Opioid agonist treatment for people who are dependent on pharmaceutical opioids.

BACKGROUND: There are ongoing concerns regarding pharmaceutical opioid-related harms, including overdose and dependence, with an associated increase in treatment demand. People dependent on pharmaceutical opioids appear to differ in important ways from people who use heroin, yet most opioid agonist treatment research has been conducted in people who use heroin.  OBJECTIVES: To assess the effects of maintenance opioid agonist pharmacotherapy for the treatment of pharmaceutical opioid dependence. SEARCH METHODS: We updated our searches of the following databases to January 2022: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, MEDLINE, four other databases, and two trial registers. We checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs). SELECTION CRITERIA: We included RCTs with adults and adolescents examining maintenance opioid agonist treatments that made the following two comparisons. 1. Full opioid agonists (methadone, morphine, oxycodone, levo-alpha-acetylmethadol (LAAM), or codeine) versus different full opioid agonists or partial opioid agonists (buprenorphine) for maintenance treatment. 2. Full or partial opioid agonist maintenance versus non-opioid agonist treatments (detoxification, opioid antagonist, or psychological treatment without opioid agonist treatment). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. MAIN RESULTS: We identified eight RCTs that met inclusion criteria (709 participants). We found four studies that compared methadone and buprenorphine maintenance treatment, and four studies that compared buprenorphine maintenance to either buprenorphine taper (in addition to psychological treatment) or a non-opioid maintenance treatment comparison. We found low-certainty evidence from three studies of a difference between methadone and buprenorphine in favour of methadone on self-reported opioid use at end of treatment (risk ratio (RR) 0.49, 95% confidence interval (CI) 0.28 to 0.86; 165 participants), and low-certainty evidence from four studies finding a difference in favour of methadone for retention in treatment (RR 1.21, 95% CI 1.02 to 1.43; 379 participants). We found low-certainty evidence from three studies showing no difference between methadone and buprenorphine on substance use measured with urine drug screens at end of treatment (RR 0.81, 95% CI 0.57 to 1.17; 206 participants), and moderate-certainty evidence from one study of no difference in days of self-reported opioid use (mean difference 1.41 days, 95% CI 3.37 lower to 0.55 days higher; 129 participants). There was low-certainty evidence from three studies of no difference between methadone and buprenorphine on adverse events (RR 1.13, 95% CI 0.66 to 1.93; 206 participants). We found low-certainty evidence from four studies favouring maintenance buprenorphine treatment over non-opioid treatments in terms of fewer opioid positive urine drug tests at end of treatment (RR 0.66, 95% CI 0.52 to 0.84; 270 participants), and very low-certainty evidence from four studies finding no difference on self-reported opioid use in the past 30 days at end of treatment (RR 0.63, 95% CI 0.39 to 1.01; 276 participants). There was low-certainty evidence from three studies of no difference in the number of days of unsanctioned opioid use (standardised mean difference (SMD) -0.19, 95% CI -0.47 to 0.09; 205 participants). There was moderate-certainty evidence from four studies favouring buprenorphine maintenance over non-opioid treatments on retention in treatment (RR 3.02, 95% CI 1.73 to 5.27; 333 participants). There was moderate-certainty evidence from three studies of no difference in adverse effects between buprenorphine maintenance and non-opioid treatments (RR 0.50, 95% CI 0.07 to 3.48; 252 participants). The main weaknesses in the quality of the data was the use of open-label study designs, and difference in follow-up rates between treatment arms. AUTHORS' CONCLUSIONS: There is  very low- to moderate-certainty evidence supporting the use of maintenance agonist pharmacotherapy for pharmaceutical opioid dependence. Methadone or buprenorphine did not differ on some outcomes, although on the outcomes of retention and self-reported substance use some results favoured methadone. Maintenance treatment with buprenorphine appears more effective than non-opioid treatments. Due to the overall very low- to moderate-certainty evidence and small sample sizes, there is the possibility that the further research may change these findings.

Clinical correlates and outcomes associated with pregabalin use among people prescribed opioids for chronic non-cancer pain: A five-year prospective cohort study.

