Transcript Urban community office-based opiate

URBAN OFFICE-BASED
BUPRENORPHINE/NALOXONE OPIOID
MAINTENANCE THERAPY: OUTCOMES
AT 18 MONTH FOLLOW-UP
Medical Student Researcher: Mace AGa
Principle Investigators: Adelman CAa,b, Parran TVa,d
Co-Investigators: Pagano MEa,c, Merkin BJa,b, Defranco Ra,b, Ionescu RAa
a Case Western Reserve University School of Medicine, Cleveland, OH
b St. Vincent Charity Hospital,
c
Rosary Hall, University Hospitals Health System, Cleveland, OH
Division of Child Psychiatry, Department of Psychiatry, Case Western Reserve University School of Medicine, Cleveland, OH
d Department of Psychiatry, St. Vincent Charity Hospital, Cleveland, OH
Opioid Dependence
 A Significant Burden on the Patient

Increased: Mortality, Disability, Hepatitis, HIV,
Healthcare costs, Unemployment, Incarceration
 Major Public Health Problem

$21.8 Billion in medical, legal, and social costs
attributable to heroin addiction alone (1996
est.)
 Opioid dependence is a growing problem

Incidence: 2006 NSDUH
 ~2.1 million new initiates to non-medical use of
prescription pain relievers
 Surpassed marijuana
 Highest of any illicit drug
 91,000 new initiates to heroin

Prevalence: 2006 NSDUH
 5% population reports to non-medical use of
prescription pain relievers in 2006
 2 per 1000 report heroin use (0.2% population)
( Baral et. al., 2007; Blanchard et. al., 2003,; Dekker, 2007; Donaher & Welsh, 2006; Hser et. al., 2001; Mark et. al.; 2001; McLellan
et. al., 2000; White et. al., 2005)
NSDUH 2006
Past Year Initiation of Substance Use among Persons Aged 12 or Older:
Numbers in Thousands
2,500
2,150
2,063
2,000
1,500
1,112
977
1,000
860
845
783
500
267
264
91
69
Heroin
PCP
0
Pain Relievers Marijuana and Tranquilizers
Hashish
Cocaine
Ecstasy
Stimulants
Inhalants
Sedatives
LSD
NSDUH* 1990-2006
Substance Use in the Past Year: Percent Population
6
5
5
4.9
4.7
4.7
4.8
4
3.7
Pain
Relievers
3
% 3
2.9
Heroin
2.5
2.5
2.4
2.2
2.1
2
2
1.9
1.9
1.9
* Formerly NHSDA
1
0.2
0.2
0.2
0
1990
1991
1992
0.1
1993
0.1
1994
0.2
1995
0.2
1996
0.3
0.1
1997
1998
0.2
1999
0.1
2000
0.2
2001
0.2
2002
0.1
2003
0.2
2004
0.2
2005
0.2
2006
Interventions
 The Question: How do we help opioid dependent patients
achieve abstinence and return to more healthy productive
lives?
 Traditionally a difficult & lengthy road to recovery
 High rate of relapse
 Several Approaches:
 Abstinence based treatment programs
 12-step support programs
 Pharmacotherapy:
 Opioid Maintenance Therapy (Methadone, LAAM,
Buprenorphine/Naloxone)
 Opioid antagonists (Naltrexone)
 Palliative therapy for withdrawal sx. (Clonidine, Loperamide,
Trazodone, Dicyclomine, etc.)
 Multifaceted approach is most effective
Opioid Maintenance Therapy
 What is it?

Long-term opioid agonist therapy prescribed for / provided to opioid
dependent patients as an alternative to illicit opioid use and an adjunct
to more intensive treatment programs
 Use orally administered agonists with extended half lives or partial
agonists
 daily or alternate day dosing
 reduced euphoric effect
 facilitates psychosocial functioning vs. shorter-acting, stronger opioids
 Why do it?





