Professor John Strang National Addiction Centre, London, UK

1. The importance of treatment for heroin addiction: reducing drug problems, HIV and AIDS, and crime Professor John Strang National Addiction Centre, London, UK

6. Prison and health opportunities • Lifetime and recent prevalence (1% vs 50%) • Hepatitis B vaccination – universal • Immediate death risk post-release (x8 vs x80)

7. Dependence • Overdose • HIV/AIDS etc • Crime (separate lecture)

8. Reasons for interest • Individual health – treatment of addiction; Rx of related conditions • Public health – stop HIV/HCV/HBV risk behaviours (especially injecting) • Public security – break drug-crime link

9. Major international advances • Maintenance substitution treatments (different drugs in different countries) • Active recruitment, including from police, the Courts and prisons • Harm reduction - public health and public safety (needles and syringes; overdose management, etc)

10. Therapeutic objectives • No/Reduced heroin use • No/Reduced injecting • Improved physical health • Improved psychosocial well-being • No/Reduced criminal behaviour

11. Areas we should address today • Different stages of involvement in drug misuse • Maintenance treatments for heroin addiction – different drugs • Impact on HIV/AIDS and other viral infections • Strategies for improving effectiveness of treatment – medicine, programme • ((Good treatment = effective crime reduction))

12. (1) Different stages of involvement in drug misuse

13. NON USERS GENERAL POPULATION FIRST USERS

14. NON USERS GENERAL POPULATION FIRST USERS DEPENDENT USERS

15. NON USERS VARIOUS HARMS FIRST USERS DEPENDENT USERS

16. NON USERS FIRST USERS Various routes to Recovery, including half-way posts DEPENDENT USERS VARIOUS HARMS

17. NON USERS FIRST USERS RELAPSE Various routes to Recovery, including half-way posts DEPENDENT USERS VARIOUS HARMS

18. The target patient • Opiate dependent • Wishing to quit heroin • Thereby wishing to quit injecting

20. Methadone heals, but methadone also kills. The challenge is to achieve the former without incurring the latter.

21. Beyond ‘Treatment works’ …

22. (2) Maintenance treatments for heroin addiction – different drugs

23. (a) Methadone maintenance • Major treatment for heroin dependence: highly effective • 40 years of experience • Oral, long half-life (daily), cross-tolerant: • “blocks” euphoric effects of heroin • prevents withdrawal symptoms • Reduces illicit heroin use more than no treatment (USA, Australia), drug-free treatment (Sweden), placebo (Hong Kong, USA) and detoxification (Thailand, USA) in RCTs • Better retention than placebo, drug-free treatment, detoxification and wait-list controls (Mattick, 2002)

24. Gunne & Gronbladh (1981) RCT:Methadone versus no methadone • 34 subjects using heroin by injection • 17 experimental (methadone) • 17 controls (no methadone) • Controls not allowed to enter MMT for 2 years • Followed up at 2 years and again at 4 years

25. Gunne & Gronbladh (1981): Baseline

26. Gunne & Gronbladh (1981): 2 years

27. Gunne & Gronbladh (1981): 2 years

28. Gunne & Gronbladh (1981): 4 years

29. Gunne & Gronbladh (1981): 4 years

30. Gunne & Gronbladh (1981): 4 years

31. (b) Buprenorphine maintenance • Agonist with very high affinity for opiate receptor (heroin cannot compete at opioid receptor) • Similar treatment benefit as methadone, but not quite as good (MMT: 63%, Bup:53%; Mattick, 2002) • No significant difference between methadone and buprenorphine in reducing heroin use, cocaine use, benzodiazepine use or crime (Mattick, 2002) • Probably less overdose risk (not yet firmly demonstrated how much better)

32. 20 15 # Remaining in treatment 10 5 0 0 50 100 150 200 250 300 350 Treatment duration (days) 1 year retention during buprenorphinemaintenance (16 mg qd) Control (6 day taper) buprenorphine maintained 75% retained at 1 year; no deaths 75% of urine drug screens negative Kakko et al. (2003)

33. (c) Levo-alpha-acetylmethadol (LAAM) • Full opiate agonist with longer duration of action than methadone (48 or 72 hours or longer), 3x week dosing • 10 cases of life threatening cardiac arrhythmias: withdrawn (Europe) and not be used as first line therapy (US) • Need to clarify risks of LAAM treatment, particularly cardiac arrhythmia from QT prolongation

34. Retention in treatment: methadone, buprenorphine, LAAM maintenance

35. (d) Prolonged-release oral morphine • Oral, long duration of action (24 hours) • comparable retention and illicit drug use to methadone treatment and significantly lower depression, anxiety and physical complaints (Eder, 2005) • An open label 3-week study of 110 opioid dependent subjects showed high retention, reduced somatic complaints and reduced cravings for heroin and cocaine (Kraigher, 2005) • MMT patients transferring to SROM (n=18) showed similar outcomes for drug use and health as methadone, improved social functioning, and less side-effects (Mitchell, 2004) • Further large scale investigations now starting

36. Naltrexone – the classic antagonist • Opioid antagonist – oral, 24-hour, remarkably effective • However - only rarely prescribed by doctors • Widespread disappointment of poor uptake by patients • Also - separately used (unlicensed) in opiate detox • Also - long-acting depot form recently developed (2006) • Separate alcohol interest in relapse-preventing benefit (perhaps ?? anti-craving effect for alcohol??)

37. Retention in treatment: methadone, buprenorphine, LAAM maintenance

38. Retention in treatment methadone, buprenorphine & LAAM vs. naltrexone

39. (3) Impact on HIV/AIDS and other viral infections

40. The benefit of retaining patients in treatment - HIV infection rates in and out of methadone maintenance treatment(Metzger et al. 1993) Out of tx % In tx %

41. The benefit of retaining patients in treatment - HIV infection rates in and out of methadone maintenance treatment(Metzger et al. 1993) Out of tx % In tx %

42. The benefit of retaining patients in treatment - HIV infection rates in and out of methadone maintenance treatment(Metzger et al. 1993) Out of tx % In tx %

43. (4) Strategies for improving effectiveness of treatment – medicine, programme

44. How Can We Optimise Methadone Maintenance Treatment? • Retention in treatment is an important indicator of long term outcome • Higher doses of methadone are more effective in keeping patients in treatment, decreasing illicit drug use and reducing crime • Ancilliary support and additional necessary work • Look to achieve good compliance

45. Levels of Treatment in Methadone Maintenance Programs Random Assignment 6 Months Level 1Level 2Level 3 (n=29) (n=34) (n=36) Methadone: > 65mg >65mg >65mg Counseling: Regular Regular Other Services Employment Family Therapy Psychiatric Care Treatment Research Institute Mc Lellan et al

46. Levels of care Study Target behaviours at 6 months

47. Thank you