Matters PRACTICE PRACTICE Matters

FEBRUARY 2001 VOL. 6 ISSUE 2

EFFECTIVE

TREATMENT

FOR OPIOID

DEPENDENCE

A publication of the Management Decision and Research Center

A program within the Department of Veterans Affairs Health Services Research and Development Service

• As many as 900,000 Americans are dependent on

heroin or other illicit opioids.

• VA is the largest provider of substance abuse treatment in the world, and treated almost 30,000

opioid-dependent patients in 1999.

• The majority of heroin users administer drugs

intravenously. In the U.S., injection drug use is

responsible for 24% of new HIV infections among

men and 47% among women. Up to 90% of

intravenous drug users contract Hepatitis C.

• Opioid agonist treatment (OAT) with methadone

or L-alpha acetyl methadol (LAAM) is an effective

treatment that reduces substance use, HIV transmission, criminal behavior, and mortality.

• Many opioid dependent individuals who could

benefit from OAT never receive it because ideological and practical factors have limited access to this

form of care.

• VA research shows that methadone maintenance is

extremely cost-effective. It has a cost-effectiveness

ratio of $6,000 per quality-adjusted life year

gained, far less than other widely-available medical

treatments.
2 PRACTICE Matters

BACKGROUND

Opioid dependence remains a serious health

problem across the U.S. In addition to high rates of

death from direct causes (3–8 percent per year,

mainly from overdose and trauma), opioid dependent individuals are at high risk for HIV (5-40

percent prevalence in major cities), Hepatitis C, and

soft-tissue infection (Holmberg, 1996; Austin et al,

2000).

Despite these grim statistics, there is a reason for

hope: an effective treatment exists. Opioid agonist

treatment (OAT) reduces opioid use, crime, unemployment, opioid-related mortality, and the spread

of infectious diseases, and improves patients’ quality

of life (Ball & Ross, 1991; Glanz et al., 1997; Ling

et al., 1976; Marsch, 1998; McLellan et al., 1993;

Newman & Whitehill, 1979; Sees et al., 2000; Zaric

et al., 2000). Yet less than 20% of opioid dependent

individuals are receiving treatment (NIH consensus

statement, 1997).

Access to high-quality OAT is extremely limited.

VA operates only 31 opioid agonist treatment

clinics, and most of these are unable to keep up with

treatment demand in their local area. Some VISNs

have no OAT services at all despite significant

heroin use in their catchment area. Finally, some

VA OAT clinics do not adhere to treatment practices that have been demonstrated to produce the

best outcomes (Hamilton & Humphreys, 1996).

Expanding and optimizing opioid agonist treatment

should decrease the suffering and economic burden

associated with opiate dependence.

TREATMENT

Treatment for opioid dependence is directed at

decreasing morbidity and mortality, and improving

quality of life. In addition to reducing drug use,

specific treatment goals include: reducing the

prevalence of HIV transmission, hepatitis and softtissue infections; improving psychological, emotional and physical well-being; increasing employment and social stability; and reducing criminality.

Available therapies

Two major types of OAT are practiced: maintenance and medically-managed withdrawal

(O’Connor & Fiellin, 2000). Maintenance treatment involves long-term (i.e., from six months to

indefinite) administration of methadone or LAAM

(levo alpha acetyl methadol) with the aim of eliminating withdrawal symptoms and drug-craving and

blocking the effects of illicit opioids. Methadone is

typically dispensed daily, whereas LAAM is dispensed less frequently because of its longer duration

of effect (48-72 hours). Both medications are oral

opioid substitutes. Optimally, maintenance treatment is given in conjunction with psychosocial

services and is continued for an indefinite period.

By contrast, medically-managed withdrawal is a

short-term pharmacological treatment with or

without additional psychosocial services, and is

intended to minimize withdrawal symptoms associated with cessation of drug use and to stabilize the

patient psychologically. Clinical studies have

demonstrated that maintenance OAT is significantly

safer and more effective than medically-managed

withdrawal (Newman & Whitehill, 1979; Sees et al,

2000).

The preponderance of evidence shows that OAT

is the most effective treatment for most opioid

dependent patients, and care that follows treatment

guidelines produces better results. For example, for

most patients, treatment with 60-100 mg/day of

methadone more effectively blocks craving and

withdrawal symptoms and reduces illicit opiate use

than does treatment with lower doses (Ling et al,

1976; Strain et al, 1999).