Useful adjunct therapy in treatment-refractory patients
Significantly increased rates of abstinence from illicit opioid use
Improved functioning within the family and job
Decreased legal problems
Oral agents eliminate needle sharing and consequent infectious disease
risk
(Schuckit, M.A., Segal, D.S, 2005. Chapter 373. Opioid Drug Abuse and Dependence. The McGraw-Hill Companies, Inc.)
Opioid Maintenance Therapy
 Since the 1960’s: Methadone

Low Cost, but: Few clinics, Stringent
criteria, Long waitlists, Social stigma
 Only 14% of patients dependent on
opioids are treated in methadone clinics
 Drug Addiction Treatment Act of 2000

Physicians can provide office-based
treatment to opioid addicted patients
 Buprenorphine is approved by the FDA
in 2002 for office-based use as opioid
maintenance therapy

These moves by the FDA paved the way for
major changes in the way addiction is treated
in the United States, potentially making
opioid maintenance therapy available to a
much larger population of patients
Above: Methadone
Below: A Methadone Clinic
Buprenorphine

Unique Pharmacologic Profile

Partial agonist at mu-opioid receptor,
antagonist at the kappa-opioid receptor

Combined with Naloxone in a 4:1 ratio in
the Buprenorphine/Naloxone combination
tablet (Suboxone®)
 Benefits (vs. Methodone/LAAM)






Convenience of traditional pharmacy
prescription (rather than daily dose pickup at a
methadone clinic)
Decreased potential for harm in the event of
medication diversion
Decreased potential for harm in the event of
medication overdose
Ease of dosage titration
Ease and brevity of eventual tapering off the
medication
Probably a decreased impact on the patient’s
cognitive function
www.naabt.org
(Carrieri et al., 2006; Fiellin et al., 2004; Fiellin and O'Connor, 2002a; Fudala et al., 2003; Harris et al., 2000; Jasinski et al., 1978; Johnson et al., 2000; Johnson et al., 1992; Ling et al.,
1998; Ling et al., 1996; Mattick et al., 2003; Mendelson and Jones, 2003; Simoens et al., 2005; Strain et al., 1994; Walsh and Eissenberg, 2003).
Study Goals
 There are a few areas in which research on
buprenorphine OMT is lacking, which we address
with the present study:
 Long term outcome data on the use of Bup/Nx office-
based OMT in the United States
 Effectiveness of Bup/Nx office-based OMT in
disadvantaged populations
 The impact of patient characteristics on retention in
and outcomes of office-based Bup/Nx therapy
 Answers to these questions have the potential to
guide clinical decision-making as well as the
allocation of, often scarce, resources for
substance abuse rehabilitation
(Fiellin et al., 2004; Simoens et al., 2005; Alford et al., 2007; Auriacombe et al., 1994; Fhima et al., 2001; Giacomuzzi et al., 2005; Kakko et al., 2003;
Kornor et al., 2007; McLellan et al., 2000)
Parameters
 Patient characteristics – Chart Review
 Demographics
 Able to pay
 Drug use characteristics (DOC, ROA, etc.)
 Medical Comorbidities
 Legal Comorbidities
 Treatment Characteristics – Short Survey
 Adverse Effects
 Outcomes – Telephone Interview at 18 months




Substance Use (Primary)
12-Step Affiliation
Employment
Psychosocial
Hypotheses
 Hypothesis A:
 Individual patient characteristics may increase or decrease
retention in buprenorphine/naloxone office based therapy
at 18 months.
 Hypothesis B:
 Retention in buprenorphine/naloxone office-based opioid
maintenance therapy (Hereafter OBT) will decrease
substance use, increase 12-step affiliation, and improve
occupational and psychosocial function at 18 months.
 Hypothesis C:
 Treatment characteristics may increase or decrease
retention in buprenorphine/naloxone OBT at 18 months.
Patient Population
 176 opioid dependant adults
 Aged between 19 and 65 years
 Met the criteria for admission into the
treatment program
 Multiple failed attempts at abstinence
 Lack of uncontrolled major mental illness or
psychosis
 Stable living situation
Patient Population
 Two Socioeconomic Status levels
 Possessed the financial means for treatment (Private
insurance, Medicare, or Medicaid).
 Alternatively, patients with limited financial means
who met all other criteria were accepted and their care
was publically funded by a grant from ADASBCC
(Alcohol and Drug Addiction Services Board of
Cuyahoga County)
 Created two distinct populations for study
 Financially solvent patients traditionally well studied
 Indigent patients thus far poorly studied
Definitions
 Solvent:
 “Assets exceed liabilities”
 Able to meet cost of medical care
 Indigent
 i.e. “Medically indigent adult”
 “Persons who do not have health insurance and who are
not eligible for other health care coverage, such as
Medicaid, Medicare, and cannot otherwise afford
treatment”
 In our study, the patient population was separated
based on this characteristic, which was assessed using
insurance status in our research methodology
 Really a proxy for complex sets of differences in patient
characteristics and living situations
Protocol & Methods

