HomeMy WebLinkAbout2016-08-08 16-290 Council Documents (19) NIDA International Program Methadone Research Web Guide
Part B: 20 Questions and Answers Regarding Methadone
9 9
Maintenance Treatment Research
Question 1: Is methadone maintenance treatment effective for opioid addiction?
Answer: Yes.Research has demonstrated that methadone maintenance treatment is an effective
treatment for heroin and prescription narcotic addiction when measured by
• Reduction in the use of illicit drugs
• Reduction in criminal activity
• Reduction in needle sharing
• Reduction in HIV infection rates and transmission
• Cost-effectiveness
• Reduction in commercial sex work
• Reduction in the number of reports of multiple sex partners
• Improvements in social health and productivity
• Improvements in health conditions
• Retention in addiction treatment
• Reduction in suicide
• Reduction in lethal overdose
• Research Highlights
• Recent meta-analyses have supported the efficacy of methadone for the treatment of opioid
dependence. These studies have demonstrated across countries and populations that methadone
can be effective in improving treatment retention,criminal activity,and heroin use(Mattick,
Breen,Kimber,et al.,2003;Marsch, 1998).
• An overview of 5 meta-analyses and systematic reviews, summarizing results from 52 studies and
12,075 opioid-dependent participants,found that when methadone maintenance treatment was
compared with methadone detoxification treatment,no treatment,different dosages of
methadone,buprenorphine maintenance treatment,heroin maintenance treatment,and L-a-
acetylmethadol(LAAM)maintenance treatment,methadone maintenance treatment was more
effective than detoxification,no treatment,buprenorphine,LAAM,and heroin plus methadone.
High doses of methadone are more effective than medium and low doses(Amato,Davoli,
Perucci,et al.,2005).
• Patients receiving methadone maintenance treatment exhibit reductions in illicit opioid use that
are directly related to methadone dose,the amount of psychosocial counseling, and the period of
time that patients stay in treatment.Patients receiving methadone doses of 80 to 100 mg have
improved treatment retention and decreased illicit drug use compared with patients receiving 50
mg of methadone(Strain,Bigelow,Liebson,et al., 1999).Patients staying in treatment for longer
periods of time showed greater improvements than those who stayed in treatment for shorter
periods(Sells and Simpson, 1976; Simpson, 1993).
• A systematic review conducted on 28 studies involving 7,900 patients has demonstrated
significant reductions in HIV risk behaviors in patients receiving methadone maintenance
(Gowing,Farrell,Bornemann,et al.,2004).In one study that followed two separate cohorts of
• HIV-negative injection opioid users,HIV seroconversion occurred in 22 percent of 103 out-of-
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NIDA International Program Methadone Research Web Guide
treatment subjects compared with 3.5 percent of 152 subjects receiving methadone(Metzger, •
Woody,McLellan,et al., 1993).
• A randomized clinical trial in Bangkok, Thailand,included 240 heroin-dependent patients,all of
whom had previously undergone at least 6 detoxification episodes.The patients were randomly
assigned to methadone maintenance versus 45-day methadone detoxification. The study found
that the methadone maintenance patients were more likely to complete 45 days of treatment, less
likely to have used heroin during treatment,and less likely to have used heroin on the 45th day of
treatment(Vanichseni,Wongsuwan, Choopanya, et al., 1991).
• In the Treatment Outcome Prospective Study(TOPS),methadone maintenance patients who
remained in treatment for at least 3 months experienced dramatic improvements during treatment
with regard to daily illicit opioid use,cocaine use, and predatory crime. These improvements
persisted for 3 to 5 years following treatment,but at reduced levels(Hubbard,Marsden,Rachal,
et al., 1989).
• In a study of 933 heroin-dependent patients in methadone maintenance treatment programs,
during episodes of methadone maintenance,there were(1)decreases in narcotic use,arrests,
criminality,and drug dealing; (2) increases in employment and marriage; and(3)diminished
improvements in areas such as narcotic use,arrest,criminality,drug dealing,and employment for
patients who relapsed(Powers and Anglin, 1993).
• In a 2.5-year followup study of 150 opioid-dependent patients,participation in methadone
maintenance treatment resulted in a substantial improvement along several relatively independent
dimensions, including medical,social,psychological,legal,and employment problems(Kosten,
Rounsaville,and Kleber, 1987).
• A study that compared ongoing methadone maintenance with 6 months of methadone
maintenance followed by detoxification demonstrated that methadone maintenance resulted in •
greater treatment retention(median, 438.5 vs. 174.0 days)and lower heroin use rates than did
detoxification.Methadone maintenance therapy resulted in a lower rate of drug-related(mean
[SD] at 12 months,2.17 [3.88]vs.3.73 [6.86])but not sex-related HIV risk behaviors and a lower
score in legal status(mean[SD]at 12 months,0.05 [0.13]vs. 0.13 [0.19])(Sees,Delucchi,
Masson, et al., 2000).
Patient Status Before and After Methadone Maintenance Treatment—A study by McGlothlin and
Anglin(1981)examined patients from three methadone maintenance treatment programs.
Figures 1 through 5 provide the results from all three programs,which illustrate that methadone
maintenance treatment is effective in improving patients' lives in terms of time spent(1)using narcotics
daily, (2)unemployed,(3)involved in crime, (4)dealing drugs,and(5)incarcerated.
The left side of each graph describes patient behavior before methadone maintenance treatment,and the
right side of each graph depicts patient behavior following methadone maintenance treatment, including
the behavior of patients who left treatment before the year ended.
•
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NIDA International Program Methadone Research Web Guide
• Time Using Narcotics Daily Time Unemployed
so- s0-
70%
TO 70-
62%
6o- 60-
SO- s0 43.3%
40- 40-
30- 30-
20- 1616 20-
t0- 10-
0
1 Year 1 Year
Before Atter 1 Year 1 Year
Treatment Treatment Before After
Treatment Treatment
Figure 1 illustrates that the percentage of Figure 2 illustrates that the percentage of
time using daily narcotics was much time unemployed decreased after
greater before methadone maintenance methadone maintenance treatment
• treatment than after(McGlothlin and (McGlothlin and Anglin,1981).
Anglin,1981).
Days Involved In Crime Time Dealing Drugs
80- d0
TO- 70
60 60 57.7%
94- 60
40- 40
31.3%
so- 80 27.3%
20 20
12%
to- to
1 Year 1 Year 1 Year 1 Year
Before After Before Atter
Treatment Treatment Treatment Treatment
Figure 3 illustrates that the percentage of Figure 4 illustrates that the percentage of
days the patient was involved in crime time dealing drugs decreased after
decreased after methadone maintenance methadone maintenance treatment
treatment(McGlothlin and Anglin,1981). (McGlothlin and Anglin,1981).
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NIDA International Program Methadone Research Web Guide
•
Time Incarcerated
eo
70
ea
so
40
31.7%
30
20
to 6.7%
0 .M>
1Year 1Year
Before After
Treatment Treatment
Figure 5 illustrates that the percentage of
time incarcerated decreased after
methadone maintenance treatment
(McGlothlin and Anglin,1981). •
•
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NIDA International Program Methadone Research Web Guide
The Effects of Opioids(Heroin or Prescription Narcotics)and Methadone on Functional State—
Figures 6 and 7 illustrate how opioids and methadone have different effects on a patient's functional
states and moods:repeated use of heroin or prescription narcotics causes multiple cycles of elevation and
depression,but methadone promotes a relatively steady state.
Heroin Addiction: Former Addict Treated With
A Typical Addict Methadone Maintenance
P..oda.a Paectluad
State - Stat
ar
"Weight"
'Side
I —
-s
'SO"
I I
AM PM AM PM AM
AM PM AM PM AM
® Methadone Date
Figure 6 illustrates a typical day for a Hea"Intetion
person who is opioid dependent.Note that "caitneaMOW And FsnO"
the opioid-dependent person generally uses lc. k OS Mood AddEurKd°d
opioids several times each day.Each use
causes an elevation in mood:the user feels
"high."This high is followed by a rapid In contrast,Figure 7 illustrates that a
• decline in mood and functional state:the single oral dose of methadone in the
user no longer feels high and may begin to morning promotes a relatively steady state
feel sick.At the end of the day,or in the of mood and function.This graph also
morning,the user feels quite sick as the demonstrates that use of an opioid(e.g.,
result of opioid withdrawal.Overall,a injection of heroin)during methadone
typical day includes several cycles of maintenance treatment has a less intense
elevated and depressed mood and effect on mood and function than an
functional state.As an opioid-dependent injection of heroin in active users who are
person uses opioids for a period of time not in methadone treatment.The dotted
(e.g.,weeks to months),that person's level line in Figure 7 predicts the course of a
of physical dependence makes it less likely patient's mood and function if a dose of
that he or she will experience the high. methadone is omitted.Dole,Nyswander,
Continued drug use results from a desire to and Kreek(1966)found that the decline in
avoid the depressions and physical mood and function is gradual,not steep.
symptoms associated with opioid
withdrawal.
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NIDA International Program Methadone Research Web Guide
Improvements: Drugs and Crime 1 Year After the Drug Abuse Reporting Program Study •
(DARP)—The DARP study(Simpson and Sells, 1982)demonstrates that methadone maintenance
treatment is effective in reducing two problems associated with heroin addiction: illicit drug use and
crime. The study compared reductions in illicit drug use and crime by patients who received methadone
maintenance treatment and by patients who received no treatment.
Improvements:
Drugs and Crime
1 Year After DARP
so-
111 Afelhadone Mentenance
N=a9s
41% Total In overnente=58%
40- NoTreatnrent
ims N=19,?
Total Irro emeMs=4f%
30
n 27% 27%
o.
I
14%
tp.
p. 1 •
Improved: Successful:
ND Dahl;.Drug Use Abetment and No
ana No Major Crime %Nor Crime
Figure 8 illustrates that,during the first
year after treatment,41 percent of
methadone maintenance treatment patients
were no longer addicted to illicit opioids and
were not involved in major crime.In
contrast,27 percent who received no
treatment were no longer addicted to illicit
opioids and were not involved in major
crime(Simpson and Sells,1982).
Twenty-seven percent of methadone maintenance treatment patients had not used any illicit drugs and had
no arrests or incarcerations during the year after methadone maintenance treatment. In contrast, 14
percent of those not treated reported no illicit drug use or arrests.Overall,68 percent of methadone
maintenance treatment patients experienced significant improvements regarding illicit drug use and crime
in contrast to roughly 41 percent of those not treated.
•
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NIDA International Program Methadone Research Web Guide
• The Effect of Methadone Maintenance Treatment Duration on Drug Use and Crime—The DARP
study also shows that the longer patients stay in treatment,the more likely they are to remain crime free.
Time in Treatment
4o-
30.
Percent or
Pstfanes Who
Ant Abstinant
and Not Involved
in Como in l at
Posttraatmant
Year
to-
0_
tinder 3 3-12 Over 12
Montt,* Monlha Months
• Figure 9 illustrates that there is a relationship
between how long patients remain in treatment
and how well they function after treatment.In
this instance,the length of treatment was
associated with abstinence from illicit drug use
and an absence of crime.Thirty percent of
patients who stayed in treatment for more than
12 months abstained from illicit drug use and
criminal activity.Twenty-five percent of
patients in treatment from 3 to 12 months
stopped using illicit drugs and committing
crimes;of those who were in treatment for
under 3 months,20 percent abstained
(Simpson and Sells,1982).
References
Amato L, Davoli M,Perucci C,Ferri M,Faggiano F,Mattick RP.An overview of systematic reviews of
the effectiveness of opiate maintenance therapies: available evidence to inform clinical practice and
research.Journal of Substance Abuse Treatment 2005;28(4):321-29.
Dole VP,Nyswander ME,Kreek MJ.Narcotic blockade.Archives of Internal Medicine 1966;118:304-09.
Gowing L,Farrell M,Bornemann R,Ali R. Substitution treatment of injecting opioid users for prevention
of HIV infection. The Cochrane Database of Systematic Reviews, Issue 4,2004.
Hubbard RL,Marsden ME,Rachal JV,Harwood HJ,Cavanaugh ER,Ginzburg HM.Drug Abuse
Treatment:A National Study of Effectiveness.Chapel Hill: University of North Carolina Press, 1989.
• Kosten TR,Rounsaville BJ,Kleber,HD.Multidimensionality and prediction of treatment outcome in
opioid addicts: a 2.5-year follow-up. Comprehensive Psychiatry 1987;28:3-13.
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NIDA International Program Methadone Research Web Guide
Marsch LA. The efficacy of methadone maintenance interventions in reducing illicit opiate use,HIV risk •
behavior and criminality: a meta-analysis.Addiction 1998;93(4):515-32.
Mattick RP,Breen C, Kimber J,Davoli M.Methadone maintenance therapy versus no opioid replacement
therapy for opioid dependence. The Cochrane Database of Systematic Reviews, Issue 2,2003.
McGlothlin WH,Anglin MD. Shutting off methadone: cost and benefits.Archives of General Psychiatry
1981;38:885-92.
Metzger DS,Woody GE,McLellan AT,O'Brien CP,Druley P,Navaline H,et al.Human
immunodeficiency virus seroconversion among intravenous drug users in-and out-of-treatment: an 18-
month prospective follow-up.Journal of Acquired Immune Deficiency Syndrome 1993;6:1049-56.
Powers KI,Anglin MD. Cumulative versus stabilizing effects of methadone maintenance.Evaluation
Review 1993;17(3):243-70.
Sees KL,Delucchi KL,Masson C,Rosen A,Clark HW,Robillard H,et al.Methadone maintenance vs
180-day psychosocially enriched detoxification for treatment of opioid dependence.A randomized
controlled trial.JAMA 2000;283:1303-10.
Sells SB, Simpson DD(eds.). The Effectiveness of Drug Abuse Treatment. Cambridge,MA: Ballinger,
1976.
Simpson DD.Drug treatment evaluation research in the United States.Psychology of Addictive Behaviors
1993;7(2):120-28.
Simpson DD, Sells SB. Effectiveness of treatment for drug abuse: an overview of the DARP research
program.Advances in Alcohol and Substance Abuse 1982;2(1):7-29.
Strain EC,Bigelow GE,Liebson IA, Stitzer ML. Moderate-vs high-dose methadone in the treatment of
opioid dependence.A randomized trial.JAMA 1999;281:1000-05. •
Vanichseni S,Wongsuwan B,Choopanya K,Wongpanich K.A controlled trial of methadone
maintenance in a population of intravenous drug users in Bangkok: implications for prevention of HIV.
International Journal of the Addictions 1991;26(12):1313-20.
4111
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NIDA International Program Methadone Research Web Guide
111 Question 2: Does methadone maintenance treatment reduce illicit opioid use?
Answer:Yes.Patients' illicit opioid use declines,often dramatically,during methadone maintenance
treatment.However,adequate methadone dosage and basic psychosocial services are essential for
treatment effectiveness.
Research Highlights
Condelli and Dunteman(1993)examined a sample of 526 patients admitted to 17 methadone maintenance
treatment programs that participated in the Treatment Outcome Perspective Study(TOPS). This analysis
compared the length of methadone maintenance treatment with heroin use.The average short-term
treatment duration was 31 days; long-term,233 days; and continuous,725 days. The rate of heroin use
was 100 percent before treatment,39 percent after short-term treatment,40 percent after long-term
treatment,and 17 percent after continuous treatment. This study suggests that longer exposure to
methadone maintenance treatment decreases the likelihood of heroin use.
A study of 933 heroin addicts participating in methadone maintenance treatment programs compared
behavior during periods on and off methadone maintenance. The study demonstrated that during periods
on methadone maintenance,illicit narcotic use decreased significantly and reduction in illicit narcotic use
was the most prominent effect among nine indicators of treatment success(Powers and Anglin, 1993).
In the Drug Abuse Reporting Program(DARP)study,44 percent of the 895 patients who entered
methadone maintenance treatment reported no daily use of illicit narcotics in the first posttreatment year.
This represented a 56-percent decrease from 100-percent daily use in the 2 months before admission
(Simpson and Sells, 1982).
• Methadone Dose
In the Ball and Ross studies(1991),patients reduced their use of injected heroin by 71 percent compared
with preadmission levels.Illicit opioid use was directly related to methadone dosage: in patients on doses
above 71 mg per day,no heroin use was detected,whereas patients on doses below 46 mg per day were
5.16 times more likely to use heroin than those receiving higher doses.
The impact of methadone dose has been demonstrated consistently across studies and countries.Higher
(e.g.,greater than 50 mg)doses of methadone are associated with better treatment retention and decreased
illicit drug use(Strain, Stitzer,Liebson,et al., 1993; Strain,Bigelow,Liebson,et al., 1999; Capplehorn
and Bell, 1991;Caplehorn,Bell,Kleinbaum,et al., 1993;Faggiano,Vigna-Taglianti,Versino,et al.,
2003).
A meta-analysis(Faggiano et al.,2003)of 21 studies concluded that methadone dosages ranging from 60
to 100 mg per day were more effective than lower dosages in retaining patients and in reducing use of
heroin and cocaine during treatment.
The following outcomes in the meta-analysis were noted:
Retention rate—randomized clinical trials:high versus low doses at short duration followup:RR= 1.36
[1.13 to 1.63], and at longer duration followup:RR= 1.62 [0.95 to 2.77]
Self-reported opioid use—randomized clinical trials:high versus low doses WMD=-2.00 [4.77 to
0.77],high versus medium doses WMD=-1.89 [-3.43 to-0.35]
Opioid abstinence by urine toxicology at greater than 3 to 4 weeks—randomized clinical trials:high
•
versus low doses RR= 1.59 [1.16 to 2.18],high versus medium doses RR= 1.51 [0.63 to 3.61]
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NIDA International Program Methadone Research Web Guide
Cocaine abstinence by urine toxicology at greater than 3 to 4 weeks—randomized clinical trials:high •
versus low doses RR= 1.81 [1.15 to 2.85]
Overdose mortality—high dose versus low dose at 6 years' followup:RR=0.29 [0.02 to 5.34];high
dose versus medium dose at 6 years'followup:RR=0.38 [0.02 to 9.34];medium dose versus low dose at
6 years'followup:RR=0.57 [0.06 to 5.06]
One study noted lower rates of opioid-positive urine samples(53%vs. 62%,p<.05)in patients who were
being treated with 80 to 100 mg of methadone compared with those who were being treated with 40 to
50 mg(Strain et al., 1999).
