Opioid use and harms associated with a sustained-release tapentadol formulation: a postmarketing study protocol

Introduction It has been argued that tapentadol may pharmacologically have lower abuse potential than other pharmaceutical opioids currently available. However, there has been no comprehensive triangulation of data regarding use and harms associated with this formulation. A sustained-release formulation (SRF) of tapentadol (Palexia) was released in Australia in 2011 and listed for public subsidy in 2013. We summarise here the methods of a postmarketing study which will measure postintroduction: (1) population level availability, (2) extramedical use and diversion, (3) attractiveness for extramedical use and (4) associated harms, of tapentadol compared against other pharmaceutical opioids. Methods and analysis We evaluated key sources on pharmaceutical use and harms in Australia. This review indicateddata from four sources that disaggregate pharmaceutical opioid formulations and capture tapentadol SRF could be triangulated. These data sources comprised: (1) national pharmaceutical opioid community sales data from 2011 to 2017, (2) national pharmaceutical opioid poisonings reported to Poison Information Centres (PICs) from 2011 to 2017, (3) number of vendors on online marketplaces listing pharmaceutical opioids for sale and (4) data on pharmaceutical opioid extramedical use, attractiveness and harms from interviews with people who regularly inject drugs in Australia. Ethics and dissemination Ethics approval is not required for use of pharmaceutical sales data. Ethics approval has been obtained for use of national pharmaceutical opioid poisonings reported to PICs (LNR/16/SCHN/44) and for use of online marketplace data and interview data from people who inject drugs (HC12086). Key findings will be published mid-2018 in a peer-reviewed academic journal, and presented at various conferences and professional meetings.This work was supported by investigator-initiated untied educational funding from Seqirus Pty Ltd (the marketer of tapentadol SRF in Australia) granted to AP, BL, MF, RC, and LD. BL, AP and LD are supported by NHMRC research fellowships (#1073858, #1109366 and #1041472). The National Drug and Alcohol Research Centre at UNSW Australia is supported by funding from the Australian Government under the Substance Misuse Prevention and Service Improvements Grant Fund

A typology of predictive risk factors for non-adherent medication-related behaviors among chronic non-cancer pain patients prescribed opioids: a cohort study

Background: There has been no previous prospective examination of the homogeneity of chronic non-cancer pain (CNCP) patients in risk factors for non-adherent opioid use

Diversion of prescribed opioids by people living with chronic pain: Results from an Australian community sample

Introduction and Aims 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. Design and Methods 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. Results 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. Discussion and Conclusion 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

Agreement between definitions of pharmaceutical opioid use disorders and dependence in people taking opioids for chronic non-cancer pain (POINT): a cohort study

Background Classification of patients with pharmaceutical opioid use disorder and dependence varies depending on which definition is used. We compared how WHO\u27s ICD-10 and proposed ICD-11 and the American Psychiatric Association\u27s DSM-IV and DSM-5 classified individuals in a community-based sample of Australians with chronic non-cancer pain for which opioids have been prescribed. Methods We studied participants in the Pain and Opioid IN Treatment (POINT) cohort, a 2 year prospective cohort study of 1514 people prescribed pharmaceutical opioids for their chronic pain who were recruited in 2012–13 from community-based pharmacies across Australia. After giving patients the Composite International Diagnostic Interview about their opioid use, we assessed which patients would be categorised as having disorders of pharmaceutical opioid use by ICD-10, the draft ICD-11, DSM-IV, and DSM-5. We examined agreement between classification systems, and tested the unidimensionality of the syndrome with confirmatory factor analysis. Findings We included 1422 participants (median time of pain disorder 10 years [IQR 5–20]; median length of strong opioid prescription 4 years [IQR 1·5–10·0]; mean age 58 years). Similar proportions of individuals met lifetime criteria for dependence with DSM-IV (127; 8·9%), ICD-10 (121; 8·5%), and ICD-11 (141; 9·9%). Criteria in DSM-5 classified 127 (8·9%) participants with moderate or severe use disorder. There was excellent agreement between ICD-10, ICD-11 and DSM-IV dependence (κ\u3e0·90). However, there was only fair to moderate agreement between ICD-10 and DSM-IV dependence diagnoses, and DSM-5 use disorder (mild, moderate, or severe). There was only good agreement between moderate to severe use disorder in DSM-5 and the other definitions. Criteria for all definitions loaded well on a single factor; the best model fit was for the definition for dependence in the draft ICD-11, the worst was in DSM-5. Interpretation Classification of problematic pharmaceutical opioid use varies across editions of ICD and DSM. The much lower levels of agreement between DSM-5 and other definitions than between other definitions might be attributed to DSM-5 containing an increased number of criteria and treating dependence and problematic use as a continuum. The more parsimonious ICD-11 dependence definition showed excellent model fit and excellent agreement with previous classificatory systems

