to optimise aspects of current arrangement. This raised the challenging issue of the extent to which opinions of patients need to be taken into consideration in shaping future treatment provision. Future research may need to examine the extent of expectations 'fit' and the relationship between treatment sought and received.

Few general practitioners (GP) prescribe opioid substitution therapy. Our aim was to analyse their previously identified motivating factors by describing their frequency and demographic associations.An anonymous, cross-sectional questionnaire-based survey on opioid prescribing in pain and dependency was distributed across five New South Wales Divisions of GPs. Questions elicited opinions on 11 barriers and five facilitators previously described in qualitative literature. Data were analysed against demographic variables, including opioid substitution therapy prescriber (OSTP) status and postgraduate training status. 'Profiles' of non-OSTPs were then constructed using latent class analysis.Of the 1735 surveys posted, there were 404 responses (23.3%), with 16% respondents being OSTPs. Frequently reported barriers included: 'negative experiences with the opioid dependent' (72%), 'heavy workload' (60%) and 'lack of specialist support' (58%), with most barriers less frequent among OSTPs. Facilitating factors included: 'more accessible specialist support' (75%), 'more accessible training' (67%) and 'better evidence of safety and efficacy' (64%), with the latter two significantly less frequently among OSTPs. Latent class analysis of the non-OSTPs revealed three distinct clusters. The smallest ('class 3') had the least barriers and resembled OSTPs demographically.The pattern of motivating factors towards the psychological, social and behavioural challenges of the management of dependency has a predominantly negative bias. However, this lessens with postgraduate training and OSTP experience. Structural and logistical options are identified to promote OSTP recruitment and retention. GPs resembling class 3 may be more amenable to becoming OSTPs and may be worth targeting for recruitment.

The limited literature on pain in opioid-treatment samples indicates that it is highly prevalent. Understanding the implications of pain on treatment outcomes is important, particularly in light of ageing opioid-treatment cohorts. This study explores correlates of pain, including aberrant behaviours related to prescribed opioids. Our hypothesis is that pain may increase aberrant opioid-related behaviours, including illicit substance use, among opioid-dependent people.We examined pain in methadone or buprenorphine patients (n = 141) from three treatment services. Measures included basic demographics, Brief Pain Inventory, general mental health, physical health and quality of life measures, pain history and treatments, and an aberrant opioid-related behaviour scale. Univariate and multivariate analyses were used to examine correlates of pain.Forty percent reported current pain, measured with the first question of the Brief Pain Inventory. Correlates of pain were depression ratings [adjusted odds ratio (OR) 2.24, 95% confidence interval (CI) 1.04, 4.83], anxiety ratings (adjusted OR 4.29, 95% CI 1.88, 9.80) and self-reported health ratings (adjusted OR 0.35, 95% CI 0.16, 0.76). Contrary to our hypothesis, pain was not associated with greater use of illicit opioids, nor any aberrant opioid-related behaviours. Pain was comparable among methadone and buprenorphine patients.The lack of association with pain and aberrant behaviours suggest that it should not be assumed that those in opioid treatment misuse medications in response to pain. The high prevalence of depression/anxiety symptoms indicates a need for further work with larger samples to explore pain and co-morbidity among opioid-dependent people.