Counseling Services
Counseling services improve treatment outcomes over the provision of methadone alone(Amato,
Minozzi,Davoli,et al.,2004). The importance of adding counseling services to methadone maintenance
was demonstrated in a study that randomly assigned new patients to three levels of care: (1)methadone
alone,(2)methadone plus standard counseling services,and(3)methadone plus enhanced services
(counseling,medical/psychiatric,employment,and family therapy services).Patients who received the
standard or enhanced services had higher treatment retention rates and less opiate use than those who
received methadone alone(McLellan,Arndt,Metzger,et al., 1993).A cost-effectiveness analysis of these
subjects after 1 year revealed that the standard counseling services were most cost-effective(Kraft,
Rothbard,Hadley,et al., 1997).
Treatment Duration
In one study, 82 percent of 105 patients who discontinued methadone relapsed to intravenous drug use
within 12 months(Ball and Ross, 1991). Concerns over high relapse rates have led authorities to advocate •
for maintenance treatment as long as the patient(1)continues to benefit, (2)wishes to remain, (3)is at
risk of relapse,(4)suffers no significant side effects,and(5)stays in treatment as long as treatment is
needed, as determined by the clinician(Payte and Khuri, 1993).
DARP studies of opioid-dependent patients 12 years following admission to treatment showed that illicit
opioid use declined progressively over time until year 6,when it stabilized at about 40 percent for"any"
use and 25 percent for"daily"use(Simpson,Joe,Lehman,et al., 1986).
In both the DARP and TOPS studies,long treatment duration was the strongest predictor of reduced
heroin use among methadone maintenance patients.
Reductions in Illicit Opioid Use During and After Methadone Maintenance Treatment—The DARP
and TOPS studies of two different groups of heroin-addicted patients were conducted several years apart.
Both demonstrated about a 40-percent reduction in illicit opioid use at the end of 1 year after methadone
maintenance treatment.
•
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NIDA International Program Methadone Research Web Guide
• TOPS Study DARP Study
100- N=4,184
ioo 100% N=ass
So
00-
SO-
00-
ss 70- sss%
70
Weekly Heroin ea
-
so- Users
6" 44%
40
a 4p
30-
30
30- -1816 +1096 " 24%
20
10-
10-
II • i
1 Year ist Year 3-S Years e t
Before After After 2 taonem tat Year 3rd Year
TreMment Treatment Treatment Before Atter After
Treatment Treatment Treatment
Daily Opioid Users
Figure 10 illustrates that,in the TOPS
study,almost 64 percent of the patients Figure 11 illustrates that in the DARP
used heroin at least weekly in the year study,44 percent of methadone
before treatment;however,about 18 maintenance treatment patients used
• percent used heroin at least weekly in the heroin daily in the year following
year after treatment,and about 19 treatment and 24 percent used heroin
percent continued heroin use weekly 3 to daily 3 years after treatment.This
5 years after treatment(Hubbard, represents significant reductions from the
Marsden,Rachal,et al.,1989). 100 percent who had used heroin daily in
the 2 months before admission(Simpson
and Sells,1982).Daily illicit opioid use
continued to decline steadily for the next 3
years.
•
Part B-11
NIDA International Program Methadone Research Web Guide
DARP: Changes in Illicit Opioid Use: Pretreatment to 12-Year Followup—Among patients in the •
DARP studies, (1)methadone maintenance treatment resulted in a rapid decline in illicit opioid use and
(2)this reduction in illicit opioid use remained steady for 12 years(Simpson and Sells, 1990).
Percent Using Opioids
Each Year
140
ao
4o
to
D
PretreahnnA Year 1 Year 2 Year b Year 8 Year 12
fl N9ArtlOpiaiiUsg
■Lowe Mae Deily lige
■Date
Figure 12 illustrates that improvements
among patients who used no illicit opioids
and who used opioids less than daily
persisted into the 12th year after treatment.
About one-half of those patients treated with
methadone maintenance reported no illicit
drug use after 12 years.The benefits •
associated with methadone maintenance
treatment seem to improve over time.For
example,at the end of 1 year,about 50
percent of the subjects reported daily illicit
drug use,but by year 12,the proportion
using illicit drugs on a daily basis was
reduced to about 25 percent(Simpson and
Sells,1990).
•
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NIDA International Program Methadone Research Web Guide
. Reduction of Heroin Use by Length of Stay in Methadone Maintenance Treatment—The length of
stay in methadone maintenance treatment is associated with a reduction in heroin use: longer lengths of
stay are associated with greater reductions in heroin use. In addition, leaving methadone maintenance
treatment is associated with a return to injection drug use in 82 percent of patients within 1 year(Ball and
Ross, 1991).
Percentage of Heroin Use
Among New Admissions
,co- 97% Nat 617
90-
so-
.Q TO_ O#%
g0
.Si
23%
iii
40-
30-
20-
0
• Prtlra.On.nt LessThen Average alay LameAran
8Methsof • aths te Wreatinoat
Tamanlnt 45 VOW! 4.5 Yaw.
of Tr.atinrrt o.neon
Figure 13 illustrates that heroin use among
a group of 617 new admissions was nearly
100 percent.Among patients who stayed in
treatment for less than 6 months,about 67
percent reported using heroin.Among
patients whose average stay in methadone
maintenance treatment was 6 months to
4.5 years,about 23 percent reported using
heroin.Among patients who remained in
treatment more than 4.5 years,about 8
percent reported using heroin(Ball and
Ross,1991).
References
Amato L,Minozzi S,Davoli M, Vecchi S,Ferri M,Mayet S.Psychosocial combined with agonist
maintenance treatments versus agonist maintenance treatments alone for treatment of opioid dependence.
The Cochrane Database of Systematic Reviews,Issue 4,2004.
Ball JC,Ross A. The Effectiveness of Methadone Maintenance Treatment.New York,NY: Springer-
Verlag Inc., 1991.
Caplehorn JRM,Bell J.Methadone dosage and retention of patients in maintenance treatment. The
Medical Journal ofAustralia 1991;154:195-99.
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NIDA International Program Methadone Research Web Guide
Caplehorn JRM,Bell J,Kleinbaum DG, Gebski VJ.Methadone dose and heroin use during maintenance •
treatment.Addiction 1993;88:119-24.
Condelli WS,Dunteman GH. Exposure to methadone programs and heroin use.American Journal of
Drug and Alcohol Abuse 1993;19:65-78.
Faggiano F, Vigna-Taglianti F, Versino E,Lemma P.Methadone maintenance at different dosages for
opioid dependence. The Cochrane Database of Systematic Reviews,Issue 3,2003.
Hubbard RL,Marsden ME,Rachal JV,Harwood HJ,Cavanaugh ER, Ginzburg HM.Drug Abuse
Treatment:A National Study of Effectiveness. Chapel Hill:University of North Carolina Press, 1989.
Kraft KM,Rothbard AB,Hadley TR,McLellan AT,Asch DA.Are supplementary services provided
during methadone maintenance really cost-effective?American Journal of Psychiatry 1997;154:1214-19.
McLellan AT,Arndt IO,Metzger DS,Woody GE,O'Brien CP.The effects of psychosocial services in
substance abuse treatment.JAMA 1993;269(15):1953-59.
Payte JT,Khuri ET. Treatment duration and patient retention.In:State Methadone Treatment Guidelines.
Rockville,MD: Center for Substance Abuse Treatment, 1993.
Powers KI,Anglin MD. Cumulative versus stabilizing effects of methadone maintenance.Evaluation
Review 1993;17(3):243-70.
Simpson DD,Joe GW,Lehman WEK, Sells SB.Addiction careers: etiology,treatment,and 12-year
follow-up outcomes.Journal of Drug Issues 1986;16(1):107-21.
Simpson DD, Sells SB.Effectiveness of treatment for drug abuse:an overview of the DARP research
program.Advances in Alcohol and Substance Abuse 1982;2(1):7-29.
Simpson DD, Sells SB(eds.). Opioid Addiction and Treatment:A 12-Year Follow-Up.Malabar,FL:
Krieger Publishing Company, 1990.
Strain EC,Bigelow GE,Liebson IA, Stitzer ML.Moderate-vs high-dose methadone in the treatment of
opioid dependence.A randomized trial.JAMA 1999;281:1000-05.
Strain EC, Stitzer ML,Liebson IA,Bigelow GE.Dose-response effects of methadone in the treatment of
opioid dependence.Annals of Internal Medicine 1993;119:23-37.
•
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NIDA International Program Methadone Research Web Guide
• Question 3: Does methadone maintenance treatment reduce HIV risk behaviors
and the incidence of HIV infection among opioid-dependent injection drug users?
Answer: Yes.The daily oral administration of adequate dosages of methadone reduces the need for
opioid-dependent individuals to inject drugs.By decreasing injection drug use,methadone maintenance
treatment helps reduce the spread of diseases transmitted through needle sharing,such as human
immunodeficiency virus(HIV)infection,hepatitis C virus(HCV),and other bloodborne infections
(Sullivan,Metzger,Fudala,et al.,2005;Gowing,Farrell,Bornemann, et al., in press).
Research Highlights
A systematic review of 23 studies of 7,900 patients in diverse countries and settings reported significant
decreases in the following HIV risk behaviors among patients receiving methadone maintenance
treatment:(1)the proportion of opioid-dependent injection drugs,(2)the reported frequency of injection,
(3)levels of sharing of injection equipment, (4)illicit opioid use,(5)reduction in the proportion of
opioid-dependent injection drug users reporting multiple sex partners or exchanges of sex for drugs or
money,and(6)reductions in cases of HIV infection among opioid-dependent injection drug users.
However, it should be noted that methadone treatment had little or no effect on the use of condoms. The
authors concluded that the provision of agonist treatment for opioid dependence should be supported in
countries with emerging HIV and injection drug use problems as well as in countries with established
populations of injection drug users(Gowing,Farrell,Bornemann,et al.,2004).
These results support an earlier meta-analysis of 11 studies that found a consistent, statistically significant
relationship between methadone maintenance treatment and the reduction of HIV risk behaviors. This
meta-analysis found that methadone maintenance treatment had a small-to-moderate effect in reducing
• HIV risk behaviors(Marsch, 1998).
• A study that evaluated HIV risk behavior in patients receiving ongoing methadone maintenance
compared with patients receiving 6 months of methadone maintenance followed by detoxification
demonstrated that those patients who received ongoing methadone maintenance treatment
reported lower HIV drug(but not sex)risk behaviors after 6 and 12 months of treatment(Sees,
Delucchi,Masson,et al.,2000).
• In New Haven, CT, 107 methadone-maintained injection drug users who were not in treatment
were surveyed regarding their risk behaviors.The frequency of injections was found to be 50 to
65 percent(p<.001)higher among the out-of-treatment subjects(Meandzija, O'Connor,
Fitzgerald,et al., 1994).
• In a 3-year field study of methadone maintenance treatment programs in New York,NY,
Philadelphia,PA,and Baltimore,MD,treatment was found to be effective in reducing injection
drug use and needle sharing by most heroin addicts. Of 388 patients who remained in treatment
for 1 year or more,71 percent had stopped injection drug use.Conversely, 82 percent of patients
who left treatment relapsed rapidly to injection drug use(Ball,Lang,Meyers,et al., 1988).
• Abdul-Quader,Friedman,Des Jarlais,et al. (1987)reported that both the frequency of drug
injection and the frequency of drug injection in shooting galleries were significantly reduced by
the amount of time spent in methadone maintenance treatment.
• A study by Serpelloni,Carrieri,Rezza,et al. (1994)examined the effect of methadone
maintenance treatment on HIV infection incidence among injection drug users.The study found
that the amount of time spent in methadone maintenance treatment was the major determinant in
I remaining HIV-free,which confirms the effectiveness of long-term programs in reducing the risk
of HIV infection.Indeed,the risk of HIV infection increased 1.5 times for every 3 months spent
• out of methadone treatment in the past 12 months immediately preceding seroconversion.The
study noted that higher daily methadone doses were associated with a reduction in HIV infection.
Part B-15
NIDA International Program Methadone Research Web Guide
• A study by Weber,Ledergerber, Opravil, et al. (1990)examined the role of methadone •
maintenance treatment in reducing the progression of HIV infection among 297 current and
former injection drug users with asymptomatic HIV infection. The study showed that HIV
infection progresses significantly more slowly in those who receive methadone maintenance
treatment and those who are drug free than in active injection drug users.
• In Philadelphia,PA,a longitudinal study of HIV infection and risk behaviors among 152 injection
drug users in methadone maintenance treatment and 103 out-of-treatment injection drug users
found significantly lower rates of risk behavior, including needle sharing, injection frequency,
shooting gallery use,and visits to crack houses among the methadone-maintained users.While 70
percent of the out-of-treatment cohort reported sharing needles during the 6 months before entry
into the study,only 30 percent of those in treatment reported sharing needles during this same
interval.
• At entry into this study, 18 percent of the out-of-treatment subjects and 11 percent of the
methadone-maintained clients tested positive for antibodies to HIV.After 18 months of study,33
percent of the out-of-treatment cohort were infected,whereas 15 percent of the methadone clients
tested positive(p<0.01). The incidence of new infection was strongly associated with the level
of participation in methadone treatment.Among those who remained in methadone treatment for
the entire 18-month study period, 3.5 percent became infected.Among those who remained out of
treatment,22 percent became infected with HIV(Metzger, Woody,McLellan, et al., 1993).
• Another study of HIV seroconversion followed 56 patients who were continuously enrolled in
methadone maintenance and compared them with 42 patients who had intermittent methadone
treatment. Subjects in continuous treatment had a seroconversion rate of 0.7 per 100 person years
(95%CI=0.1, 5.3),and those with interrupted treatment had a rate of 4.3 per 100 person years
(95%CI=2.2, 8.6)(Williams,McNelly, Williams,et al., 1992).
• A relatively short-term study of methadone maintenance versus control in a prison system in •
Australia found reductions in opioid use but no changes in HIV or HCV incidence(Dolan,
Shearer,MacDonald,2003).
The following two visuals—HIV Infection Rates by Methadone Maintenance Treatment Status and 18-
Month HIV Seroconversion by Methadone Maintenance Treatment Retention—depict findings from this
study.
•
Part B-16
NIDA International Program Methadone Research Web Guide
HIV Infection Rates by 18-Month HIV Seroconversion by
Methadone Maintenance Methadone Maintenance
Treatment Status Treatment Retention
so
40- -
ss%
32%
22%
ae
g za_
23%
E
A 2°" ta%
15% 15%
s6v10-
tr 1a-
3.655 4"
o ® t
In Treatment Partia t eatmant No Treatnwot
Baseline a Months 12 Months 15 Months et.35) pi a 4) (**18)
in Treatment(N= aa) Treatment Status
Out at Treatment(N-ate)
• Figure 14 illustrates that at the beginning
of this study,18 percent of the out-of- Figure 15 illustrates that among those who
remained in methadone maintenance
treatment subjects and 11 percent of the treatment for the entire 18-month study
methadone-maintained clients tested period,3.5 percent became infected with
positive for antibodies to HIV.After 18 HIV.Among those who remained out of
months,nearly twice as many(33 percent) treatment,22 percent became infected
of the out-of-treatment cohort were HIV- with HIV(Metzger et al.,1993).
positive,whereas only 15 percent of the
methadone clients tested positive(p<.01).
The incidence of new infection was
strongly associated with the level of
participation in methadone treatment.
Rapid Return to Injection Drug Use Following Premature Termination of Methadone Maintenance
Treatment—In a 3-year field study of methadone maintenance treatment programs in New York,NY,
Philadelphia,PA, and Baltimore,MD,methadone maintenance treatment was found to be effective in
reducing injection drug use and needle sharing by most heroin addicts. Of 388 patients who remained in
treatment for 1 year or more,71 percent had stopped injection drug use. Conversely,82 percent of the 105
patients who left treatment relapsed rapidly to injection drug use(Ball et al., 1988).
•
Part B-17
NIDA International Program Methadone Research Web Guide
Rapid Return to injection Drug •
Use Following Premature
Termination of Methadone
Maintenance Treatment
Ino
t 50 82,191
80 72.7%
.Y 10-12
70 � Months
ti3
57.6% _---- 7.9
$0
Months
so
Mona+s
e 40 26.844 1-3
$• 30 Months
20
10 Months Since Dropout
0
ht 9 2 4 8 6 7 6 6 10 11 12
Treatment
(N=388 Male PotienIs)
Figure 16 illustrates that methadone maintenance
treatment is associated with reductions in injection drug
use and the risks related to HIV infection.When drug users
leave methadone maintenance treatment prematurely,they
have an increased likelihood of returning to injection drug
use(Ball et al.,1988).
References
Abdul-Quader OS,Friedman SR,Des Jarlais DC,Marmor MM,Maslansky R,Bartelme S.Methadone
maintenance and behavior by intravenous drug users that can transmit HIV. Contemporary Drug
Problems 1987;14:425-33.
Ball JC,Lange WR,Meyers CP,Friedman SR.Reducing the risk of AIDS through methadone
maintenance treatment.Journal of Health and Social Behavior 1988;29:214-226.
Dolan KA, Shearer J,MacDonald M,Mattick RP,Hall W,Wodak AD.A randomized controlled trial of
methadone maintenance treatment versus wait list control in an Australian prison system.Drug&Alcohol
Dependence 2003;72(1):59-65.
Gowing L,Farrell M,Bornemann R,Ali R. Substitution treatment of injecting opioid users for prevention
of HIV infection. The Cochrane Database of Systematic Reviews,Issue 4,2004.
Gowing LR,Farrell M,Bornemann R, Sullivan L,Ali,R.Methadone treatment of injecting opioid users
for prevention of HIV infection.Journal of General Internal Medicine, in press.
Marsch LA.The efficacy of methadone maintenance interventions in reducing illicit opiate use,HIV risk
behavior and criminality: a meta-analysis.Addiction 1998;93(4):515-32.
Meandzija B,O'Connor PG,Fitzgerald B,Rounsaville BJ, Kosten TR.HIV infection and cocaine use in
methadone maintained and untreated intravenous drug users.Drug&Alcohol Dependence
1994;36(2):109-13.
Metzger DS, Woody GE,McLellan AT,O'Brien CP,Druley P,Navaline H,et al.Human
immunodeficiency virus seroconversion among intravenous drug users in-and out-of-treatment: an 18-
month prospective follow-up.Journal of Acquired Immune Deficiency Syndrome 1993;6:1049-56.
Part B-18
NIDA International Program Methadone Research Web Guide
• Sees KL,Delucchi KL,Masson C,Rosen A,Clark HW,Robillard H,et al.Methadone maintenance vs
180-day psychosocially enriched detoxification for treatment of opioid dependence. A randomized
controlled trial.JAMA 2000;283:1303-10.
