1. Overdose deaths from street heroin and prescribed methadone: analysis and prevention options Professor John Strang National Addiction Centre, London, UK

2. Issues to be covered today F Topic 1: Analysis of the overdose death problem F Topic 2: How could we respond more effectively?

3. Issues to be covered today F Topic 1: Analysis of the overdose death problem 3Why the special attention to the opiates? 3Methadone as well as heroin (in the UK) 3Injecting heroin, in particular 3Special time of risk – at start and after the end of treatment 3Special time of risk – on release from prison F Topic 2: How could we respond more effectively? 3Methadone – dose 3Methadone – supervision 3Take-Home Emergency Naloxone

4. Issues to be covered today F Topic 1: Analysis of the overdose death problem 3Why the special attention to the opiates? 3Methadone as well as heroin (in the UK) 3Injecting heroin, in particular 3Special time of risk – at start and after the end of treatment 3Special time of risk – on release from prison F Topic 2: How could we respond more effectively? 3Methadone – dose 3Methadone – supervision 3Take-Home Emergency Naloxone

5. Drug-related deaths in England and Wales 1997 – 2002 (ONS) DrugPrevalence in general population (use in last year, age 16-59) No. of deaths in the last 5 years Cannabis10.8%78 Cocaine2.4%508 Amphetamine1.5%436 Ecstasy2%200 Opiates (inc Heroin, morphine & methadone) 0.2%6,194

6. Drug-related deaths in England and Wales 1997 – 2002 (ONS) DrugPrevalence in general population (use in last year, age 16-59) No. of deaths in the last 5 years Cannabis10.8%78 Cocaine2.4%508 Amphetamine1.5%436 Ecstasy2%200 Opiates (inc Heroin, morphine & methadone) 0.2%6,194

7. Issues to be covered today F Topic 1: Analysis of the overdose death problem 3Why the special attention to the opiates? 3Methadone as well as heroin (in the UK) 3Injecting heroin, in particular 3Special time of risk – at start and after the end of treatment 3Special time of risk – on release from prison F Topic 2: How could we respond more effectively? 3Methadone – dose 3Methadone – supervision 3Take-Home Emergency Naloxone

8. Total number of drug-related deaths in England with associated substances: 1993- 2001 (ONS). 1993199720002001 (% change) Total annual -England 821123715611524(-2%) Heroin and Morphine 187445926889(-4%) Methadone 232421238207(-13%) Cocaine 12398096 (+20%) MDMA/Ecstasy 8123655(+53%)

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

12. Trends in O/D deaths – heroin and methadone (Hickman et al, IJE, 2006)

13. Trends in O/D deaths – heroin and methadone (Hickman et al, IJE, 2007)

14. Issues to be covered today F Topic 1: Analysis of the overdose death problem 3Why the special attention to the opiates? 3Methadone as well as heroin (in the UK) 3Injecting heroin, in particular 3Special time of risk – at start and after the end of treatment 3Special time of risk – on release from prison F Topic 2: How could we respond more effectively? 3Methadone – dose 3Methadone – supervision 3Take-Home Emergency Naloxone

15. London PAI Study #1: 438 Early Heroin Users [48% in first 3 years; 45% SDS  6] F Overdose history among 98 (22%) 3Of 309 ever-injectors, 96 (31%) had overdosed 3Of 125 never-injectors, 2 (2%) had overdosed (  2 =44.2, p<0.001 [data missing on 4]) (Gossop, Griffiths, Powis, Williamson and Strang, BMJ, 1996)

16. F HOW COMMON (among injectors) ?

17. London PAI Study #2: 312 injectors F Personal overdose? - 117 (38%) F Witnessed overdose? - 157 (50%) F Witnessed fatal O/D? - 46 (15%) (Strang, Griffiths, Powis, Fountain, Williamson and Gossop, Drug and Alcohol Review, 1999)

18. Aus (Adelaide) PAI Study #2: 218 heroin users (i.e. injectors) F Personal overdose? - 48% F Witnessed overdose? - 70% F (Witnessed fatal O/D? - n/a) (McGregor, Darke, Ali and Christie, Addiction, 1998)

19. Issues to be covered today F Topic 1: Analysis of the overdose death problem 3Why the special attention to the opiates? 3Methadone as well as heroin (in the UK) 3Injecting heroin, in particular 3Special time of risk – at start and after the end of treatment 3Special time of risk – on release from prison F Topic 2: How could we respond more effectively? 3Methadone – dose 3Methadone – supervision 3Take-Home Emergency Naloxone

20. When in particular? F During methadone early treatment F Post-detox/rehab

22. Risk of death during and after treatment BMJ 2010;341:c5475

23. Issues to be covered today F Topic 1: Analysis of the overdose death problem 3Why the special attention to the opiates? 3Methadone as well as heroin (in the UK) 3Injecting heroin, in particular 3Special time of risk – at start and after the end of treatment 3Special time of risk – on release from prison F Topic 2: How could we respond more effectively? 3Methadone – dose 3Methadone – supervision 3Take-Home Emergency Naloxone

24. When in particular? F Post-detox/rehab F During methadone early treatment F Prison release

26. Post-release ‘carnage’ F Seaman Brettle Gore, BMJ, 1998 F Bird & Hutchinson, Addiction, 2002 F Farrell & Marsden, Addiction, 2008

27. Prevalence of drug dependence Drug dependence prior to prison Substance Misuse in Prisoners 2002 Singleton N, Farrell M, Meltzer H ONS.