BACKGROUND: At an international level there are calls for a greater focus on women and harm reduction in recognition that female drug users have a unique set of issues that are not routinely assessed in drug treatment programs. AIMS: To assess the pregnancy history current pregnancy risk and contraceptive use of nonpregnant women attending opioid treatment programs (OTPs). METHODS: This study involved a structured questionnaire survey of 204 women attending outpatient OTP services within the Sydney South West Area Health Service. RESULTS: Two hundred and four women of 302 (67.5%) enroled in OTPs at the time completed surveys. Key findings were high pregnancy rates with 28.9% of women reporting six or more pregnancies high rates of adverse pregnancy outcomes (miscarriage termination and stillbirth) compared with national data and poor uptake of contraception with only 54.7% of sexually active women not wanting to get pregnant using a method. Women expressed diverse preferences for the type and location of womens health services they felt would meet their needs. CONCLUSION: Women in OTP clinics have unaddressed reproductive health issues particularly around contraception. Addressing these will potentially minimise the risk of material deprivation and social exclusion in these women and improve their well-being through greater control and choice over their fertility. Current womens health service provision in OTP programs involves referral to external services but an integrated model of care may best address the unmet contraceptive needs of these women. (c) 2012 The Authors ANZJOG (c) 2012 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Non-prescribed use of pharmaceutical opioid analgesics (POA) has been escalating internationally. In Australia, few studies have examined if POA users have similar characteristics and treatment needs to heroin users. The aim of this study was to compare those presenting for treatment where heroin versus POA were the primary drugs of concern.A convenience sample of 192 treatment entrants were recruited from alcohol and drug treatment services in four Australian jurisdictions. A structured interview collected data on demographic characteristics, substance use, self-perceived mental and physical health, crime and harms resulting from drug use. Multivariate analyses were performed to identify characteristics which may differentiate those seeking treatment for heroin compared with POA.Most treatment entrants sampled reported a history of injection drug use and use of both heroin and POA. However, those with primary POA problems were less likely to report an overdose history (adjusted odds ratio 0.90, 95% confidence interval 0.81-0.99) and more likely to initiate opioid use for pain (adjusted odds ratio 2.52, 95% confidence interval 1.04-6.12) than those with primary heroin problems. Latent Class Analysis found that, while most of the POA group were similar to heroin users in demographics, health and injecting drug use, there was a small, distinct group of primary POA problem users that did not typically inject and who commonly initiated opioid use for pain and also experienced elevated physical and mental health disability.While some differences existed, this study of Australian treatment seekers found many similar characteristics between those with primary problems with heroin and POA. Few non-injecting POA were recruited in this sample. This finding contrasts with reports of a growing population of opioid-dependent people with characteristics that are distinct from traditional opioid-dependent populations, which may reflect the orientation of current treatment systems in Australia towards injection drug users.

The use of opioid substitution therapy (OST) is a widely used and effective treatment for opioid dependence, yet many Australian general practitioners (GPs) authorised to administer OST, prescribe to very few or no patients. This is a particular issue within Victoria that places greater reliance on a small number of active OST prescribing GPs, compared with other jurisdictions. Given the unmet demand for treatment, the provision of accurate figures on the OST prescribing practices of Victorian GPs is necessary for workforce planning. This study aimed to ascertain information on the prescribing patterns of Victorian GPs in their first 5 years after training, and elicit any trends that may explain their reluctance to prescribe OST.The prescribing patterns over a 5 year period of 168 Victorian GPs who became first authorised to prescribe OST during the years 2001-2004 were examined by accessing the Victorian Department of Human Services OST individual patient treatment permit data.Forty-six per cent of these GPs never held a patient permit, and at any one time, approximately two-thirds did not hold a permit. The majority of active prescribers were treating fewer than 10 patients and only 12.5% ever prescribed to more than 50 patients.The study suggests the Victorian GP workforce is inadequate to address the demand for OST. Many more GPs will need to be recruited, and encouraged to prescribe for more patients. Further research is required to identify barriers to GP OST prescribing.

High-dose methadone has been associated with rate-corrected QT (QTc) prolongation and 'torsade de pointes'. The Medicines and Healthcare products Regulatory Agency (MHRA) advise electrocardiograms (ECGs) for patients on methadone with heart/liver disease, electrolyte abnormalities, concomitant QT prolonging medications/CYP3A4 inhibitors or prescribed methadone100 mg daily. The percentage of patients fulfilling MHRA criteria for ECG monitoring and prevalence of QT prolongation in patients who had an ECG was assessed.A cross-sectional study of opioid-dependent patients prescribed opioid maintenance that completed a screening questionnaire prior to referral for an ECG. MHRA criteria were assessed in the referred group. The automated QTc score was analysed with methadone dose, substance use and QT risk factors.Of 155 patients screened; 57.4% (n = 89) fulfilled MHRA criteria for ECG monitoring (75.5% (n = 117) if cocaine included as QT prolonging drug). Eighty-three (53.5%) had ECGs; 19.3% (n = 16) prescribed QT prolonging medication, 22.9% (n = 19) prescribed100 mg methadone and 47% (n = 39) used cocaine. Mean QTc interval was 429.0 ms (SD 26.4, 351-489). Eighteen per cent exceeded QTc gender-specific thresholds (≥450 ms men and≥470 ms women). Linear regression found total daily methadone dose (β = 0.318, P = 0.003) and stimulant use (β = -0.213, P = 0.043) predictive of QTc length.Over half to three-quarters of methadone maintenance patients fulfilled MHRA criteria for ECG monitoring, which has costly implications. QTc prolongation prevalence was 18.1% with no 'clinically significant' QTc prolongation500 ms or torsade de pointes known to be present. Methadone dose and stimulant use were associated with longer QTc intervals. Further research on the clinical management of QTc prolongation with methadone is required.