AIMS: Pregabalin has become widely used as an alternative to opioids in treating certain types of chronic non-cancer pain, but few studies have examined its clinical efficacy outside trials. We address this gap by examining the utilization, correlates and clinical outcomes of pregabalin use among an Australian community-based cohort of people prescribed opioids for chronic non-cancer pain. METHODS: Through a five-year prospective cohort study (n = 1514) we examined associations between pregabalin use and pain severity and interference, mental health, opioid dose and past month use of ambulance and emergency department services. We used fixed-effects regression models to examine within-participant differences, and random-effects regression models to examine within- and between-participant differences in clinical outcomes. RESULTS: In an analysis of cases with complete data over five-years (n = 896), the prevalence of pregabalin use ranged from 16% at cohort entry to 29% at 36- and 48-months, and 46% reported pregabalin use at any time during the five years. Pregabalin use was associated with greater pain severity and interference and greater use of high-risk opioid doses (>90 oral morphine equivalents/day). Pregabalin use was not associated with changes in mental health symptoms, ambulance or emergency department attendance in the fixed or random effects models. CONCLUSIONS: Pregabalin use was common, but for most people use was not associated with clinically meaningful improvements in pain or functioning.

Feasibility of a Mobile Health App for Routine Outcome Monitoring and Feedback in SMART Recovery Mutual Support Groups: Stage 1 Mixed Methods Pilot Study.

BACKGROUND: Mutual support groups are an important source of long-term help for people impacted by addictive behaviors. Routine outcome monitoring (ROM) and feedback are yet to be implemented in these settings. SMART Recovery mutual support groups focus on self-empowerment and use evidence-based techniques (eg, motivational and behavioral strategies). Trained facilitators lead all SMART Recovery groups, providing an opportunity to implement ROM. OBJECTIVE: The aim of this stage 1 pilot study is to explore the feasibility, acceptability, and preliminary outcomes of a novel, purpose-built mobile health ROM and feedback app (SMART Track) in mutual support groups coordinated by SMART Recovery Australia (SRAU) over 8 weeks. METHODS: SMART Track was developed during phase 1 of this study using participatory design methods and an iterative development process. During phase 2, 72 SRAU group participants were recruited to a nonrandomized, prospective, single-arm trial of the SMART Track app. Four modes of data collection were used: ROM data directly entered by participants into the app; app data analytics captured by Amplitude Analytics (number of visits, number of unique users, visit duration, time of visit, and user retention); baseline, 2-, and 8-week follow-up assessments conducted through telephone; and qualitative telephone interviews with a convenience sample of study participants (20/72, 28%) and facilitators (n=8). RESULTS: Of the 72 study participants, 68 (94%) created a SMART Track account, 64 (88%) used SMART Track at least once, and 42 (58%) used the app for more than 5 weeks. During week 1, 83% (60/72) of participants entered ROM data for one or more outcomes, decreasing to 31% (22/72) by the end of 8 weeks. The two main screens designed to provide personal feedback data (Urges screen and Overall Progress screen) were the most frequently visited sections of the app. Qualitative feedback from participants and facilitators supported the acceptability of SMART Track and the need for improved integration into the SRAU groups. Participants reported significant reductions between the baseline and 8- week scores on the Severity of Dependence Scale (mean difference 1.93, SD 3.02; 95% CI 1.12-2.73) and the Kessler Psychological Distress Scale-10 (mean difference 3.96, SD 8.31; 95% CI 1.75-6.17), but no change on the Substance Use Recovery Evaluator (mean difference 0.11, SD 7.97; 95% CI -2.02 to 2.24) was reported. CONCLUSIONS: Findings support the feasibility, acceptability, and utility of SMART Track. Given that sustained engagement with mobile health apps is notoriously difficult to achieve, our findings are promising. SMART Track offers a potential solution for ROM and personal feedback, particularly for people with substance use disorders who attend mutual support groups. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12619000686101; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377336. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/15113.

Development of a Brief Patient-Administered Screening Tool for Prescription Opioid Dependence for Primary Care Settings.

OBJECTIVE: To develop a short, patient-administered screening tool that will allow for earlier assessment of prescription opioid dependence (often referred to as addiction) in primary care settings. DESIGN AND SETTING: Cross-sectional analysis (N = 1,134) from the two-year time point of the Pain and Opioids IN Treatment (POINT) cohort was used in the scale development. SUBJECTS: Participants who completed two-year interviews in the POINT study, a prospective cohort study that followed people with chronic noncancer pain over a five-year period, and who were prescribed strong opioids for a minimum of six weeks at baseline. METHODS: An advisory committee provided advice on wording and content for screening in primary care settings. Univariate logistic regression identified individual items that were significantly associated with meeting ICD-11 criteria for prescription opioid dependence. Exploratory and confirmatory factor analysis (EFA and CFA) were conducted, and items were reduced to identify a small item set that were discriminative and shared a simple underlying structure. RESULTS: Sixty-four variables associated with ICD-11 criteria for prescription opioid dependence were initially identified. Four rounds of EFA were performed, resulting in five items remaining. CFA identified two possible four-item combinations, with the final combination chosen based on greater item endorsement and the results of goodness-of-fit indices. CONCLUSIONS: Addressing prescription opioid dependence is an important part of the global public health challenge surrounding rising opioid-related harm. This study addresses an important initial requisite step to develop a brief screening tool. Further studies are required to validate the tool in clinical settings.