Moreover, the effectiveness of methadone is

significantly improved when the medication is

supplemented with psychosocial services (McLellan

et al, 1993). Perhaps most importantly, trials show

that patients should have the option of continuing

in OAT indefinitely. Discontinuation of treatment,

even after years of successful abstinence from illicit

opioids, leads to increased incidence of relapse to

heroin use (Greenfield, 1999). Even though it

must be provided long-term, OAT is a highly costeffective intervention, as detailed below.

Benefits of treatment

Numerous benefits of OAT have been documented. Proper maintenance treatment has

consistently been shown to sharply reduce the use

of heroin and, more variably, other drugs of abuse.

Treatment reduces high-risk injection practices, as

well as mortality (1 – 2 percent annual death rate

Continued on page 4
PRACTICE Matters 3

EXPERT OPINION

Science continues to provide an ever-increasing

array of tools with which to combat addiction. In

the past 25 years, a variety of effective medications

and behavioral therapies have been developed for

treating substance dependence, particularly heroin

addiction. Well-known medications such as LAAM

and methadone, for example, occupy the same brain

receptors as heroin and eliminate withdrawal

symptoms that often accompany the sudden cessation of drug use. When administered in adequate

doses, these medications stabilize the patient’s brain,

allowing them to function normally and to perform

mental or physical tasks without impairment.

When medications such as these are coupled with

behavioral treatments, patients are able to lead

productive lives.

Unfortunately, although these treatments have

been determined to be safe, effective, and cost

effective, they are not nearly as widely used as

they should be. One set of impediments is the

broad misunderstanding about these agonist

medications – the belief that they are simply

substitutes for heroin. This of course runs

counter to our understanding that methadone and

LAAM actually stabilize the brain of a heroin

addict. Moreover, there are strict state and

federal regulations that control the use of these

medications, frequently making it difficult for the

estimated 900,000 individuals in need of opiate

treatment to receive it. This point was made

strongly by the 1997 NIH Consensus Development Conference on the Effective Medical Treatment of Opiate Addiction. A positive note in this

treatment gap scenario is the fact that Congress

has just recently passed legislation that will allow

qualifying physicians to dispense or prescribe in

their offices several of the pending new medications for heroin addiction. These new medications, such as buprenorphine and buprenorphine/

naloxone, have been shown to have a higher

safety and lower diversion potential than other

available treatments. Patients enrolled in clinical

trials with these products have also reported that

the withdrawal syndrome associated with

buprenorphine is minimal. Once these medications are approved by the Food and Drug Administration, the fact that qualified physicians will be

able to prescribe them from their offices should

greatly expand the diversity of the anti-addiction

clinical toolbox and thus provide expanded

treatment options for the diverse opiate addict

patient population.

Alan I. Leshner, Ph.D.

Director, National Institute on Drug Abuse

RECOMMENDATIONS

• To enhance patient outcomes, OAT clinics

should more consistently follow clinical practice

guidelines. Treatment that complies with guidelines, which specify that the dose be sufficient to

prevent withdrawal and craving (generally

equivalent to at least 60 mg/day methadone;

LAAM is given at 1.2 to 1.3 times the methadone

dose every other day), has been shown to be most

effective. Appropriate psychosocial services

would enhance patient outcomes and should be

continued as needed. Higher methadone/LAAM

doses, more extensive psychosocial services, and

continuance of treatment have been demonstrated to optimize outcome.

• Access to OAT should be improved by expanding

existing programs and by establishing new

programs in locations where treatment is not yet

available.

• The implementation and facilitation of new

therapies, including buprenorphine and other

office-based opioid agonist treatments, should be

seriously considered as they become available.

Please take a moment and tell us how you feel

about Practice Matters by using our new

Instant Feedback Site for VA Health Services

Research Publications on the web at (http://

www.va.gov/resdev/prt/idp/). Your comments

and suggestions will guide us in our efforts to

provide you with important HSR&D information in future issues.
4 PRACTICE Matters

TREATMENT

Continued from page 2

for patients in treatment versus 2-8 percent for

those not in treatment). Further, opioid maintenance patients typically experience increased

psychosocial stability, increased income, and

improved quality of life.

OAT also has significant benefits to the general

population. Opioid agonist treatment reduces the

spread of HIV to the general population, and saves

societal resources by reducing criminal behavior

and unemployment among patients. Cost-benefit

research indicates that, collectively, such benefits to

society at large are sufficient to fully justify the cost

of providing OAT to opiate dependent individuals

(Zaric et al, 2000).

Barriers to treatment access

Despite the large body of evidence supporting the

effectiveness of OAT, this treatment is not available to

many opioid-dependent individuals. Neither VA nor

non-VA programs can fully accommodate the demand

for treatment; there are many long waiting lists and

few openings. Travel distance to clinics compounds

these limitations on access to care because OAT

patients typically attend clinics 3-7 days a week.