Serpelloni G, Carrieri MP,Rezza G,Morganti S,Gomma M,Binkin N.Methadone treatment as a
determinant of HIV risk reduction among injecting drug users: a nested case-control study.AIDS Care
1994;6:215-20.
Sullivan LE,Metzger DS,Fudala PJ,Fiellin DA. Decreasing international HIV transmission:the role of
expanding access to opioid agonist therapies for injection drug users.Addiction 2005;100(2):150-58.
Weber RB,Ledergerber M,Opravil M,Siegenthaler W,Luthy R.Progression of HIV infection in misuers
of injected drugs who stop injecting or follow a programme of maintenance treatment with methadone.
British Medical Journal 1990;301:1362-5.
Williams AB,McNelly EA, Williams AE,D'Aquila RT.Methadone maintenance treatment and HIV type
1 seroconversion among injecting drug users.AIDS Care 1992;4(1):35-41.
•
•
Part B-19
NIDA International Program Methadone Research Web Guide
Question 4: Does methadone maintenance treatment reduce criminal activity? •
Answer: Yes.Patients are less likely to become involved in criminal activity while in methadone
maintenance treatment.
• Patients who remain in methadone maintenance treatment for long periods of time are less likely
to be involved in criminal activity than patients in treatment for short periods.
• The availability of methadone maintenance treatment in a community is associated with a
decrease in that community's criminal activity,particularly theft.
Research Highlights
• In a meta-analysis of 24 studies,results indicate an overall small-to-medium effect of r=-0.25
(unweighted)of the impact of methadone maintenance on criminal activity.A large effect size of
r=0.70(unweighted)was seen in those studies that investigated the efficacy of methadone
maintenance treatment in reducing drug-related criminal behaviors.A small-to-moderate effect of
r=0.23 (unweighted)was obtained when both drug and property-related criminal activities were
evaluated. Finally,a small effect of r=0.17(unweighted)was demonstrated when drug-and
nondrug-related criminal behaviors were combined(Marsch, 1998).
• In the Treatment Outcome Perspective Study(TOPS),32 percent of the methadone maintenance
patients acknowledged committing one or more predatory crimes in the year before treatment,but
only 10 percent continued these activities during treatment. By 3 to 5 years after leaving
treatment, only 16 percent of the patients reported predatory criminal activity—a reduction of
one-half the pretreatment level(Hubbard,Marsden,Rachal,et al., 1989).
• Among the 617 patients studied by Ball and Ross(1991),there was a 70.8-percent decline in •
crime-days within the 4-month methadone maintenance treatment period.This decline was
followed by continuing,but less dramatic, declines in mean crime-days among those in treatment
for 1 to 3 years. Those in treatment for 6 or more years had the lowest rate of crime-days per year
(14.5).
• The Powers and Anglin(1993)retrospective study of 933 heroin addicts demonstrated that rates
of criminality, arrests, and drug dealing decreased during episodes of methadone maintenance
treatment when compared with addicts not in treatment.
• In the National Treatment Outcome Research Study,acquisitive criminal behavior decreased in
the majority of the 333 patients except those(n=88)who were felt to have a poor treatment
response. In these patients,there was no change in this type of criminal activity(Gossop,
Marsden, Stewart, et al.,2000).
• The meta-analysis by Mattick,Breen,Kimber, et al. (2003)revealed that criminal activity
declined in consort with reductions in heroin use,although the advantage for methadone beyond
control in reducing criminal activity was not statistically significant(3 studies,363 patients:RR=
0.39,95%CI: 0.12-1.25).
The Effects of Methadone Maintenance Treatment on Crime-Days—The Ball and Ross study(1991)
of 617 patients demonstrated that methadone maintenance treatment is associated with a dramatic decline
in the average number of crime-days per year.
•
Part B-20
NIDA International Program Methadone Research Web Guide
11110
Effect of Methadone Treatment
on Crime Days
250 237.5
200—
70.8% a4%
Dachas an Crime Days
150—
Mean
Crime Days
Per Year
100-
de.3
50—
29.3 921 322.8
21.1
12.4 a 14.5
MM MI0
23.5 Months it-Month 1 2 .3 4 5 Ss
Ptelreabmnl Adrfies on Yearn In Methadone Mee tenance
Pence Treetrnec1
Figure 17 illustrates that the average number of crime-days
per year before treatment was 237.During the 4-month
• initial methadone maintenance treatment,the average
number of crime-days per year was 69.This represents
about a 71-percent decline.This dramatic decline was
followed by continuing,but less dramatic,declines in the
average number of crime-days among those in methadone
maintenance treatment for 1 to 3 years.Patients who
remained in methadone maintenance treatment for 6 or
more years reported only 14.5 crime-days per year,
representing a 94-percent decline in average number of
crime-days(Ball and Ross,1991).
Crime Before and During Methadone Maintenance Treatment at Six Programs—Ball and Ross
(1991)found a dramatic decline in crime when comparing pretreatment crime-days per year and the
number of crime-days per year after 6 months or more in methadone maintenance treatment.
I •
Part B-21
NIDA International Program Methadone Research Web Guide
Average Number of Crime •
Days Reported
300'- 1‘14191
792
273
264
250-
224
210
200s.
IV 189
2.
a 150-
a
a
100"
50 37
27 21
15 14 19
0
Program: A B C DE. F
Crime Days Pet Yeat When Addicted
Crime Days Per Year After 6 Months at More in Treatment
Figure 18 illustrates the average number of •
crime-days reported by patients in six
methadone maintenance treatment programs.
Although there are differences among
programs,the dramatic decrease in crime-days
before and during methadone maintenance
treatment occurs for all six programs.Crime
was reduced by approximately 90 percent in
program A,95 percent in program B,93
percent in program C,87 percent in program
D,92 percent in program E,and 90 percent in
program F.The average reduction in crime for
those in methadone maintenance treatment
was just over 91 percent(Ball and Ross,1991).
The cost benefits of methadone maintenance treatment become obvious when one compares the costs of
providing treatment with the social costs that would have occurred if the crime level had continued.
References
Ball JC,Ross A. The Effectiveness of Methadone Maintenance Treatment:Patients, Programs, Services,
and Outcomes.New York: Springer-Verlag, 1991.
Gossop M,Marsden J, Stewart D,Rolfe A.Patterns of improvement after methadone treatment: 1 year
follow-up results from the National Treatment Outcome Research Study.Drug&Alcohol Dependence
2000;60(3):275-86.
Hubbard RL,Marsden ME,Rachal JV,Harwood HJ, Cavanaugh ER, Ginzburg HM.Drug Abuse
Treatment:A National Study of Effectiveness. Chapel Hill:University of North Carolina Press, 1989. •
Part B-22
NIDA International Program Methadone Research Web Guide
• Marsch LA. The efficacy of methadone maintenance interventions in reducing illicit opiate use,HIV risk
behavior and criminality: a meta-analysis.Addiction 1998;93(4):515-32.
Mattick RP,Breen C,Kimber J,Davoli M.Methadone maintenance therapy versus no opioid replacement
therapy for opioid dependence. The Cochrane Database of Systematic Reviews,Issue 2,2003.
Powers KI,Anglin MD. Cumulative versus stabilizing effects of methadone maintenance.Evaluation
Review 1993;17(3):243-70.
•
III
Part B-23
NIDA International Program Methadone Research Web Guide
Question 5: Does methadone maintenance treatment improve the likelihood of •
obtaining and retaining employment?
Answer: Yes. The likelihood of becoming and remaining employed is increased for patients who
participate in methadone maintenance treatment.
• In an early study of 100 chronic heroin users who were admitted to methadone maintenance
treatment,the employment rate increased from 21 percent at admission to 65 percent 1 year later
(Maddux and McDonald, 1973;Maddux and Desmond, 1979).
• A study of 92 males admitted to methadone maintenance treatment programs from 1971 through
1973 demonstrated that,following methadone maintenance treatment,employment increased
about 18 percent(Harlow and Anglin, 1984).
• In a 10-year followup study,95 chronic opioid users who spent at least 1 cumulative year in
methadone maintenance treatment were compared with 77 chronic opioid users who spent less
than 1 cumulative year in methadone maintenance treatment. Those who were on methadone
maintenance treatment for more than 1 year had a higher average time employed(mean of 42
months)than those who were in treatment for less than 1 year(mean of 35 months)(Maddux and
Desmond, 1992).
• The Powers and Anglin(1993)study of 933 heroin addicts in methadone maintenance treatment
demonstrated that rates of employment(and marriage)increased during treatment.
• Methadone maintenance patients in the Treatment Outcome Perspective Studies(TOPS)had
small changes in employment rates during and following treatment compared with pretreatment
rates.Although 24 percent of the patients reported full-time employment in the year before
admission,this rate did not increase significantly during treatment.It declined abruptly in the 3 •
months following discharge, improved to 29 percent by year 2,and dropped off again to less than
pretreatment rates by years 3 to 5 following treatment(Hubbard,Marsden,Rachal, et al., 1989).
• In a study that compared ongoing methadone maintenance with 6 months of methadone
maintenance followed by detoxification,no difference was seen in employment,although nearly
50 percent of patients were employed at entry into the study(Sees,Delucchi,Masson,et al.,
2000). Similarly,a study comparing methadone maintenance with methadone-free treatment saw
improvements in both groups over time but no difference in outcomes across treatment type
(Abbot,Moore,Delaney, et al., 1999). The McLellan trial,which evaluated varying levels of
ancillary services,provides some insight into these negative findings. Specifically,the group of
patients in the McLellan trial that received enhanced psychosocial services(including
employment counseling)was noted to have improvements in employment status with methadone
treatment compared with patients who received no or standard services(McLellan,Arndt,
Metzger, et al., 1993).
Changes in Employment During and After Methadone Maintenance Treatment—Figures 19 and 20
illustrate the effects of methadone maintenance treatment on full-time employment as demonstrated by
the TOPS and DARP studies.In one study,there was little effect,but in the other,methadone
maintenance treatment was associated with significant increases in full-time employment.
•
Part B-24
NIDA International Program Methadone Research Web Guide
Changes In Employment During Employment Before and After
Treatment Treatment
r0- N 285 r+a- N a 895
50- 00- 39 59 6$
Percent of 50..
Patients
Employed
40 at 40-
33
30- 29% 30-
24% 25%
20- 2095 18% 20-
10- iQ-
f
0
U
1 Year 1 at ist Year eed Teat 3 to 6 1 Year 1 Year and Year 3rd Year
Before 3 Months After Alter Years After Wore After After Atter
Treatment Wino Treatment Treatment Treatment Treatment Treatment Treatment Treatment
Vestment
Source: DARP(Simpson and Sells,1982)
Source: TOPS(Hubbard et al.,1989)
411 Figure 19 illustrates that patients in TOPS studies In contrast,Figure 20 illustrates that the
experienced small and inconsistent changes in full- DARP studies reported an abrupt increase
time employment rates during and after from 33-percent full-time employment before
treatment.Employment rates were about 24 treatment to nearly 60 percent after treatment
percent 1 year before treatment,ranged from 20 (Simpson and Sells,1982).
to 25 percent during the first year after treatment,
rose to 29 percent during the second year after
treatment,and declined to 18 percent 3 to 5 years
after treatment(Hubbard et al.,1989).
References
Abbott PJ,Moore B,Delaney H,Weller S.Retrospective analyses of additional services for methadone
maintenance patients.Journal of Substance Abuse Treatment 1999;17(1-2):129-37.
Harlow LL,Anglin MD.Time series design to evaluate effectiveness of methadone maintenance
intervention.Journal of Drug Education 1984;14(1):53-72.
Hubbard RL,Marsden ME,Rachal JV,Harwood HJ, Cavanaugh ER, Ginzburg HM.Drug Abuse
Treatment:A National Study of Effectiveness. Chapel Hill:University of North Carolina Press, 1989.
Maddux JF,Desmond DP. Crime and treatment of heroin users. The International Journal of the
Addictions 1979;14(7):891-904.
Maddux JF,Desmond DP.Ten-year follow-up after admission to methadone maintenance.American
Journal of Drug and Alcohol Abuse 1992;18(3):289-303.
Maddux JF,McDonald LK. Status of 100 San Antonio addicts one year after admission to methadone
maintenance.Drug Forum 1973;2:239-52.
•
Part B-25
NIDA International Program Methadone Research Web Guide
McLellan AT,Arndt IO,Metzger DS, Woody GE, O'Brien CP. The effects of psychosocial services in •
substance abuse treatment.JAMA 1993;269(15):1953-59.
Powers KI,Anglin MD. Cumulative versus stabilizing effects of methadone maintenance.Evaluation
Review 1993;17(3):243-70.
Sees KL,Delucchi KL,Masson C,Rosen A, Clark HW,Robillard H, et al. Methadone maintenance vs
180-day psychosocially enriched detoxification for treatment of opioid dependence.A randomized
controlled trial.JAMA 2000;283:1303-10.
Simpson DD, Sells SB. Effectiveness of treatment for drug abuse:an overview of the DARP research
program.Advances in Alcohol and Substance Abuse 1982;2(1):7-29.
•
•
Part B-26
NIDA International Program Methadone Research Web Guide
• Question 6: What effect can methadone maintenance treatment have on the use
of alcohol and other drugs?
Answer: Research outcomes are mixed regarding the effect of methadone maintenance treatment on the
use of illicit drugs other than opioids. That is,some research indicates that methadone maintenance
treatment is associated with decreases in the use of alcohol,cocaine, and marijuana;other research
indicates increases in the use of these drugs. It is important to note that the medication methadone has no
direct effect and is not intended to have an effect on rates of alcohol and other drug use.Patients receiving
methadone maintenance who disengage from interactions with others who are actively using drugs are
less likely to engage in these behaviors. In addition,reductions in alcohol and drug use result from the
counseling services included in methadone maintenance treatment. When these services ares specifically
designed to reduce alcohol and other drug use, such reductions are likely.
Research Highlights
• In the Drug Abuse Reporting Program(DARP)studies,there were reductions in nonopioid drug
use(except marijuana)among 895 methadone maintenance patients, comparing the 2-month
period before admission and the year following discharge. The reduction in nonopioid use was 13
percent—from 54 percent of patients who reported any use before admission to 41 percent at the
1-year followup point(Simpson and Sells, 1982).
• In the 12-year DARP followup study, "heavy drinking"was reported by 21 percent of the sample
in the month before treatment; it rose to 31 percent during the first year afterward and then
declined to 22 percent by year 12. One-half of the patients reported substituting alcohol for
opioids after stopping daily illicit opioid use(Lehman,Barrett,and Simpson, 1990).
• • In a study comparing buprenorphine maintenance with methadone maintenance for patients with
opioid dependence and cocaine abuse, both treatments resulted in significant declines in opioid
use but were indistinguishable in terms of their effect on comorbid cocaine use(Schottenfeld,
Pakes,Oliveto,et al., 1997).
Methadone Maintenance Treatment and General Drug Abuse—Among three cohorts of new-
admission patients in methadone maintenance treatment,Ball and Ross(1991)found that the use of all
illicit drugs,except marijuana,decreased markedly in relation to time in treatment. These three cohorts
had been in treatment 6 months,4.5 years,or more than 4.5 years.
In the Treatment Outcome Perspective Study(TOPS),90 percent of methadone maintenance treatment
patients who reported drug use at intake reported a reduction in use during the first 3 months of treatment.
For 80 percent,this reduction is large. In the year before treatment, less than 10 percent of methadone
maintenance treatment patients were minimal drug users.During treatment,more than 50 percent of the
patients were minimal drug users.During the 3 to 5 years after discharge,less than 32.5 percent were
minimal drug users(Hubbard,Marsden,Rachal,et al., 1989).
In the National Treatment Outcome Research Study(NTORS),of 333 patients receiving methadone
maintenance in the United Kingdom,overall declines were seen in the use of heroin,barbiturates,
amphetamines,cocaine, and crack cocaine among patients receiving methadone maintenance.Alcohol
use,however,did not change over time(Gossop,Marsden, Stewart, et al.,2000).
In another evaluation of 513 heroin users in methadone treatment in TOPS,a decline was observed in the
use of cocaine, amphetamines, illegal methadone,tranquilizers,and marijuana,but not alcohol(Fairbank,
Dunteman,and Condelli, 1993).
• The Powers and Anglin study(1993)of 933 heroin addicts in methadone maintenance programs
demonstrated that during episodes of methadone maintenance treatment,illicit opioid use decreased,but
Part B-27
NIDA International Program Methadone Research Web Guide
alcohol and marijuana levels increased moderately.Kreek(1991)observed that by 1990,alcoholism was •
identified in 40 or 50 percent of new admissions to methadone maintenance treatment programs,and
cocaine abuse was found in 70 to 90 percent. She also estimated that 20 to 46 percent of patients in
effective methadone maintenance treatment programs continue using cocaine,and 15 to 20 percent of
methadone maintenance treatment patients regularly inject cocaine.
Methadone Maintenance Treatment and Cocaine Use—Among the TOPS patients who remained in
methadone maintenance treatment at least 3 months,26.4 percent had used cocaine regularly the year
before treatment. This rate fell to 10 percent during the first 3 months of treatment but returned to 16
percent by 3 to 5 years after discharge.Altogether,40 percent of methadone maintenance treatment
patients who regularly used cocaine before treatment and stayed in treatment for at least 3 months
abstained from cocaine use in the year after treatment(Hubbard et al., 1989).
In the TOPS studies, although 70 percent of heroin abusers had frequently used cocaine the year before
treatment, it was the primary drug of choice for only 2 percent of methadone maintenance treatment
patients(Hubbard et al., 1989).
In the new admissions group of a six-program study(n=345),46.8 percent of 126 patients had used
cocaine in the past 30 days.Among the average-stay group(up to 4.5 years in treatment),27.5 percent
still used cocaine;this rate dropped to 17.2 percent among the long-term group of 146 patients who had
been in continuous treatment for more than 4.5 years(Ball and Ross, 1991).
