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Pre-provision of naloxone to prevent heroin overdose deaths: evidence, myths and UK experience

Professor John Strang

National Addiction Centre, London, UK

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Declaration (personal & institutional)

DH, NTA, Home Office, NACD, EMCDDA, WHO, UNODC, NIDA

NHS provider (community & in-patient); also Phoenix House, Lifeline, Clouds House, KCA

(Kent Council on Addictions)

Reckitt-Benckiser, Schering-Plough, Genus-Britannia, Napp, Titan, Martindale, Catalent,

Auralis, Lundbeck, Astra-Zeneca, Alkermes, UCB, Fidelity, Rusan, Mundipharma

Europe, Lannacher, Lightlake & others, including trying to work with possible pharma-

manufacturers

UKDPC (UK Drug Policy Commission), SSA (Society for the Study of Addiction); and two

Masters degrees (taught MSc and IPAS)

Work also with several charities (and received support) including Action on Addiction, and

also with J Paul Getty Charitable Trust (JPGT) and Pilgrim Trust

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caveat

I’m a doctor, not a lawyer

I’m a doctor, working with my patients

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Why does the take-home naloxone issue matter?

Overdose is the major cause of death among drug users – mainly opiates

Most heroin overdoses are witnessed

Most witnesses intervene actively (often wrongly)

Many family members witness overdose

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Structure of today’s talk:

take-away naloxone and overdose deaths

What is the problem?

When does it occur?

How could naloxone help?

Areas of confusion

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Oxygen saturation: IV versus IM

0 10 20 30 40 50 60

90

92

94

96IV

IM

Minutes post-injection

Sp

O2

(%)

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Oxygen saturation: IV versus IM

0 10 20 30 40 50 60

90

92

94

96IV

IM

Minutes post-injection

Sp

O2

(%)

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Oxygen saturation: case study

0 10 20 30 40 50 60

84

87

90

93

96

Male, age 49Intravenous diamorphine (6 years)This dose = 120 mgDaily dose = 400mg

Minutes post-injection

Sp

O2

(%)

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WHICH DRUG?

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Drug use prevalence and Drug-related deaths: England &Wales 2011/12 (ONS)

Drug Prevalence in general

population (use in

last year, age 16-59)

No. of deaths in 2011

Cannabis 6.9%

Cocaine 2.2%

Amphetamine 0.8%

Ecstasy 1.4%

Opiates (inc heroin &

methadone)

0.3%

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Drug use prevalence and Drug-related deaths: England &Wales 2011/12 (ONS)

Drug Prevalence in general

population (use in

last year, age 16-59)

No. of deaths in 2011

Cannabis 6.9% 7

Cocaine 2.2% 112

Amphetamine 0.8% 62

Ecstasy 1.4% 13

Opiates (inc heroin &

methadone)

0.3% 1,082

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Conclusion number 1: Drugs involved with overdose

HEROIN

Heroin and sedative mixtures

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HOW COMMON?

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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)

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INTERVENTION OPPORTUNITY?

Sydney - 86% had witnessed O/D

Adelaide - 70% had witnessed O/D

London PAI injectors - 50%

(London treatment sample - 83/97%)

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Conclusion number 2

Overdose is common hazard

Overdose frequently witnessed

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Resusc training and naloxone?

opiates involved?

home context?

peers present?

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Naloxone? - personal O/D

Treatment sample (n=142)

Community sample (n=312)

Ever overdosed? 78/142 (55%) 118/312 (38%)

last personal overdose…

-involved opiates

-at own or friends home own home

friends home

-in company of others

sexual partner

close friends

72/78 (92%)

61/78 (78%) 43

18

66/78 (85%)

33

27

102/118 (86%)

84/118 (80%) 52

42

95/118 (81%)

32

57

(Strang, Powis, Best, Vingoe, Griffiths, Taylor, Welch and Gossop, Addiction, 1999)

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Naloxone? -witnessed O/D

Treatment sample

(n=142)

Community sample

(n=312) Witnessing overdoses Ever witnessed overdose? Witnessed O/D in last year?

44/48* (92%)

13/48 (27%)

167/ 312 (52%)

81/312 (26%) last overdose witnessed…

-involved opiates -O/D by sexual partner close friend casual acq. stranger

44/44 (100%) 6

32 1 5

153/159*(96%) 18 84 53 10

* data collected from only 48 * data missing on 8 cases (Strang, Powis, Best, Vingoe, Griffiths, Taylor, Welch and Gossop, Addiction 1999)

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Naloxone? - witnessed fatal O/D

Treatment sample

(n=142)

Community sample

(n=312)

Witnessing fatal overdoses Ever witnessed overdose fatality?