New developments in treatment

Several new opioid agonist treatments have been

developed to improve access, outcome, and flexibility in

therapy. Buprenorphine, both alone and in combination with naloxone, is in trials as an alternative to

methadone and LAAM. The pharmacological properties of this medication confer several potential advantages over methadone: it has reduced potential for

overdose, morbidity and mortality, abuse, and diversion

to illicit sale, and may decrease the dysphoria associated

with opioid withdrawal (Ling et al, 1996, O’Connor &

Fiellin, 2000). When approved by the FDA, this form

of OAT could be given to large numbers of patients.

To increase its accessibility, buprenorphine will be

available through primary care practices as well as

OAT clinics. Primary care-based methadone maintenance may also one day be available; the Substance

Abuse and Mental Health Services Administration is

currently piloting and evaluating such a program in

San Francisco. Although the exact number of Americans who would seek some form of OAT through a

primary care provider is unknown, the experience of

other nations that offer OAT in this fashion (e.g.,

Germany) suggests than many individuals would

prefer to receive treatment in this fashion.

ACKNOWLEDGEMENTS:

This issue of VA Practice Matters on Effective

Treatment for Opioid Dependence was written by:

Jodie Trafton, Ph.D., Director of the QUERI

Multi-site Opiate Substitution Treatment Study;

Paul Barnett, Ph.D., Director of the Health Economics Resource Center; John Finney, Ph.D.,

Project Director of the QUERI Substance Abuse

Module; Rudolf Moos, Ph.D. Research Coordinator for the QUERI Substance Abuse Module; Mark

Willenbring, M.D., Clinical Coordinator for the

QUERI Substance Abuse Module, and Keith

Humphreys, Ph.D., Associate Director of the

Program Evaluation and Resource Center. Other

contributors included QUERI Substance Abuse

Module Executive Committee Members Thomas

Kosten, M.D., Dan Kivlahan, Ph.D., Dennis

Raisch, Ph.D., Richard Suchinsky, M.D., and

George Woody, M.D. Eric C. Strain, MD, Johns

Hopkins University School of Medicine, and Laura

F. McNicholas, MD, PhD, Philadelphia VA Medical

Center and the University of Pennsylvania, served

as reviewers. The issue was edited by Geraldine

McGlynn, M.Ed. and Diane Hanks, MA, of VA’s

Management Decision and Research Center.

VA Practice Matters is a publication for VA decision

makers and practitioners that summarizes the results

of important research to help inform policy and to

promote the application of research for improved

health care delivery and decision making within VA.

It is produced by HSR&D’s Information Dissemination Program in collaboration with topic experts

in the field. For more information or to provide us

with your suggestions, please contact:

Information Dissemination Program

Management Decision and Research Center (152-M)

VA Boston Health Care System

150 South Huntington Avenue

Boston, MA 02130

Phone: (617) 278-4433

FAX: (617) 278-4438

Email: geraldine.mcglynn@med.va.gov

VA Practice Matters is also available on the VA R&D

internet at www.va.gov/resdev/prt, and on our Fax on

Demand system by dialing (617) 278-4492 and following

the voice prompts.
PRACTICE Matters 5

Evidence Chart

Study Participants Intervention Outcome

Per group

AINTENANCE VS. n=50 patients with Methadone mainte- After 32 weeks, 72% of maintenance patients were

ITHDRAWAL heroin addiction nance (100 mg) vs. still in treatment, but only 10% of the dosemethadone dose- reducing group remained. Only the maintenance

ewman & Whitehill. reduction (decreased by group showed reductions in heroin use.

ancet 1979: 485-8 1 mg/day from 60 mg

start)

AINTENANCE VS. n=88-91 patients with Ongoing psychosocial Methadone maintenance patients stayed in

ITHDRAWAL opioid dependence services with metha- treatment longer and showed greater opioid

done as a maintenance abstinence than medically-managed withdrawal

ees et al. JAMA 2000; vs. detoxification patients.

83: 1303-10 treatment. (p<0.01).

OSE n=142-146 VA patients LAAM (80 mg) vs. Low High dose methadone patients had the best

with opioid dependence (50 mg) vs. High (100 retention in treatment. Both LAAM and high

ing et al. Arch Gen mg) dose methadone dose methadone groups had better global drug use

sychiatry 1976; 33: outcomes than the low dose methadone group

09-20 (P<0.005).