A study evaluating the effect of methadone dose on treatment outcomes noted that patients receiving 50
mg of methadone, compared with those receiving 20 mg or 0 mg,had a reduced rate of opioid-positive
urine samples(56.4%vs. 67.6%and 73.6%,respectively;p<0.05)and cocaine-positive urine samples
(52.6%vs. 62.4%and 67.1%,respectively;p<0.05)(Strain, Stitzer,Liebson,et al., 1993). •
A systematic review examined the impact of methadone dose on cocaine use and found three studies that
addressed the question.Results from the one study in which cocaine use was based on self-reported use
showed no significant excess of use of cocaine among subjects treated with higher doses compared with
subjects treated with lower doses.Pooled results from the two studies that used urine analysis and looked
at an abstinence period longer than 3 weeks showed that higher methadone doses increased the
probability that patients would stay abstinent from cocaine,compared with lower doses(RR= 1.81 [1.15,
2.85])(Faggiano, Vigna-Taglianti, Versino, et al.,2003).
Methadone Maintenance and Marijuana Use—Among TOPS subjects,marijuana use was common: 55
percent of methadone maintenance patients who stayed in treatment for 3 months reported regular use in
the year before admission. This decreased to 47 percent during the first 3 months of treatment,continued
to decline immediately posttreatment, and decreased even more to 36.4 percent in the 3-to 5-year period
after discharge.However,marijuana use appeared more resistant to change than other illicit substances
(Hubbard et al., 1989). It should be considered that the treatment programs likely did not clinically
address marijuana or other drug use.
Ball and Ross(1991)found that marijuana continued to be used quite regularly(an average of 13 to 16
days per month)by high percentages of all patient groups in methadone maintenance treatment:48.4
percent of the new admissions,47.7 percent of the average-stay group, and 37.2 percent of the patients in
treatment more than 4.5 years.
In one studyof 132 opioid addicts participating in methadone maintenance treatment programs,it was
P p g
noted that during episodes of methadone maintenance treatment, levels of alcohol and marijuana use
increased modestly(Powers and Anglin, 1993). •
Part B-28
NIDA International Program Methadone Research Web Guide
• Methadone Maintenance and the Nonmedical Use of Prescription Drugs—In the TOPS studies,the
regular nonmedical use of psychoactive prescription drugs by methadone maintenance treatment patients
during the first posttreatment year decreased by one-third from the pretreatment period.Although 30.3
percent of this methadone maintenance group reported regular nonmedical use of prescription drugs(i.e.,
barbiturates, amphetamines,tranquilizers, sedatives,and hypnotics),nonmedical prescription drug use
was a primary problem for only 1.9 percent of these patients at admission(Hubbard et al., 1989).
In the NTORS study,a decline was seen in the use of benzodiazepines among patients receiving
methadone maintenance(Gossop et al.,2000). In the TOPS studies,nonmedical prescription drug use
declined during methadone maintenance treatment,increased immediately following discharge,and
declined again to 10 percent of patients 3 to 5 years following discharge(Hubbard et al., 1989).
Ball and Ross(1991)found that although the nonmedical use of sedatives other than barbiturates was
acknowledged by 31.8 percent of new admissions to methadone maintenance treatment,the percentage of
sedative-using patients who had been in treatment for more than 4.5 years was less than half that of the
new admission group(14.5 percent).
Methadone Maintenance Treatment and Alcohol and Other Drug Use—In the TOPS studies,
improvements in the use of illicit and nonprescription drugs follow a pattern of(1)a dramatic reduction
during treatment,(2)a sharp increase immediately after discharge, and(3)a leveling off at an
impressively reduced rate for up to 5 years of followup contacts(Hubbard et al., 1989).
•
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Part B-29
NIDA International Program Methadone Research Web Guide
Methadone Treatment and •
Drug Use
100- Na4,184
4 Year Pretreatment 111
1 veal Poeareeb»ent
70-
68%
r 54%
50- 1894
:^ 25% 25'fe Ii24%20- 1111111
t0- Any Any Any Alaska
Opioid Cocaine Mequene Abuse
Use use use
Source: TOPS(Hubbard et a1_,1989)
Figure 21 illustrates that as reported by
the TOPS study of 4,184 patients, •
methadone maintenance treatment was
associated with reductions in(1)any illicit
opioid use,(2)any cocaine use,(3)any
marijuana use,and(4)alcohol abuse(the
1-percent reduction noted here is not
statistically significant)(Hubbard et al.,
1989).
"Any opioid use"declined from 63 percent pretreatment to 17 percent 1 year posttreatment. This was the
most dramatic decline."Any cocaine use"declined from 26 percent to 18 percent."Any marijuana use"
declined from 55 percent pretreatment to 46 percent 1 year posttreatment.Alcohol abuse remained almost
steady, declining slightly from 25 percent to 24 percent.
References
Ball JC,Ross A. The Effectiveness of Methadone Maintenance Treatment:Patients, Programs, Services,
and Outcomes.New York:Springer-Verlag, 1991.
Faggiano F, Vigna-Taglianti F, Versino E,Lemma P.Methadone maintenance at different dosages for
opioid dependence. The Cochrane Database of Systematic Reviews,Issue 3,2003.
Fairbank JA,Dunteman GH, Condelli WS.Do methadone patients substitute other drugs for heroin?
Predicting substance use at 1-year follow-up.American Journal of Drug&Alcohol Abuse
1993;19(4):465-74.
Gossop M,Marsden J, Stewart D,Rolfe A.Patterns of improvement after methadone treatment: 1 year
follow-up results from the National Treatment Outcome Research Study.Drug&Alcohol Dependence
2000;60(3):275-86. •
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NIDA International Program Methadone Research Web Guide
• Hubbard RL,Marsden ME,Rachal JV,Harwood HJ, Cavanaugh ER,Ginzburg HM.Drug Abuse
Treatment:A National Study of Effectiveness. Chapel Hill: University of North Carolina Press, 1989.
Kreek MJ.Using methadone effectively: achieving goals by application of laboratory,clinical,and
evaluation research and by developing of innovative programs.In: Pickens RW,Leukefeld CG, Schuster
CR(eds.).Improving Drug Abuse Treatment.NIDA Research Monograph Series 196. Rockville,MD:
National Institute on Drug Abuse, 1991.
Lehman WEK,Barrett ME, Simpson DD. Alcohol use by heroin addicts 12 years after drug abuse
treatment.Journal of Studies in Alcohol 1990;51(3):233-44.
Powers KI,Anglin MD. Cumulative versus stabilizing effects of methadone maintenance.Evaluation
Review 1993;17(3):243-70.
Schottenfeld RS,Pakes JR,Oliveto A,Ziedonis D,Kosten TR.Buprenorphine vs methadone
maintenance treatment for concurrent opioid dependence and cocaine abuse.Archives of General
Psychiatry 1997;54(8):713-20.
Simpson DD, Sells SB.Effectiveness of treatment for drug abuse: an overview of the DARP research
program.Advances in Alcohol and Substance Abuse 1982;2(1):7-29.
Strain EC, Stitzer ML,Liebson IA,Bigelow GE.Dose-response effects of methadone in the treatment of
opioid dependence.Annals of Internal Medicine 1993;119:23-37.
•
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NIDA International Program Methadone Research Web Guide
Question 7: What components of methadone maintenance treatment account for •
reductions in AIDS risk behaviors?
Answer: Reductions in drug use and related AIDS risk behaviors among methadone-maintained
individuals have been associated with both physiological and psychosocial factors. Recent studies have
confirmed that adequate methadone dose levels are required to achieve significant reductions in opioid
abuse.At the same time,research has demonstrated that methadone alone will have,at best,limited
impact.Additional psychosocial support services are needed to maximize the effectiveness of methadone
maintenance treatment.
Research Highlights
• A study examining the impact of psychosocial services in methadone treatment found that
outcomes were significantly improved for those injection drug users who received services in
addition to methadone(McLellan,Arndt,Metzger, et al., 1993).In this study,methadone patients
were randomly assigned to one of three groups that received either: (1)methadone alone with no
other services; (2)methadone and regular counseling;or(3)methadone with counseling and
medical/psychiatric services,employment services, and family therapy.Although methadone
doses were the same in each group,outcomes were significantly better in the groups that also
received psychosocial services. Sixty-nine percent of the methadone-only group had to be
"protectively transferred"due to unremitting use of opiates or cocaine or medical/psychiatric
emergencies.
• Counseling programs specifically designed to reduce HIV risk behavior among methadone-
maintained patients have been shown to be effective(Margolin,Avants,Warburton, et al.,2003).
• Patients with comorbid psychiatric disease are less likely to decrease their HIV risk behaviors •
during methadone maintenance treatment,compared with those without,although both groups
receive benefit(King,Kidorf, Stoller,et al.,2000).
• A study of 291 patients that evaluated a high-intensity day treatment along with methadone
versus enhanced methadone treatment saw decreases in drug use and HIV risk behavior in both
groups;however,the study was unable to detect a significant difference in these outcomes
between treatment groups(Avants,Margolin, Sindelar,et al., 1999).
• Similarly, a study that compared methadone dose(50 mg vs. 80 mg)and visit frequency(two
visits per week vs.five visits per week)saw reductions in HIV risk behavior with methadone
maintenance treatment but was unable to demonstrate a difference in HIV risk reduction between
the four groups(Rhoades, Creson,Elk, et al., 1998).
• Hartel, Schoenbaum, Selwyn,et al. (1995)examined the drug use patterns and treatment
characteristics of 652 methadone patients receiving treatment from the Montefiore Methadone
Treatment Program in New York. The study found that those who were maintained on less than
70 mg per day of methadone were 2.1 times(p<.005)more likely to be using heroin.It is
important to note that the observed effects of higher doses were found even after controlling for
the length of time in treatment.
• A meta-analysis of HIV risk reduction interventions in substance abuse treatment programs found
that these programs succeeded in changing knowledge, attitudes,and beliefs; sexual behavior;
and injection practices. The impact of the intervention programs was negatively correlated with
the presence of ethnic/minority samples and positively correlated with the number of intervention
techniques used,the intensity of the intervention, interventions that were delivered within
methadone treatment, and specific intervention techniques(Prendergast,Podus,Chang,et al.,
2002).
•
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NIDA International Program Methadone Research Web Guide
• References
Avants SK,Margolin A, Sindelar JL,Rounsaville BJ, Schottenfeld R, Stine S,et al.Day treatment versus
enhanced standard methadone services for opioid-dependent patients:a comparison of clinical efficacy
and cost.American Journal of Psychiatry 1999;156(1):27-33.
Hartel DM, Schoenbaum EE, Selwyn PA,Kline J,Davenny K,Klein RS,et al.Heroin use during
methadone maintenance treatment:the importance of methadone dose and cocaine use.American Journal
of Public Health 1995;85:83-88.
King VL,Kidorf MS, Stoller KB,Brooner RK. Influence of psychiatric comorbidity on HIV risk
behaviors:changes during drug abuse treatment.Journal of Addictive Diseases 2000;19(4):65-83.
Margolin A,Avants SK,Warburton LA,Hawkins KA, Shi J.A randomized clinical trial of a manual-
guided risk reduction intervention for HIV-positive injection drug users.Health Psychology
2003;22(2):223-28.
McLellan AT,Arndt IO,Metzger DS,Woody GE,O'Brien CP. The effects of psychosocial services in
substance abuse treatment.JAMA 1993;269(15):1953-59.
Prendergast ML,Podus D,Chang E,Urada D.The effectiveness of drug abuse treatment: a meta-analysis
of comparison group studies.Drug&Alcohol Dependence 2002;67(1):53-72.
Rhoades HM,Creson D,Elk R, Schmitz J,Grabowski J.Retention,HIV risk, and illicit drug use during
treatment:methadone dose and visit frequency.American Journal of Public Health 1998;88(1):34-39.
•
•
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NIDA International Program Methadone Research Web Guide
Question 8: Do risk factors for HIV infection acquisition and transmission differ •
for women compared with men in methadone maintenance treatment?
Answer: Yes.Despite nearly equal HIV infection rates for men and women in drug treatment,female
injection drug users differ from males in the types and contexts of their risk behaviors. While the main
HIV infection risk for both male and female injection drug users is needle sharing,women frequently
support themselves and their addiction habit through sex work and are more likely to have an injection
drug user as a sexual partner. The most common needle-sharing context for women is with their sex
partners.
In addition,women may transmit HIV infection to their infants in utero,during delivery,or through
breastfeeding.Women in methadone treatment need HIV infection prevention programs that take these
gender differences into account.
Research Highlights
• Patterns of needle sharing are different for males and females. Women tend to share needles in
the context of a sexual relationship. This type of needle sharing may be more difficult to change
than other types of injection risk behavior because the perception of risk or ability to negotiate
safe needle use by women may be limited. In research conducted among 19,716 males and 6,609
females in the National AIDS Demonstration Research(NADR)project addressing street-
recruited injection drug users,women were more likely than men to share needles with their sex
partners. The majority of the participants injected only heroin or heroin in combination with
cocaine(Brown and Weissman, 1994).
Research in other countries has shown a tendency for female injection drug users to share needles •
with their sex partners.For example,women in Glasgow,Scotland,were frequently injected with
used needles and syringes from their partners(Barnard, 1993).
• Sexual risk behavior has been shown to be less likely to change among both male and female
injection drug users than needle-sharing risk behavior. In addition,women who inject drugs are
less likely than men to be in control of safer sex practices,such as condom use.Although
methadone maintenance treatment may reduce drug use and prostitution or the exchange of sex
for drugs,women may be at risk for HIV infection by their habitual sex partners.Female injection
drug users tend to have drug users as sex partners,even after enrollment in treatment,and are not
likely to practice safer sex with these partners.HIV risk reduction programs for women in
methadone maintenance treatment must take into account the social and interpersonal context of
sexual risk behavior in order to be effective(Finnegan,Davenny,and Hartel, 1993;Hartel, 1994).
• Women with HIV who are maintained on methadone may improve their access to medical care
for HIV infection and disease and possibly reduce their chance of transmitting HIV to infants in
utero.Both zidovudine(AZT)and nevaripine have been shown to reduce significantly the risk of
mother-to-infant transmission of HIV infection(Connor, Sperling,Gelber,et al., 1994;
Brocklehurst and Volmink, 2002).
• It is likely that some infants are infected during labor and delivery or after delivery through
breastfeeding. Careful attention to factors that can place the infant at risk during birth and
afterwards is needed to further reduce infant infection.In areas with a high community level of
HIV infection among injection drug users,methadone programs often incorporate HIV primary
health care services into the treatment program through onsite services or linkages to services
nearby. These services often include obstetrical care by providers skilled in working with HIV-
infected women(Finnegan et al., 1993).
•
Part B-34
NIDA International Program Methadone Research Web Guide
• Differences Between Men and Women in HIV Infection Rates and Risk Behaviors—Figure 22
illustrates that overall HIV infection rates are roughly the same for males and females entering drug abuse
treatment in the United States: 5.4 percent for males and 4.4 percent for females. These rates vary greatly
(0 to 48 percent)by geographic area,with the highest rates found in urban centers that have the greatest
density of injection drug users(Allen,Onorato,and Green, 1992).
Differences Between Men and
Women in HIV infection Rates
and Risk Behaviors
Go- 57' 111 Moran
a Mee
50 -
45%
a
0
40-
i
"S 30
I
23%
14-
4.4% 54% 5%
• 0 HIV toreetion I or More Engafll.rm!nt l^
Rates at MI6 as Sete Work
Entrance to Sex Partner
Drug Abuse
Treatment
Figure 22 illustrates that overall HIV
infection rates are roughly the same for men
and women entering drug abuse treatment
in the United States:5.4 percent for men
and 4.4 percent for women.These rates vary
greatly(0 to 48 percent)by geographic area,
with the highest rates found in urban
centers that have the greatest density of
injection drug users(Allen et al.,1992).
In research conducted in New York,NY,among 452 methadone-recruited injection drug users early in
the HIV epidemic,having an injection drug user as a sex partner was associated with HIV infection status
independent of or in addition to injection risk behavior. In this same study,women reported a higher level
of sexual risk behavior than men: 57 percent of women compared with 45 percent of men reported one or
more injection drug users as sex partners since 1978. In addition,women were more likely than men to
have engaged in sex work:23 percent of women compared with 5 percent of men(Schoenbaum,Hartel,
Selwyn, et al., 1989).
Part B-35
NIDA International Program Methadone Research Web Guide
References
41110
Allen D,Onorato I,Green T.HIV infection in intravenous drug users entering drug treatment,United
States, 1988 to 1989.American Journal of Public Health 1992;82:541-46.
Barnard,M.Needle sharing in context:patterns of sharing among men and women injectors and HIV
risks.Addiction 1993;88:805-12.
Brocklehurst P,Volmink J.Antiretrovirals for reducing the risk of mother-to-child transmission of HIV
infection. The Cochrane Database of Systematic Reviews,Issue 2,2002.
Brown V, Weissman G. Women and men injection drug users: an updated look at gender differences and
risk factors.In: Brown B,Beschner G(eds.).Handbook on Risk of AIDS:Injection Drug Users and
Sexual Partners.Westport, CT: Greenwood Press, 1994.
Connor E,Sperling R, Gelber R,Kiselev P, Scott G,O'Sullivan MJ,et al. Reduction of maternal-infant
transmission of human immunodeficiency virus type 1 with zidovudine treatment.New England Journal
of Medicine 1994;331:1173-80.
Finnegan L,Davenny K,Hartel D.Drug use in HIV-infected women. In:Johnson M,Johnstone F(eds.).
HIV Infection in Women.London:Churchill Livingstone, 1993.
Hartel D. Context of HIV Risk Behavior Among Female Injecting Drug Users and Female Sexual
Partners of Injecting Drug Users.NIDA Research Monograph Series 143.Rockville,MD:National
Institute on Drug Abuse, 1994.
Schoenbaum EE,Hartel D, Selwyn P,Klein RS,Davenny K,Rogers M,et al.Risk factors for HIV
infection in intravenous drug users.New England Journal of Medicine 1989;321:874-79.
•
Part B-36
NIDA International Program Methadone Research Web Guide
• Question 9: Is methadone maintenance treatment effective for women?
Answer: Yes. Since the earliest methadone maintenance treatment programs in the United States,
women have been treated successfully with methadone through all phases of their lives,including
pregnancy. There is consensus that the major outcomes of the effectiveness of methadone maintenance
treatment,especially cessation of illicit drug use and lifestyle stabilization,apply to both men and women.
However,gender-specific issues,which are often related to the social status of women, are important to
treatment effectiveness for female injection drug users.
Compared with men,women are more likely to
• Have total responsibility for child care
• Have lower socioeconomic status
• Encounter greater barriers to treatment entry,retention in treatment, and economic independence
• Have different psychological,counseling,and vocational training needs
• Have difficulty with transportation to treatment.