Induction (60 Hours)




Stabilization (6 wks)






Preadmission assessment of addictive disorder
Admitted to the SVCH – Rosary Hall detoxification unit for buprenorphine induction therapy
When clinical stability was ascertained, discharged to home or a residential program with a
written prescription for a 2 week supply of Bup/Nx sublingual combination tablet
(Suboxone®).
Intensive outpatient treatment (Residential facility for grant funded patients)
Random urine toxicology screening
Participation in aftercare group psychotherapy
Regular 12-step meeting (e.g. AA or NA)
Pattern of noncompliance resulted in administrative discharge
Follow-Up (2-4 week intervals)



Follow up appointments at Rosary Hall were scheduled on a strictly regular basis
A questionnaire comprised of severity ratings on 7 symptom parameters was completed by
the patient at each follow up visit.
If continued participation in the program was deemed appropriate by the physician, a new
prescription for Suboxone was written and given to the patient.
Protocol & Methods
 Chart Review
 Basic demographic information
 Medical history
 Drug abuse history
 Information from the patient’s stabilization phase
of treatment
Protocol & Methods
 Telephone Interview
 Confidential interview conducted at 18mo post-
induction
 Questions




Opioid use history
Current Bup/Nx medication
Current illicit drug use
Presence of both long and short term opioid
complications
 Fifteen questions measuring social role and
occupational function
Results
 176 subjects were initially enrolled in our study
 110 (63%) completed the follow-up telephone
interview at 18 months
 No significant differences in the baseline characteristic
variables between subjects who completed the
telephone interview and those who did not
 Exception: Subjects who could not be scheduled for a
telephone interview were more likely to have an arrest
history than those available for follow-up (44% vs.
26% respectively, χ2[1]=4.96, p=0.03).
Subjects Available for Follow-up: Ethnicity
80
74
70
60
50
% 40
30
21
20
10
4
1
0
African American
Hispanic
White, Non-Hispanic
Other
Subjects Available for Follow-up: Able to Pay
60
56%
50
44%
40
% 30
20
10
0
Solvent
Indigent
Subjects Available for Follow-up: Drug of Choice
100
90
89
80
70
60
% 50
40
30
20
11
10
0
Heroin
Prescription Opioid
Subjects Available for Follow-up: Preferred Route of
Administration
80
71
70
60
50
% 40
30
20
16
13
10
0
Injection
Nasal
Oral
Subjects Available for Follow-up: Medical History
45
39
40
38
35
30
30
25
%
20
20
15
10
8
5
5
0
Abscess
Depression
Hepatitis C
Injury
Overdose
Prior Psych.
Treatment
Subjects Available for Follow-up: Legal History
70
60
60
50
40
%
30
26
20
10
0
Arrest
Prior Legal Probs
Results
Subgroup Analysis: Buprenorphine/Naloxone Status
 At follow-up, the majority of subjects reported that they
had remained on Bup/Nx-OBT (77%)
 Those still using Bup/Nx were:
 ~24% Less likely to be using any substance (χ2 =6.26, p=0.0123)
 21% Less likely to be using heroin (χ2=8.1, p=0.0044)
 ~29% More likely to be AA Affiliated (χ2=5.49, p=0.0191)
 31% More likely to have a sponsor (χ2=4.72, p=0.0298)
 8% More likely to have been employed at baseline (χ2=4.92,
p=0.0266).
 30% More likely to be employed at follow-up (χ2=4.89, p=0.0271)
Preexisting medical and legal comorbidity were important covariates in our analysis and all subgroup analyses have been controlled for
baseline medical and legal comorbidity.
Outcome Measures at 18-month Follow-up: By Bup/Nx
Status
100
93
Still On Bup/Nx
87.5
90
Discontinued Bup/Nx
80
70
65
64.5
60
56.5
% 50
40
35
32
28
30
27.5
19.5
20
10
8.5
7
0
Any Substance
Use
Heroin Use
AA Affiliated
Has Sponsor
Employed:
Baseline
Employed:
Follow-up
Results
Subgroup Analysis: Buprenorphine/Naloxone Status
 Interesting trends that didn’t quite meet the
significance level
 Those remaining on Bup/Nx at follow-up were:
 Less likely to be using alcohol (4% vs. 16.5%, χ2=3.8, p=0.0513)
 More likely to have a home group (85% vs. 49%, χ2=3.40, p=0.0654)
 More likely to have reported prescription opioid use at baseline (13%
vs. 7.5%, χ2=3.13, p=0.0768)
 More likely to be newly employed at follow-up (65% vs. 35.5%,
χ2=2.84, p=0.0918)
 May be directions for future research
Results
Subgroup Analysis: Solvent vs. Indigent Patients
 Sixty two of the 110 patients completing the follow-up telephone
interview were indigent (56%).
 No significant difference between indigent and solvent patients
was noted in:


Bup/nx use at follow-up (80% vs. 73% p=0.33)
Employment status across the study period
 One Exception – insured were more likely to be employed at baseline
(37% vs. 10%, χ2=4.84, p=0.028)*
 Indigent patients were

8% More likely to report substance use at follow-up (18% vs. 10%,
χ2=4.09, p=0.0432 )
 9% More Alcohol use (11% vs. 2%, χ2=4.95, p=0.026)
 12% More Heroin use (18%vs/ 6%, χ2=7.97, p=0.0047)
 No significant differences were observed for cocaine use.

Less likely to be from a minority background (16% vs. 35%, χ2=6.82
p=0.009)
 Less likely to have a significant other (36.5% vs. 81.5%, χ2 =12.36
p=0.0004)
90
Patient Characteristics & Primary Outcome Data: By Insurace
Status
81.5
Indigent
80
Solvent
70
60
50
%
40
35
36.5
30
20
18
16
18
10
10
11
6
2
0
Minority
Significant Other
Any Substance
Use
Alcohol Use
Heroin Use
Results
Psychosocial Outcome Measures

Those remaining on Bup/Nx use at follow-up were Less likely to have
reported










Damaging a close relationship (26% vs. 52%, χ2=6.07, p=0.014)
Doing regretful or impulsive things (28% vs. 52%, χ2=4.89, p=0.027)
Hurting family (28% vs. 60%, χ2=8.52, p=0.004)
Experiencing negative personality changes (26% vs. 48%, χ2=4.43, 0.035)
Failing to do things expected of them (24% vs. 56%, χ2=9.54, p=0.002)
Taking foolish risks (21% vs. 56%, χ2=11.36, p=0.0008)
Being unhappy (27% vs. 60%, χ2=9.27, p=0.002)
Having spent too much/lost money (27% vs. 52%, χ2=5.46, p=0.0195)
Were significantly less likely to report having money problems generally (29% vs.
56%, χ2=5.97, p=0.015).
Unfortunately, our study design did not allow these results to be
controlled for illicit opioid abstinence.
 Therefore, the improved psychosocial outcomes we observed in
subjects who remained on Bup/Nx are just as likely due to the markedly
decreased rate of substance use observed in that population (8.5% vs.
32% respectively, χ2=6.26, p=0.0123).
Results
Adverse Effects
 No differences in opioid use complications
were found between patients who were and
were no longer taking Bup/Nx with two
exceptions:
 Patients still taking Bup/Nx reported:
 more constipation (p=.04)
 lower craving (p=.0001)
 However, those data may be confounded by
interviewees’ conception of the questions
being posed at follow-up
Discussion

110 patients (63%) completed the telephone interview, we believe this
study to be the largest US case-series to date to report outcomes of
Bup/Nx OBT at long term follow-up.
 This study examines outcomes in a different population than other
studies conducted to date.



Most researchers have studied insured, financially solvent patients
One group has studied the homeless
Our indigent patients lie somewhere in between.
 Most of the patients involved in our study were housed, however, the majority of
our indigent patients were also:
 unemployed (89%)
 unmarried (86%)
 injection drug users (82%)
 As well as unable to afford the costs of treatment (by definition)


In this understudied population, it is possible that unique risk factors and the
decreased level of stability associated with their life situation may make officebased Bup/Nx therapy a less effective option.
Our data show this to be untrue by demonstrating no significant differences in
OBT retention between our solvent and indigent patients.
Discussion
 One overarching goal of this study: determine the proportion of
subjects retained in the Bup/Nx OBT protocol at follow-up and
thus characterize the effectiveness of our outpatient Bup/Nx
treatment program, which was, in part, publically funded.