Substance Use and Co-occurring Physical Health Problems: File Review of a Residential Drug and Alcohol Treatment Service.

Objectives: Physical health conditions cause significant disability and mortality among people living with alcohol and other drug problems. There has been limited research on the prevalence of health problems among clinical samples of people with substance use disorders, particularly among those in residential treatment. Yet residential settings provide unique opportunity for responding to health needs. To better understand the health of people attending treatment for substance use disorders, this study conducted a file review to examine the prevalence of physical health problems as identified during routine residential care. Methods: A retrospective review of client files collected between 2013 and 2017 (N = 172) was completed at a residential treatment service in NSW, Australia. Data were extracted to examine the prevalence of physical health problems recorded at entry into treatment. Correlates of health problems were estimated using bivariate descriptive analyses and logistic regression. Results: The majority of clients in treatment for substance use had a comorbid physical health problem (80.7%). Musculoskeletal problems were the most frequently reported medical issue (38.6%). Odds for some physical health problems were related to client gender, age, and primary substance of concern. Male gender remained the strongest predictor of dental health problems when controlling for age and substance type (odds ratio [OR] = 3.60). Primary alcohol use remained the strongest predictor of nutritional deficiencies when controlling for client age (OR = 4.43). Among clients with a physical health problem and who had a treatment episode of at least 14 days (n = 110), just over half (55.5%) were referred to a health-related practitioner or service during their treatment episode. Conclusions: This study contributes to the literature by reporting on the incidence of physical health problems among people in residential treatment for substance use disorders. The high prevalence of physical health morbidity iterates the role of non-medical staff working within drug and alcohol services in the identification of client health needs. The findings support calls for systematic screening of physical health as part of routine care for substance use disorders improved integration of substance treatment and the broader primary health care system.

A population-based study of transdermal fentanyl initiation in Australian clinical practice.

PURPOSE: Although guidelines caution against initiation of transdermal (TD) fentanyl among those who are opioid naïve, there is concern that not all people receive adequate prior opioid exposure. This study examined the percentage of people who are opioid naïve at the time of TD fentanyl initiation in Australia; strengths initiated; and characteristics associated with being opioid naïve. METHODS: This is a national retrospective cohort study derived from a 10% sample of Pharmaceutical Benefits Scheme concessional beneficiaries initiating TD fentanyl between 29 September 2009-31 December 2013. Individuals were deemed opioid naïve if they had no opioid dispensings in the previous 90 days. Logistic regression was used to determine characteristics associated with being opioid naïve, including socio-demographics, likely comorbidities and previous analgesic use. RESULTS: A total of 13,166 people initiated TD fentanyl; 60.4% were female and 76.2% were aged ≥ 65 years. Three in ten (30.4%) were opioid naïve and 63.2% initiated the 12 mcg/h patch. Those who were opioid naïve were more likely to be female (adjusted odds ratio (aOR) 1.35; 95% CI 1.25-1.46), older (aOR 1.85; 95% CI 1.54-2.28 for those ≥ 85 years) and previously dispensed medicines for dementia (aOR 1.37; 95% CI 1.04-1.80). People previously dispensed medicines for cancer were less likely to be opioid naïve (aOR 0.57; 95% CI 0.48-0.67). CONCLUSIONS: Three in ten Australians initiating TD fentanyl are opioid naïve. Our findings suggest that specific patient sub-populations already at increased risk of opioid-related adverse events are not receiving prior opioid treatment before initiation, highlighting the need for greater adherence to current treatment guidelines.

Increases in controlled-release oxycodone utilisation following the subsidy of oxycodone with naloxone formulations: An Australian population-based study.