Research Highlights
• In the past,little emphasis was placed on gender-specific biopsychosocial problems in drug
treatment. One reason was the predominance of drug-addicted men,estimated in the United
States to be three males to every female.Although mild forms of psychoactive substance use
show converging usage rates and patterns for males and females,opioid addiction and other
forms of chemical dependency continue to show a male predominance(Kandel, 1992).
• Drug Abuse Reporting Program(DARP)studies showed that 19 to 28 percent of admissions to
drug treatment programs from 1969 to 1973 were women.In 12 years of followup of 84 females
and 91 males in methadone maintenance,there were no differences between men and women in
overall reduction of opioid use.Women required more government financial assistance and had
lower rates of employment than men. Compared with men,women were more likely to enter
treatment for health reasons(Simpson, 1990;Marsh and Simpson, 1986).
• A study of 567 methadone-maintained patients in California found overall shorter duration of
time from first entry to first discharge from treatment for women compared with men(Anglin,
Hser,and Booth, 1987).Factors related to poor retention of women in treatment were likely to be
a lack of child care and inadequate social and psychological support from domestic partners and
other family members(Rosenbaum, 1981;Murphy and Irwin, 1992).
• A study of white,Latina,and African American women in methadone maintenance found that,in
general,Latinas were more likely to report familial influences and to display evidence of low
self-esteem and self-efficacy,inconsistent condom use,and high-risk injection behavior.White
women reported the highest levels of regular condom use at followup;however,they were the
least likely to report safer injection practices.African American women expressed the highest
levels of self-esteem,yet they reported more alcohol use at intake and crack cocaine use both
before and after treatment entry. African American women showed the greatest gains in adopting
safer injection practices and were the least likely to report multiple sex partners after treatment
entry(Grella,Annon, and Anglin, 1995).
• Drug-using women are likely to experience clinical depression,anxiety disorders,and low self-
esteem to a much greater degree than their male counterparts. Women entering treatment have
experienced unique gender-specific life events.In particular, female drug users often have been
abused physically, sexually,and emotionally.Experiences of sexual violence,especially during
• childhood,have profound, lifelong psychological effects and often underlie addiction,
complicating successful recovery.Methadone maintenance treatment of women requires
Part B-37
NIDA International Program Methadone Research Web Guide
awareness of these issues and appropriate counseling.Confrontational styles of therapy and •
counseling are not effective for most women in treatment(Mondanaro, 1987;Marsh and Miller,
1985;Beschner,Reed, and Mondanaro, 1981;Hartel, 1989/1990).
Potential Treatment Issues for Women—Figure 23 delineates key treatment issues derived from the
discussion above.
Potential Treatment Issues
for Women
issues:
• Social isolation
• Poor self-esteem
• Clinical depression and anxiety disorders
• physical and sexual abuse
Need for;
• Child care
• Transportation to treatment
• Nonconfrontational therapy and counseling
• Vocational job skills training and education
designed specifically for women
Figure 23 illustrates the potential treatment
issues for women. •
References
Anglin D,Hser Y,Booth M. Sex differences in addict careers.American Journal of Drug and Alcohol
Abuse 1987;13(3):253-80.
Beschner G,Reed B,Mondanaro J. Treatment Services for Drug Dependent Women.Rockville,MD:
National Institute on Drug Abuse, 1981.
Grella CE,Annon JJ,Anglin MD. Ethnic differences in HIV risk behaviors, self-perceptions,and
treatment outcomes among women in methadone maintenance treatment.Journal of Psychoactive Drugs
1995;27(4):421-33.
Hartel D. Cocaine use, inadequate methadone does increase risk of AIDS for IV drug users in treatment.
NIDA Notes 1989/1990;5(1).
Kandel D.Epidemiological trends and implications for understanding the nature of addiction.In: O'Brien
D,Jaffe J(eds.).Addictive States.New York: Raven Press, 1992.
Marsh J,Miller N. Female clients in substance abuse treatment.International Journal of the Addictions
1985;20:995-1019.
Marsh K, Simpson D. Sex differences in opioid addiction careers.American Journal of Drug and Alcohol
Abuse 1986;12:309-29.
Mondanaro J. Strategies for AIDS prevention: motivating health behavior in drug dependent women.
Journal of Psychoactive Drugs 1987;19:143-49.
Murphy S,Irwin J.Living with the dirty secret:problems of disclosure for methadone maintenance
clients.Journal of Psychoactive Drugs 1992;24:257-64. •
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NIDA International Program Methadone Research Web Guide
• Rosenbaum M. Sex roles among deviants;the women addict.International Journal of the Addictions
1981;16,859-77.
Simpson DD.Longitudinal outcome patterns. In: Simpson DD, Sells SB (eds). Opioid Addiction and
Treatment:A 12-Year Followup.Malabar,FL: Krieger Publishing, 1990.
III
•
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NIDA International Program Methadone Research Web Guide
Question 10: Is methadone safe for pregnant women and their infants? •
Answer: Yes. Since the early 1970s,methadone maintenance treatment has been used successfully with
pregnant women. There is consensus that methadone can be safely administered during pregnancy with
little risk to mother and infant. Maintenance on methadone is necessary to prevent relapse to illicit opioid
use and thus to maintain optimal health during pregnancy.
Research Highlights
A systematic review revealed that randomized controlled studies of methadone treatment in pregnancy
demonstrate an approximate threefold reduction in heroin use and a threefold increase in retention in
treatment relative to nonpharmacologic treatment(Rayburn and Bogenschutz,2004).
• All drug-using women are considered to be at higher-than-normal risk for medical and obstetrical
complications.Methadone-maintained women show a far greater improvement in obstetrical
health than untreated women.Hepatitis types A,B, and C and other sexually transmitted diseases;
bacterial endocarditis; septicemia; and cellulites are common among active injection drug users,
particularly those who share needles. Women maintained on methadone who have stopped illicit
drug use and injection before pregnancy are less likely to experience these and other medical
complications during pregnancy. Obstetrical complications such as spontaneous abortion,
placental insufficiency,and other conditions also occur at a lower rate among methadone-
maintained women than among opioid-dependent women not enrolled in treatment. When
compared with opioid-addicted women not in treatment,women in methadone maintenance
treatment have been observed to maintain better overall health and nutritional status during
pregnancy because of stability provided through treatment. In addition,methadone clinics can
provide onsite prenatal services or link patients to these services in nearby clinics, coordinating
1111 addiction treatment and prenatal care to optimize both(Finnegan, 1991;Kaltenbach, Silverman,
and Wapner, 1993).
• Some women in methadone maintenance treatment are infected with HIV before pregnancy.
Treatment programs that link women to appropriate medical care during pregnancy may reduce
the burden of illness suffered by HIV-infected women. In a study of 191 methadone-maintained
women in a New York City clinic with extensive medical linkages, medical and obstetrical
complications did not differ among women with and without HIV infection.HIV infection
occurred among 37 percent of women,most of whom were asymptomatic for HIV disease and
AIDS before pregnancy.Adverse birth outcomes were relatively infrequent and occurred at
approximately the same rates as observed in studies of methadone-maintained women before the
HIV epidemic(Selwyn, Schoenbaum,Davenny,et al., 1989).
• U.S.research in the 1970s demonstrated that methadone does cross the placenta.Passive
exposure to methadone in utero can result in neonatal abstinence syndrome among exposed
infants. The syndrome varies considerably and depends on a number of factors, including the use
of other drugs during pregnancy,anesthesia during delivery,the maturational and nutrional status
of the infant, and other aspects of maternal health that affect the fetal environment.The
relationship of maternal methadone dose in the last trimester of pregnancy has been explored in a
number of studies,but results have not consistently delineated a dose-response relationship
between maternal dose and severity of infant abstinence syndrome. For those neonates
experiencing withdrawal,the length and severity of the withdrawal vary greatly;however,
pharmacotherapy for neonatal methadone abstinence syndrome is simple and effective.
Methadone maintenance treatment affords protection of the fetus from erratic maternal opioid
levels and repeated episodes of withdrawal typically seen in users of illicit opioids(Finnegan,
1991).
•
Part B-40
NIDA International Program Methadone Research Web Guide
• • The majority of infants exposed to methadone in utero are healthy and have fewer adverse
outcomes than infants exposed to heroin and other illicit drugs. Methadone maintenance
treatment for pregnant women can reduce in utero growth retardation and neonatal morbidity and
mortality, in comparison with women not in treatment(Finnegan, 1991). Such infants may be
smaller at birth than nondrug-exposed infants,but differences tend to disappear over time.A
careful review of the major studies of long-term neurobehavioral effects of methadone on
exposed infants revealed no methadone-associated adverse effects(Kaltenbach and Finnegan,
1984).
A review of the literature on methadone and lactation reveals that the amount of methadone in breast milk
is very small and depends on the dose of methadone that a mother is receiving.The amount of methadone
received by an infant from breast milk is not enough to prevent neonatal abstinence syndrome. Therefore,
even though a mother is receiving methadone,her infant may require additional opiate treatment of
neonatal abstinence syndrome(Jansson,Velez,and Harrow,2004).
Methadone Safety for Pregnant Women and Their Infants—Figure 24 outlines key points discussed
in the research citations above regarding the safety of methadone maintenance treatment for pregnant
women.
Methadone Safety for Pregnant
Women and Their Infants
Methadone Maintenance:
• • Reduces adverse pregnancy outcomes
• Reduces adverse birth outcomes
• Infant withdrawal is treatable
• Shows no tcng-tern adverse neurobehavioral
consequences to to utero exposure
Figure 24 illustrates the safety of methadone
maintenance treatment for pregnant women and
their infants.
References
Finnegan L.Treatment issues for opioid-dependent women during the perinatal period.Journal of
Psychoactive Drugs 1991;23:191-201.
Jansson LM,Velez M,Harrow C.Methadone maintenance and lactation: a review of the literature and
current management guidelines.Journal of Human Lactation 2004;20(1):62-71.
Kaltenbach K,Finnegan L.Developmental outcome of children born to methadone maintained women: a
review of longitudinal studies.Neurobehavioral Toxicology and Teratology 1984;6:271-75.
Kaltenbach K, Silverman N, Wapner R.Methadone maintenance during pregnancy.In:State Methadone
Treatment Guidelines.Rockville MD:U.S.Department of Health and Human Services, 1993.
Rayburn WF,Bogenschutz MP.Pharmacotherapy for pregnant women with addictions.American
Journal of Obstetrics& Gynecology 2004;191(6):1885-97.
Selwyn P,Schoenbaum E,Davenny K,Robertson VJ,Feingold AR, Shulman JF,et al.Prospective study
of human immunodeficiency virus infection and pregnancy outcomes in intravenous drug users.JAMA
1989;261:1289-94.
•
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NIDA International Program Methadone Research Web Guide
Question 11: Is it necessary to reduce methadone dose or detoxify women from •
methadone during pregnancy to protect the fetus?
Answer:No. Women have been safely maintained on stable methadone dosage during pregnancy
without adverse long-term effects on their health and the health of their infants. Withdrawal of medication
during pregnancy leads to opioid abstinence syndrome, which is harmful to the pregnancy and often leads
to relapse to illicit drug use.Dosage change in pregnancy must be carefully evaluated on an individual
basis. Some women experience lowered blood levels of the methadone during pregnancy and may need
an increase in dosage or split(e.g.,twice daily)dosing.It is important to determine the relapse risk for
each woman when considering a dosage change because a woman steadily maintained on methadone is
more likely to have a healthy pregnancy and infant than a woman who uses alcohol and other drugs. The
intermittent periods of withdrawal that typically occur with illicit opioid use and can adversely affect the
fetus do not occur when methadone is individually determined and properly administered.
Research Highlights
• Optimal methadone dosage for pregnant women in methadone maintenance treatment should be
based on careful consideration of risks and benefits to both mother and fetus on an individual
basis.Individual dose should be evaluated,taking into account the stage of pregnancy,the relapse
risk potential of the mother,pre-pregnancy methadone dose,previous experience with
methadone, and history of addiction recovery. When the mother does not relapse to illicit drug
use,short-term reductions in maternal dose have been effectively administered during the last
stage of pregnancy.However,many women in treatment have been successfully maintained on a
constant dose and,in some cases,on an increased dose to keep blood levels stable throughout
pregnancy(Finnegan, 1991).
• Some women in treatment experience decreased blood levels of methadone during pregnancy, •
causing withdrawal symptoms.This decrease in blood levels of methadone during pregnancy can
be accounted for by an increased fluid space, a large tissue reservoir that can store methadone,
and drug metabolism by both the placenta and the fetus. Pregnant women in treatment with low
blood levels of methadone frequently experience a high level of discomfort,withdrawal
symptoms, and drug craving and anxiety and may be at high risk of relapse to opioid use and
treatment dropout.Determination of methadone blood levels and possibly raising the methadone
dosage to maintain sufficient blood levels may be warranted in such cases but must be carefully
evaluated.Dosages should be evaluated in conjunction with ongoing medical monitoring of the
pregnancy. Since the greatest risks to maternal and infant health occur when women in treatment
relapse to illicit drug use, it is important to promote methadone dosage stability during and after
pregnancy to optimize both maternal and child health(Kreek, Schecter,Gutjahr,et al., 1974;
Pond,Kreek, Tong, et al., 1985).
Methadone Dosage Adjustment During Pregnancy—Figure 25 outlines the three main considerations
regarding dosage for pregnant women in methadone maintenance treatment.
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NIDA International Program Methadone Research Web Guide
• Methadone Dose Adjustment
During Pregnancy
• Pregnancy can lower methadone blood bevels.
• Lower blood methadone levels can increase
relapse risk.
• Dosage levels should be evaluated and
individually tailored to reduce risk of relapse
and to stabilize both mother and fetus.
Figure 25 illustrates three main
considerations regarding methadone
dosage adjustment during pregnancy.
References
Finnegan L. Treatment issues for opioid-dependent women during the perinatal period.Journal of
Psychoactive Drugs 1991;23:191-201.
Kreek M, Schecter A,Gutjahr C,Bowen D,Field F,Queenan J,et al.Analyses of methadone and other
drugs in maternal and neonatal body fluids:use in evaluation of symptoms in a neonate of mother
maintained on methadone.American Journal of Drug and Alcohol Abuse 1974;1:409.
Pond S,Kreek M, Tong T,Raghunath J,Benowitz NL.Altered methadone pharmacokinetics in
methadone-maintained pregnant women.Journal of Pharmacology and Experimental Therapeutics
1985;233:1-6.
' i
Part B-43
NIDA International Program Methadone Research Web Guide
Question 12: Is the long-term use of methadone medically safe, and is it well •
tolerated by patients?
Answer: Yes. Studies of the long-term administration of methadone confirm that it is a medically safe
drug. Long-term methadone maintenance treatment at doses of 80 to 120 mg per day is not toxic or
dangerous to any organ system after continuous treatment for 10 to 14 years in adults and 5 to 7 years in
adolescents.
Research Highlights
• Methadone has few adverse biological effects. There appear to be no dangerous or troubling
psychological effects from long-term administration(Kreek, 1979;Lowinson,Marion, Joseph,et
al., 1992),although one study demonstrated a delay in neuropsychological tests in patients
receiving methadone compared with abstinent(not active)former heroin-dependent patients
(Verdejo,Toribio, Orozco, et al.,2005).
• Methadone sometimes causes minor side effects,such as sweating, constipation,temporary skin
rashes,weight gain,water retention,and changes in sleep and appetite(Jaffe and Martin, 1985;
Kreek, 1979). These side effects are more likely to occur when the methadone dosages are first
being established in a patient, and the side effects generally subside or diminish over time. They
can be reduced or eliminated by raising or lowering the methadone dose(Lowinson et al., 1992).
• Methadone prescribed in high doses for a long period of time has no toxic effects and only
minimal side effects for adult patients maintained in treatment for up to 14 years and for
adolescent patients treated for up to 5 years(Hartel, 1989/1990;Kreek, 1978).
• Although early studies demonstrated no persisting abnormalities directly attributable to
methadone in the functioning of five organ systems(pulmonary,cardiovascular,renal, •
ophthalmologic,and liver)(Kleber,Mezritz,and Slobetz, 1980),later reports have focused on the
potential effect of methadone on QTc interval(Martell,Amsten,Krantz,et al.,2005)and central
sleep apnea(Wang,Teichtahl,Drummer,et al.,2005). It should be noted,however,that cardiac
complications with methadone are more commonly seen in patients who are prescribed very high
doses(mean doses greater than 350 mg per day)for treatment of pain and those who are receiving
concomitant medications that affect methadone metabolism(Krantz,Lewkowiez,Hays, et al.,
2002).
• Patients maintained on methadone have no impairment in driving and have no more frequent
motor vehicle accidents than people not receiving methadone maintenance treatment(Maddux,
Williams, and Ziegler, 1977;Lenne,Dietze,Rumbold,et al.,2003; Schindler,Ortner,Peternell,
et al.,2004).
• The most common and enduring complaints after 6 months to 3 years of continuous methadone
treatment are sweating, constipation,abnormalities in libido and sexual functioning, sleep
abnormalities(insomnia and nightmares),and altered appetite(mild anorexia,weight gain)
(Kreek, 1979;Jaffe and Martin, 1985).Most of these symptoms can be medically managed
(Kreek, 1979).A study of 92 methadone-maintained patients found that the rate of global sexual
dysfunction in methadone-treated men was similar to the general population but that orgasm
dysfunction may respond to methadone dose reduction.
• Although euphoria and drowsiness,with occasional nausea and vomiting, can occur before
tolerance develops,these side effects are most noticeable when doses are increased too rapidly.
Conversely,if a heroin habit has been particularly heavy,initial methadone doses may be too low
to prevent the onset of early withdrawal symptoms(Kreek, 1979).
•
Part B-44
NIDA International Program Methadone Research Web Guide
• • Life-threatening interactions of methadone with other drugs have not been identified.Drugs
found to affect the metabolism of methadone include phenytoin(Dilantin)and rifampin. Opioid
antagonists such as pentazocine(Talwin)and buprenorphine can cause withdrawal symptoms in
methadone patients and should not be prescribed(Kreek, 1978).