These studies compared the diversion and injection of buprenorphine-naloxone (BNX), buprenorphine (BPN) and methadone (MET) in Australia.Surveys were conducted with regular injecting drug users (IDUs) (2004-2009, N=881-943), opioid substitution treatment (OST) clients (2008, N=440) and authorised OST prescribers (2007, N=291). Key outcome measures include the unsanctioned removal of supervised doses, diversion, injection, motivations, drug liking and street price. Levels of injection among IDUs were adjusted for background availability of medications. Doses not taken as directed by OST clients were adjusted by total number of daily doses dispensed.Among regular IDUs, levels of injection were lower for BNX relative to BPN, but comparable to those for MET, adjusting for background availability. Among OST clients, fewer BNX clients (13%) reported recently injecting their medication, than BPN (28%) and MET clients (23%). Fewer MET clients (10%) reported removal of supervised doses, than BPN (35%) and BNX clients (22%). There were no differences in prevalence of recent diversion (28% of all OST clients). Adjusting for the total doses dispensed, more BPN was injected (10%), removed (12%) and diverted (5%), than MET (5%,1% and 2% respectively) and BNX (5%, 9% and1% respectively). In 2009, the median street price of BNX was equivalent to that for BPN.BNX was less commonly and less frequently injected than BPN, but both sublingual medications were diverted more than liquid MET.

Some heroin addicts persistently fail to benefit from conventional treatments. We aimed to compare the effectiveness of supervised injectable treatment with medicinal heroin (diamorphine or diacetylmorphine) or supervised injectable methadone versus optimised oral methadone for chronic heroin addiction.In this multisite, open-label, randomised controlled trial, we enrolled chronic heroin addicts who were receiving conventional oral treatment (or=6 months), but continued to inject street heroin regularly (or=50% of days in preceding 3 months). Randomisation by minimisation was used to assign patients to receive supervised injectable methadone, supervised injectable heroin, or optimised oral methadone. Treatment was provided for 26 weeks in three supervised injecting clinics in England. Primary outcome was 50% or more of negative specimens for street heroin on weekly urinalysis during weeks 14-26. Primary analysis was by intention to treat; data were adjusted for centre, regular crack use at baseline, and treatment with optimised oral methadone at baseline. Percentages were calculated with Rubin's rules and were then used to estimate numbers of patients in the multiple imputed samples. This study is registered, ISRCTN01338071.Of 301 patients screened, 127 were enrolled and randomly allocated to receive injectable methadone (n=42 patients), injectable heroin (n=43), or oral methadone (n=42); all patients were included in the primary analysis. At 26 weeks, 80% (n=101) patients remained in assigned treatment: 81% (n=34) on injectable methadone, 88% (n=38) on injectable heroin, and 69% (n=29) on oral methadone. Patients on injectable heroin were significantly more likely to have achieved the primary outcome (72% [n=31]) than were those on oral methadone (27% [n=11], OR 7.42, 95% CI 2.69-20.46, p0.0001; adjusted: 66% [n=28] vs 19% [n=8], 8.17, 2.88-23.16, p0.0001), with number needed to treat of 2.17 (95% CI 1.60-3.97). For injectable methadone (39% [n=16]; adjusted: 30% [n=14]) versus oral methadone, the difference was not significant (OR 1.74, 95% CI 0.66-4.60, p=0.264; adjusted: 1.79, 0.67-4.82, p=0.249). For injectable heroin versus injectable methadone, a significant difference was recorded (4.26, 1.63-11.14, p=0.003; adjusted: 4.57, 1.71-12.19, p=0.002), but the study was not powered for this comparison. Differences were evident within the first 6 weeks of treatment.Treatment with supervised injectable heroin leads to significantly lower use of street heroin than does supervised injectable methadone or optimised oral methadone. UK Government proposals should be rolled out to support the positive response that can be achieved with heroin maintenance treatment for previously unresponsive chronic heroin addicts.Community Fund (Big Lottery) Research section, through Action on Addiction.