PURPOSE: Despite increasing use of oxycodone/naloxone controlled-release (CR) in Australia, little is known about how it has affected the overall oxycodone CR market since its subsidy in 2011. METHODS: We used Pharmaceutical Benefits Scheme dispensing claims (2006-2016) and interrupted time series analysis to examine changes in the quarterly rates of dispensing of oral oxycodone CR formulations (oxycodone/naloxone CR and single-ingredient oxycodone CR) and new oxycodone CR treatment episodes. We also performed a retrospective cohort study in a sample of people initiating a new oxycodone CR treatment episode in 2009, 2012/2013, and 2016 to compare opioid utilisation patterns over time. RESULTS: The subsidy of oxycodone/naloxone CR was associated with a 1.6-fold increase in the growth rate of oxycodone CR dispensing, resulting from rapid uptake of low strength (≤5 mg) oxycodone/naloxone CR. In our cohort of initiators, the number of new oxycodone CR treatment episodes increased 2.1-fold between 2009 and 2016; in 2016, 91.4% of new treatment episodes involved oxycodone/naloxone CR. Comparing 2016 with 2009, we observed an increase in people initiating with a tablet strength less than or equal to 5-mg (risk difference [RD] = 21.1%, 95% CI, 19.9%-22.4%) in people initiating with no other opioid dispensing 90 days prior to initiation (RD = 5.2%, 3.8%-6.6%) and with no further opioid dispensing 90 days after initiation (RD = 8.8%, 7.4%-10.2%). CONCLUSIONS: After its subsidy, the uptake of low-dose oxycodone/naloxone CR was greater than expected if it were substituting the single-ingredient oxycodone CR, resulting in an expansion of the oxycodone CR market.

Concerns and Help-Seeking Among Patients Using Opioids for Management of Chronic Noncancer Pain.

BACKGROUND: The safety and efficacy of long-term opioid treatment for chronic noncancer pain (CNCP) remains controversial. This study examined whether patients who report problematic opioid use sought help and/or perceived barriers to help-seeking. METHODS: Data were collected from 1,086 people prescribed opioids for CNCP via a large prospective cohort called the Pain and Opioids IN Treatment (POINT) study. Patients' characteristics and help-seeking were examined according to scores on the Prescribed Opioids Difficulties Scale (PODS). RESULTS: Participants scoring "intermediate" (17%) or "high" (30%) on the PODS were younger and reported more complex pain presentations, higher opioid doses, poorer physical health, moderate to severe anxiety and depression, aberrant behavior, past month opioid use disorder and help-seeking (compared with the "low" PODS group, 53%). One-quarter (26%) had sought help, most commonly from a primary care physician, specialist pain clinic, family member/partner, counselor/psychologist, and the Internet. Participants in the "high" PODS group were more likely to have sought help from an alcohol or other drug service, addiction specialist, or drug information helpline. Common barriers to help-seeking were desire for self-management and concern that their opioid treatment may be discontinued. Although 35% met criteria for likely opioid use disorder, only 4.8% reported lifetime treatment with methadone or buprenorphine; participants' ratings indicated significant perceived stigma associated with these medications. CONCLUSIONS: The PODS is effective in identifying patients who are concerned about their opioid use. Strategies to address stigma related to drug treatment, including better integration of primary health, specialist pain, and addiction services, are important in reducing opioid-related harm.

Antidepressant Use Among People Prescribed Opioids for Chronic Noncancer Pain.

OBJECTIVE: Although depression and chronic pain often coexist, few studies have examined antidepressant use among people with pain. This study examines the prevalence and characteristics associated with antidepressant use among people prescribed opioids for chronic noncancer pain (CNCP). DESIGN: Baseline data from a prospective cohort study. SETTING: Australian community. SUBJECTS: A total of 1166 people prescribed opioids for CNCP. METHODS: Baseline data collection consisted of a self-completed seven-day medication diary and telephone interview to collect information on sociodemographic characteristics and mental/physical health using validated questionnaires. Logistic regression was used to examine characteristics associated with antidepressant use, reporting adjusted odds ratios (AORs) and 95% confidence intervals (CIs). RESULTS: Of the 1166 participants, 668 (57.3%) were female, and the median (interquartile range) age was 59 (49-68) years. About half the cohort (N = 637, 54.6%) used antidepressants. Of these, 329 (51.7%) reported moderate to severe depression. Amitriptyline was the most commonly used antidepressant (17.3%). Factors independently associated with antidepressant use were being female (AOR = 1.47, 95% CI = 1.13-1.92), more years lived in pain (AOR = 1.01, 95% CI = 1.00-1.02), and use of nonopioid analgesics (AOR = 1.34, 95% CI = 1.01-1.78), benzodiazepines and related drugs (AOR = 1.84, 95% CI = 1.36-2.49), antiepileptics (AOR = 1.86, 95% CI = 1.38-2.51), and antipsychotics (AOR = 2.15, 95% CI = 1.22-3.77). CONCLUSIONS: Antidepressant use is common among people with CNCP prescribed opioids. Those using antidepressants were more likely to use other psychotropic medicines concurrently, highlighting that they are a high-risk population requiring comprehensive assessment to optimize outcomes and reduce potential harms from polypharmacy.