Common Side Effects After 6 Months
to 3 Years of Methadone
Maintenance Treatment
Intermediate Levgth Long.Temi,11 .eae
Symptoms Trammed Treatment
and Signs l3 Mons or More; (3 Years or More;
eel to 40 meld) 90 to 120 mew)
Percent Pawed
Increased Svidelind 47 46
C.ondpaiinn 57 17
t bidoAlmennaltrati 26 22
LPpasrridenormatit es — 14
Eked Abnormalities ginwwr,4 l 23 16
donettiie Almennaloes 19 4
Nausea 2$ —
t]ramminesa. 23 —
NsngwnessTansiion 21 --
Headetnes 12 —
doily Aches and Pains It
Chine 10 —
—=no dela a4ae&4e
Figure 26 illustrates that methadone maintenance patients,
• in the early stages of treatment,can experience several
minor side effects:sweating,constipation,orgasm
abnormalities,alterations of sexual interest,alterations of
sleep and appetite,nausea,drowsiness,nervousness,
headaches,body aches and pains,and chills.However,the
figure also shows that many of these side effects almost
disappear with long-term,high-dose methadone
maintenance treatment(Kreek,1979;Jaffe and Martin,
1985;Hartel,1989/1990).
References
Hartel D.Cocaine use, inadequate methadone does increase risk of AIDS for IV drug users in treatment.
NIDA Notes 1989/1990;5(1).
Jaffe JH1,Martin WR. Opioid analgesics and antagonists.In: Goodman& Gilman's the Pharmacological
Basis of Therapeutics.New York:Pergamon Press, 1985.
Kleber HD,Mezritz M, Slobetz F.Medical Evaluation of Long-Term Methadone-Maintained Clients.
Rockville,MD:National Institute on Drug Abuse, 1980.
Krantz MJ,Lewkowiez L,Hays H,Woodroffe MA,Robertson AD,Mehler PS. Torsade de pointes
associated with very-high-dose methadone.Annals of Internal Medicine 2002;137(6):501-04.
Kreek MJ.Medical complications in methadone patients.Annals of the New York Academy of Science
1978;311(29):110-34.
Kreek MJ. Methadone in treatment:physiological and pharmacological issues.In: DuPont RL,Goldstein
A,O'Donnell J,Brown B(eds.).Handbook on Drug Abuse. Rockville,MD:National Institute on Drug
Abuse, 1979.
i
Part B-45
NIDA International Program Methadone Research Web Guide
Lenne MG,Dietze P,Rumbold GR,Redman JR,Triggs TJ. The effects of the opioid pharmacotherapies •
methadone,LAAM and buprenorphine,alone and in combination with alcohol,on simulated driving.
Drug&Alcohol Dependence 2003;72(3):271-78.
Lowinson JH,Marion IJ,Joseph H,Dole VP. Methadone maintenance. In:Lowinson JH,Ruiz P,
Millman RB (eds.).Substance Abuse:A Comprehensive Textbook. Second Edition.Baltimore,MD:
Williams&Wilkins, 1992.
Maddux JF,Williams TR,Ziegler JA.Driving records before and during methadone maintenance.
American Journal of Drug and Alcohol Abuse 1977;4(1):91-100.
Martell BA,Arnsten JH, Krantz MJ, Gourevitch MN.Impact of methadone treatment on cardiac
repolarization and conduction in opioid users.American Journal of Cardiology 2005;95(7):915-18.
Schindler SD,Ortner R, Peternell A,Eder H,Opgenoorth E,Fischer G. Maintenance therapy with
synthetic opioids and driving aptitude.European Addiction Research 2004;10(2):80-87.
Verdejo A, Toribio I, Orozco C,Puente KL,Perez-Garcia M.Neuropsychological functioning in
methadone maintenance patients versus abstinent heroin abusers.Drug&Alcohol Dependence
2005;78(3):283-88.
Wang D, Teichtahl H,Drummer 0, Goodman C,Cherry G, Cunnington D,et al. Central sleep apnea in
stable methadone maintenance treatment patients. Chest 2005;128(3):1348-56.
11110
•
Part B-46
NIDA International Program Methadone Research Web Guide
• Question 13: Are there program characteristics associated with the success of
methadone maintenance treatment?
Answer: Yes.There are several program characteristics associated with a variety of improved treatment
outcomes in patients receiving methadone maintenance.These program characteristics are as follows:
• Establishment of evidence-based dosing policies and dose ranges
• Availability of a variety of psychosocial services for those who require them
• Attention to staff training and quality
• When possible,integration of medical,counseling, and administrative services
Research Highlights
• A meta-analysis of 12 trials involving 981 people comparing varying levels of psychosocial
treatment added to methadone maintenance showed additional benefit in adding any psychosocial
treatment to standard methadone maintenance treatment in relation to the use of heroin during the
treatment;relative risk was 0.69(95%CI 0.53 to 0.91). However,no statistically significant
additional benefit was shown in terms of retention in treatment—relative risk was 0.94(95%CI
0.85 to 1.02)—or proportion of patients retained or abstinent at followup—relative risk was 0.90
(95%CI 0.76 to 1.07)(Amato,Minozzi,Davoli,et al.,2004).
• Ball and Ross(1991)noted wide differences among the six methadone maintenance clinics
studied with respect to the reduction of injection drug use by patients.Factors that account for
treatment success include(1)adequate dosing;(2)participation in programs that had high
retention rates,high rates of scheduled attendance, low treatment staff
• gturnover,and a close,
consistent, and enduring relationship between staff and patients;(3)an effective treatment
director;(4)combined medical,counseling,and administrative services;(5)experienced
counselors providing comprehensive counseling services;and(6)staff/patient agreement about
the status of patients and their treatment needs.
• In a United Kingdom study of 262 patients who were admitted to and retained in methadone
treatment programs at 6 months, structural equation models were used to evaluate relationships
between treatment process variables and heroin use at 1 and 6 months.Patients'perceptions of
program characteristics and methadone dose were related to reduced heroin use at 1 month.In
addition,early engagement with treatment services was associated with decreased heroin use at 6
months(Gossop, Stewart,and Marsden,2003).
• Studies comparing methadone treatment in general practice or primary care with treatment in
specialty treatment clinics are limited, but at least two have demonstrated similar treatment
outcomes between these two locations of care(Gossop,Marsden, Stewart,et al., 1999;Fiellin,
O'Connor,Chawarski,et al.,2001).
• The Treatment Outcome Perspective Study(TOPS)examined a sample of 606 methadone
maintenance treatment patients from 21 different clinics to identify treatment process factors
related to improved patient retention rates. Results showed higher patient retention rates for
programs(1)using organized and professional staff to diagnose problems and define treatment
plans, (2)meeting and satisfying the needs perceived as important by clients,and(3)using higher
methadone doses(Joe, Simpson,and Hubbard, 1991).
• A 6-to 7-year followup study of 347 methadone maintenance treatment patients examined
different retention policies. Two programs had a high-dose, long-retention policy in which
involuntary termination was used as a last resort.A third program had a low-dose,2-year
retention policy with strict terminations for program violations.Retention rates were longer in the
• two less structured programs(means of 4.3 and 3.2 years)than in the more structured program
(mean of 2.2 years)(McGlothlin and Anglin, 1981).
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NIDA International Program Methadone Research Web Guide
• One study randomly assigned 69 patients at admission to structured and unstructured treatment ,
groups. Structured groups had limits on illicit drug use that,if exceeded, resulted in withdrawal
from methadone. The unstructured groups had no limits on illicit drug use.At the end of 1 year,
53 percent of the patients in structured groups remained in treatment,but only 30 percent of the
patients in unstructured groups remained in treatment(McCarthy and Borders, 1985).
• A nationwide U.S.telephone survey of a randomized and stratified representative sample of 172
outpatient methadone units found that relatively high methadone dosage levels and patient
participation in dosage decisions are related to higher retention rates(D'Aunno and Vaughn,
1992).
• According to Kreek(1991),adequate staff numbers,training, and concern for patient needs and
high staff stability(low staff turnover)are associated with improved patient outcomes(Center for
Substance Abuse Treatment, 1993).
The Effects of Dosage on Methadone Maintenance Treatment—Research regarding methadone
dosage levels clearly establishes that low average doses are inappropriate in methadone maintenance
treatment.No single level is effective for all patients, although NIDA-supported research has suggested
that the minimum effective dosage for most methadone maintenance patients is 60 mg per day. The
specific dosage for a patient cannot be determined arbitrarily because patients metabolize methadone at
different rates.In addition,the appropriate dosage can change over time or in response to specific
situations such as pregnancy or the use of other medications. Overall,methadone dosage should be based
on the patient's individual needs,goals of treatment,and progress in treatment.
In the Ball and Ross studies(1991),illicit opioid use was directly related to methadone dosage levels.In
methadone maintenance patients on dosages of about 71 mg per day,no heroin use was detected,but
methadone maintenance patients on dosages below 46 mg were 5.16 times more likely to use heroin than 111
those on higher dosages.
Ball and colleagues(1988)found that 18.6 percent of 490 patients who were in methadone maintenance
treatment for 6 months to 4.5 years used heroin within the last 30 days,but use correlated strongly with
methadone dosage level.At doses of 75 mg per day and above,the continuing use of heroin stopped
altogether. In contrast, 64 percent of patients maintained on 10 mg per day or less continued frequent
heroin use.A dose of 40 mg per day seemed to be the cutoff point for a large decrease in heroin use.
Despite recent attention to the importance of adequate methadone dosages,a large-scale survey of
methadone maintenance treatment programs conducted in the United States in 1992 found that 50 percent
of patients nationwide receive suboptimum methadone doses(D'Aunno and Vaughn, 1992).A
subsequent evaluation found that the percentage of patients receiving methadone doses less than 60 mg
per day has decreased from 79.5 percent in 1988 to 35.5 percent in 2000. Programs with a greater
percentage of African American patients were more likely to dispense low doses of methadone, and
programs with Joint Commission on Accreditation of Healthcare Organizations accreditation were more
likely to provide adequate methadone doses(D'Aunno and Pollack,2002).
In an exhaustive review of 22 studies that compared the effects of different methadone dosages on
outcomes such as patient retention,continuing illicit opioid use,and symptoms,Hargreaves(1983)
concluded that daily methadone doses of 100 mg were superior to those of 50 mg during the first 5 to 10
months of methadone maintenance treatment for a sizeable subgroup(10 percent to 30 percent)of opioid
addicts.
In a study of 2,400 patients enrolled in methadone maintenance over a 15-year period,those patients
maintained on a daily dose of 60 mg or more had longer retention in treatment;less use of heroin and •
Part B-48
NIDA International Program Methadone Research Web Guide
• other drugs,including cocaine;and a lower incidence of HIV infection and AIDS(Hartel, Selwyn,and
Schoenbaum, 1988a and 1988b).
In a multiclinic study of 12 Veterans Administration hospitals,methadone maintenance treatment patients
were assigned to two dosage levels of methadone: 50 mg and 100 mg. The percentage of patients retained
for 10 months was higher in the 100-mg group(52 percent)than in the 50-mg group(42 percent),but the
difference was not statistically significant(Ling,Charuvastra,Kaim, et al., 1976).
Studies that examined the relationship between methadone maintenance treatment dosage and retention
suggest that,although many patients will continue in treatment on methadone doses of less than 50 mg,
some patients need higher doses.In a review of five well-designed dose-retention studies,three found
statistically nonsignificant trends toward increased retention with higher doses and two did not(Maddux,
Vogtsberger,Desmond,et al., 1993).
In a study of 180 methadone maintenance treatment patients randomly assigned at admission to three
groups that received doses of 30 mg, 50 mg,and 100 mg,the percentages retained for 53 weeks were as
follows:45 percent of the 30-mg group,55 percent of the 50-mg group,and 35 percent of the 100-mg
group. The 100-mg group had the lowest retention rate,but the differences were not statistically
significant(Garbutt and Goldstein, 1972).
A study of 322 methadone maintenance treatment patients receiving an average daily dose of 30 mg
demonstrated a high dropout rate. Only 17 percent of the sample remained in treatment at the end of 6
months, and only 10 percent remained by the end of a year.Moreover,patients who dropped out within
the first 30 days had the same drug-using behavior as they did before treatment(Craig, 1980).
• Methadone dose should not be rapidly increased or decreased—or used in contingency management—
because such changes tend to disrupt the normalization of physiological function achieved by steady dose
treatment. If the stabilized methadone dose/plasma levels are disrupted,drug hunger and drug-seeking
behaviors are likely to reappear(Kreek, 1991;Kreek, 1992).
Need for Comprehensive Services in Methadone Maintenance Treatment—In a study of 351 daily or
weekly heroin users who were admitted to 1 of 17 publicly funded methadone maintenance treatment
programs,nearly all(85 percent)reported having difficulty in at least one of the following problem areas:
medical or physical;mental health or emotional; family or friends;police or legal;job,work,or school;
and financial or money.Nearly one-half(44 percent)reported having difficulties in more than three of
these areas(Condelli, 1993).
Program Characteristics Associated With Success of Methadone Maintenance Treatment—Other
program characteristics that appear to improve treatment success include having sufficient staff,low staff
turnover and high staff stability, sufficient staff training, and close and enduring relationships between
staff and patients.
•
Part B-49
NIDA International Program Methadone Research Web Guide
Program Characteristics Role of Psychological Services in •
Associated With Reducing Illicit Opiaid Use
Success of Methadone
Maintenance Treatment
a 80_
Successful programs hamin 7a s
e a Tamunaeod By
• Comprehensive services so-4, �� Rerrrt
• Integrated medical,counseling,and t• so s�-0
administrative services
• Individualized treatment 40= 0
• Adequate dosing policies ▪ 30; +� n a t' +�, �, ...■.
• Sufficient and stable staff $ 20= a -
• Sufficient stafftraining �o ,a .• , ... •. .., w
to' u 1 . , . , I . - . , I . . ,
4 B 12 t$ 20 24
a Treatment Melt
Figure 27 illustrates the program o f101S—MrtrmwrnMeha aneSermon
Se
characteristics,identified by numerous $"�" '"� 1fiad0j° `""°'
■ EMS....Enhanced Methadone Services
research studies,that contribute to
methadone maintenance treatment success
(McLellan,Arndt,Metzger,et al.,1993; Figure 28 illustrates that in a recent study,102 patients
Ball and Ross,1991;Joe et a1.,1991). were divided into three groups: (1)minimum
methadone maintenance treatment services
(methadone alone);(2)standard methadone
maintenance treatment services(methadone plus
counseling);and(3)enhanced methadone maintenance
treatment services(methadone,counseling,and onsite •
medical,psychiatric,employment,and family therapy
services).At 24 weeks,methadone alone resulted in
minimal improvements;methadone plus counseling
resulted in significant improvements over methadone
alone;and enhanced Services,including a broad range
of psychosocial services plus methadone,had the best
outcomes of all(McLellan et al.,1993).Patients
receiving the most comprehensive array of treatment
services were the most likely to have opioid-free urine
tests for the 24 weeks of the study.Patients receiving
minimal services were the most likely to have urine
tests that were positive for illicit opioids.Note:These
patients were removed from participation in the study
because of drug use and psychiatric difficulties.
Additional treatment services were made available.
•
Part B-50
NIDA International Program Methadone Research Web Guide
• References
Amato L,Minozzi S,Davoli M,Vecchi S,Ferri M,Mayet S.Psychosocial combined with agonist
maintenance treatments versus agonist maintenance treatments alone for treatment of opioid dependence.
The Cochrane Database of Systematic Reviews,Issue 4,2004.
Ball JC,Lange WR,Meyers CP,Friedman SR.Reducing the risk of AIDS through methadone
maintenance treatment.Journal of Health and Social Behavior 1988;29:214-26.
Ball JC,Ross A. The Effectiveness of Methadone Maintenance Treatment:Patients, Programs, Services,
and Outcomes.New York: Springer-Verlag, 1991.
Center for Substance Abuse Treatment.State Methadone Treatment Guidelines. Treatment Improvement
Protocol Series 1.Rockville,MD: Center for Substance Abuse Treatment, 1993.
Condelli WS. Strategies for increasing retention in methadone programs.Journal of Psychoactive Drugs
1993;25(2):143-47.
Craig RJ.Effectiveness of low dose methadone maintenance for the treatment of inner city heroin addicts.
International Journal of the Addictions 1980;15(5):701-10.
D'Aunno T,Pollack HA.Changes in methadone treatment practices:results from a national panel study,
1988-2000.JAMA 2002;288(7):850-86.
D'Aunno T,Vaughn TE.Variations in methadone treatment practices. Results from a national study.
JAMA 1992;267(2):253-58.
Fiellin DA,O'Connor PG,Chawarski M,Pakes JP,Pantalon MV, Schottenfeld RS. Methadone
maintenance in primary care: a randomized controlled trial.JAMA 2001;286(14):1724-31.
• Garbutt GD,Goldstein A.Blind comparison of three methadone maintenance dosages in 180 patients. In:
Proceedings of the Fourth National Conference on Methadone Treatment.New York:National
Association for the Prevention of Addiction to Narcotics, 1972,pp.411-14.
Gossop M,Marsden J, Stewart D,Lehmann P, Strang J.Methadone treatment practices and outcome for
opiate addicts treated in drug clinics and in general practice:results from the National Treatment
Outcome Research Study.British Journal of General Practice 1999;49(438):31-34.
Gossop M, Stewart D,Marsden J. Treatment process components and heroin use outcome among
methadone patients.Drug&Alcohol Dependence 2003;71(1):93-102.
Hargreaves WA.Methadone dose and duration for maintenance treatment.In:Research on the Treatment
of Narcotic Addiction:State of the Art.National Institute on Drug Abuse Research Monograph Series.
Rockville,MD:National Institute on Drug Abuse, 1983.
Hartel D, Selwyn PA, Schoenbaum EE.Methadone maintenance treatment and reduced risk of AIDS and
AIDS-specific mortality in intravenous drug users.Abstract No. 8546.Fourth International Conference on
AIDS, Stockholm, Sweden,June 1988a.
Hartel D, Selwyn PA, Schoenbaum EE. Temporal patterns of cocaine use and AIDS in intravenous drug
users in methadone maintenance.Abstract 8526.Fourth International Conference on AIDS. Stockholm,
Sweden,June 1988b.
Joe GW, Simpson DD,Hubbard RL. Treatment predictors of tenure in methadone maintenance.Journal
of Substance Abuse 1991;3(1):73-84.
Kreek MJ.Rationale for maintenance pharmacotherapy of opiate dependence. In:O'Brien CP,Jaffe JH
(eds.).Addictive States.New York:Raven Press, 1992.
III
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NIDA International Program Methadone Research Web Guide
Kreek MJ. Using methadone effectively: achieving goals by application of laboratory,clinical, and
411
evaluation research and by developing of innovative programs. In:Pickens RW,Leukefeld CG, Schuster
CR(eds.).Improving Drug Abuse Treatment.NIDA Research Monograph Series 196. Rockville,MD:
National Institute on Drug Abuse, 1991.