Background: Buprenorphine (Subutex) is the most abused opioid in Finland. In order to curb the abuse potential of this drug, many treatment centers and prisons crush Subutex tablets before administering them to patients. To date, there are no published studies comparing the efficacy and bioavailability of crushed and whole Subutex tablets. Methods: A total of 16 opioid-dependent patients stabilized on 24 mg of buprenorphine were enrolled in a double-blind, double-dummy, randomized cross-over study comparing crushed and whole buprenorphine tablets on a range of pharmacokinetic and pharmacodynamic variables. Buprenorphine tablets (either crushed or whole) and placebo tablets (either crushed or whole) were administered to subjects simultaneously. Buprenorphine and norbuprenorphine serum levels were measured at 30, 60, 90, 120, 180, 240 and 360 min, as well as 24 h, after tablet administration. After 1 week, the experiment was repeated in a cross-over design so that, by the end of the study, each patient had received the active drug (buprenorphine) as both crushed and whole tablets. Results: Pharmacokinetic parameters (mean serum levels, Cmax, Tmax, AUC) of buprenorphine or norbuprenorphine did not differ significantly between crushed and whole tablets, although serum levels were slightly higher after administration of the crushed tablets. There were also no significant differences in dissolution/absorption time, withdrawal signs or opiate craving. Conclusion: We conclude that crushing Subutex tablets does not significantly alter serum buprenorphine or norbuprenorphine levels or the drug’s clinical effect. Our results indicate that crushing Subutex tablets may be used as an alternative method to counter the risk of buprenorphine diversion.

The prescription of heroin (diamorphine) for the management of heroin dependence is a controversial treatment approach that was limited to Britain until the 1990s. Since then a number of countries have embarked upon clinical trials of this approach, and it is currently licensed and available in several European countries. To date, six randomized controlled trials (RCTs) with over 1600 patients and several cohort studies have examined injected (or inhaled) heroin treatment. This article reviews relevant clinical pharmacology, how heroin treatment programmes are delivered, and the evidence regarding safety, efficacy and cost-effectiveness from RCTs. Heroin is usually prescribed in intravenous dosages of 300–500 mg/day, divided in two or three doses. Uncommon but serious side effects include seizures and respiratory depression immediately following injection. Despite methodological shortcomings, RCTs generally indicate that heroin treatment results in a comparable retention, improved general health and psychosocial functioning, and less self-reported illicit heroin use than oral methadone treatment. Cost-effectiveness studies indicate heroin treatment to be more expensive to deliver but to result in savings in the criminal justice sector. There has been debate regarding how heroin treatment should be positioned within the range of treatment approaches for this condition. There is increasing consensus that, in countries that have robust and accessible treatment systems for heroin users, heroin treatment is suited to a minority of heroin users as a second-line treatment for those individuals who do not respond to methadone or buprenorphine treatment delivered under optimal conditions.

Objectives: We investigated how a randomised controlled trial (RCT) could be designed to incorporate features known or thought likely to enhance the uptake of the new treatment into clinical practice post-trial. Method and Results: Between 1999 and 2001, we trialled buprenorphine treatment for heroin dependence in community settings throughout Victoria, using 28 experienced methadone prescribers and 34 pharmacists across 19 sites. In this case study, we describe how we incorporated seven features considered important in treatment uptake: skilled and experienced practitioners, government and policy support, incentives to prescribe the new treatment, specialist support services, clinical guidelines, training programs and patient involvement and information. We also present information showing that uptake of buprenorphine treatment was substantially boosted in Victoria compared with other Australian jurisdictions immediately after the trial in 2001 and that this increase was sustained until at least 2006. Conclusion: While we cannot prove that our trial design was responsible for the increased uptake of buprenorphine treatment in Victoria, we do show that design has been a neglected aspect of clinical trials in terms of enhancing post-trial uptake of the treatment being tested. Implications: Those interested in closing the ‘know-do’ gap between research and practice may wish to further explore this very promising lead. Imaginative linking of features known to enhance treatment uptake to pressing research questions may lead to new information on efficacy, as well as getting valuable drugs into the treatment system more rapidly.