14/48* (29%)

55/312 (18%)

last fatal O/D witnessed… -involved opiates -death of sexual partner close friend casual acquaintance stranger

14/14(100%)

34/38* (89%)

2 33 15 3

* data collected from only 48 ** data missing on 8 cases * data available from only 38 subjects

(Strang, Powis, Best, Vingoe, Griffiths, Taylor, Welch and Gossop, Addiction, 1999)

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Conclusion number 3: O/D intervention opportunity?

opiates involved? - YES

home context? - YES

peers present? - YES

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Structure of today’s talk:

take-away naloxone and overdose deaths

What is the problem?

When does it occur?

How could naloxone help?

Areas of confusion

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When in particular excess?

Post-detox and post-rehab

During methadone early treatment

* Prison release *

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Risk of death during and after treatment

Cornish et al, BMJ 2010; 341: c5475

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When in particular excess?

Post-detox/rehab

During methadone early treatment

Prison release

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Prevalence of drug dependence

Drug dependence prior to prison

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

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Excess mortality ratio for different time periods post-release by

cause of death (Singleton, Farrell, Marsden et al 2003)

0

5

10

15

20

25

30

35

40

45

Up to

1

1 up to 2

2 up to 4

4 up to 8

8 up to 13

13 up to 26

26 up to 52

>=52Total

Time since release (w eeks)

Excess m

ort

alit

y r

atio

Drug-related deaths Not drug-related

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Structure of today’s talk:

take-away naloxone and overdose deaths

Where is the problem?

When does it occur?

How could naloxone help?

Areas of confusion

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

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First mooted:

JS - Keynote on Harm reduction - pushing at the envelope (Melbourne Harm Reduction conference, 1992) (and the linked Heather et al book)

First serious consideration:

Strang, J., Darke, S., Hall, W., Farrell, M. & Ali, R. (1996) Heroin overdose: the case for take-home naloxone? British Medical Journal,

312: 1435.

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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.

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Why does the take-home naloxone issue matter?

Overdose is the major cause of death among drug users – mainly opiate

Most heroin overdoses are witnessed

Most witnesses intervene actively (often wrongly)

Many family members witness overdose

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Training - scope

Training elements

(a) how to recognise overdose

(b) how to manage situation – general

(c) how to give naloxone

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How to Recognise Opiate Overdose

Person unconscious, cannot be woken – UNROUSABLE

CYANOSIS – BLUE lips or tongue

Not breathing at all or breathing slowly – deep snoring.

Pin point pupils

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Actions on Discovering Overdose

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

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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

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Target audience

Anyone with possibility/probability of being in the house with opiate user at time of overdose

(family member; (parent, partner, sib, son/daughter); flatmate etc)

n.b. not just those in treatment

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Possible target populations (Training)

Non-medic drug workers

Key agency personnel

Patients

Carers

Wider clients (e.g. NSX, etc)

Users (i.e. not linked to patient status)

Strang, Kelleher et al, BMJ, 2006

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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.

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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

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The MRC N-ALIVE Pilot Trial: NALoxone InVEstigation

N-ALIVE Chief Investigators

Prof. John Strang, Prof. Mahesh Parmar, Prof. Sheila Bird

N-ALIVE CTU Trial Team

Dr. Angela Meade, Laura Nichols, Lizzie Armstrong, Tracey Pepple

Funding and support: MRC with research support from MHRN.

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N-ALIVE trial – pilot & main phase

N-ALIVE research trial to test/prove reduced deaths post-release

Pilot – current, ongoing (n=>500)

Main study – n=30,000 (15k + 15k)

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Heroin-related deaths account for 8% of all UK deaths in individuals aged 15-44 yrs.

One in 200 prisoners with history of heroin use by injection dies from a drugs-related death (DRD) within 2–4 weeks of leaving prison.

Current approaches have not prevented high rate of post-release overdose deaths.

Background

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Structure of today’s talk:

take-away naloxone and overdose deaths

Where is the problem?

When does it occur?

How could naloxone help?

Areas of confusion

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Possible concerns

Short half-life - does naloxone last long enough?

What about date-expiry?

Safety net - might it increase risk-taking?

Might witnesses be less likely to call ambulance?

Are witnesses sufficiently skilled?

Will the naloxone be available?

Might family be afraid to give injection?

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Next steps – ‘to do’ list Improve naloxone (route, device, drug)

Extend to other populations

- Non-medical drug workers (health)

- High-risk population agency staff (hostels)

- Carers

- High risk clients (not in Tx, prison release hostels)

Implementation inertia – ‘Just do it’

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Thank you