Same-day use of opioids and other central nervous system depressants amongst people who tamper with pharmaceutical opioids: A retrospective 7-day diary study

Objective The aims were to determine: (i) quantity and frequency of same-day use of opioids with benzodiazepines and/or alcohol amongst people who regularly tamper with pharmaceutical opioids; and (ii) socio-demographic, mental health, harms and treatment profile associated with same-day use of high doses. Method The cohort (n = 437) completed a retrospective 7-day diary detailing opioid, benzodiazepine, and alcohol intake. Oral morphine equivalent (OME) units and diazepam equivalent units (DEU) were calculated, with \u3e200 mg OME, \u3e40 mg DEU and \u3e4 standard alcoholic drinks (each 10 g alcohol) considered a high dose . Results One-half (47%) exclusively consumed opioids without benzodiazepines/alcohol; 26% had days of opioid use with and without benzodiazepines/alcohol; and 26% always used opioids and benzodiazepines/alcohol. Same-day use of opioids with benzodiazepines/alcohol typically occurred on 1-3 days in the past week. Six in ten (61%) participants reported high dose opioid use on at least one day; one in five (20%) reported high dose opioid and high dose benzodiazepine/alcohol use on at least one day. The latter group were more likely to use prescribed opioid substitution therapy, often alongside diverted pharmaceutical opioids. Socio-demographic and clinical profiles did not vary according to high dose opioid, alcohol and benzodiazepine use, and there was no association with harms. Conclusions Same-day use of opioids with benzodiazepines/alcohol, and high dose combinations, are common amongst people who tamper with pharmaceutical opioids. Assessment of concomitant benzodiazepine/alcohol use during opioid therapy, implementation of real-time prescription monitoring systems, and research to clarify upper safe limits for polydrug depressant use, are potential implications

Perceptions of extended-release buprenorphine injections for opioid use disorder among people who regularly use opioids in Australia

2019 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction Aims: To examine perceptions of extended-release (XR) buprenorphine injections among people who regularly use opioids in Australia. Design: Cross-sectional survey prior to implementation. XR-buprenorphine was registered in Australia in November 2018. Setting: Sydney, Melbourne and Hobart. Participants. A total of 402 people who regularly use opioids interviewed December 2017 to March 2018. Measurements: Primary outcome concerned the proportion of participants who believed XR-buprenorphine would be a good treatment option for them, preferred weekly versus monthly injections and perceived advantages/disadvantages of XR-buprenorphine. Independent variables concerned the demographic characteristics and features of current opioid agonist treatment (OAT; medication-type, dose, prescriber/dosing setting, unsupervised doses, out-of-pocket expenses and travel distance). Findings: Sixty-eight per cent [95% confidence interval (CI) = 63-73%] believed XR-buprenorphine was a good treatment option for them. They were more likely to report being younger [26-35 versus \u3e 55 years; odds ratio (OR) = 3.16, 95% CI = 1.12-8.89; P = 0.029], being female (OR = 1.67, 95% CI = 1.04-2.69; P = 0.034), \u3c 10 years school education (OR = 1.87, 95% CI = 1.12-3.12; P = 0.016) and past-month heroin (OR = 1.81, 95% CI = 1.15-2.85; P = 0.006) and methamphetamine use (OR = 1.90, 95% CI = 1.20-3.01; P = 0.006). Fifty-four per cent reported no preference for weekly versus monthly injections, 7% preferred weekly and 39% preferred monthly. Among OAT recipients (n = 255), believing XR-buprenorphine was a good treatment option was associated with shorter treatment episodes (1-2 versus ≥ 2 years; OR = 3.93, 95% CI = 1.26-12.22; P = 0.018), fewer unsupervised doses (≤ 8 doses past-month versus no take-aways; OR = 0.50; 95% CI = 0.27-0.93; P = 0.028) and longer travel distance (≥ 5 versus \u3c 5 km; OR = 2.10, 95% CI = 1.20-3.65; P = 0.009). Sixty-nine per cent reported \u27no problems or concerns\u27 with potential differences in availability, flexibility and location of XR-buprenorphine. Conclusions: Among regular opioid users in Australia, perceptions of extended-release buprenorphine as a good treatment option are associated with being female, recent illicit drug use and factors relating to the (in)convenience of current opioid agonist treatment