Background/Aims: The femoral region (‘groin’) appears to be increasingly commonly used by injecting drug users in the UK. With the advent of Britain’s first supervised prescribed injectable opioid treatment clinic, unprecedented decisions and judgements were required about the safe supervision of this practice, or whether to permit this behaviour on site at all. This paper reports the reasons for, and outcome of, development of a clinical policy on injecting into the deep femoral vein (groin injecting). Method: A small in-depth audit of the complications of femoral injecting was undertaken in a supervised injecting clinic. Results: All femoral injectors had had either local site-related medical complications or other health problems which could potentially be worsened by ongoing injection. This finding along with the personal and professional issues raised by staff for supervision of femoral injecting led to a revised policy focussing on achieving a shift towards lower-risk peripheral venous and intramuscular sites. Conclusion: While the clinic staff’s training may be more compatible with professional duties of care by encouraging cessation of femoral injecting, this does not tell us what advice harm reduction workers in the field should offer groin injectors. More research is needed into this high-risk, controversial injecting practice.

Background The hepatitis C virus (HCV) is a major cause of drug-related morbidity and mortality, with incidence data implicating a wide range of HCV transmission risk practices. The Blood-Borne Virus Transmission Risk Assessment Questionnaire (BBV-TRAQ) is a content valid instrument that comprehensively assesses HCV risk practices. This study examines the properties of a new weighted BBV-TRAQ designed to quantify HCV transmission risk among injecting drug users (IDU). Methods Analyses of cross-sectional surveys of Australian IDU (N = 450) were used to generate normative data and explore the properties of a weighted BBV-TRAQ. Items weights were assigned according to expert key informant ratings of HCV risk practices performed during the development stages of the BBV-TRAQ. A range of item weights was tested and psychometric properties explored. A weighting scheme was recommended based on the plausibility of normative subscale data in relation to research evidence and the ability of BBV-TRAQ scores to discriminate between HCV positive and negative participants. Results While retaining the psychometric properties of the unweighted scale and demonstrating good internal reliability. By taking into account the relative transmission risk of a broad range of putative HCV practices, the weighted BBV-TRAQ produced promising predictive validity results among IDU based on self-report HCV status, particularly among young and less experienced injectors. Conclusion Brief, easy to administer and score, and inexpensive to apply, the utility of the BBV-TRAQ for community based education and prevention is enhanced by the application of item weights, potentially offering a valid surrogate measure for HCV infection among IDU.

Briony Larance1, Amy Peacock2, Gabrielle Campbell1, Raimondo Bruno2, Nicholas Lintzeris4, Milton Cohen1, Suzanne Nielsen1, Wayne Hall5, Richard P. Mattick1, Louisa Degenhardt3 1 National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW, Australia 2 School of Psychology, University of Tasmania, Hobart, TAS, Australia 3 National Drug and Alcohol Reseacrh Centre, University of NSW, Sydney, NSW, Australia 4 Langton Centre, South Eastern Sydney and Illawarra Local Health District, Sydney, NSW, Australia 5 University of Queensland, Brisbane, QLD, Australia