30. Issues to be covered today F Topic 1: Analysis of the overdose death problem 3Why the special attention to the opiates? 3Methadone as well as heroin (in the UK) 3Injecting heroin, in particular 3Special time of risk – at start and after the end of treatment 3Special time of risk – on release from prison F Topic 2: How could we respond more effectively? 3Methadone – dose 3Methadone – supervision 3Take-Home Emergency Naloxone

31. Issues to be covered today F Topic 1: Analysis of the overdose death problem 3Why the special attention to the opiates? 3Methadone as well as heroin (in the UK) 3Injecting heroin, in particular 3Special time of risk – at start and after the end of treatment 3Special time of risk – on release from prison F Topic 2: How could we respond more effectively? 3Methadone – dose 3Methadone – supervision 3Take-Home Emergency Naloxone

32. Cochrane review of dose and methadone Faggiano et al (2007) Cochrane review of significance of dose in methadone OST Retention rate - RCTs: High versus low doses at shorter follow-ups: RR=1.36 [1.13,1.63], and at longer ones: RR=1.62 [0.95,2.77]. Opioid use (self reported), times/w - RCTs: high versus low doses WMD= -2.00 [-4.77,0.77] high vs middle doses WMD= -1.89[-3.43, -0.35] Opioid abstinence, (urine based) at >3-4w -RCTs: high versus low doses: RR=1.59 [1.16,2.18] high vs middle doses RR=1.51[0.63,3.61] Cocaine abstinence (urine based) at >3-4 w - RCTs: high versus low doses RR=1.81 [1.15,2.85] Overdose mortality : high dose versus low dose at 6 years follow up: RR=0.29 [0.02-5.34] high dose vs middle dose at 6 years follow-up: 0.38 [0.02-9.34] middle dose vs low dose at 6 years follow-up: RR=0.57 [0.06-5.06]

33. Issues to be covered today F Topic 1: Analysis of the overdose death problem 3Why the special attention to the opiates? 3Methadone as well as heroin (in the UK) 3Injecting heroin, in particular 3Special time of risk – at start and after the end of treatment 3Special time of risk – on release from prison F Topic 2: How could we respond more effectively? 3Methadone – dose 3Methadone – supervision 3Take-Home Emergency Naloxone

35. F What is the OD4 Index? F OD4 = ODDDD (Overdose Deaths per Daily Dispensed Dose) F Thus essentially a measure of safety of a medication, as applied

39. Issues to be covered today F Topic 1: Analysis of the overdose death problem 3Why the special attention to the opiates? 3Methadone as well as heroin (in the UK) 3Injecting heroin, in particular 3Special time of risk – at start and after the end of treatment 3Special time of risk – on release from prison F Topic 2: How could we respond more effectively? 3Methadone – dose 3Methadone – supervision 3Take-Home Emergency Naloxone

42. Pre-filled syringe 1 mg per ml, 2 ml syringe available from: Antigen, Aurum, Mayne £6.30

43. F First investigated: F Strang J, Powis B, Best D et al (1999) Preventing opiate overdose fatalities with take-home naloxone: pre-launch study of possible impact and acceptability. Addiction, 94 (2): 199-204.

45. Structure – 4 areas F Training elements 3(a) how to recognise overdose 3(b) how to manage situation – general 3(c) how to give naloxone

46. Person unconscious, and cannot be woken – UNROUSABLE CYANOSIS – BLUE lips or tongue Not breathing at all or breathing slowly – deep snoring. Pin point pupils

47. A – Ambulance - CALL AMBULANCE B- Breathing - Check Airway – clear if blocked, Check breathing. C – reCovery - If breathing, place in recovery position – if not breathing, begin basic life support Administer naloxone

48. How to inject Naloxone – intramuscular (into muscle) F Remove syringe from box and packet F Attach needle to syringe F Inject into the outer thigh, upper arm or outer part of buttock F Hold needle 90 degree above skin F Insert needle into muscle (needs pressure) F Slowly and Steadily push plunger all the way down F Put syringe back in box. Don’t cover needle

51. Changes in knowledge after training ***All significant at p<0.001

53. Carers – the overlooked intervention workforce 102 carers attending 4 organisations 80% parents, 20% other relative/partner 96% of opiate users, 87% IDU, 57% in Tx, 1/3 used in presence of carer, 47% had past OD 20% of carers had witnessed an OD 5 had lost user to fatal OD (3 children 2 partners) 16% would ‘panic’ or ‘not know what to do’ 83% expressed an interest OD management & N training Evidence of potential to extend naloxone… Strang, Manning, Mayet et al, (2008) Family carers and prevention of heroin overdose deaths: …… Drugs: Education, Prevention & Policy, 15: 211-218.

54. Does the naloxone ever get used? F Initial experience …… F Berlin/Jersey – about 10% used within a year F New Mexico, USA – 2/100 within few months F Chicago, USA – 52/550 3Dettmer, Saunders and Strang, BMJ, 2001 3Baca et al, BMJ, 2001 3Bigg, BMJ, 2002

55. N-ALIVE trial – pilot & main phase F N-ALIVE research trial proposal to test/prove reduced deaths post-release F Pilot – n=5600 F Main study – n=56000 (28k + 28k)

57. ConclusionaConclusiona F Topic 1: Analysis of the overdose death problem 3Why the special attention to the opiates? 3Methadone as well as heroin (in the UK) 3Injecting heroin, in particular 3Special time of risk – at start and after the end of treatment 3Special time of risk – on release from prison F Topic 2: How could we respond more effectively? 3Methadone – dose 3Methadone – supervision 3Take-Home Emergency Naloxone

58. Thank you