Person-level changes in oxycodone use after the introduction of a tamper-resistant formulation in Australia.

BACKGROUND: Australia introduced tamper-resistant controlled-release (CR) oxycodone in April 2014. We quantified the impact of the reformulation on dispensing, switching and poisonings. METHODS: We performed interrupted time-series analyses using population-representative national dispensing data from 2012 to 2016. We measured dispensing of oxycodone CR (≥ 10 mg), discontinuation of use of strong opioids and switching to other strong opioids after the reformulation compared with a historical control period. Similarly, we compared calls about intentional opioid poisoning using data from a regional poisons information centre. RESULTS: After the reformulation, dispensing decreased for 10-30 mg (total level shift -11.1%, 95% confidence interval [CI], -17.2% to -4.6%) and 40-80 mg oxycodone CR (total level shift -31.5%, 95% CI -37.5% to -24.9%) in participants less than 65 years of age but was unchanged in people 65 years of age or older. Compared with the previous year, discontinuation of use of strong opioids did not increase (adjusted hazard ratio [HR] 0.95, 95% CI 0.91 to 1.00), but switching to oxycodone/naloxone did increase (adjusted HR 1.54, 95% CI 1.32 to 1.79). Switching to morphine varied by age (p < 0.001), and the greatest increase was in participants less than 45 years of age (adjusted HR 4.33, 95% CI 2.13 to 8.80). Participants switching after the reformulation were more likely to be dispensed a tablet strength of 40 mg or more (adjusted odds ratio [OR] 1.40, 95% CI 1.09 to 1.79). Calls for intentional poisoning that involved oxycodone taken orally increased immediately after the reformulation (incidence rate ratio (IRR) 1.31, 95% CI 1.05-1.64), but there was no change for injected oxycodone. INTERPRETATION: The reformulation had a greater impact on opioid access patterns of people less than 65 years of age who were using higher strengths of oxycodone CR. This group has been identified as having an increased risk of problematic opioid use and warrants closer monitoring in clinical practice.

To what extent do data from pharmaceutical claims under-estimate opioid analgesic utilisation in Australia?

PURPOSE: Although pharmaceutical claims are an essential data source for pharmacoepidemiological studies, these data potentially under-estimate opioid utilisation. Therefore, this study aimed to quantify the extent to which pharmaceutical claims from Australia's national medicines subsidy programs (Pharmaceutical Benefits Scheme [PBS] and Repatriation Schedule of Pharmaceutical Benefits [RPBS]) under-estimate prescription-only and total national opioid utilisation across time and for different opioids. A secondary aim was to examine the impact of the 2012 policy change to record all PBS/RPBS dispensed medicines, irrespective of government subsidy, on the degree of under-estimation. METHODS: Aggregated data on Australian opioid utilisation were obtained for the 2010 to 2014 calendar years, including all single ingredient and combination opioid analgesic preparations available on prescription or over-the-counter (OTC). Total opioid utilisation (oral morphine equivalent kilogrammes) was quantified using sales data from IMS Health and compared with pharmaceutical claims data from the PBS/RPBS. RESULTS: PBS/RPBS claims data did not account for 12.4% of prescription-only opioid utilisation in 2014 and 19.1% in 2010, and 18.4% to 25.4% of total opioid use when accounting for OTC preparations. Between 2010 and 2014, 5.6% to 5.3% of buprenorphine, 8.1% to 6.3% fentanyl, 17.7% to 10.7% oxycodone, 18.4% to 11.0% tramadol, 38.4% to 21.0% hydromorphone, and 28.6% to 21.0% of prescription-only codeine utilisation were not accounted for in PBS/RPBS claims. CONCLUSIONS: Despite increased capture of less expensive (under co-payment) opioid items since 2012, PBS/RPBS claims still under-estimate opioid use in Australia, with varying degrees across opioids. The estimates generated in this study allow us to better understand the degree of under-estimation and account for these in research using Australia's national pharmaceutical claims data.

Knowledge of Opioid Overdose and Attitudes to Supply of Take-Home Naloxone Among People with Chronic Noncancer Pain Prescribed Opioids.

