Gecontroleerde Heroneverstrekking

1
GecontroleerdeHeroïneverstrekking

• Wim van den Brink, MD PhD
• Vincent M Hendriks, PhD
• Peter Blanken, MA
• Jan M van Ree, PhD
• Central Committee on theTreatment of Heroin
  Addicts (CCBH)
• Academic Medical Center Dept of Psychiatry
• Amsterdam Institute for Addiction Research (AIAR)

2
Table of Contents

• General Treatment Principles
• Epidemiological and Treatment Situation
• 12 months Efficacy, 12 months Cost-Effectiveness
• 48 months Outcome
• Effectiveness in Routine Practice
• Current Situation and New Plans
• Conclusions

3
General Treatment Principles
4
Treatment Career and Treatment GoalsGeneral Model
5
Treatment Career and Treatment GoalsApplied
General Model
6
Goals and Interventions Heroin Addiction
Van den Brink and Haasen, 2006 Lingford-Hughes
et al., 2004, Vocci et al., 2005 OBrien, 2005
7
Epidemiological and Treatment Situation
8
Treatment Heroin Addicts in The Netherlands
TOTAL N24,000 15 injectors, 85 smokers
.29
.71
In Treatment N17,000
Not in Treatment N7,000
.74
.26
METHADONE MAINTENANCE N12,500
DRUGFREE TREATMENT N4,500
.36
.40
.24
Integrated N4,500
Not Integrated N5,000
Extremely Problematic N3,000
9
Health Council of the Netherlands (1995)

• Continuation existing programmes
• drugfree, methadone reduction, methadon
  maintenance
• Improving liaison between legal and treatment
  system
• diversion, drugfree prison programmes
• Ultrarapid detoxification with/without anesthesia
• High dosage methadone maintenance
• Controlled medical prescription of heroin

10
Efficacy Heroin prescriptionThe Dutch Trials

• Design, Execution, Results
• (Van den Brink et al, BMJ, 2003 Blanken et al.,
  Addiction, 2005)

11
Basic Principles of the Dutch study

• Separate RCTs for inhalable and intravenous
  heroin
• Explicit inclusion and exclusion criteria
• Standardized assessment procedures
• Pre-defined measure of effect pre-specified
  analysis plan
• Adequate statistical power
• Quality assurance according to GCP

12
Design of the Study
Moral methadone Hheroin inhinhalable
ivintravenous
13
Inclusion and Exclusion Criteriachronic,
treatment-resistant heroin addicts
Inclusion Criteria
Exclusion Criteria

• DSM-IV heroin dep gt 5 yrs
• registered in MMT last 12 mths
• gt30-50 visits to MMT last 6 mths
• gt50-60 mg meth gt 4 wks last 5 yrs
• (nearly) daily use of heroin
• poor social integration and/or
• poor physical and/or mental health
• age gt 25 yrs
• legal resident in The Netherlands
• registered in area gt 3 yrs
• willing to be randomized
• written informed consent

• not meeting ALL inclusion criteria
• illness with high safety risk
• illness or behaviour likely to interfere with
  study completion
• pregnant or lactating
• awaiting long imprisonment
• other drugs dominating heroin dep
• short life-time expectancy
• voluntary abstin gt 2 mths past yr
• requiring gt 150 mg oral methadone
• requiring gt 1000 mg heroin
• participating in other study

14
Experimental and Control Treatment
Control Treatment
Experimental Treatment

• oral methadone lt 150 mg/day
• standard psychosocial offer

• oral methadone lt 150 mg/day
• standard psychosocial offer
• heroin inhalable or intravenous
• 0-7 days/week
• 0-3 times/day
• lt 400 mg/administration
• lt 1000 mg/day
• dosages individually titrated
• no prescription of other illicit drugs

ADD ON
15
Response definition

• 40 improvement in physical health

or 40 improvement in mental status
or 40 improvement in social functioning
and no serious deterioration (40 in any
domain) and no increase in cocaine (or other
drug) use
16
Patient CharacteristicsChronic
Treatment-Resistant Heroin Addicts

• Age 39 years
• Female patients 19
• Dutch/Western 86

Heroin 16 years 26 days Methadone 12 years 29 days
Cocaine 10 years (92) 18 days (86) Poly drug
use 17 years 29 days
Physical problems 66 Psychiatric
problems 60 Social problems 72
17
Participation in the trial

• Injectable heroin 174 patients randomized (250
  planned)
• Inhalable heroin 375 patients randomized (375
  planned)

Injectable heroin 93 month 12 endpoint
assessments Inhalable heroin 94 month 12
endpoint assessments
18
OR2.99
OR2.77
57
48
32
25
19
?25 ? 23 32
57 25 48
4
3
23
13
5
4
27
30
32
21
injectable heroin
inhalable heroin
20
Changes among Responders
baseline
12 months
21
Discontinuation

• completers 217
• responders 115 (53)
• deteriorated responders 94 (82)

22
Changes among deteriorated responders
baseline
12 months
14 months
23
Outcome Predictors and Matching EffectBlanken et
al. 2005 (Addiction)
24
Cost-Effectiveness

