Facilitating detoxification and dose reduction from methadone using baclofen

INTERVENTION: Intervention arm: after randomisation, which will take place using Sealed Envelope within OpenClinica, participants will be titrated up to a minimum of 10 mg baclofen TID, to be taken orally, up to a maximum of 20 mg TID over a period of 7‐12 days. Study medication will be taken in addition to the prescribed methadone dose, for up to 12 weeks, or less if abstinence is achieved earlier. During this time participants will complete weekly follow‐up questionnaires and attend in‐person visits every three weeks. At the end of the study, participants will be tapered off baclofen over a period of 7‐10 days, attend an exit visit and provide follow‐up data on methadone dose for up to 3 months following trial exit. Control arm: after randomisation, which will take place using Sealed Envelope within OpenClinica, participants will be titrated up to a minimum of three placebo tablets TID, to be taken orally, up to a maximum of si Xplacebo tablets TID over a period of 7‐12 days. Study medication will be taken in addition to the prescribed methadone dose, for up to 12 weeks, or less if abstinence is achieved earlier. During this time participants will complete weekly follow‐up questionnaires and attend in‐person visits every 3 weeks. At the end of the study, participants will be tapered off placebo over a period of 7‐10 days, attend an exit visit and provide follow‐up data on methadone dose for up to 3 months following trial exit. CONDITION: Opioid dependency ; Mental and Behavioural Disorders ; Mental and behavioural disorders due to use of opioids PRIMARY OUTCOME: Reduction in methadone dose with baclofen compared with placebo at 12 weeks, or time of abstinence if sooner. The difference in methadone dose will be measured by calculating the difference in methadone dose (in mg) at baseline compared with 12 weeks (or time of abstinence). SECONDARY OUTCOME: 1. Successful abstinence, defined as the first instance of a reduction in methadone dose to 0 mg for 3 or more days between initiation of study treatment and the end of the 12‐week maintenance period; 2. Time to successful abstinence measured between initiation of study treatment and the first instance of a reduction in methadone dose to 0 mg for 3 or more days up to the end of the 12‐week maintenance period; 3. Days of abstinence from methadone between initiation of study treatment and the end of the 12‐week maintenance phase or until time of successful abstinence if earlier, measured using the total number of days 0 mg methadone taken as reported by patients using electronic data capture (ePRO).; 4. Number of methadone dose changes from initiation of study treatment up to end of the 12‐week maintenance period or until time of successful abstinence if earlier, as measured by (i) patient report and (ii) prescribing service.; 5. Methadone dose regardless of any period of abstinence, measured using prescribed methadone dose at Week 12, extracted from clinical records; 6. Maximum baclofen/placebo dose administered during the 12‐week maintenance phase or from the start of the maintenance phase to the time of successful abstinence if earlier, as measured by (i) patient report and (ii) prescribing service.; 7. Proportion of time over the 12‐week maintenance phase or from the start of the maintenance phase till the time of successful abstinence if earlier at (a) minimum target dose of baclofen/placebo (10 mg tds) and (b) maximum target dose (20 mg tds) as measured by (i) patient report and (ii) prescribing service.; 8. Patient rating of psychological health, physical health and overall quality of life in last 7 days at 12 weeks or time of successful abstinence if earlier, measured using the Treatment Outcomes Profile (TOP); 9. Patient rating of craving, measured using 0 to 100 visual analogues scales (VAS‐Need and VAS‐Want) for heroin and cocaine in the last 7 days at 12 weeks or time of successful abstinence if earlier; 10. Patient rating of anxiety, withdrawal, sleep disturbance, and restless legs symptoms in the last 7 days, measured using 0 to 10 Likert scales at 12 weeks or time of successful abstinence if earlier; 11. Patient rating of drug effect ‘liking’ and ‘want more’ over last 7 days, measured using a 0 to 10 Likert scale at 12 weeks or time of successful abstinence if earlier; 12. Total number of days using heroin during the 12‐week maintenance phase or from the start of the maintenance phase till the time of successful abstinence if earlier, measured using the Treatment Outcomes Profile (TOP); 13. Total number of days using other substances (e.g. alcohol, nicotine, cocaine, etc) during the 12‐week maintenance phase or from the start of the maintenance phase till the time of successful abstinence if earlier, measured using the Treatment Outcomes Profile (TOP); 14. Total number of days abstinent from all illicit substances during the 12‐week maintenance phase or from the start of the maintenance phase till the time of successful abstinence if earlier, measured using the Treatment Outcomes Profile (TOP); 15. Total number of days abstinent from all substance use during the 12‐week maintenance phase or from the start of the maintenance phase till the time of successful abstinence if earlier, measured using the Treatment Outcomes Profile (TOP); 16. The number of days using heroin in the last 28 days at 12 weeks or time of successful abstinence if earlier, measured using the Treatment Outcomes Profile (TOP); 17. The number of days using other substances (e.g. alcohol, cocaine, smoking cigarettes/e‐cigarettes, etc) in the last 28 days at 12 weeks or time of successful abstinence if earlier, measured using the Treatment Outcomes Profile (TOP); 18. Score for Opioid Use Disorder (OUD) severity (PRO‐S; baseline) and improvement (PRO‐I) measured at 12 weeks or time of successful abstinence if earlier; 19. Score for Clinical Opiate Withdrawal Scale (COWS) at 12 weeks or time of successful abstinence if earlier; 20. Number of baclofen/placebo dose changes during the 12‐week maintenance phase or from the start of the maintenance phase to the time of successful abstinence if earlier, as measured by (i) patient report and (ii) prescribing service INCLUSION CRITERIA: 1. Classified or determined by their addiction service as ready for dose reduction or detox 2. >18 years old 3. Current or previous DSM‐5 moderate to severe opioid use disorder or ICD10/11 opioid dependence 4. Currently treated with methadone substitution therapy 5. The client wishes to undergo methadone detoxification and/or dose reduction