Objective: Take-home naloxone (THN) is recommended in response to pharmaceutical opioid-related mortality. Some health professionals are reluctant to discuss THN for fear of causing offense. The aims of this study were to assess knowledge of opioid overdose and attitudes toward THN for opioid overdose reversal in people with chronic noncancer pain (CNCP). Design: Prospective cohort study. Setting: Australia, September to October 2015. Subjects: A subset of participants (N = 208) from a cohort of people prescribed restricted opioids for CNCP. Methods: Questions added in the two-year telephone interviews examined knowledge of overdose symptoms and attitudes toward community supply of naloxone. Associations with overdose risk factors and naloxone supply eligibility criteria with attitudes toward naloxone were explored. Results: Fourteen percent reported ever experiencing opioid overdose symptoms. Participants correctly identified fewer than half of the overdose signs and symptoms. After receiving information on naloxone, most participants (60%), thought it was a "good" or "very good" idea. Few participants reported that they would be "a little" (N = 21, 10%) or "very" offended (N = 7, 3%) if their opioid prescriber offered them naloxone. Positive attitudes toward THN were associated with male gender (odds ratio [OR] = 1.96, 95% confidence interval [CI] = 1.09-3.50), past year cannabis use (OR = 2.52, 95% CI = 1.03-6.16), and past year nicotine use (OR = 2.11, 95% CI = 1.14-3.91). Conclusions: Most participants had positive attitudes toward THN but low knowledge about opioid overdose symptoms. Strategies for educating patients and their caregivers on opioid toxicity are needed. THN may be best targeted toward those with risk factors in terms of overdose prevention and acceptability.

Prescription Opioid Access Patterns and Factors Associated with Increasing Number of Prescribers, Pharmacies, and Dispensings: An Observational Study Using Pharmaceutical Claims.

Objective: To examine associations between patient factors and increasing opioid access measured by three metrics: number of unique prescribers, pharmacies, and dispensings in 12 months. Methods: We used pharmaceutical claims for a random 10% sample of Australians age 18 years or older initiating or reinitiating strong opioid treatment (≥90 days of no strong opioid dispensing) between July 2010 and December 2012. We report the distribution of opioid access by metric. We used three separate zero-truncated negative binomial regressions to explore associations. We censored individuals 365 days after index date or at death, whichever occurred first. Results: Approximately 69,088 persons initiated or reinitiated strong opioid treatment; they were predominantly female (59.7%) with a median age of 71 years (interquartile range [IQR] = 58-81). Over one year, persons visited a median of two prescribers (IQR = 1-3), visited one dispensing pharmacy (IQR = 1-2), and had four opioid dispensings (IQR = 2-10). Three percent of people were in the top decile of opioid access distribution for all three metrics (four or more prescribers, three or more dispensing pharmacies, and 20 or more dispensings). Increasing opioid access was strongly associated with male sex, history of pain treatment (3 to 12 months prior to index date), malignancy treatment, or treatment for three or more other medical conditions. Conclusions: Delineating legitimate from extramedical opioid use based on pharmaceutical claims is imprecise. We demonstrated that "high" levels of access, defined in previous research, may reflect routine care for complex patients. Pharmaceutical claims have utility in examining population norms of prescription drug use and access patterns, and flagging persons at the extreme end of access, for at least one measure, who may warrant further investigation.

Defined daily doses (DDD) do not accurately reflect opioid doses used in contemporary chronic pain treatment.

OBJECTIVE: To assess how well the defined daily dose (DDD) metric reflects opioid utilisation among chronic non-cancer pain patients. DESIGN: Descriptive, cross-sectional study, utilising a 7-day medication diary. SETTING: Community-based treatment settings, Australia. SUBJECTS: A sample of 1101 people prescribed opioids for chronic non-cancer pain. METHODS: Opioid dose data was collected via a self-completed 7-day medication diary capturing names, strengths and doses of each medication taken in the past week. Median daily dose was calculated for each opioid. Comparisons were made to the World Health Organization's (WHO) DDD metric. RESULTS: WHO DDDs ranged from 0.6 to 7.1 times the median opioid doses used by the sample. For transdermal fentanyl and oral hydromorphone, the median dose was comparable with the DDD. The DDD for methadone was 0.6 times lower than the median doses used by this sample of chronic pain patients. In contrast, the DDD for oxycodone and transdermal buprenorphine, the most commonly used strong opioids for chronic pain in Australia, was two to seven times higher than actual doses used. CONCLUSIONS: For many opioids, there are key differences between the actual doses used in clinical practice and the WHO's DDDs. The interpretation of opioid utilisation studies using population-level DDDs may be limited, and a recalibration of the DDD for many opioids or the reporting of opioid utilisation in oral morphine equivalent doses is recommended. Copyright © 2017 John Wiley & Sons, Ltd.

Protecting Pain Patients. The Evaluation of a Chronic Pain Educational Intervention.

