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Overdose deaths from street heroin and prescribed methadone: analysis and prevention options Professor John Strang National Addiction Centre, London, UK Issues to be covered today Topic 1: Analysis of the overdose death problem Topic 2: How could we respond more effectively? Issues to be covered today Topic 1: Analysis of the overdose death problem Why the special attention to the opiates? Methadone as well as heroin (in the UK) Injecting heroin, in particular Special time of risk – at start and after the end of treatment Special time of risk – on release from prison Topic 2: How could we respond more effectively? Methadone – dose Methadone – supervision Take-Home Emergency Naloxone Issues to be covered today Topic 1: Analysis of the overdose death problem Why the special attention to the opiates? Methadone as well as heroin (in the UK) Injecting heroin, in particular Special time of risk – at start and after the end of treatment Special time of risk – on release from prison Topic 2: How could we respond more effectively? Methadone – dose Methadone – supervision Take-Home Emergency Naloxone Drug-related deaths in England and Wales 1997 – 2002 (ONS) Drug Prevalence in general population (use in last year, age 16-59) No. of deaths in the last 5 years Cannabis 10.8% 78 Cocaine 2.4% 508 Amphetamine 1.5% 436 Ecstasy 2% 200 Opiates (inc Heroin, morphine & methadone) 0.2% 6,194 Drug-related deaths in England and Wales 1997 – 2002 (ONS) Drug Prevalence in general population (use in last year, age 16-59) No. of deaths in the last 5 years Cannabis 10.8% 78 Cocaine 2.4% 508 Amphetamine 1.5% 436 Ecstasy 2% 200 Opiates (inc Heroin, morphine & methadone) 0.2% 6,194 Issues to be covered today Topic 1: Analysis of the overdose death problem Why the special attention to the opiates? Methadone as well as heroin (in the UK) Injecting heroin, in particular Special time of risk – at start and after the end of treatment Special time of risk – on release from prison Topic 2: How could we respond more effectively? Methadone – dose Methadone – supervision Take-Home Emergency Naloxone Total number of drug-related deaths in England with associated substances: 19932001 (ONS). 1993 1997 2000 2001 (% change) Total annual -England 821 1237 1561 1524 (-2%) Heroin and Morphine 187 445 926 889 (-4%) Methadone 232 421 238 207 (-13%) Cocaine 12 39 80 96 (+20%) MDMA/Ecstasy 8 12 36 55 (+53%) “Methadone heals, but methadone also kills. The challenge is to achieve the former without incurring the latter”. 1600 1400 1200 1000 800 600 400 200 0 19 90 19 91 19 92 19 93 19 94 19 95 19 96 19 97 19 98 19 99 20 00 20 01 20 02 prescriptions per annum (x 1000) NHS methadone prescriptions per annum (England 1990-2002) 35 30 25 20 15 10 5 2004 2003 2002 2001 2000 1999 1998 1997 1996 1995 1994 0 1993 Directly age-standardised mortality rate per million Trends in O/D deaths – heroin and methadone (Hickman et al, IJE, 2006) METHADONE Male METHADONE Female HEROIN/MORPHINE Male HEROIN/MORPHINE Female 35 30 25 20 15 10 5 2004 2003 2002 2001 2000 1999 1998 1997 1996 1995 1994 0 1993 Directly age-standardised mortality rate per million Trends in O/D deaths – heroin and methadone (Hickman et al, IJE, 2007) METHADONE Male METHADONE Female HEROIN/MORPHINE Male HEROIN/MORPHINE Female Issues to be covered today Topic 1: Analysis of the overdose death problem Why the special attention to the opiates? Methadone as well as heroin (in the UK) Injecting heroin, in particular Special time of risk – at start and after the end of treatment Special time of risk – on release from prison Topic 2: How could we respond more effectively? Methadone – dose Methadone – supervision Take-Home Emergency Naloxone London PAI Study #1: 438 Early Heroin Users [48% in first 3 years; 45% SDS6] Overdose history among 98 (22%) Of 309 ever-injectors, 96 (31%) had overdosed Of 125 never-injectors, 2 (2%) had overdosed (c2=44.2, p<0.001 [data missing on 4]) (Gossop, Griffiths, Powis, Williamson and Strang, BMJ, 1996) HOW COMMON (among injectors)? London PAI Study #2: 312 injectors Personal overdose? - 117 (38%) Witnessed overdose? - 157 (50%) Witnessed fatal O/D? - 46 (15%) (Strang, Griffiths, Powis, Fountain, Williamson and Gossop, Drug and Alcohol Review, 1999) Aus (Adelaide) PAI Study #2: 218 heroin users (i.e. injectors) Personal overdose? - 48% Witnessed overdose? - 70% (Witnessed fatal O/D? - n/a) (McGregor, Darke, Ali and Christie, Addiction, 1998) Issues to be covered today Topic 1: Analysis of the overdose death problem Why the special attention to the opiates? Methadone as well as heroin (in the UK) Injecting heroin, in particular Special time of risk – at start and after the end of treatment Special time of risk – on release from prison Topic 2: How could we respond more effectively? Methadone – dose Methadone – supervision Take-Home Emergency Naloxone When in particular? During methadone early treatment