Overdose deaths from sOverdose deaths from street treet heroin and prescribed heroin and prescribed

methadone:methadone:analysis and prevention analysis and prevention

optionsoptions

Professor John StrangProfessor John Strang

National Addiction Centre, London, UKNational Addiction Centre, London, UK

Issues to be covered todayIssues to be covered todayIssues to be covered todayIssues to be covered today

Topic 1: Analysis of the overdose death problem

Topic 2: How could we respond more effectively?

Issues to be covered todayIssues to be covered todayIssues to be covered todayIssues to be covered today

Topic 1: Analysis of the overdose death problemWhy the special attention to the opiates?Methadone as well as heroin (in the UK) Injecting heroin, in particularSpecial time of risk – at start and after the end of treatmentSpecial time of risk – on release from prison

Topic 2: How could we respond more effectively?Methadone – doseMethadone – supervisionTake-Home Emergency Naloxone

Issues to be covered todayIssues to be covered todayIssues to be covered todayIssues to be covered today

Topic 1: Analysis of the overdose death problemWhy the special attention to the opiates?Methadone as well as heroin (in the UK) Injecting heroin, in particularSpecial time of risk – at start and after the end of treatmentSpecial time of risk – on release from prison

Topic 2: How could we respond more effectively?Methadone – doseMethadone – supervisionTake-Home Emergency Naloxone

Drug-related deaths in England and Drug-related deaths in England and Wales 1997 – 2002 (ONS)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 Drug-related deaths in England and Wales 1997 – 2002 (ONS)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 todayIssues to be covered todayIssues to be covered todayIssues to be covered today

Topic 1: Analysis of the overdose death problemWhy the special attention to the opiates?

Methadone as well as heroin (in the UK) Injecting heroin, in particularSpecial time of risk – at start and after the end of treatmentSpecial time of risk – on release from prison

Topic 2: How could we respond more effectively?Methadone – doseMethadone – supervisionTake-Home Emergency Naloxone

Total number of drug-related deaths in Total number of drug-related deaths in England with associated substances: 1993-England with associated substances: 1993-

2001 (ONS).2001 (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”.

NHS methadone prescriptions per annum(England 1990-2002)

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

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

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Issues to be covered todayIssues to be covered todayIssues to be covered todayIssues to be covered today

Topic 1: Analysis of the overdose death problemWhy the special attention to the opiates?Methadone as well as heroin (in the UK)

Injecting heroin, in particularSpecial time of risk – at start and after the end of treatmentSpecial time of risk – on release from prison

Topic 2: How could we respond more effectively?Methadone – doseMethadone – supervisionTake-Home Emergency Naloxone

London PAI Study #1:London PAI Study #1:438 Early Heroin Users438 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

(2=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:London PAI Study #2:312 injectors312 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:Aus (Adelaide) PAI Study #2:218 heroin users (i.e. injectors)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 todayIssues to be covered todayIssues to be covered todayIssues to be covered today

Topic 1: Analysis of the overdose death problemWhy 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 – doseMethadone – supervisionTake-Home Emergency Naloxone

When in particular?When in particular?

During methadone early treatment

Post-detox/rehab

Risk of death during and after Risk of death during and after treatmenttreatment

BMJ 2010;341:c5475

Issues to be covered todayIssues to be covered todayIssues to be covered todayIssues to be covered today

Topic 1: Analysis of the overdose death problemWhy the special attention to the opiates?Methadone as well as heroin (in the UK) Injecting heroin, in particularSpecial 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 – doseMethadone – supervisionTake-Home Emergency Naloxone

When in particular?When in particular?

Post-detox/rehab

During methadone early treatment

Prison release

Post-release ‘carnage’Post-release ‘carnage’

Seaman Brettle Gore, BMJ, 1998

Bird & Hutchinson, Addiction, 2002

Farrell & Marsden, Addiction, 2008

Prevalence of drug dependencePrevalence of drug dependence

Drug dependence prior to prison

Substance Misuse in Prisoners 2002 Singleton N, Farrell M, Meltzer H ONS.Substance Misuse in Prisoners 2002 Singleton N, Farrell M, Meltzer H ONS.

Excess mortality ratio for different time periods post-release by cause of death (Singleton, Farrell, Marsden et al 2003)

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Issues to be covered todayIssues to be covered todayIssues to be covered todayIssues to be covered today

Topic 1: Analysis of the overdose death problemWhy the special attention to the opiates?Methadone as well as heroin (in the UK) Injecting heroin, in particularSpecial time of risk – at start and after the end of treatmentSpecial time of risk – on release from prison

Topic 2: How could we respond more effectively?Methadone – doseMethadone – supervisionTake-Home Emergency Naloxone

Issues to be covered todayIssues to be covered todayIssues to be covered todayIssues to be covered today

Topic 1: Analysis of the overdose death problemWhy the special attention to the opiates?Methadone as well as heroin (in the UK) Injecting heroin, in particularSpecial time of risk – at start and after the end of treatmentSpecial time of risk – on release from prison

Topic 2: How could we respond more effectively?Methadone – doseMethadone – supervisionTake-Home Emergency Naloxone

Cochrane review of dose and Cochrane review of dose and methadone methadone

Faggiano et al (2007) Cochrane review of significance of dose in methadone OSTRetention 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 todayIssues to be covered todayIssues to be covered todayIssues to be covered today

Topic 1: Analysis of the overdose death problemWhy the special attention to the opiates?Methadone as well as heroin (in the UK) Injecting heroin, in particularSpecial time of risk – at start and after the end of treatmentSpecial time of risk – on release from prison

Topic 2: How could we respond more effectively?Methadone – dose

Methadone – supervisionTake-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 todayIssues to be covered todayIssues to be covered todayIssues to be covered today

Topic 1: Analysis of the overdose death problemWhy the special attention to the opiates?Methadone as well as heroin (in the UK) Injecting heroin, in particularSpecial time of risk – at start and after the end of treatmentSpecial time of risk – on release from prison

Topic 2: How could we respond more effectively?Methadone – doseMethadone – supervision

Take-Home Emergency Naloxone

Pre-filled syringePre-filled syringe1 mg per ml, 2 ml syringe 1 mg per ml, 2 ml syringe

available from: Antigen, Aurum, Mayne £6.30available 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 areasStructure – 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 How to inject Naloxone – intramuscular (into muscle)(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 trainingChanges in knowledge after training

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***All significant at p<0.001

Carers – the overlooked intervention Carers – the overlooked intervention workforceworkforce

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?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, 2001Baca et al, BMJ, 2001Bigg, BMJ, 2002

N-ALIVE trial – pilot & main phaseN-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)

ConclusionaConclusionaConclusionaConclusiona

Topic 1: Analysis of the overdose death problemWhy the special attention to the opiates?Methadone as well as heroin (in the UK) Injecting heroin, in particularSpecial time of risk – at start and after the end of treatmentSpecial time of risk – on release from prison

Topic 2: How could we respond more effectively?Methadone – doseMethadone – supervisionTake-Home Emergency Naloxone

Thank youThank you