s / Drug and Alcohol Dependence 156 (2015) e102–e182 e163 effects were recorded. Scores were subtracted from −15min baseline value and then saline values subtracted from cocaine values to yield subjective effect score. Participants were genotyped for the SLC6A4 (serotonin transporter) 5-HTTLPR, TPH1 rs1799913, and TPH2 rs4290270 variants. Repeatedmeasures ANOVA corrected for population structure was used to analyze the data. Results: Participants had amean age of 43 years, were 80%male and 73% black, and smoked 2.3 g cocaine per day. Self-report of “Desire” and “Access” were found to be in association with the triallelic5-HTTLPR (p=3×10−5,p=2×10−4, respectively). Self-report of “Stimulated” and “Access” were found to be in association with the TPH1 rs1799913 (p=3×10−4, p=4×10−5, respectively). Selfreport of “Good effect”was found to be in associationwith the TPH2 rs4290270 (p=4×10−4). Conclusions: The serotonergic system may contribute to the subjective effects produced by acute cocaine exposure, which has relevance to models of drug-induced relapse. The role that these serotonergic genes and variants moderate these effects may aid in the development of specific pharmacotherapies tailored to those with specific genetic backgrounds. Financial support: Supported in part by NIH/NIDA P50 DA018197 (TK), for DN throughMDAnderson’s Cancer Center SupportGrantNIH/NIDADA026120, and the ToomimFamily Fund. This material is the result of work supportedwith resources and the use of facilities at the Michael E. DeBakey VAMedical Center, Houston, TX. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.443 Hanging patterns of treatment seeking for pharmaceutical opioids in Australia (2002–2011) Suzanne Nielsen3,1, Amanda Roxburgh2, Raimondo Bruno4,3, Nicholas Lintzeris1, Amber Jefferson5, Louisa Degenhardt3 1 Drug and Alcohol, SESLHD, Sydney, NSW, Australia 2 National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW, Australia 3 National Drug and Alcohol Research Centre, University of NSW, Sydney, NSW, Australia 4 School of Psychology, University of Tasmania, Hobart, TAS, Australia 5 AIHW, Canberra, ACT, Australia Aims:Despitewell-documented increase in use and harmswith pharmaceutical opioids (PO), few detailed studies have examined treatment delivery, particularly for interventions other than opioid substitution treatment. We aimed to explore changes in opioid treatment for PO over time using national treatment data. Methods:Data fromcloseddrugandalcohol 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 2010–2011were examined. In the four jurisdictions where detailed data was available, episodeswhere heroinwas the principal drug of concernwere compared to episodeswhere the fourmost frequently reportedopioids (morphine, codeine, fentanyl and oxycodone) were recorded as the principal drug of concern. Results: In 2002–2003,most (93%) opioid treatmentwas related to heroinwith 7% 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 pharmaceutical opioids. Distinct changes over time were observed for different opioids: an increase in the average age at the start of the episode was seen for heroin and oxycodone; and a reduction in the proportion of females in codeine episodes, with 67% in 2002–2003 compared with 44% in 2010–2011. Codeine and oxycodone users had the lowest current or past injection. Conclusions: Clear differences were observed over time and betweendifferent opioids.Monitoring theseemergingpatternswill be important to inform treatment needs, particularly in light of different patterns of poly drug use, different routes of administration and changing demographic characteristics. Financial support: NHMRC Research Fellowships (#1013803, #1041472). http://dx.doi.org/10.1016/j.drugalcdep.2015.07.444 Substance dependence criteria, not substance use, associated with HIV virologic control Seonaid Nolan1, Alexander Walley2, Timothy Heeren2, Greg Patts2, Alicia S. Ventura2, Meg Sullivan2, Jeffrey Samet2, Richard Saitz2 1 Department of Medicine, University of British Columbia, Vancouver, BC, Canada 2 Boston University, Boston, MA, United States Aims: This study aims to (a) describe a cohort of HIV-infected people on antiretroviral therapy (ART) who use substances and (b) explore which substance use-related factors are associated with lack of virologic control. Methods: Participants were selected from the Boston ARCH cohort (i.e. HIV-infected adults with 12-month DSM-IV substance dependence or ever injection drug use) who were currently taking ART. Substance use predictors of interest included number of DSMIV alcohol and drug dependence criteria and past 30 day substance specific use. Associations with HIV virologic control (HIV viral load [HVL] 200 copies/mL) were tested using logistic regression models. Multivariable analyses were adjusted for age, gender, homelessness and anxiety or depression. Results: Participants (n=200) were median age 50 years, 67% male, 51% African American, 76% self-reported >90% ART adherence, and 80% HVL 90% ART adherence. Substance dependence criteria (drug dependence in particular), and not substance specific use, were associated with a lack of virologic control. This suggests that substance dependence criteriawarrant particular clinical attention by HIV care providers. Financial support: U01AA020784, U24AA020778, U24AA020779, R25DA033211. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.445

Die zunehmende Verschreibung von Opioiden bei Patienten mit chronischen, nicht durch ein Malignom bedingten Schmerzen wird heftig diskutiert. Die gleichzeitige Verordnung von Benzodiazepinen dagegen fallt haufig unter den Tisch, obwohl es bei Patienten mit chronischen Schmerzen nur wenige gesicherte Indikationen fur diese Wirkstoffgruppe gibt.

