Introduction There are concerns about rising drug-related deaths and the potential contribution of prescription analgesics. There is limited understanding regarding the role of prescription analgesics in non-fatal overdoses (NFODs), nor is there a good understanding of what factors are associated with more severe overdose. Objectives To explore risk factors and characteristics of NFODs among people attending a specialist community-based substance misuse service. Methods After Caldicott approval, data on NFODs, in people attending the Tayside Substance Misuse Service (TSMS), were extracted from the Scottish Ambulance Service database, along with opioid replacement therapy (ORT) prescribing data. Statistical analysis was performed using R studio and Microsoft Excel. Results 557 people (78% [434/556] male, mean age ± standard deviation 38.4 ± 7.95) had an NFOD. Repeat NFODs were more likely in males compared to females ( p < .0065). Males were more likely to be administered naloxone (OR = 1.94, 95% CI = 1.10–3.40, p < .02). NFODs at home were more likely to be moderate to severe (categorized by Glasgow Comma Scale [ p < .02, OR = 4.95, 95% CI = 1.24–24.38]). Methadone (321/557, 57.63%), benzodiazepines (281/557, 50.45%) and heroin (244/557, 43.81%) were the commonest substances: prescribed methadone overdose was more likely than buprenorphine ( p < .00001). Opioids and benzodiazepines were often taken together (275/557, 49.40%), with almost all gabapentinoid NFODs also involving opioids (60/61, 98.40%). Conclusions Polysubstance use with opioids prescribed for ORT, such as methadone, is highly likely to be implicated in NFOD, with males being at the highest risk of severe and repeat NFOD. Future work should focus on strategies to further reduce NFODs.

Background Sublingual tablet buprenorphine (BUP-SL) and oral liquid methadone (MET) are the daily, standard-of-care (SOC) opioid agonist treatment medications for opioid use disorder (OUD). A sizable proportion of the OUD treatment population is not exposed to sufficient treatment to attain the desired clinical benefit. Two promising therapeutic technologies address this deficit: long-acting injectable buprenorphine and personalised psychosocial interventions (PSI). This study will determine (A) the effectiveness and cost-effectiveness — monthly injectable, extended-release (BUP-XR) in a head-to-head comparison with BUP-SL and MET, and (B) the effectiveness of BUP-XR with adjunctive PSI versus BUP-SL and MET with PSI. Safety, retention, craving, substance use, quality-adjusted life years, social functioning, and subjective recovery from OUD will be also evaluated. Methods This is a pragmatic, multi-centre, open-label, parallel-group, superiority RCT, with a qualitative (mixed-methods) evaluation. The study population is adults. The setting is five National Health Service community treatment centres in England and Scotland. At each centre, participants will be randomly allocated (1:1) to BUP-XR or SOC. At the London study co-ordinating centre, there will also be allocation of participants to BUP-XR with PSI or SOC with PSI. With 24 weeks of study treatment, the primary outcome is days of abstinence from non-medical opioids during study weeks 2–24 combined with up to 12 urine drug screen tests for opioids. For 90% power (alpha, 5%; 15% inflation for attrition), 304 participants are needed for the BUP-XR versus SOC comparison. With the same planning parameters, 300 participants are needed for the BUP-XR and PSI versus SOC and PSI comparison. Statistical and health economic analysis plans will be published before data-lock on the Open Science Framework. Findings will be reported in accordance with the Consolidated Standards of Reporting Trials and Consolidated Health Economic Evaluation Reporting Standards. Discussion This pragmatic randomised controlled trial is the first evaluation of injectable BUP-XR versus the SOC medications BUP-SL and MET, with personalised PSI. If there is evidence for the superiority of BUP-XR over SOC medication, study findings will have substantial implications for OUD clinical practice and treatment policy in the UK and elsewhere. Trial registration EU Clinical Trials register 2018-004460-63.

