treatment approaches in the addiction field professor john strang national addiction centre, london,...

Treatment approaches in the addiction field

Professor John StrangNational Addiction Centre, London, UK

2MMF conference Palermo, September 2008

declaration

* DH, NTA, Home Office, NACD, WHO, UNODC

* Diamo, Reckitt-Benkiser, Schering-Plough, Genus-Britannia, GW, Napp, Titan, Catalent, Auralis

* Phoenix House, Clouds House, Action on Addiction, Society for the Study of Addiction

NHS University

Development and pilot testing of new

Prevention and Treatment Interventions

Research into the causes,consequences and influences

upon Addictions

Policy analysis and input into

Policy formation

Structure of today’s talk

Some initial thoughts

Old wine in old bottles

Old wine in new bottles

New wine, well worth drinking

Wine still in development

… from Faith to Science …

How do we define ‘drug’?

‘les drogues sont des substances qui provoquent des comportements irrationnels et deliriants …..

…chez ceux qui n’en prennent jamais’.

(Timothy Leary)

Opiate, stimulant, hallucinogen, sedative, alcohol, nicotine

Outcome measures

Outcome Measures

Drug use UDS & self-report

((Treatment retention)) Clinic records (& self report)

Injecting practices Frequency, risk & complications

Psychosocial functioning & Quality of Life Measures

SF-36, EQ-5D, OTI

((Crime)) Self-report (drug related expenditure & criminal activity)

((Cost effectiveness)) Service costs (internal & external)

((Community Impact Evaluation))

‘Nuisance’ issues for local community

benefit matrix

Health Social Economic

Individual

Community

Societal

Which harms and benefits are the most important?

Scientist must measure

Society must assign weightings


MMT (and, more recently, BMT)

… but …

(a) Methadone maintenance

• Major treatment for heroin dependence: highly effective

• 40 years of experience

• Oral, long half-life (daily), cross-tolerant: • prevents withdrawal symptoms• ‘universal anodyne’ psychological effect• To some extent it “blocks” euphoric effects of heroin

• 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)

Evidence and interpretation:Clinical effectiveness

Most trials used a fixed-dose designMTD 50-150mg/dayBP 1-15mg/day

2 main outcomes reported:Retention in treatment Illicit use of opioids [proportion of people taking illicit

opioids, mean rate of heroin intake assessed by self-report and/or urinalysis]

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

Gunne & Gronbladh (1981): Baseline

Experimental Group (methadone)

Control group (no methadone)

U U U U U U U U

U U U U U U U U

U U U U U U U U

U U U U U U U U

U U

U – ongoing daily heroin Use

Gunne & Gronbladh (1981): 2 years

Experimental group (methadone)


U U U A

U U U U

U U U U

U U U D

D

A – Abstinent U – on-going daily UseD – Deceased


Experimental group (methadone)


A A A A U U U A

A A A A U U U U

A A A A U U U U

U U U U U U U D

U D




Control group (methadone)


U A

U U

U D

D D

D






A A A A U A

A A A A U U

A A A A U D

U U U A D D

U D






A A A A U U U A

A A A A A A U U

A A A A A A U D

U U U A A A D D

U D


29

42

89

15

85

1716 14

82

13

2228

0

20

40

60

80

100

Heroin (Weekly)*

Cocaine (Weekly)*

Heavy Alcohol

Illegal Activity*

No FT Work SuicidalIdeation

Pre Post

% of DATOS Sample (N=727)

USA - Outpatient Methadone Treatment

Changes from Before to After Treatment

*p<.001

Hubbard, Craddock, Flynn, Anderson, & Etheridge 1997, PAB

The benefit of retaining patients in treatment - HIV infection rates in and

out of methadone maintenance treatment (Metzger et al. 1993)