Methods: Cocaine-dependent subjects (N=302) with past-year opioid dependence/abuse, or past-year opioid use and a history of lifetime opioid dependence were randomly assigned to one of three medication conditions provided on a platform of naltrexone: daily 4mg buprenorphine, 16mg buprenorphine, or placebo, for 8 weeks and had once-weekly cognitive behavioral therapy in the CTN-0048 CocaineUse Reductionwith Buprenorphine clinical trial. DNA (N=234) was genotyped for 13 variants in six genes. Treatment efficacy was evaluated by the percent cocaine positive urines per two-week period. Results: Similar but modest reductions in percent positive urineswere observed in the 4mgand16mgbuprenorphine groups. Therefore, the 4mg and 16mg groups were combined and contrasted with the placebo group using repeated measures ANOVA. Experiment-wise significant interactions of variant x treatment were found for two variants of the proopiomelanocortin (POMC) gene (both p=0.003). In the POMC rs1009388C allele-carrier group, placebo increased positive urines from 57% to 60%, while the buprenorphine decreased positive urines from 43% to 39%, with no difference between placebo and buprenorphine for the GG group. Conclusions:Thesedata implicate POMCpeptides and thepathways in which they participate as targets for future studies on cocaine addiction therapy. Financial support: NIH/NIDA P50 DA018197 (TK, DN), NIH/NIDA U10DA020024 (RW), for DN through MD Anderson’s CancerCenterSupportGrantNIH/NIDADA026120, and theToomim Family Fund. This material is the result of work supported with resources and the use of facilities at the Michael E. DeBakey VA Medical Center, Houston, TX.

Benzodiazepine use by patients in methadone and buprenorphine substitution treatment is common, despite safety concerns regarding these drug interactions. The relative safety of diazepam use by methadone- or buprenorphine-treated patients has not been systematically examined. This study aimed to examine the effect of single diazepam doses, within normal therapeutic range (doses: 0, 10, and 20 mg), upon physiological, subjective, and performance measures in stable methadone and buprenorphine-treated patients. In a double-blind, randomized crossover design, methadone- or buprenorphine-treated patients were administered their normal opioid dose and either placebo, 10-, or 20-mg diazepam, in balanced order over 3 sessions. Eight methadone- and 8 buprenorphine-prescribed patients with no concurrent benzodiazepine dependence or significant comorbidity were recruited from an outpatient addiction clinic in London. Measures were taken at baseline and for 6 hours after dosing, and included physiological responses (pulse rate, blood pressure, pupil size, respiratory rate, and peripheral pO2), subjective drug effects (Addiction Research Center Inventory subscales, visual analog scales of strength of drug effect, drug-liking, and sedation), and performance measures (simple reaction time, cancellation task, digit symbol substitution task, and balance). The 10- and 20-mg diazepam doses resulted in comparable subjective experiences of greater sedation and strength of drug effects in both patient groups, and had minimal impact on physiological parameters. However, diazepam had greater peak effects on performance measures (simple reaction time, digit symbol substitution task, and cancellation time) in methadone-treated than in buprenorphine-treated patients. Diazepam may significantly alter the response to opioid substitution treatment with methadone or buprenorphine.

Data regarding criminal behaviour and expenditure on illicit drugs by 300 methadone patients and 997 heroin users who participated in the Australian National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD) were analysed to measure the effects of pharmacotherapy and to identify predictor variables. At baseline, more heroin users than methadone patients reported recent involvement in any crime (39%, 13% respectively), and in each of four subtypes of crime (property, drug dealing, fraud, violence). Heroin users spent more on heroin than methadone patients (means of $3148, $617 in the past month, respectively). Younger age at first use of heroin was associated with higher reported levels of all four crime types, males reported more drug dealing and violent crime than females, lower employment status was associated with more property crime and drug dealing, lower educational status was associated with more property crime, and younger participants reported more violent crime. For participants who were heroin users at baseline and who were still in treatment at 3 months, mean monthly expenditure on heroin dropped from $2345 to $230. Involvement in any crime dropped from 39% to 20%, and also dropped in three of the four crime subtypes. There were no significant differences between the effects of methadone, buprenorphine, LAAM, and naltrexone treatment on criminal behaviour or expenditure on most types of illicit drug, although the pharmacotherapies did differ in terms of their effects on heroin expenditure. Improving treatment retention and expanding treatment availability to increase participation by heroin users would be likely to reduce drug-related crime, and would be a good social investment.