INTRODUCTION: Advocacy and commercially funded education successfully reduced barriers to the provision of long-term opioid analgesia. The subsequent escalation of opioid prescribing for chronic noncancer pain has seen increasing harms without improved pain outcomes. METHODS: This was a one-group pretest-posttest design study. A multidisciplinary team developed a chronic pain educational package for general practitioner trainees emphasizing limitations, risk-mitigation, and deprescribing of opioids with transition to active self-care. This educational intervention incorporated prereadings, a resource kit, and a 90-minute interactional video case-based workshop incorporated into an education day. Evaluation was via pre- and postintervention (two months) questionnaires. Differences in management of two clinical vignettes were tested using McNemar's test. RESULTS: Of 58 eligible trainees, 47 (response rate = 81.0%) completed both questionnaires (36 of whom attended the workshop). In a primary analysis including these 47 trainees, therapeutic intentions of tapering opioid maintenance for pain (in a paper-based clinical vignette) increased from 37 (80.4%) pre-intervention to 44 (95.7%) postintervention (P = 0.039). In a sensitivity analysis including only trainees attending the workshop, 80.0% pre-intervention and 97.1% postintervention tapered opioids (P = 0.070). Anticipated initiation of any opioids for a chronic osteoarthritic knee pain clinical vignette reduced from 35 (74.5%) to 24 (51.1%; P = 0.012) in the primary analysis and from 80.0% to 41.7% in the sensitivity analysis (P = 0.001). CONCLUSIONS: Necessary improvements in pain management and opioid harm avoidance are predicated on primary care education being of demonstrable efficacy. This brief educational intervention improved hypothetical management approaches two months subsequently. Further research measuring objective changes in physician behavior, especially opioid prescribing, is indicated.

Opioid Agonist Treatment for Patients With Dependence on Prescription Opioids.

Clinical Question: Are different opioid agonist treatments (eg, methadone vs buprenorphine) associated with differences in efficacy for treating prescription opioid dependence, and is long-term maintenance of opioid agonist treatment associated with differences in efficacy compared with opioid taper or psychological treatments alone? Bottom Line: For patients who are dependent on prescription opioids, long-term maintenance of opioid agonists is associated with less prescription opioid use and better adherence to medication and psychological therapies for opioid dependence compared with opioid taper or psychological treatments alone. Methadone maintenance was not associated with differences in therapeutic efficacy compared with buprenorphine maintenance treatment. Evidence quality was low to moderate.

Initiation of strong prescription opioids in Australia: cohort characteristics and factors associated with the type of opioid initiated.

AIMS: To describe the characteristics of Australians initiating strong opioids and examine the factors associated with the type of opioid initiated. METHODS: Pharmaceutical Benefits Scheme dispensing records were extracted for a 10% sample of people who initiated a strong opioid treatment episode (buprenorphine, fentanyl, hydromorphone, morphine, oxycodone) between 29 September 2009 and 31 December 2013, as evidenced by the absence of a strong opioid dispensing for at least 90 days. The cohort was restricted to people with complete medicines ascertainment. Socio-demographic characteristics, previous dispensing histories and index opioid use were examined. Multinomial logistic regression was used to calculate adjusted relative risk ratios (aRRRs) and 95% confidence intervals (CIs) to determine the factors associated with the type of opioid medicine initiated, relative to oxycodone. RESULTS: The cohort consisted of 125 335 people: 58.3% were female and 63.7% were aged ≥65 years. The most commonly initiated strong opioid was oxycodone (72.8%), usually 5 mg immediate-release tablets (76.1%). Compared to people aged 18-44 years, those ≥85 years were 14.18 times as likely (95% CI 12.67-15.87) to initiate morphine than oxycodone. Compared to people without a cancer treatment history, those with a cancer treatment history were 2.34 times as likely (95% CI 2.11-2.60) to initiate morphine than oxycodone. CONCLUSIONS: The most commonly initiated strong opioid was oxycodone, usually at lower strengths. Those who initiated oxycodone were more likely to be younger with no previous cancer treatment history. As these are high-risk characteristics for potential harms, a judicious approach when initiating strong opioids for this group is necessary.

An ecological study of the extent and factors associated with the use of prescription and over-the-counter codeine in Australia.