21

273536 3639 39 42484951

13

15 1617 1718 19 1921

Out of tx %

In tx %



21

273536 3639 39 42484951

13 15 16 17 17 18 18 19 19 20 21Out of tx %

In tx %



2127

35 3636

39 39 42 48 49 51

13 15 16 17 17 18 18 19 19 20 21Out of tx %

In tx %

(b) Buprenorphine maintenance

• Agonist with very high affinity for opiate receptor (heroin cannot compete at opioid receptor)

• Similar treatment retention 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 (but not yet firmly demonstrated how much better)

1 year retention during buprenorphine

maintenance (16 mg qd)

Kakko et al. (2003)Treatment duration (days)

# R

emai

ning

in t

reat

men

t

0

5

10

15

20

0 50 100 150 200 250 300 350

Control (6 day taper)

buprenorphine maintained

75% retained at 1 year; no deaths

75% of urine drug screens negative

0 1 2 4 8 16 32

10

11

12

13

14

15

16

17

Bre

aths

/Min

ute

PL Buprenorphine (mg, sl)

Human respiratory rate

Adapted from Walsh et al., 1994

Ceiling effect on respiratory depression

(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

Retention in treatment: methadone, buprenorphine, LAAM maintenance

(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 (Kraigher, 2005)

MMT patients transferring to SROM (n=18) showed similar outcomes as methadone, improved social functioning, and less side-effects (Mitchell, 2004)

(e) Codeine or dihydrocodeine

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??)

… but …

Retention in treatment: methadone, buprenorphine, LAAM maintenance

Retention in treatment methadone, buprenorphine & LAAM vs. naltrexone

Move to NICE slides

U.K. Methadone treatment:benefits in the first month

(Strang, Finch et al, Addiction Research)

4.7

6.36

1.2

2.2

3.5

1.8

2.56

0.50.8

0.5

0

1

2

3

4

5

6

7

herointimes/ wk

heroinmgX10

cocainetimes/ wk

coc mgX10 shopliftingper week

pre-entry1 month

U.K. Methadone maintenance –changes in heroin use over time

0

0.5

1

1.5

2

2.5

3

3.5

Am

ou

nt

of

he

roin

in

Gm

pe

r w

eek

Methadone maintenance

Source: Finch 2000 MD thesis

Opioid Overdose Deaths 1964-1997 (per million Australian adults, 15-44 years)

(Hall, Degenhardt & Lynskey, 1999)

15 44 yrs

0

10

20

30

40

50

60

70

80

1964

1966

1968

1970

1972

1974

1976

1978

1980

1982

1984

1986

1988

1990

1992

1994

1996

15 44 yrs


(Naltrexone in alcohol field)

(Disulfiram with cocaine)

Heroin maintenance (re-conceptualisation)

Naloxone ‘technology transfer’

WHAT INJECTABLE PRODUCTS?

Two products:

- heroin ampoules (dry amps) (1%)

- methadone ampoules (wet amps) (3-10%)

What is the RIOTT trial?

Results

…… to follow ……

However, as a clinician I can tell you …We are seeing some transformational changesEnough to guide policy-making process?

Retention approx 85% at 6/12 (vs 50% typical)Follow-up approx 95% (vs 75% typical)

Opioid Overdose Deaths 1964-1997 (per million Australian adults, 15-44 years)

(Hall, Degenhardt & Lynskey, 1999)

15 44 yrs

0

10

20

30

40

50

60

70

80

1964

1966

1968

1970

1972

1974

1976

1978

1980

1982

1984

1986

1988

1990

1992

1994

1996

15 44 yrs

Oxygen saturation: IV versus IM

0 10 20 30 40 50 60

90

92

94

96IV

IM

Minutes post-injection

Sp

O2

(%)

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

(%)

Actions on Discovering Overdose

CALL AMBULANCE

Check Airway – clear if blocked, Check breathing.

