Opioid Agonist Pharmacotherapy Of Opioid Dependence: Evidence Of Treatment Effectiveness

Assoc. Professor Robert Ali

Discipline of Pharmacology

School of Medical Sciences

University of Adelaide

robert.ali@adelaide.edu.au

 

Opioid Dependence

•      chronic and relapsing disorder

•      significant premature mortality and morbidity

–   1 to 3 percent untreated die per year

•    half due to heroin overdose

•    Around 13 times more likely to die than age sex matched

–    Globally around 10% of HIV assoc with IDU

•    Some countries over 70% of HIV assoc with IDU

–   significant social and economic costs

•     crime, unemployment, psychosocial problems and the cost of law enforcement

Globally

•      13.5 million using opioids

–  4.3 million dependent opioid users

•      At best only 40-60% in treatment

–   0.5 Million in MMT

–   0.1 Million BMT

Key Outcomes of Maintenance Pharmacotherapy Programs

•      Ý Retention in treatment

–    Facilitates reduction/cessation of opioid use

–    Reduces risky behaviours associated with opioid use

•      ß Mortality and morbidity

•      Ý Psychological, emotional and physical wellbeing of patients

•      ß Social costs associated with illicit drug use

•      ß Crime.

 

Australia NEPOD Background

•      Mid-1960’s heroin first came into Australia

•      By 1997 an estimated 74,000 dependent heroin users

–   10% 25-34 years deaths due to heroin overdose

–   Heroin-related crime cost between Aus$ 0.5-1.5 billion (9 billion CNY)

–  Only 36% of dependent heroin users in treatment

 

Scale of the project

•      13 treatment trials

•      1,425 patients (355 already in MMT)

•      More than 250 clinical and research staff

Trials

Retention in treatment
Methadone, buprenorphine, LAAM maintenance

Retention in treatment 
Methadone, buprenorphine and LAAM vs naltrexone

Heroin-free days in past 28 days
Heroin users still in treatment

Spending by heroin users in treatment
$ spent in past 28 days

Crime by heroin users in treatment
% reporting crime in past 28 days

Cost-effectiveness: maintenance
Cost per extra heroin-free day in 6th month

Cost-effectiveness: maintenance
Cost per extra heroin-free day in 6th month

•       Methadone is the most cost-effective treatment currently available

 

•       Naltrexone treatment is the least cost-effective

 

•       Treatment in primary health care setting is more cost-effective than in specialist clinics

NEPOD outcomes

•       Demonstrated treatment significantly reduces heroin use, associated crime and morbidity

•       Agonist maintenance treatment:

–    heroin-free days 3 days in the month before treatment to 22–24 days in the third month of treatment

–    same period criminal behaviour reduced more than 50%, expenditure on heroin reduced by more than 75%

•       Antagonist successful treatment for much smaller proportion

•       Detoxification not sufficient “stand-alone” treatment

Abstinence rates in NTORS – client treated in methadone programmes

Outpatient Methadone Treatment
 Changes from Before to After Treatment

 

HIV infection rates in and out of substitution treatment (Metzger et al. 1993)

Australian Treatment Outcome Study

•      12 month longitudinal outcome study

•      Treatment for heroin dependency

•      825 participants recruited in 3 Australian States

–    745 treatment participants:

•    Detoxification (n=288)

•    Pharmacotherapy maintenance (n=277)

•    Residential rehabilitation (n=180)

–    80 participants not in treatment

•      Interviewed at baseline 3 and 12 months

•      657 interviewed at 12 months (79.6% follow up)

Treatment pathways
 Maintenance pharmacotherapy

Maintenance pharmacotherapy I

Maintenance pharmacotherapy II

Drug Substitution Treatment

F  Strong evidence for the benefits of oral methadone treatment  RCTs +++  REASONABLE EFFECT SIZE

F  REDUCES DRUG CRIME     .70 

F   REDUCES OPIATE CONSUMPTION .35

F  REDUCES INJECTING & RISK TAKING 0.22

F  Now good evidence for buprenorphine and LAAM RCTs ++

COST EFFECTIVENESS

F    NTORS three pound saving for every one pound extra spent on treatment

 

F    CALDATA 7 dollars for every dollar spent on treatment

 

F    Cost of imprisonment significantly higher than cost of care in community but savings for criminal justice sector and costs for health and social services sector

 

F    Zarkin 2005. Benefit–cost ratio of treatment from lifetime model (37.72) exceeds the benefit–cost ratio from a static model (4.86).

 

 

Opioid replacement pharmacotherapy

•      Opportunity to stabilise health and social status before addressing physical adaptation

•      Mortality rate in MMT 1/3 that for heroin dependent people not in treatment

•      For each person in MMT for 12 months, cost saving to society of $180,000 p.a.

•      MMT has good record of retention in treatment, reduction of injecting drug use, reduction of criminal activity.