Grant funding from ADABSCC allowed us to provide Bup/Nx OBT to our
indigent participants, but also necessitated that we prove the
effectiveness of the therapeutic approach in that population.
 To that end, our data show that, at 18 months post-induction, 85 of 110
(77%) subjects remained on Bup/Nx, and within that group:
 Substance use was ~24% decreased
 12-step program affiliation was ~29% increased
 Employment was ~24% increased

This result definitively demonstrates Bup/Nx-OBT to be an effective
adjunct to more intensive treatment programs and may improve
abstinence, as well as psychosocial and occupational functioning, in
opioid dependent patients, regardless of their socioeconomic status.
Discussion
 Another goal of this study was to examine what effect, if
any, patient characteristics had on treatment retention and
outcomes, and whether these characteristics differed
significantly between our two distinct patient populations.
To that end:
 We did not find any patient characteristics to be reliably
associated with retention in the Bup/Nx OBT protocol, with
exception of being employed at entry into the study. This finding
may indicate that patients with a more stable occupational
environment at entry into treatment are more likely to maintain
their Bup/Nx-OBT over the long term.
 Interestingly, our data also show that at follow-up, our indigent
subjects were 8% more likely to report substance use. That result
may indicate different environmental and other risk factors for
relapse in this population, independent of continued Bup/NxOBT.
Discussion
 Limitations