If breathing, place in recovery position – if not breathing, begin basic life support or place in recovery position to maintain a good airway and prevent them from choking

Administer naloxone

http://images.google.co.uk/imgres?imgurl=http://www.crinigeria.com/images/looklistenfeel.jpg&imgrefurl=http://www.crinigeria.com/selfhelp/childcpr.htm&h=151&w=201&sz=10&tbnid=3b2RK2neoCwJ:&tbnh=74&tbnw=99&hl=en&start=42&prev=/images%3Fq%3Dcheck%2Bbreathing%26s

Naloxone Administration

Quickest route of injection is intravenous However INTRAMUSCULAR injection

recommended as easier. Inject into a muscle Upper outer buttock, thigh area or upper arm. Hold needle 90 degree above skin Insert needle into muscle Slowly and Steadily push plunger all the way down

Client confidence in administering naloxone

0

10

20

30

40

50

60

V.confident Confident Unsure Not confident Not at allconfident

level of confidence

%

pre-training

post-training

Interviews in confidence (n=1009)

Face-to-face

Independent research staff

Enquiry about sexual and injecting behaviours

Now; recent past; distant past

Table 1. Persistence of drug use on imprisonment

Ever used(n=557 out of 1009)

Year beforeprison

Month beforeprison

Heroin (n=324) 63% a (n=204)

52%(n=169)

Cocaine (n=387)

72%(n=280)

54%(n=209)

Amphetamines (n=417)

52%(n=216)

30%(n=125)

a All percentages are calculated based on the numbers who have ever used


Ever used Year beforeprison

Month beforeprison

First month in

prison

Ever used it in

prison

Ever injected it

inprison


52%(n=216)

30%(n=125)

5%(n=19)

26%(n=108)

4%(n=15)




Month beforeprison

First month in

prison

Ever used it in

prison

Ever injected it

inprison

Cocaine (n=387)

72%(n=280)

54%(n=209)

11%(n=41)

35%(n=135)

3%(n=10)


52%(n=216)

30%(n=125)

5%(n=19)

26%(n=108)

4%(n=15)




Month beforeprison

First month in

prison

Ever used it in

prison

Ever injected it

inprison

Heroin (n=324) 63% a (n=204)

52%(n=169)

36%(n=118)

71%(n=230)

16%(n=51)

Cocaine (n=387)

72%(n=280)

54%(n=209)

11%(n=41)

35%(n=135)

3%(n=10)


52%(n=216)

30%(n=125)

5%(n=19)

26%(n=108)

4%(n=15)


Post-release ‘carnage’

Seaman Brettle Gore, BMJ, 1998

Bird & Hutchinson, Addiction, 2002

Farrell & Marsden, Addiction, 2008

Prevalence of drug dependence

15%

11%

17%

9%

10%

8%

16%

8%

24%

17%

11%

2%

13%

10%

12%

5%

0

10

20

30

40

50

60

%

M remand M sentenced F remand F sentenced

Opiates & stimulants Opiates only Stimulants only Cannabis only

Drug dependence prior to prison

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)

05

1015202530354045

Time since release (w eeks)

Exce

ss m

orta

lity ra

tio

Drug-related deaths Not drug-related

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)

Treatment Research Institute Mc Lellan et al

Levels of Treatment in Methadone Maintenance Programs

Random Assignment 6 Months

‘Bare-bones’ Standard ‘deluxe’ (n=29) (n=34) (n=36)

Methadone: > 65mg >65mg >65mgCounseling: Regular RegularOther Services Employment

Family Therapy Psychiatric Care

Levels of care Study

0

10

20

30

40

50

60

70

Using Heroin Using Cocaine Sharing Needles Illegal Acts Unemployed

barebones standard deluxe

Target behaviors at 6 months

Move to NICE Forest plots of meta-analyses

Wines in development

(migrant medications)

Tele-prompting/monitoring

Vaccines

Ultra-long duration meds (nx; bup; …)

HR moderation medications (?nalmef; ?)

… add cocaine vaccine slide …

conclusion

… exciting times

Thank you

Bup-nalox effects –by different routes

(version 1)

Bup Nalox

Su

b-lingu

alBup Nalox

Bup Nalox

Inject

Bup Nalox

treatment approaches in the addiction field professor john strang national addiction centre, london,...

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