Post-detox/rehab Risk of death during and after treatment BMJ 2010;341:c5475 Issues to be covered today Topic 1: Analysis of the overdose death problem Why the special attention to the opiates? Methadone as well as heroin (in the UK) Injecting heroin, in particular Special time of risk – at start and after the end of treatment Special time of risk – on release from prison Topic 2: How could we respond more effectively? Methadone – dose Methadone – supervision Take-Home Emergency Naloxone When in particular? Post-detox/rehab During methadone early treatment Prison release Post-release ‘carnage’ Seaman Brettle Gore, BMJ, 1998 Bird & Hutchinson, Addiction, 2002 Farrell & Marsden, Addiction, 2008 Prevalence of drug dependence Drug dependence prior to prison Substance Misuse in Prisoners 2002 Singleton N, Farrell M, Meltzer H ONS. Excess mortality ratio Excess mortality ratio for different time periods post-release by cause of death (Singleton, Farrell, Marsden et al 2003) 45 40 35 30 25 20 15 10 5 0 U Drug-related deaths o1 t p 3 6 2 1 2 5 o2 o4 o8 t t t o o o t t t p p p p up up 1u 2u 4u 8u 3 6 1 2 Time since release (w eeks) Not drug-related 2 5 >= l a t To Issues to be covered today Topic 1: Analysis of the overdose death problem Why the special attention to the opiates? Methadone as well as heroin (in the UK) Injecting heroin, in particular Special time of risk – at start and after the end of treatment Special time of risk – on release from prison Topic 2: How could we respond more effectively? Methadone – dose Methadone – supervision Take-Home Emergency Naloxone Issues to be covered today Topic 1: Analysis of the overdose death problem Why the special attention to the opiates? Methadone as well as heroin (in the UK) Injecting heroin, in particular Special time of risk – at start and after the end of treatment Special time of risk – on release from prison Topic 2: How could we respond more effectively? Methadone – dose Methadone – supervision Take-Home Emergency Naloxone 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] Issues to be covered today Topic 1: Analysis of the overdose death problem Why the special attention to the opiates? Methadone as well as heroin (in the UK) Injecting heroin, in particular Special time of risk – at start and after the end of treatment Special time of risk – on release from prison Topic 2: How could we respond more effectively? Methadone – dose Methadone – supervision Take-Home Emergency Naloxone What is the OD4 Index? OD4 = ODDDD (Overdose Deaths per Daily Dispensed Dose) Thus essentially a measure of safety of a medication, as applied Issues to be covered today Topic 1: Analysis of the overdose death problem Why the special attention to the opiates? Methadone as well as heroin (in the UK) Injecting heroin, in particular Special time of risk – at start and after the end of treatment Special time of risk – on release from prison Topic 2: How could we respond more effectively? Methadone – dose Methadone – supervision Take-Home Emergency Naloxone Pre-filled syringe 1 mg per ml, 2 ml syringe available from: Antigen, Aurum, Mayne £6.30 First investigated: 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. Structure – 4 areas Training elements (a) how to recognise overdose (b) how to manage situation – general (c) how to give naloxone Person unconscious, and cannot be woken – UNROUSABLE CYANOSIS – BLUE lips or tongue Not breathing at all or breathing slowly – deep snoring. Pin point pupils 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 How to inject Naloxone – intramuscular (into muscle) Remove syringe from box and packet Attach needle to syringe Inject into the outer thigh, upper arm or outer part of buttock Hold needle 90 degree above skin Insert needle into muscle (needs pressure) Slowly and Steadily push plunger all the way down Put syringe back in box. Don’t cover needle Changes in knowledge after training ***All significant at p<0.001 10 9 Before training 8 After training 7 6 5 4 3 2 1 0 risks (7) signs (8) Clinicians actions (11) risks (7) signs (8) Clients actions (11) 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. Does the naloxone ever get used? Initial experience …… Berlin/Jersey – about 10% used within a year New Mexico, USA – 2/100 within few months Chicago, USA – 52/550 Dettmer, Saunders and Strang, BMJ, 2001 Baca et al, BMJ, 2001 Bigg, BMJ, 2002 N-ALIVE trial – pilot & main phase N-ALIVE research trial proposal to test/prove reduced deaths post-release Pilot – n=5600 Main study – n=56000 (28k + 28k) Conclusiona Topic 1: Analysis of the overdose death problem Why the special attention to the opiates? Methadone as well as heroin (in the UK) Injecting heroin, in particular Special time of risk – at start and after the end of treatment Special time of risk – on release from prison Topic 2: How could we respond more effectively? Methadone – dose Methadone – supervision Take-Home Emergency Naloxone Thank you