PURPOSE: The extent and factors associated with codeine use in the community remain poorly understood despite the widespread global use of codeine. The aim of this study was to examine the use of prescription and over-the-counter (OTC) codeine in Australia and identify the geographic and socio-demographic characteristics associated with prescription and OTC codeine use. METHODS: National sales data for prescription and OTC codeine (supplied by IMS Health) were used to estimate codeine utilisation (in pack sales and milligrammes) in Australia during 2013, mapped to Australian Bureau of Statistics (ABS) Statistical Local Areas (SLAs) and Remoteness Areas. Socio-demographic characteristics and total population estimates of SLAs were obtained from the ABS. SLA-level data on sex, age distribution, income, occupations involving physical labour and number of pharmacies were included in linear regression analyses to examine their association with total, prescription and OTC codeine use. RESULTS: In total, 27,780,234 packs of codeine were sold in Australia during 2013, equating to 12,376 kg. OTC codeine preparations accounted for 15,490,207 packs (55.8 %) or 4967.30 kg (40.1 %). Nationally, an estimated 1.24 packs (or 554.10 mg) of codeine were sold per person; utilisation was higher in more remote areas. SLAs with a higher percentage of low-income earning households had the highest rates of prescription codeine use (ß 0.16, p < 0.001), whereas SLAs with a higher percentage of males had the highest rates of OTC codeine use (ß 0.22, p < 0.001). CONCLUSIONS: Codeine use is common in Australia, with clear distinctions in the geographic and socio-demographic characteristics associated with prescription and OTC codeine use.

The extent and correlates of community-based pharmaceutical opioid utilisation in Australia.

PURPOSE: There has been concern regarding the increasing use of opioids and related harm. We present data on opioid utilisation across Australia and consider sociodemographic factors that may affect utilisation rates. METHODS: IMS Health national sales data for over-the-counter (codeine) and prescription opioids (buprenorphine, codeine, dextropropoxyphene, fentanyl, hydromorphone, methadone, morphine, oxycodone, tapentadol and tramadol) were used to estimate total utilisation rates in the community during 2013, mapped to Statistical Local Areas (SLAs) and Remoteness Areas. All opioid amounts were measured in pack sales and milligrammes then converted to oral morphine equivalent milligrammes (OME mg) for comparison across opioids. Data on the demographic characteristics of SLAs were obtained from the ABS (sex and age distribution, income and levels of physical labour) and other sources (number of pharmacies in SLAs) and were included in linear regression analyses. RESULTS: In 2013, an estimated 10 747 kg (OME) of opioids were sold across Australia, equating to 481 OME mg per person. There was considerable geographic variation in opioid utilisation, with higher rates of use in rural and regional areas. Geographic areas that were less populated, had more men and older people, proportionally more low-income earning households and greater proportions in jobs requiring physical labour had higher utilisation rates. CONCLUSIONS: Substantial geographic variation in opioid utilisation was identified, with areas outside of major cities having higher rates of utilisation of all types of opioids. Prescription monitoring and best practice interventions aimed at improving opioid use need to have a particular focus on areas outside of major cities. Copyright © 2016 John Wiley & Sons, Ltd.

Geographic Variation in Health Service Use and Perceived Access Barriers for Australian Adults with Chronic Non-Cancer Pain Receiving Opioid Therapy.

OBJECTIVE: Rates of chronic non-cancer pain are increasing worldwide, with concerns regarding poorer access to specialist treatment services in remote areas. The current study comprised the first in-depth examination of use and barriers to access of health services in Australia according to remoteness. METHODS: A cohort of Australian adults prescribed pharmaceutical opioids for chronic non-cancer pain (n = 1,235) were interviewed between August 2012 and April 2014, and grouped into 'major city' (49%), 'inner regional' (37%), and 'outer regional/remote' (14%) according to the Australian Standard Geographical Classification based on postcode. Multinomial logistic regression analyses were conducted to determine geographical differences in socio-demographic and clinical characteristics, health service use, and perceived barriers to health service access. RESULTS: The 'inner regional group' and 'outer regional/remote group' were more likely to be male (relative risk ratio (RRR)=1.38,95%CI 1.08-1.77 and RRR = 1.60, 95%CI 1.14-2.24) and have no private health insurance (RRR = 1.53, 95%CI 1.19-1.97 and RRR = 1.65, 95%CI 1.16-2.37) than the 'major city group' (49%). However, the 'inner regional group' reported lower pain severity and better mental health relative to the 'major city group' = 0.92, 95%CI 0.86-0.98 and RRR = 1.02, 95%CI 1.01-1.03, respectively). Although rates of health service access were generally similar, the 'outer regional/remote group' were more likely to report client-practitioner communication problems (RRR = 1.57, 95%CI 1.03-2.37), difficulties accessing specialists (RRR = 1.56, 95%CI 1.01-2.39), and perception of practitioner lack of confidence in prescribing pain medication (RRR = 1.73, 1.14-2.62), relative to both groups. CONCLUSION: Perceived communication, access, and financial barriers to healthcare indicate the need for increased efforts to address geographic inequality in pain treatment.