• Results
• Dijkgraaf et al., BMJ, 2005

25
Cost-Effectiveness HA TreatmentDijkgraaf et al,
2005, BMJ
26
Cost-Effectiveness HA-TreatementDijkgraaf et al
(2005), BMJ
Better and More Expensive
Better and Cheaper
Better and Cheaper
Cost-Effectiveness Plane
27
Long-Term OutcomeThe Dutch Trials
28
Follow-up of patients re-instated on heroin
29
Reasons for discontinuation oflongterm heroin
assisted treatment (n 66)

• non-stabilized response n 16 24
• misbehavior in treatment center n 19 29
• physical health situation n 7 11
• incarceration n 3 5
• abstinence n 7 11
• other - patient related reasons n 9 14
• - treatment related reasons n 5 8
• Total n66 100

30
long-term course responders (24 months n 128
36 months n 95 48 months n 79)
31
(No Transcript)
32
Effectiveness
33
Baseline Characteristics New Inclusions (n140)
vs RCTs (n193)
34
Baseline Characteristics New Inclusions (n140)
vs RCTs (n193)
35
Effectiveness

• Routine HA Treatment
• Patient profile similar to RCTs, but slightly
  more severe
• Retention very similar to RCTs 72 routine vs
  70 RCT
• Response very similar tot RCTs 56 routine vs
  53 RCT

36
Current SituationandNew Plans
37
Current Situation and New Plans

• Approximately 300 patients in 6 cities in HA
  treatment
• Registration for injectable and inhalable heroin
  under review at Dutch registration authority
• Approved plans for extension of HA treatment to
  1000 patients in 12-15 cities
• RCT contingency management within contexts of HA
  treatment to further reduce cocaine abuse and to
  enhance treatment effectiveness

38
Application for Registration
39
heroin assisted treatment units in the
Netherlands
40
Schottenfeld et al., 2005MMT vs BMT with/without
CM retention drug-free urines
Treatment retention/reduction drug use better in
METH than BUP short-term effect CM
41
Schottenfeld et al, 2005MMT vs BMT with/without
CM cocaine-free urines
Positive short-term effects of CM (during
increase incentives), but no long-term effects of
CM
42
Silverman et al. 1999Effect of CM voucher
magnitude on cocaine use in MMT
max 3000 max 300 max 0
CM effective but expensive
43
Pierce et al. (2006)MMT with/without CM
(low-cost/lottery 120/pt) on stimulant and
alcohol
44
Rawson et al. (2002)MMT with/without 16 weeks CM
and/or CBT directed at cocaine use
of cocaine-free urine samples
CM more short-term effective, CBT more long-term
effective
45
Contingency Management Cocaine
46
Contingency Management Cocaine
2-3 times per week, quick-test lab test
47
Contingency Management Cocaine
48
Conclusions
49
Treatment Goals and Modalities in NL
USER ROOMS
Therapeutic Community
4 500
12 500
1.000
Prison TC
50
Treatment Goals and Modalities

Buprenorphine
Methadone
Dextramoramide
Codeine Morphine SR
Naltrexone
Heroin
51
Agonist treatment and the risk of increased
incidenceNordt Stohler, Lancet, 2006
MMT HAT
The harm reduction policy of Switzerland and its
emphasis on the medicalisation of the heroin
problem seems to have contributed to the image of
heroin as unattractive for young people.
52
Conclusions

• Co-prescription of heroin to chronic,
  treatment-resistant heroin addicts is effective
  and safe in RCTs and routine practice
• HA treatments are cost-effective
• Co-prescription of heroin results in stable
  improvements in those patients who remain in HA
  treatment (30-40)
• More data needed on patients who leave HA
  treatment
• More data needed on added effect of psychosocial
  interventions, e.g. CM

53
Selection of References

• van den Brink W, Hendriks VM, van Ree JM (1999)
  Medical co-prescription of heroin to chronic,
  treatment-resistant methadone patients in the
  Netherlands a randomized clinical trial. Journal
  of Drug Issues, 29, 587-608.
• Hendriks VM, van den Brink W, Blanken P, Bosman
  IJ, van Ree JM (2001) Heroin self-administration
  by means of chasing the dragon
  pharmacodynamics and bioavailability of inhaled
  heroin. European Neuropsychopharmacology, 11,
  241-252.
• van den Brink W, Hendriks VM, Blanken P, van
  Zwieten BJ, van Ree JM (2003) Medical
  prescription of heroin to chronic,
  treatment-resistant heroin dependent patients
  two randomised controlled trials. BMJ, 327,
  310-312.
• Blanken P, Hendriks VM, Koeter MWJ, van Ree JM,
  van den Brink W (2005) Predicting efficacy of
  medical prescription of heroin to treatment
  resistant heroin dependent patients results from
  two randomised controlled trials. Addiction, 100,
  89-95.
• Dijkgraaf MGW, van der Zanden BP, Borgie CAJM,
  Blanken P, van Ree JM, van den Brink W (2005)
  Cost utility of medical co-prescription of
  herroin compared with methadone maintenance
  treatment for chronic, treatment resistant heroin
  addicts. BMJ, 330, 1297.

54
WWW.CCBH.NL
55
Treatment completers

• Injectable heroin trial
• methadone dose 60 mg (methadone alone71 mg)
• heroin dose 549 mg/day, 254 mg/visit
• visits during trial 352/year, 2.1/day
• Inhalable heroin trial
• methadone dose 57 mg (methadone alone67 mg)
• heroin dose 547 mg/day, 263 mg/visit
• visits during trial 353/year, 2.1/day