Convenient Sample: our data are derived from a clinical cohort stabilized
on Bup/Nx as part of a private insurance and publically funded substance
abuse treatment program.
 An important weakness was the necessity of different treatment of our
solvent and indigent populations:
 Because treatment of uninsured subjects was publicly funded, these
individuals were required to undergo 4-8 weeks of residential treatment
that was not required of the insured subjects in our population.
 This created a treatment bias and a selection bias
 Treatment bias: Indigent patients received longer and more intensive substance
abuse treatment
 Selection bias: Only the indigent subjects who were willing to undergo and/or
were able to complete residential therapy were included in follow-up.
 We plan to address these biases in an ongoing version of the
present study in which constraints of public funding no longer
require residential treatment for all subsidized individuals.
Conclusions
 One hope is that the results of this
study and others like it may justify
increased funding to cover the costs
of combined treatment programs for
indigent opioid dependent patients
 The benefits reaped from improved
biopsychosocial functioning and
return to gainful employment of
these individuals will likely far out
weigh the cost of subsidizing such
programs
References 1
1.
Alford, D.P., LaBelle, C.T., Richardson, J.M., O'Connell, J.J., Hohl, C.A., Cheng, D.M., Samet, J.H., 2007. Treating homeless opioid dependent patients with buprenorphine in
an office-based setting. J Gen Intern Med 22, 171-176.
2.
Amass, L., Bickel, W.K., Higgins, S.T., Hughes, J.R., 1994. A preliminary investigation of outcome following gradual or rapid buprenorphine detoxification. J Addict Dis 13, 3345.
3.
Auriacombe, M., Grabot, D., Daulouede, J.P., Vergnolle, J.P., O'Brien, C., Tignol, J., 1994. A naturalistic follow-up study of French-speaking opiate-maintained heroinaddicted patients: effect on biopsychosocial status. J Subst Abuse Treat 11, 565-568.
4.
Baral, S., Sifakis, F., Cleghorn, F., Beyrer, C., 2007. Elevated risk for HIV infection among men who have sex with men in low- and middle-income countries 2000-2006: a
systematic review. PLoS Med 4, e339.
5.
Bickel, W.K., Amass, L., Higgins, S.T., Badger, G.J., Esch, R.A., 1997. Effects of adding behavioral treatment to opioid detoxification with buprenorphine. J Consult Clin
Psychol 65, 803-810.
6.
Blanchard, K.A., Morgenstern, J., Morgan, T.J., Lobouvie, E.W., Bux, D.A., 2003. Assessing consequences of substance use: psychometric properties of the inventory of drug
use consequences. Psychol Addict Behav 17, 328-331.
7.
Bouchez, J., Vignau, J., 1998. The French experience--the pharmacist, general practitioner and patient perspective. Eur Addict Res 4 Suppl 1, 19-23.
8.
Caldiero, R.M., Parran, T.V., Jr., Adelman, C.L., Piche, B., 2006. Inpatient initiation of buprenorphine maintenance vs. detoxification: can retention of opioid-dependent
patients in outpatient counseling be improved? Am J Addict 15, 1-7.
9.
Carrieri, M.P., Amass, L., Lucas, G.M., Vlahov, D., Wodak, A., Woody, G.E., 2006. Buprenorphine use: the international experience. Clin Infect Dis 43 Suppl 4, S197-215.
10.
Cunningham, C.O., Sohler, N.L., McCoy, K., Kunins, H.V., 2006. Attending physicians' and residents' attitudes and beliefs about prescribing buprenorphine at an urban
teaching hospital. Fam Med 38, 336-340.
11.
Dekker, A.H., 2007. What is being done to address the new drug epidemic? J Am Osteopath Assoc 107, ES21-26.
12.
Donaher, P.A., Welsh, C., 2006. Managing opioid addiction with buprenorphine. Am Fam Physician 73, 1573-1578.
13.
Drug Addiction Treatment Act of 2000, 21USC, §3501 (2000). Accessed online, January 04, 2008, at: http://buprenorphine.samhsa.gov/data.html.
14.
Fhima, A., Henrion, R., Lowenstein, W., Charpak, Y., 2001. [Two-year follow-up of an opioid-user cohort treated with high-dose buprenorphine (Subutex)]. Ann Med Interne
(Paris) 152 Suppl 3, IS26-36.
15.
Fiellin, D.A., Kleber, H., Trumble-Hejduk, J.G., McLellan, A.T., Kosten, T.R., 2004. Consensus statement on office-based treatment of opioid dependence using
buprenorphine. Journal of Substance Abuse Treatment 27, 153-159.
16.
Fiellin, D.A., O'Connor, P.G., 2002. Clinical practice. Office-based treatment of opioid-dependent patients. New England journal of medicine 347, 817.
17.
Fiellin, D.A., O'Connor, P.G., 2002. New federal initiatives to enhance the medical treatment of opioid dependence. Ann Intern Med 137, 688-692.