IntroductionOpioid use disorder (OUD) is a debilitating and persistent disorder. The standard-of-care treatment is daily maintenance dosing of sublingual buprenorphine (BUP-SL) or oral methadone (MET). Monthly, extended-release, subcutaneous injectable buprenorphine (BUP-XR) has been developed to enhance treatment effectiveness. This study aims to investigate the experiences of participants who have been offered BUP-XR (evaluation 1), health-related quality-of-life among participants who have opted to receive BUP-XR longer term (evaluation 2) and the experiences of participants allocated to receive BUP-XR or BUP-SL or MET with the offer of adjunctive personalised psychosocial intervention (evaluation 3).Methods and analysisThree qualitative–quantitative (mixed-methods) evaluations embedded in a five-centre, head-to-head, randomised controlled trial of BUP-XR versus BUP-SL and MET in the UK. Evaluation 1 is a four-centre interview anchored on an OUD-related topic guide and conducted after the 24-week trial endpoint. Evaluation 2 is a two-centre interview anchored on medications for opioid use disorder-specific quality-of-life topic guide conducted among participants after 12–24 months. Evaluation 3: single-centre interview after the 24-week trial endpoint. All evaluations include selected trial clinical measures, with evaluation 2 incorporating additional questionnaires. Target participant recruitment for evaluations 1 and 2 is 15 participants per centre (n=60 and n=30, respectively). Recruitment for evaluation 3 is 15 participants per treatment arm (n=30). Each evaluation will be underpinned by theory, drawing on constructs from the behavioural model for health service use or the health-related quality-of-life model. Qualitative data analysis will be by iterative categorisation.Ethics and disseminationStudy protocol, consent materials and questionnaires were approved by the London-Brighton and Sussex research ethics committee (reference: 19/LO/0483) and the Health Research Authority (IRAS project number 255522). Participants will be provided with information sheets and informed written consent will be obtained for each evaluation. Study findings will be disseminated through peer-reviewed scientific journals.Trial registration number2018-004460-63.

BACKGROUND: Sublingual buprenorphine (BUP-SL) and liquid methadone (MET) and are the standard-of-care (SOC), daily maintenance medications for the treatment of opioid use disorder (OUD). A sizable proportion of the OUD treatment population does not adhere to treatment and achieve desired clinical benefit. Two promising therapeutic technologies address this deficit: new medication formulations and psychosocial interventions (PSI). This study will determine: (A) the effectiveness and cost-effectiveness – monthly injectable, extended-release (BUP-XR) a novel formulation in a head-to-head comparison with BUP-SL or MET; and (B) the effectiveness of BUP-XR with PSI versus BUP-SL or MET with PSI. Safety, retention, craving, substance use, quality-adjusted life years, social functioning, and subjective recovery will be also evaluated. METHODS: This is a pragmatic, multi-centre, open-label, four-arm, parallel group, superiority RCT, with a qualitative (mixed-methods) evaluation. The study population is adults. The setting is five specialist National Health Service community treatment programmes in England and Scotland. In all sites, participants will be randomly allocated (1:1) to BUP-XR and BUP-SL or MET. At the London study co-ordinating centre, there will also be allocation of participants to BUP-XR with PSI and BUP-SL or MET with PSI. With 24 weeks of study treatment, the primary outcome is days of abstinence from all non-medical opioids during study weeks 2–24 combined with up to 12 urine drug screen tests for opioids. For 90% power (alpha, 5%; 15% inflation for attrition), 304 participants are needed for the BUP-XR and BUP-SL or MET comparison. Using the same planning parameters, 300 participants are needed for the comparison of BUP-XR and BUP-SL or MET with PSI. Statistical and health economic analysis plans will be published before data-lock on the Open Science Framework. Findings will be reported in accordance with the Consolidated Standards of Reporting Trials and Consolidated Health Economic Evaluation Reporting Standards. DISCUSSION: This pragmatic randomised controlled trial is the first evaluation of injectable BUP-XR versus the SOC medications BUP-SL or MET, and with an adjunctive personalised PSI. If there is evidence for the superiority of BUP-XR over SOC, this will have substantial implications for clinical practice and OUD treatment policy in the UK and elsewhere. TRIAL REGISTRATION: EU Clinical Trials register (number: 2018-004460-63).