Effect of cannabis use in people with chronic non-cancer pain prescribed opioids: findings from a 4-year prospective cohort study

Background Interest in the use of cannabis and cannabinoids to treat chronic non-cancer pain is increasing, because of their potential to reduce opioid dose requirements. We aimed to investigate cannabis use in people living with chronic non-cancer pain who had been prescribed opioids, including their reasons for use and perceived effectiveness of cannabis; associations between amount of cannabis use and pain, mental health, and opioid use; the effect of cannabis use on pain severity and interference over time; and potential opioid-sparing effects of cannabis. Methods The Pain and Opioids IN Treatment study is a prospective, national, observational cohort of people with chronic non-cancer pain prescribed opioids. Participants were recruited through community pharmacies across Australia, completed baseline interviews, and were followed up with phone interviews or self-complete questionnaires yearly for 4 years. Recruitment took place from August 13, 2012, to April 8, 2014. Participants were asked about lifetime and past year chronic pain conditions, duration of chronic non-cancer pain, pain self-efficacy, whether pain was neuropathic, lifetime and past 12-month cannabis use, number of days cannabis was used in the past month, and current depression and generalised anxiety disorder. We also estimated daily oral morphine equivalent doses of opioids. We used logistic regression to investigate cross-sectional associations with frequency of cannabis use, and lagged mixed-effects models to examine temporal associations between cannabis use and outcomes. Findings 1514 participants completed the baseline interview and were included in the study from Aug 20, 2012, to April 14, 2014. Cannabis use was common, and by 4-year follow-up, 295 (24%) participants had used cannabis for pain. Interest in using cannabis for pain increased from 364 (33%) participants (at baseline) to 723 (60%) participants (at 4 years). At 4-year follow-up, compared with people with no cannabis use, we found that participants who used cannabis had a greater pain severity score (risk ratio 1·14, 95% CI 1·01-1·29, for less frequent cannabis use; and 1·17, 1·03-1·32, for daily or near-daily cannabis use), greater pain interference score (1·21, 1·09-1·35; and 1·14, 1·03-1·26), lower pain self-efficacy scores (0·97, 0·96-1·00; and 0·98, 0·96-1·00), and greater generalised anxiety disorder severity scores (1·07, 1·03-1·12; and 1·10, 1·06-1·15). We found no evidence of a temporal relationship between cannabis use and pain severity or pain interference, and no evidence that cannabis use reduced prescribed opioid use or increased rates of opioid discontinuation. Interpretation Cannabis use was common in people with chronic non-cancer pain who had been prescribed opioids, but we found no evidence that cannabis use improved patient outcomes. People who used cannabis had greater pain and lower self-efficacy in managing pain, and there was no evidence that cannabis use reduced pain severity or interference or exerted an opioid-sparing effect. As cannabis use for medicinal purposes increases globally, it is important that large well designed clinical trials, which include people with complex comorbidities, are conducted to determine the efficacy of cannabis for chronic non-cancer pain

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

Perceived stigma and social support in treatment for pharmaceutical opioid dependence

Introduction and Aims The dramatic increase in pharmaceutical opioid (PO) use in high‐income countries is a growing public health concern. Stigma and social support are important as they may influence treatment uptake and outcomes, yet few studies exist regarding perceived stigma and social support among people with PO dependence. The aims of the study are to: (i) compare characteristics of those with PO dependence from iatrogenic and non‐iatrogenic causes; (ii) document perceived stigma and its correlates in people in treatment for PO dependence; and (iii) examine correlates of social support in people in treatment for PO dependence. Design and Methods This prospective cohort study included (n = 108) PO‐dependent people referred from treatment services. Telephone interviews were conducted at baseline, 3, 12 and 24 months. Multivariate linear regression was used to examine correlations. Results Mean age was 41 (SD = 10.5). Half (n = 56, 52%) were female. Two in five met the criteria for iatrogenic dependence (n = 41, 38%), with iatrogenic dependence associated with chronic pain, and no history of injection or heroin use. One quarter of study subjects reported past month unsanctioned opioid use (n = 25, 23%). Being married/de facto or female was associated with higher levels of perceived stigma. Unsanctioned opioid use, iatrogenic dependence and mental health conditions were associated with lower social support. Discussion and Conclusions Stigma affects all people in treatment. Those who are married/de facto and female may benefit from interventions to address stigma. The association of low social support with poorer mental health and ongoing substance use indicate that treatment could focus more on this area