References 2
18.
Fiellin, D.A., Pantalon, M.V., Chawarski, M.C., Moore, B.A., Sullivan, L.E., O'Connor, P.G., Schottenfeld, R.S., 2006. Counseling plus buprenorphine-naloxone maintenance
therapy for opioid dependence. N Engl J Med 355, 365-374.
19.
Fiellin, D.A., Pantalon, M.V., Pakes, J.P., O'Connor, P.G., Chawarski, M., Schottenfeld, R.S., 2002. Treatment of heroin dependence with buprenorphine in primary care. Am
J Drug Alcohol Abuse 28, 231-241.
20.
Fiellin, D.A., Rosenheck, R.A., Kosten, T.R., 2001. Office-based treatment for opioid dependence: reaching new patient populations. Am J Psychiatry 158, 1200-1204.
21.
Fudala, P.J., Bridge, T.P., Herbert, S., Williford, W.O., Chiang, C.N., Jones, K., Collins, J., Raisch, D., Casadonte, P., Goldsmith, R.J., Ling, W., Malkerneker, U., McNicholas, L.,
Renner, J., Stine, S., Tusel, D., 2003. Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone. N Engl J Med 349, 949958.
22.
Gandhi, D.H., Jaffe, J.H., McNary, S., Kavanagh, G.J., Hayes, M., Currens, M., 2003. Short-term outcomes after brief ambulatory opioid detoxification with buprenorphine in
young heroin users. Addiction 98, 453-462.
23.
Giacomuzzi, S.M., Ertl, M., Kemmler, G., Riemer, Y., Vigl, A., 2005. Sublingual buprenorphine and methadone maintenance treatment: a three-year follow-up of quality of
life assessment. ScientificWorldJournal 5, 452-468.
24.
Gibson, A.E., Doran, C.M., Bell, J.R., Ryan, A., Lintzeris, N., 2003. A comparison of buprenorphine treatment in clinic and primary care settings: a randomised trial. Med J
Aust 179, 38-42.
25.
Harris, D.S., Jones, R.T., Welm, S., Upton, R.A., Lin, E., Mendelson, J., 2000. Buprenorphine and naloxone co-administration in opiate-dependent patients stabilized on
sublingual buprenorphine. Drug Alcohol Depend 61, 85-94.
26.
Hser, Y.I., Hoffman, V., Grella, C.E., Anglin, M.D., 2001. A 33-year follow-up of narcotics addicts. Arch Gen Psychiatry 58, 503-508.
27.
Jaffe, J.H., O'Keeffe, C., 2003. From morphine clinics to buprenorphine: regulating opioid agonist treatment of addiction in the United States. Drug Alcohol Depend 70, S3S11.
28.
Jasinski, D.R., Pevnick, J.S., Griffith, J.D., 1978. Human pharmacology and abuse potential of the analgesic buprenorphine: a potential agent for treating narcotic addiction.
Arch Gen Psychiatry 35, 501-516.
29.
Johnson, R.E., Chutuape, M.A., Strain, E.C., Walsh, S.L., Stitzer, M.L., Bigelow, G.E., 2000. A comparison of levomethadyl acetate, buprenorphine, and methadone for opioid
dependence. N Engl J Med 343, 1290-1297.
30.
Johnson, R.E., Eissenberg, T., Stitzer, M.L., Strain, E.C., Liebson, I.A., Bigelow, G.E., 1995. A placebo controlled clinical trial of buprenorphine as a treatment for opioid
dependence. Drug Alcohol Depend 40, 17-25.
31.
Johnson, R.E., Jaffe, J.H., Fudala, P.J., 1992. A controlled trial of buprenorphine treatment for opioid dependence. Jama 267, 2750-2755.
32.
Johnson, R.E., Strain, E.C., Amass, L., 2003. Buprenorphine: how to use it right. Drug Alcohol Depend 70, S59-77.
33.
Kakko, J., Svanborg, K.D., Kreek, M.J., Heilig, M., 2003. 1-year retention and social function after buprenorphine-assisted relapse prevention treatment for heroin
dependence in Sweden: a randomised, placebo-controlled trial. Lancet 361, 662-668.
34.
Kornor, H., Waal, H., Sandvik, L., 2007. Time-limited buprenorphine replacement therapy for opioid dependence: 2-year follow-up outcomes in relation to programme
completion and current agonist therapy status. Drug Alcohol Rev 26, 135-141.
References 3
35.
Kosten, T.R., Schottenfeld, R., Ziedonis, D., Falcioni, J., 1993. Buprenorphine versus methadone maintenance for opioid dependence. J Nerv Ment Dis 181, 358-364.
36.
Kovas, A.E., McFarland, B.H., McCarty, D.J., Boverman, J.F., Thayer, J.A., 2007. Buprenorphine for acute heroin detoxification: diffusion of research into practice. J Subst
Abuse Treat 32, 199-206.
37.
Krook, A.L., Brors, O., Dahlberg, J., Grouff, K., Magnus, P., Roysamb, E., Waal, H., 2002. A placebo-controlled study of high dose buprenorphine in opiate dependents
waiting for medication-assisted rehabilitation in Oslo, Norway. Addiction 97, 533-542.
38.
Lapeyre-Mestre, M., Llau, M.E., Gony, M., Navel, A.M., Bez, J., Grau, M., Montastruc, J.L., 2003. Opiate maintenance with buprenorphine in ambulatory care: a 24-week
follow-up study of new users. Drug Alcohol Depend 72, 297-303.
39.