OSE n=95-97 patients with Low (40-50 mg) vs. Both groups decreased illicit opioid use; high dose

opioid dependence High (80-100 mg) dose had significantly greater reductions in opioid use

train et al. JAMA methadone (p=0.01)

999; 281: 1000-5

SYCHOSOCIAL n=32-35 patients with Methadone prescrip- All treatments decreased illicit drug use. Increases

ERVICES opioid dependence tion only vs. with in services led to a greater percentage of patients

standard psychosocial showing heroin abstinence (p<.01). The enhanced

cLellan et al. JAMA services vs. with service group had better employment, alcohol use,

993; 269: 1953-9 enhanced psychosocial and legal outcomes (p<0.05).

services

OST- N/A Cost-effectiveness Methadone maintenance treatment has an

FFECTIVENESS analysis to compare incremental cost-effectiveness ratio of less than

methadone mainte- $6,000/quality adjusted life year, well below the

arnett. Addiction, nance treatment to $50, 000 standard for cost-effectiveness.

999; 94: 479-88 standard care

M

W

N

L

M

W

S

2

D

L

P

7

D

S

1

P

S

M

1

C

E

B

1
6 PRACTICE Matters

REFERENCES

Austin GE, Jensen B, Leete J, De L’Aune W, Bhatnagar J, Racine M,

Braun JE. Prevalence of hepatitis C virus seropositivity among

hospitalized US veterans. American Journal of Medical Science 2000;

319:353-9.

Ball JC, Ross A. The effectiveness of methadone maintenance

treatment. New York: Springer Verlag, 1991.

Barnett P. The cost-effectiveness of methadone maintenance as a health

care intervention. Addiction 1999; 94: 479-488.

Greenfield L. Methadone treatment outcomes in the National

Treatment Improvement Evaluation Study (NTIES). Bethesda, MD:

Center for Substance Abuse Treatment, Substance Abuse and Mental

Health Services Administration, 1999.

Glanz M, Klawansky S, McAullipe W, Chalmers T. Methadone vs. Lalpha acetyl methadol (LAAM) in the treatment of opiate addiction: A

meta-analysis of randomized controlled trials. American Journal of

Addiction 1997; 6: 339-349.

Hamilton EG, Humphreys, K. Outpatient methadone services in the

Department of Veterans Affairs. Palo Alto, CA: Department of

Veterans Affairs, Program Evaluation and Resource Center, 1996.

Holmberg SD. The estimated prevalence and incidence of HIV in 96

large US metropolitan areas. American Journal of Public Health 1996;86:

642-654.

Ling W, Charuvastra C, Kaim SC, Klett CJ. Methadyl acetate and

methadone as maintenance treatment for heroin addicts: A Veterans

Administration cooperative study. Archives of General Psychiatry 1976;

33: 709-720.

Ling W, Wesson DR, Charuvastra C, Klett CJ. A controlled trial

comparing buprenorphine and methadone maintenance in opioid

dependence. Archives of General Psychiatry 1996; 53:401-7

Marsch LA. The efficacy of methadone maintenance interventions in

reducing illicit opioid use, HIV risk behavior, and criminality: A metaanalysis. Addiction 1998; 93: 515-532.

McLellan AT, Arndt IO, Metzger DS, Woody GE, O’Brien CP. The

effects of psychosocial services in substance abuse treatment. Journal of

the American Medical Association 1993; 269:1953-1959.

Newman RG, Whitehill WB. Double-blind comparisons of methadone and placebo maintenance treatments of narcotic addicts. The

Lancet 1979; 8141: 485-488.

NIH Consensus Conference. Effective medical treatment of opioid

addiction. National Consensus Development Panel on Effective

Medical Treatment of Opiate Addiction. Journal of the American

Medical Association 1998; 280: 1936-43.

O’Connor PG, Fiellin DA Pharmacological Treatment of HeroinDependent Patients. Annals of Internal Medicine 2000; 133: 40-54.

Sees KL, Delucchi KL, Masson C, Rosen A, Clark HW, Robillard H,

Banys P, Hall S. Methadone maintenance versus 180-day psychosocially enriched detoxification for treatment of opioid dependence: A

randomized controlled trial. Journal of the American Medical Association

2000; 283: 1303-1310.

Strain EC, Bigelow GE, Liebson IA, Stitzer ML. Moderate- vs. highdose methadone in the treatment of opioid dependence: a randomized

trial. Journal of the American Medical Association 1999; 281:1000-5.

Zaric GS, Barnett P, Brandeau M. HIV transmission and the costeffectiveness of methadone maintenance. American Journal of Public

Health 2000; 90: 1100-1111.