Ling W, Charuvastra VC,Kaim SC, Klett CF.Methadyl acetate and methadone as maintenance
treatments for heroin addicts.Archives of General Psychiatry 1976;33:709-20.
Maddux JF,Vogtsberger KN,Desmond DP,Esquivel M.Program changes and retention on methadone.
Journal of Substance Abuse Treatment 1993;10:585-88.
McCarthy JJ,Borders OT.Limit setting on drug abuse in methadone maintenance patients.American
Journal of Psychiatry 1985;142(12):1419-23.
McGlothlin WH,Anglin MD. Shutting off methadone: cost and benefits.Archives of General Psychiatry
1981;38:885-92.
McLellan AT,Arndt IO,Metzger DS,Woody GE,O'Brien CP. The effects of psychosocial services in
substance abuse treatment.JAMA 1993;269(15):1953-59.
•
•
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NIDA International Program Methadone Research Web Guide
Question 14: Are there patient characteristics associated with the success of
methadone maintenance treatment?
Answer: Yes.Patient characteristics associated with treatment success include the following:
• Age
• Age of first heroin use
• Overall drug-use history
• Severity and duration of drug use
• Emotional health
• Psychiatric health
• Social health
• Vocational stability
• Criminal history
Research Highlights
One review found the following characteristics to be associated with improved methadone outcomes:
older age,absence of criminal behavior,shorter duration of opioid use, less severe psychopathology,
being employed,being married,less polysubstance use,and higher expressed desire in getting help with a
drug problem(Ward,Mattick,Hall,et al., 1998).
• In a review of 113 studies that attempted to evaluate the relationship of patient characteristics to
• retention and other outcomes(reported from 1971 to 1983),it was noted that patient
characteristics probably accounted for only 25 to 45 percent of the variance in retention
(McLellan, 1983).
• For methadone maintenance treatment patients in the Drug Abuse Reporting Program(DARP)
studies,the most important predictors of posttreatment outcomes were(1)preadmission
criminality and(2)measurements of crime,drug use,and employment during treatment. Of all
the patient characteristics, chronic criminality is the strongest predictor of unfavorable
posttreatment outcomes(Simpson and Sells, 1982).
• Ball and Ross's work(1991)supports the finding that a younger age at the onset of heroin use is
associated with poorer treatment outcomes.Overall,however,this study noted that patient
characteristics had less impact on outcomes than program variables.
• Anglin and Hser(1990)note that better psychosocial adjustment predicts superior treatment
outcomes.Psychosocial adjustment was described as an intact marriage,a job,a shorter history of
drug abuse,lower levels of psychiatric dysfunction,and minimal or no criminal history.
• Rounsaville,Glazer,Wilber,et al.(1983)assessed 123 opioid addicts who were followed for 6
months after admission and found that outcome was predicted by the behavior examined: greater
pretreatment criminality predicts criminal activity following discharge.Conversely,pretreatment
employment predicts posttreatment employment. This study found that patients who abuse
alcohol, are unemployed,are dually diagnosed,manifest psychopathology,and engage in
criminality have poor outcomes.
I •
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NIDA International Program Methadone Research Web Guide
411)Patient Characteristics
Associated With Success of
Methadone Maintenance
Treatment
• Age: Older than 25
• Minimal criminal involvement
• Short history of dug abuse
• Mild to moderate drug abuse severity
+ Emotional and psychiatric stability
• Intact social support network
• Positive employment history
Figure 29 illustrates that,overall,patients who
demonstrate emotional,psychological,and
social well-being generally experience greater
treatment success than patients who have
emotional,psychological,and social problems.
Several studies have noted that certain patient
characteristics,which are listed in Figure 29,
are associated with success in methadone
maintenance treatment(McLellan,1983;
Simpson and Sells,1982;Ball and Ross,1991;
Anglin and Hser,1990).
References •
Anglin MD,Hser IY. Treatment of drug abuse.In:Tonry M,Wilson JQ(eds.).Drugs and Crime.
Chicago: University of Chicago, 1990.
Ball JC,Ross A. The Effectiveness of Methadone Maintenance Treatment:Patients, Programs, Services,
and Outcomes.New York: Springer-Verlag, 1991.
McLellan AT.Patient characteristics associated with outcome.In:Cooper JR,Altman F,Brown BS,
Czechowicz D(eds.).Research in the Treatment of Narcotic Addiction.NIDA Treatment Research
Monograph Series. Rockville,MD:National Institute on Drug Abuse, 1983.
Rounsaville BJ, Glazer W,Wilber CH, Weissman MM,Kleber HD. Short-term interpersonal
psychotherapy in methadone maintained opiate addicts.Archives of General Psychiatry 1983;40:629-36.
Simpson DD,Sells SB.Effectiveness of treatment for drug abuse: an overview of the DARP research
program.Advances in Alcohol and Substance Abuse 1982;2(1):7-29.
Ward J,Mattick RP,Hall W.Duration of methadone maintenance treatment.In:Ward J,Mattick RP,Hall
W(eds.).Methadone Maintenance Treatment and Other Opioid Replacement Therapies.Amsterdam:
Harwood Academic Publishers, 1998,p. 571.
•
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NIDA International Program Methadone Research Web Guide
• Question 15: Are there cost benefits to methadone maintenance treatment?
Answer: Yes.Research has demonstrated that methadone maintenance treatment is beneficial to society,
cost-effective,and pays for itself in basic economic terms.
Research Highlights
A cost-effectiveness analysis reviewed five policy questions from an economic perspective: (1)whether
methadone should be a healthcare benefit; (2)what level of ancillary services is optimal;(3)what
methadone dose is appropriate;(4)what length of treatment is appropriate; and(5)whether contingency
contracts should be employed. The analysis found that expanded access to methadone maintenance had an
incremental cost-effectiveness ratio of less than$11,000 per quality-adjusted life year(QALY).Ancillary
services were shown to be an effective part of methadone maintenance therapy,especially during the
beginning of a treatment episode. The cost of additional methadone was found to be low compared with
the benefits of adequate doses. Short episodes of methadone maintenance were felt not likely to be cost-
effective(Barnett and Hui,2000).
A unique and timely analysis was performed that focused on the cost-effectiveness of methadone
treatment based on its impact on the HIV epidemic. The analysis considered populations in which HIV
prevalence among injection drug users ranged from 5 percent to 40 percent. The results demonstrated that
increased methadone maintenance capacity costs$8,200 per QALY gained in high-prevalence
communities and$10,900 per QALY gained in low-prevalence communities. Interestingly,the majority
of benefits were gained by individuals who do not inject drugs(Zaric,Barnett,and Brandeau,2000).
• A standard cost-effectiveness evaluation of methadone considered the incremental effect of
• methadone on the lifespan and treatment cost of a cohort of 25-year-old heroin users. The results
demonstrated that providing opioid-dependent patients with methadone maintenance had an
incremental cost-effectiveness ratio of$5,915 per life-year gained.A sensitivity analysis
determined that the ratio was less than$10,000 per life-year over a range of assumptions. This
cost-effectiveness ratio was lower than that of many common medical therapies and well within
the$50,000 threshold typically used in developed countries for judging cost-effectiveness
(Barnett, 1999).
• A systematic review from Lithuania on studies of the cost-effectiveness of methadone noted that
methadone maintenance had higher economic efficiency with daily doses of 80 to 100 mg,and
daily doses lower than 40 mg were considered inefficient.In addition,short treatment episodes
were not likely to be cost-effective, and ancillary services were more cost-effective at the
beginning of methadone maintenance than in the later stages.Economic efficiency was found to
be higher as treatment program census increased as opposed to the provision of more ancillary
services(Vanagas,Padaiga,and Subata,2004).
• The most comprehensive examination of economic benefits and costs was performed on data
from the Treatment Outcome Perspective Study(TOPS).After examining the average cost of a
methadone maintenance treatment day,detailed measurements of criminal activities rates,and the
cost to society of various crimes,the study yielded a final benefit-to-cost ratio of 4 to 1
(Harwood,Hubbard,Collins, et al., 1988).
• Rufener,Rachal,and Cruz(1977)studied the cost-effectiveness of methadone maintenance(and
other treatment modalities)and determined a benefit-to-cost ratio of 4.4 to 1.
• McGlothlin and Anglin(1981),using data from low-dose programs,compared patients who left
methadone maintenance treatment when a community clinic was closed in Bakersfield,
California,with patients in another community's program that remained open.For men,the ratio
411 of crime-related economic benefits to treatment costs was 1.7 to 1 over a 2-year period.In
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NIDA International Program Methadone Research Web Guide
addition,the continuous treatment group reported significantly higher rates of employment than •
those who had been closed out of treatment,although the factor was not formally assessed in the
study.
• Methadone maintenance treatment,when implemented at sufficient resource levels,provides
individual and social benefits for at least several years that are substantially higher than the cost
of delivering this treatment.The daily benefits equal the daily costs in virtually every case,even
among those who continue drug use at a reduced level(Gerstein and Harwood, 1990).
• There are many more costs to society associated with active heroin use(Rufener et al., 1977).
These include medical costs, law enforcement costs,judicial system costs,corrections costs,
nondrug crime costs,drug traffic control,drug abuse prevention costs,reducing housing stock
costs,absenteeism costs,unemployment costs,and drug-related deaths. Thus,when all costs to
society are considered,methadone maintenance treatment is extremely cost-effective and
beneficial to society.
• A study that randomly assigned new patients to three levels of care(methadone alone,methadone
plus standard counseling services, and methadone plus enhanced services [counseling,
medical/psychiatric,employment,and family therapy services])found that methadone plus
standard counseling was most cost-effective.At 12 months,the annual cost per abstinent client
was$16,485, $9,804, and$11,818 for the low, intermediate,and high levels of counseling,
respectively(Kraft,Rothbard,Hadley,et al., 1997).A similar finding was obtained in a cost-
effectiveness study of varying levels of care provided along with methadone maintenance in
Spain(Puigdollers, Cots,Brugal, et al.,2003).
• In a study comparing ongoing methadone maintenance with 6 months of methadone maintenance
followed by detoxification,total healthcare costs were greater for maintenance than detoxification
treatment($7,564 vs. $6,687;p<0.001).However,detoxification patients incurred significantly •
higher costs for substance abuse and mental healthcare services.Methadone maintenance
appeared to provide a small survival advantage compared with detoxification.The cost per life-
year gained was$16,967. Sensitivity analysis revealed a cost-effectiveness ratio of less than
$20,000 per QALY over a range of modeling assumptions(Masson,Barnett, Sees, et al.,2004).
Comparison of Treatment and Societal Costs of Active Heroin Addiction—A study of the cost
benefits of methadone maintenance treatment showed that the costs to society of the criminal activities
related to active heroin use can run as high as four times more than the costs for methadone maintenance
treatment(Harwood et al., 1988).
111
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NIDA International Program Methadone Research Web Guide
• Comparison of Treatment and
Societal Costs of Active
Heroin Addiction
51,000,000 $990.000
900,000
N=100
$00,000-
700,000-
' $00,000-
500,000
a400,000-
800,000-
$240,000
800,000-
100,000-
0
Methadone Costs to Society
Maintenance for Criminal
Treatment Act attles
• Figure 30 illustrates the cost-benefit relationship.
For example,if the approximate annual cost for
providing methadone maintenance treatment is
$2,400 per person,it would cost about$240,000
to provide treatment for 100 patients for 1 year.
In contrast,the annual costs to society related to
the criminal activities of 100 active heroin
addicts not in treatment would exceed$960,000
(Harwood et al.,1988).
Through the New York State Department of Substance Abuse Services,NIDA researchers have estimated
the yearly cost to maintain an opioid addict in New York:untreated and on the street($43,000),in prison
($34,000), in a residential drug-free program($11,000), and in methadone maintenance treatment
($2,400)(New York State Committee of Methadone Program Administrators, 1991).
•
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NIDA International Program Methadone Research Web Guide
Average Cost Per Year for
•
One Heroin Addict
$50,000—
40,000./-
3""
/-30' — ThPR pk
AMR
ROW
20,000 r 104
hitt
10,000 .r:e^ natrdrosal
Cmsost
i+arenant
On Street Incarcerated Residential Methadone
Treatment Maintenance
Treatment
Figure 31 illustrates the cost of active heroin
use for one addict for a year at about$43,000 •
in 1991.This includes the cost of the heroin,
the loss of property related to theft and
burglary,and the costs of security measures to
References combat such crimes.
Barnett PG,Hui SS.The cost-effectiveness of methadone maintenance.Mount Sinai Journal of Medicine
2000;67(5-6):365-74.
Barnett PG. The cost-effectiveness of methadone maintenance as a health care intervention.Addiction
1999;94(4):479-88.
Gerstein DR,Harwood HJ(eds.). Treating Drug Problems. Volume I. Washington,DC:National
Academy Press,Institute of Medicine, 1990.
Harwood HJ,Hubbard RL,Collins JJ,Rachal JV. The costs of crime and the benefits of drug abuse
treatment: a cost-benefit analysis using TOPS data. In:Leukefeld CG,Time FM(eds.). Compulsory
Treatment of Drug Abuse:Research and Clinical Practice.NIDA Research Monograph Series 86.
Rockville,MD:National Institute on Drug Abuse, 1988.
Kraft MK,Rothbard AB,Hadley TR,McLellan AT,Asch DA.Are supplementary services provided
during methadone maintenance really cost-effective?The American Journal of Psychiatry
1997;154(9):1214-19.
Masson CL,Barnett PG, Sees KL,Delucchi KL,Rosen A, Wong W,Hall SM. Cost and cost-
effectiveness of standard methadone maintenance treatment compared to enriched 180-day methadone
detoxification.Addiction 2004;99(6):718-26.
McGlothlin WH,Anglin MD.Long-term follow-up of clients of high-and low-dose methadone
programs.Archives of General Psychiatry 1981;38:1055-63. •
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NIDA International Program Methadone Research Web Guide
• New York State Committee of Methadone Program Administrators. COMPA's Five Year Plan for the
Methadone Treatment System in New York State.New York:New York State Committee of Methadone
Program Administrators, 1991.
Puigdollers E,Cots F,Brugal MT,Torralba L,Domingo-Salvany A.Methadone maintenance programs
with supplementary services:a cost-effectiveness study. [Spanish] Gaceta Sanitaria 2003;17(2):123-30.
Rufener BL,Rachal JV,Cruz AM.Management Effectiveness Measures for NIDA Drug Abuse Treatment
Programs. Cost Benefit Analysis.Rockville,MD:National Institute on Drug Abuse, 1977.
Vanagas G,Padaiga Z, Subata E.Economic efficiency of methadone maintenance and factors affecting it.
[Lithuanian]Medicina(Lith)2004;40(7):607-13.
Zaric GS,Barnett PG,Brandeau ML.HIV transmission and the cost-effectiveness of methadone
maintenance.American Journal of Public Health 2000;90(7):1100-11.
•
•
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NIDA International Program Methadone Research Web Guide
Question 16: What are the retention rates for methadone maintenance treatment? •
Answer: Retention in methadone is related to the dose of methadone but not the provision of ancillary
services.
Research Highlights
• A meta-analysis of studies comparing the provision of methadone maintenance with and without
ancillary services demonstrated decreased illicit heroin use with ancillary services but found no
statistically significant additional benefit in terms of retention in treatment,RR 0.94(95%CI,
0.85 to 1.02)(Amato,Davoli,Perucci, et al.,2005).
• An observational study of 351 patients in the United Kingdom receiving methadone maintenance
compared with those receiving methadone dose reduction found the following retention rates:
88 percent vs. 86 percent at 1 month,71 percent vs. 58 percent at 2 months,62 percent vs. 50
percent at 1 year, and 42 percent vs. 30 percent at 2 years(Gossop,Marsden, Stewart, et al.,
2001).
• An Italian study followed 1,503 heroin-dependent patients who received treatment in the form of
methadone maintenance, a drug-free program, or naltrexone. The retention rate after 1 year was
40 percent for patients in methadone maintenance, 18 percent in naltrexone, and 15 percent in the
drug-free program.Patients receiving methadone greater than or equal to 60 mg per day and 30 to
59 mg per day were respectively 70 and 50 percent more likely to remain in treatment than those
receiving less than 30 mg per day. Patients receiving methadone maintenance were 30 percent
more likely to remain in treatment than those not receiving methadone(D'Ippoliti,Davoli,
Perucci,et al., 1998).
• Thirty-eight percent of the new patient group(total 126)in the Ball and Ross(1991)studies of six
4111 methadone maintenance treatment programs remained in treatment after a year;63 percent of the
moderate-stay group(total 345)were still in treatment a year later;and 84 percent of the long-
term patients(total 146)continued their methadone maintenance treatment for another year.
• In a study of 311 admissions to three methadone maintenance treatment programs during 1990
and 1991,24 percent dropped out within 60 days. The significant predictors of retention were
social stability(being married, employed,and having few prior arrests);previous treatment
experience;high dosage levels;and motivation for treatment(Simpson and Joe, 1993).
Additional Studies
• In a study of 351 daily or weekly heroin users who were admitted to 1 of 17 publicly funded
methadone treatment programs,predictors of retention in methadone maintenance treatment
programs included(1)positive patient evaluations of the quality of social services received
during the first month after admission(e.g.,family, legal,educational,employment,financial
services); (2)positive patient ratings of how easily accessible the program was; and(3)
participation in programs that informed patients of their methadone dosage levels(Condelli,
1993).
•
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NIDA International Program Methadone Research Web Guide
• 1-Year Treatment Retention Predictors of Retention for
Rates for Three Large Studies Methadone Maintenance
Treatment
so-
Program variables:
40-60%
60- • Prompt,high-quality social services
* Accessibility of program
a Disclosure of dose
o 40-
34% 25444% Patient variables;
1 • Use of marijuana
30- • Age
20-
a
Figure 33 illustrates that in the Treatment
10_ Outcome Perspective Study(TOPS),patient
self-report ratings of the quality(not the
number)of social services received during
0 a the first month of methadone maintenance
(Sells and (Hubbard et al. (Ball and Ross, treatment were a strong predictor of
slrgpson,19T8) im) retention(Condelli and Dunteman,1993).
The study suggests that methadone
maintenance treatment programs should
Figure 32 illustrates 1-year treatment provide patients with high-quality social
retention rates for three large studies. services as soon as possible after admission
Sin order to promote retention.The study
found that three program and two patient
variables predicted retention.It also noted
that patients who were 25 years of age or
younger were more likely than older
patients to drop out of methadone
maintenance treatment programs,possibly
because they lacked the motivation,
maturity,and life goals that often
characterize older patients.