Ling, W., Charuvastra, C., Collins, J.F., Batki, S., Brown, L.S., Jr., Kintaudi, P., Wesson, D.R., McNicholas, L., Tusel, D.J., Malkerneker, U., Renner, J.A., Jr., Santos, E.,
Casadonte, P., Fye, C., Stine, S., Wang, R.I., Segal, D., 1998. Buprenorphine maintenance treatment of opiate dependence: a multicenter, randomized clinical trial. Addiction
93, 475-486.
40.
Ling, W., Wesson, D.R., Charuvastra, C., Klett, C.J., 1996. A controlled trial comparing buprenorphine and methadone maintenance in opioid dependence. Arch Gen
Psychiatry 53, 401-407.
41.
Mark, T.L., Woody, G.E., Juday, T., Kleber, H.D., 2001. The economic costs of heroin addiction in the United States. Drug Alcohol Depend 61, 195-206.
42.
Marsch, L.A., Stephens, M.A.C., Mudric, T., Strain, E.C., Bigelow, G.E., Johnson, R.E., 2005. Predictors of outcome in LAAM, buprenorphine, and methadone treatment for
opioid dependence. Experimental and Clinical Psychopharmacology 13, 293-302.
43.
Mattick, R.P., Ali, R., White, J.M., O'Brien, S., Wolk, S., Danz, C., 2003. Buprenorphine versus methadone maintenance therapy: a randomized double-blind trial with 405
opioid-dependent patients. Addiction 98, 441-452.
44.
McLellan, A.T., Lewis, D.C., O'Brien, C.P., Kleber, H.D., 2000. Drug dependence, a chronic medical illness: implications for treatment, insurance, and outcomes evaluation.
Jama 284, 1689-1695.
45.
McMurphy, S., Shea, J., Switzer, J., Turner, B.J., 2006. Clinic-based treatment for opioid dependence: a qualitative inquiry. Am J Health Behav 30, 544-554.
46.
Mendelson, J., Jones, R.T., 2003. Clinical and pharmacological evaluation of buprenorphine and naloxone combinations: why the 4:1 ratio for treatment? Drug Alcohol
Depend 70, S29-S37.
47.
Mintzer, I.L., Eisenberg, M., Terra, M., MacVane, C., Himmelstein, D.U., Woolhandler, S., 2007. Treating opioid addiction with buprenorphine-naloxone in community-based
primary care settings. Ann Fam Med 5, 146-150.
48.
Moore, B.A., Fiellin, D.A., Barry, D.T., Sullivan, L.E., Chawarski, M.C., O'Connor, P.G., Schottenfeld, R.S., 2007. Primary care office-based buprenorphine treatment:
comparison of heroin and prescription opioid dependent patients. J Gen Intern Med 22, 527-530.
49.
Muthén, B.O.M., L. K., 2001. Mplus User’s Guide. Muthén & Muthén, Los Angeles, CA.
50.
O'Connor, P.G., Oliveto, A.H., Shi, J.M., Triffleman, E.G., Carroll, K.M., Kosten, T.R., Rounsaville, B.J., Pakes, J.A., Schottenfeld, R.S., 1998. A randomized trial of
buprenorphine maintenance for heroin dependence in a primary care clinic for substance users versus a methadone clinic. Am J Med 105, 100-105.
51.
Rounsaville, B.J., Kosten, T.R., 2000. Treatment for opioid dependence: quality and access. Jama 283, 1337-1339.
References 4
52.
Schuckit, M.A., Segal, D.S, 2005. Chapter 373. Opioid Drug Abuse and Dependence. The McGraw-Hill Companies, Inc.
53.
Simoens, S., Matheson, C., Bond, C., Inkster, K., Ludbrook, A., 2005. The effectiveness of community maintenance with methadone or buprenorphine for treating opiate
dependence. Br J Gen Pract 55, 139-146.
54.
Stein, M.D., Cioe, P., Friedmann, P.D., 2005. Buprenorphine retention in primary care. J Gen Intern Med 20, 1038-1041.
55.
Strain, E.C., Stitzer, M.L., Liebson, I.A., Bigelow, G.E., 1994. Comparison of buprenorphine and methadone in the treatment of opioid dependence. Am J Psychiatry 151,
1025-1030.
56.
Thirion, X., Micallef, J., Barrau, K., Djezzar, S., Lambert, H., Sanmarco, J.L., Lagier, G., 2001. Recent evolution in opiate dependence in France during generalisation of
maintenance treatments. Drug Alcohol Depend 61, 281-285.
57.
U.S. Dept. of Health and Human Services, S.A.a.M.H.S.A., Office of Applied Studies., 2006-10-17. NATIONAL SURVEY ON DRUG USE AND HEALTH, 1990-2006 [Computer
file]. ICPSR04138-v2. . Research Triangle Park, NC: Research Triangle Institute [producer], 2004. Ann Arbor, MI: Inter-university Consortium for Political and Social Research
[distributor].
58.
Walker, R.D., Howard, M.O., Suchinsky, R., Kaple, J., Anderson, B., 1994. Drug dependence treatment within the Department of Veterans Affairs: emerging issues. Int J
Addict 29, 53-69.
59.
Walsh, S.L., Eissenberg, T., 2003. The clinical pharmacology of buprenorphine: extrapolating from the laboratory to the clinic. Drug Alcohol Depend 70, S13-27.
60.
White, A.G., Birnbaum, H.G., Mareva, M.N., Daher, M., Vallow, S., Schein, J., Katz, N., 2005. Direct costs of opioid abuse in an insured population in the United States. J
Manag Care Pharm 11, 469-479.