•
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NIDA International Program Methadone Research Web Guide
Likelihood of Relapse After Leaving Methadone Treatment—Of 105 patients who were followed in •
the community after leaving methadone maintenance treatment after 1 month to 1 year or longer,two-
thirds(67.6 percent)relapsed to injection drug use(Ball and Ross, 1991).
References
Amato L,Davoli M,Perucci C,Ferri M,Faggiano F,Mattick RP.An overview of systematic reviews of
the effectiveness of opiate maintenance therapies:available evidence to inform clinical practice and
research.Journal of Substance Abuse Treatment 2005;28(4):321-29.
Ball JC,Ross A. The Effectiveness of Methadone Maintenance Treatment:Patients, Programs, Services,
and Outcomes.New York: Springer-Verlag, 1991.
Condelli WS. Strategies for increasing retention in methadone programs.Journal of Psychoactive Drugs
1993;25(2):143-47.
Condelli WS,Dunteman GH.Exposure to methadone programs and heroin use.American Journal of
Drug and Alcohol Abuse 1993;19:65-78.
D'Ippoliti D,Davoli M,Perucci CA,Pasqualini F,Bargagli AM. Retention in treatment of heroin users in
Italy:the role of treatment type and of methadone maintenance dosage.Drug&Alcohol Dependence
1998;52(2):167-71.
Faggiano F, Vigna-Taglianti F,Versino E,Lemma P.Methadone maintenance at different dosages for
opioid dependence. The Cochrane Database of Systematic Reviews,Issue 3,2003.
Gossop M,Marsden J, Stewart D, Treacy S. Outcomes after methadone maintenance and methadone
reduction treatments:two-year follow-up results from the National Treatment Outcome Research Study.
Drug&Alcohol Dependence 2001;62(3):255-64.
Hubbard RL,Marsden ME,Rachal JV,Harwood HJ,Cavanaugh ER, Ginzburg HM.Drug Abuse •
Treatment:A National Study of Effectiveness.Chapel Hill:University of North Carolina Press, 1989.
Sells SB, Simpson DD(eds.). The Effectiveness of Drug Abuse Treatment. Cambridge,MA:Ballinger,
1976.
Simpson DD,Joe GW. Motivation as a predictor of early dropout from drug abuse treatment.
Psychotherapy 1993;30(2):357-68.
•
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NIDA International Program Methadone Research Web Guide
IIIQuestion 17: Is mandated methadone maintenance treatment as effective as
voluntary treatment?
Answer: Yes.Mandated methadone maintenance treatment(being forced to attend treatment by the
criminal justice system)is as effective as voluntary treatment.
Research Highlights
A study examined the relationship between length of stay in methadone maintenance treatment and
referral by legal and nonlegal sources of 2,200 patients. It was determined that patients who are legally
referred to methadone maintenance treatment stay in treatment longer than,and do at least as well as,
those who seek treatment voluntarily(Collins and Allison, 1983).
A study of 121 male veterans in a 90-day Veterans Administration drug rehabilitation program compared
court-referred and voluntary patients.Objective and subjective measures both indicate that the court-
referred patient is potentially as responsive to methadone maintenance treatment as the voluntary patient.
Sixty-two percent of the court-referred patients were judged to have a good prognosis compared with 58
percent of the voluntary patients(McLellan and Druley, 1977).
Three samples of methadone maintenance treatment admissions,who were treated during the years of
1971 to 1973,participated in a followup study 7 years later. These groups included(1)a random sample
of 100 patients,(2)a sample of 136 patients who had a minimum of 30 months remaining on civil addict
parole status at the time of admission, and(3)a matched sample of 136 patients not on parole.The
addition of parole supervision with urine testing resulted in only marginal improvements in behavior over
that attributable to methadone maintenance treatment alone;however,parole status did significantly
• reduce the length of intervals of daily heroin use both before and after admission(Anglin,McGlothlin,
and Speckart, 1981).
Mandated Methadone Maintenance Treatment and Three Treatment Outcomes—Patients who are
legally coerced into methadone maintenance treatment experience treatment success at about the same
rate as patients who participate voluntarily in treatment.
A study by Anglin,Brecht,and Maddahian(1990)examined patients who were mandated to treatment
and those who entered voluntarily.One group was forced to participate in methadone maintenance
treatment(high coercion).A second group(not represented in Figures 34 through 36)had moderate legal
pressure to participate in methadone maintenance treatment(medium coercion).A third group had mild
legal pressure to participate in methadone maintenance treatment(low coercion).
III
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NIDA International Program Methadone Research Web Guide
Percentage of Employed Time Percentage of Daily •
■Low Coercion Narcotics Use
High Coercion
00 Total N=297 50-
75% ■Low Coercion
High Coercion
669464%
70- 57% . :, Total N 997
50-
4794
60-
4t%
40- 30r
30- 40
3394 31%
30-
20-
70-
10- 10-
0 Pretreatment Posttreatment 0 Pretreatment Posttreatment
Figure 35 compares the behaviors of
Figure 34 compares the behaviors of individuals in the high-coercion group with
individuals in the high-coercion group those of individuals in the low-coercion
with those of individuals in the low- group for the treatment outcome of daily
coercion group for the treatment outcome narcotics use.As the figure illustrates,
4111
of time employed.As the figure illustrates, patients who are coerced in treatment
patients who are coerced in treatment achieve this treatment outcome at about the
achieve this treatment outcome at about same rate as patients who voluntarily
the same rate as patients who voluntarily participate in methadone maintenance
participate in methadone maintenance treatment(Anglin et al.,1990).
treatment(Anglin et al.,1990).
III
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NIDA International Program Methadone Research Web Guide
• Percentage of Burglary Time
31%
30` a tow coercion
a ttigh Coercion
Toter N-201
zd_
14%
10- 9% 9%
0 Pretreatment Posttreatment
Figure 36 compares the behaviors of
individuals in the high-coercion group with
those of individuals in the low-coercion
group for the treatment outcome of criminal
4110
involvement.As the figure illustrates,
patients who are coerced in treatment
achieve this treatment outcome at about the
same rate as patients who voluntarily
participate in methadone maintenance
treatment(Anglin et al.,1990).
References
Anglin MD,Brecht ML,Maddahian E.Pre-treatment characteristics and treatment performance of legally
coerced versus voluntary methadone maintenance admissions. Criminology 1990;27:537-57.
Anglin MD,McGlothlin WH, Speckart GR.The effect of parole on methadone patient behavior.
American Journal of Drug and Alcohol Abuse 1981;8:153-70.
Collins JJ,Allison M.Legal coercion and retention in drug abuse treatment.Hospital and Community
Psychiatry 1983;34(12):1145-49.
McLellan AT,Druley KA.A comparative study of response to treatment in court-referred and voluntary
drug patients.Hospital and Community Psychiatry 1977;28:241-45.
•
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NIDA International Program Methadone Research Web Guide
Question 18: What is the role of L-alpha-acetyl-methadol (LAAM)? •
Answer: L-alpha-acetyl-methadol(LAAM), a potent opioid with a longer duration of action than
methadone,can suppress opioid withdrawal for up to 72 hours.Research on both LAAM and methadone
maintenance treatment provides comparable results regarding patients' reported clinic attendance, opioid
withdrawal symptoms,illicit drug use,employment status,and criminal activity. Both treatments are
similar regarding overall effectiveness.
Due to concerns over reports of QT interval prolongation and episodes of Torsades de Point,LAAM was
removed from the European markets and subsequently had limited use in the United States.
•
•
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NIDA International Program Methadone Research Web Guide
• Question 19: How do buprenorphine and methadone compare?
Answer: Buprenorphine is approved for use in the treatment of opioid dependence in a large number of
countries, including Australia,Belgium,Canada,Croatia, Germany,Iran,England,France,the United
Kingdom, and the United States.Buprenorphine is a partial agonist at the opioid receptor,as opposed to a
full agonist such as methadone or heroin.This means that buprenorphine has a unique pharmacologic
profile leading to a lower likelihood of overdose or respiratory depression. Like methadone,
buprenorphine has the ability to suppress opioid craving and withdrawal,block the effects of self-
administered opioids,retain patients in treatment,and decrease illicit opioid use.Because it is a partial
agonist,buprenorphine maintains patients in a milder degree of physical dependence and is associated
with milder withdrawal syndrome following cessation.
Clinical trials comparing the efficacy of buprenorphine to methadone on the outcomes of retention and
illicit opioid use have demonstrated similar results when compared with low doses of methadone(20 to
30 mg)(Johnson,Jaffe,and Fudala, 1992;Ling,Wesson,Charuvastra,et al., 1996).Comparisons to
higher doses(35 to 90 mg)of methadone have yielded mixed results(Strain, Stitzer,Liebson,et al., 1994;
Kosten, Schottenfeld,Ziedonis, et al., 1993).
lonw 1i4,.•.r11
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11111
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Figure 37a
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C Win.05.4.1 teem3Arnra.rm.cram 219952999•2592,'r..
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Figure 37b
Figures 37a and 37b illustrate that a meta-analysis of 13 clinical trials that compared
buprenorphine maintenance with methadone maintenance had the following findings:
"Buprenorphine given in flexible doses appeared statistically significantly less effective than
methadone in retaining patients in treatment(RR=0.82;95%CI:0.69-0.96).Low-dose
buprenorphine is not superior to low-dose methadone.High-dose buprenorphine does not
retain more patients than low-dose methadone,but may suppress heroin use better.There
was no advantage for high-dose buprenorphine over high-dose methadone in retention(RR=
0.79;95%CI:0.62-1.01),and high-dose buprenorphine was inferior in suppression of heroin
use.Buprenorphine was statistically significantly superior to placebo medication in retention
of patients in treatment at low doses(RR=1.24;95%CI: 1.06-1.45),high doses(RR=1.21;
95%CI: 1.02-1.44),and very high doses(RR=1.52;95%CI: 1.23-1.88).However,only high
and very high dose buprenorphine suppressed heroin use significantly above placebo."
• (Mattick,Kimber,Breen,et al.,2003.)(Please note,this review will be updated.)
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NIDA International Program Methadone Research Web Guide
Patients receiving buprenorphine can be either(1)discontinued without significant withdrawal,(2) •
maintained,or(3)transferred to opioid antagonist treatment, such as naltrexone.Patients with a higher
level of physical dependence and whose needs cannot be met by buprenorphine can be transferred to an
opioid agonist, such as methadone or L-alpha-acetyl-methadol(LAAM).
Research Highlights
• Mello and Mendelson showed that buprenorphine suppresses heroin self-administration by
opioid-dependent primates and humans(Mello and Mendelson, 1980;Mello,Mendelson,and
Kuehnle, 1982;Mello,Bree,and Mendelson, 1983).
• Findings from a subsequent dose-ranging study at the Los Angeles Addiction Treatment Research
Center(LAATRC)suggest that the median doses of buprenorphine for adequate clinical
stabilization may be in the 12-to 16-mg range(Compton,Ling, Charuvastra, et al., in press).
• A NIDA-sponsored, 12-site LAATRC/Veterans Administration/NIDA multicenter study
compared doses of 1,4, 8,and 16 mg of buprenorphine in 631 patients. The primary comparison
between the 8-mg and the 1-mg groups shows that the 8-mg group used fewer illicit opioids and
remained in treatment longer(Ling,Charvastra,Collins, et al., 1998).
A clinical trial comparing buprenorphine,the buprenorphine/naloxone combination,and placebo
was terminated early because buprenorphine and naloxone in combination and buprenorphine
alone were found to have greater efficacy than placebo. Opioid-negative urine samples were
found more frequently in the buprenorphine and buprenorphine/naloxone groups(17.8%and
20.7%,respectively)than in the placebo group(5.8%,p<0.001 for both comparisons)(Fudala,
Bridge,Herbert, et al.,2003).
Potential Benefits of Buprenorphine •
Research on buprenorphine has shown that it has the potential to be a feasible alternative to methadone
maintenance treatment. One potential benefit of buprenorphine compared with methadone that needs
further investigation is a lower prevalence of medication interactions between buprenorphine and highly
active antiretroviral treatment used to treat patients with HIV(Sullivan and Fiellin,2005).Additional
potential benefits of buprenorphine treatment are outlined in Figure 38.
Potential Benefits of
Buprenorphine
• Low abuse potential
• Relatively mild withdrawal symptoms
• May facilitate transfer to opioid antagonist
treatment
• High safety profile
• May attract broader range of addicts
Figure 38 illustrates the potential benefits
of buprenorphine.
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NIDA International Program Methadone Research Web Guide
References
Compton P,Ling W,Charuvastra C,Wesson DR.Buprenorphine as a pharmacotherapy for opioid
addiction: what dose provides a therapeutic response?American Journal of the Addictions, in press.
Fudala PJ,Bridge TP,Herbert S,Williford WO,Chiang CN,Jones K, et al.Buprenorphine/Naloxone
Collaborative Study Group. Office-based treatment of opiate addiction with a sublingual-tablet
formulation of buprenorphine and naloxone.New England Journal of Medicine 2003;349(10):949-58.
Johnson RE,Jaffe JH,Fudala JP.A controlled trial of buprenorphine treatment for opioid dependence.
JAMA 1992;267(20):2750-55.
Kosten TR, Schottenfeld R,Ziedonis D,Falcioni J.Buprenorphine versus methadone maintenance for
opioid dependence.Journal of Nervous and Mental Disease 1993;181(6):358-64.
Ling W,Charuvastra C,Collins JF,Batki S,Brown LS,Kintaudi P,et al.Buprenorphine maintenance
treatment of opiate dependence: a multicenter,randomized clinical trial.Addiction 1998;93(4):475-86.
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(5):401-47.
Mattick RP,Kimber J,Breen C,Davoli M.Buprenorphine maintenance versus placebo or methadone
maintenance for opioid dependence. The Cochrane Database of Systematic Reviews,Issue 2,2003.
Mello NK,Bree MP,Mendelson JH.Comparison of buprenorphine and methadone effects on opioid self-
administration in primates.Journal of Pharmacological Experimental Therapy 1983;225:378-86.
Mello NK,Mendelson JH.Buprenorphine suppresses heroin use by heroin addicts.Science 1980;27:
657-59.
• Mello NK,Mendelson JH,Kuehnle JC.Buprenorphine effects on human heroin self-administration: an
operant analysis.Journal of Pharmacological Experimental Therapy 1982;223:30-39.
Strain EC, Stitzer ML,Liebson IA, Bigelow GE.Buprenorphine versus methadone in the treatment of
opioid-dependent cocaine users.Psychopharmacology(Berl) 1994;116(4):401-06.
Sullivan LE,Fiellin DA.Buprenorphine: its role in preventing HIV transmission and improving the care
of HIV infected patients with opioid dependence. Clinical Infectious Diseases 2005;41(6):891-96.
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Question 20: Can methadone and buprenorphine be abused? •
Answer: Both methadone and buprenorphine can be diverted from their intended recipients. This
diversion occurs in countries that provide these medications via supervised dispensing(e.g.,pharmacies)
and by prescription. Oftentimes,this diversion is by individuals who are seeking a therapeutic benefit
(e.g.,unobserved treatment).Other times,this diversion results in abuse. The extent of these two types of
diversion varies,although most studies note that the benefits of providing the treatment outweigh the risks
associated with diversion.For instance,the efficacy of methadone has been demonstrated over the past 40
years(O'Connor and Fiellin,2000). The provision of methadone and buprenorphine treatment was
associated with a 75-percent decrease in fatal heroin overdoses in France(Lepere, Gourarier, Sanchez,et
al., 2001;Auriacombe,Fatseas,Dubernet,et al.,2004).
In studies that have compared death rates from heroin overdose among those who are untreated and those
who receive methadone, deaths are higher among untreated opioid-dependent individuals(Caplehorn,
Dalton,Haldar, et al., 1996;Zanis and Woody, 1998).
Research Highlights
Methadone Abuse
Methadone can be diverted for oral or intravenous use(Fiellin and Lintzeris,2003; Green,James,Gilbert,
et al.,2000). Some diverted methadone can result in fatal overdoses; however,the rate of overdose among
patients enrolled in methadone maintenance is low.A meta-analysis revealed a relative risk of death of
0.25 (95%CI: 0.19-0.33)for patients receiving methadone maintenance(Caplehorn et al., 1996).A study
of nearly 10,000 individuals inducted onto methadone determined that the mortality rate was 7.1 deaths
per 10,000 inductions(95%CI: 1.8± 12.4). In this same study, 51 percent of methadone-related deaths
occurred in people who were not registered in methadone maintenance(Zador and Sunjic,2002). •
In addition,while methadone may be detected in drug-related deaths, it is often not the causative agent. In
one study in the west of Scotland, during the period 1991-2001,methadone alone was judged to be the
causative agent in only 29 percent(56)of drug-related deaths(Seymour,Black,Jay, et al.,2003).
Similarly,with the increased use of methadone as a treatment for chronic pain,the majority of
methadone-related deaths in Australia and the United States are believed to be associated with the use of
this medication for pain treatment instead of treatment of opioid dependence(Williamson,Foreman,
White,et al., 1997; Center for Substance Abuse Treatment,2004).
Buprenorphine Abuse
As a partial agonist,buprenorphine has less potential for abuse than most full agonists.However,there is
a reinforcing effect that subjects can experience with buprenorphine administration,especially via the
injection route. This reinforcement is less likely if the subject has recently used a full agonist compound;
in fact,buprenorphine can lead to a painful and uncomfortable precipitated withdrawal under this
scenario. In addition,the development of a tablet that combines buprenorphine with naloxone, in a 4 to 1
ratio,has demonstrated decreased abuse potential and the ability to precipitate withdrawal in patients who
are receiving a full opioid agonist(Mendelson,Jones,Welm,et al., 1999).
When the buprenorphine/naloxone combination tablet is taken sublingually,as prescribed,naloxone is
poorly absorbed,and the patient receives a buprenorphine effect.However,if the tablet is dissolved and
injected,the naloxone will antagonize the buprenorphine,resulting in a range of reactions,including
blockade of opioid effects and precipitation of an immediate withdrawal. In this way,the combination
gives the therapeutic benefit but greatly reduces opportunities for abuse by injection.
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411
Seymour A,Black M,Jay J, Cooper G,Weir C,Oliver J. The role of methadone in drug related deaths in
the west of Scotland.Addiction 2003;98(7):995-1002.
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maintenance,New South Wales, 1996.Drug&Alcohol Review 2002;21(2):131-36.
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Alcohol Dependence 1998;52:257-60.
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