Public sector low threshold office-based

buprenorphine treatment: outcomes at year 7




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Bhatraju, E., Grossman, E., Tofighi, B., McNeely, J.,

DiRocco, D., Flannery, M., Garment, A., Goldfeld, K.,
Gourevitch, M., Lee, J. (2017). Public sector low
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threshold office-based buprenorphine treatment:
outcomes at year 7 Addiction Science & Clinical
Practice 12(1), 7. https://dx.doi.org/10.1186/
s13722-017-0072-2

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 An overview of systematic reviews of the effectiveness

of opiate maintenance therapies: available evidence to inform



clinical practice and research
AIM: To summarize the major findings of the five Cochrane reviews on substitution maintenance treatments for opioid dependence.

METHODS: We conducted a narrative and quantitative summary of systematic review findings. There were 52 studies included in the
original reviews (12,075 participants, range 577-5894): methadone maintenance treatment (MMT) was compared with methadone
detoxification treatment (MDT), no treatment, different dosages of MMT, buprenorphine maintenance treatment (BMT), heroin
maintenance treatment (HMT), and l-alpha-acetylmethadol (LAAM) maintenance treatment (LMT).

MEASUREMENTS: Outcomes considered were retention in treatment, use of heroin and other drugs during treatment, mortality,
criminal activity, and quality of life.

FINDINGS: Retention in treatment: MMT is more effective than MDT, no treatment, BMT, LMT, and heroin plus methadone. MMT proved
to be less effective than injected heroin alone. High doses of methadone are more effective than medium and low doses. Use of heroin:
MMT is more effective than waiting list, less effective than LAAM, and not different from injected heroin. No significant results were
available for mortality and criminal activity.

CONCLUSIONS: These findings confirm that MMT at appropriate doses is the most effective in retaining patients in treatment and
suppressing heroin use but show weak evidence of effectiveness toward other relevant outcomes. Future clinical trials should collect
data on a broad range of health outcomes and recruit participants from heterogeneous practice settings and social contexts to increase
generalizability of results.

Amato, L., Davoli, M., A.Perucci, C., Ferri, M., Faggiano, F., Mattick, R. (2005). 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  28(4), 321-329. Link to Pubmed
https://dx.doi.org/10.1016/j.jsat.2005.02.007
 Medication-assisted treatment of opioid use disorder: review of the

 evidence and future directions
Abstract: Medication-assisted treatment of opioid use disorder with physiological dependence at least doubles rates of
opioid-abstinence outcomes in randomized, controlled trials comparing psychosocial treatment of opioid use disorder with
medication versus with placebo or no medication. This article reviews the current evidence for medication-assisted treatment
of opioid use disorder and also presents clinical practice imperatives for preventing opioid overdose and the transmission of
infectious disease. The evidence strongly supports the use of agonist therapies to reduce opioid use and to retain patients in
treatment, with methadone maintenance remaining the gold standard of care. Combined buprenorphine/naloxone, however,
also demonstrates significant efficacy and favorable safety and tolerability in multiple populations, including youth and
prescription opioid-dependent individuals, as does buprenorphine monotherapy in pregnant women. The evidence for
antagonist therapies is weak. Oral naltrexone demonstrates poor adherence and increased mortality rates, although the early
evidence looks more favorable for extended-release naltrexone, which has the advantages that it is not subject to misuse or
diversion and that it does not present a risk of overdose on its own. Two perspectives-individualized treatment and population
management-are presented for selecting among the three available Food and Drug Administration-approved maintenance
therapies for opioid use disorder. The currently unmet challenges in treating opioid use disorder are discussed, as are the
directions for future research.

Connery, H. (2015). Medication-Assisted Treatment of Opioid Use Disorder Harvard Review of

Psychiatry  23(2), 63-75. https://dx.doi.org/10.1097/hrp.0000000000000075

Link to Pubmed
 Long-term treatment with buprenorphine/naloxone in primary

 care: results at 2-5 years
Abstract: To examine long-term outcomes with primary care office-based buprenorphine/naloxone treatment, we followed 53
opioid-dependent patients who had already demonstrated six months of documented clinical stability for 2-5 years. Primary
outcomes were retention, illicit drug use, dose, satisfaction, serum transaminases, and adverse events. Thirty-eight percent of
enrolled subjects were retained for two years. Ninety-one percent of urine samples had no evidence of opioid use, and patient
satisfaction was high. Serum transaminases remained stable from baseline. No serious adverse events related to treatment
occurred. We conclude that select opioid-dependent patients exhibit moderate levels of retention in primary care office-based
treatment.

Fiellin, D., Moore, B., Sullivan, L., Becker, W., Pantalon, M., Chawarski, M., Barry, D., O'Connor,
P., Schottenfeld, R. (2008). Long‐Term Treatment with Buprenorphine/Naloxone in Primary
Care: Results at 2–5 Years The American Journal on Addictions  17(2), 116-120. https:// Link to Pubmed
dx.doi.org/10.1080/10550490701860971

 Exposure to opioid maintenance treatment



reduces long-term mortality
AIMS: To (i) examine the predictors of mortality in a randomized study of methadone versus buprenorphine maintenance treatment; (ii) compare the
survival experience of the randomized subject groups; and (iii) describe the causes of death.

DESIGN: Ten-year longitudinal follow-up of mortality among participants in a randomized trial of methadone versus buprenorphine maintenance
treatment.

SETTING: Recruitment through three clinics for a randomized trial of buprenorphine versus methadone maintenance.

PARTICIPANTS: A total of 405 heroin-dependent (DSM-IV) participants aged 18 years and above who consented to participate in original study.

MEASUREMENTS: Baseline data from original randomized study; dates and causes of death through data linkage with Births, Deaths and
Marriages registries; and longitudinal treatment exposure via State health departments. Predictors of mortality examined through survival analysis.

FINDINGS: There was an overall mortality rate of 8.84 deaths per 1000 person-years of follow-up and causes of death were comparable with the
literature. Increased exposure to episodes of opioid treatment longer than 7 days reduced the risk of mortality; there was no differential mortality
among methadone versus buprenorphine participants. More dependent, heavier users of heroin at baseline had a lower risk of death, and also higher
exposure to opioid treatment. Older participants randomized to buprenorphine treatment had significantly improved survival. Aboriginal or Torres
Strait Islander participants had a higher risk of death.

CONCLUSIONS: Increased exposure to opioid maintenance treatment reduces the risk of death in opioid-dependent people. There was no
differential reduction between buprenorphine and methadone. Previous studies suggesting differential effects may have been affected by biases in
patient selection.

Gibson, A., Degenhardt, L., Mattick, R., Ali, R., White, J., O'Brien, S. (2008). Exposure to opioid
maintenance treatment reduces long‐term mortality Addiction  103(3), 462-468. https://
dx.doi.org/10.1111/j.1360-0443.2007.02090.x
Link to Pubmed
 1-year retention and social function after buprenorphine-
assisted relapse prevention treatment for heroin dependence

 in Sweden: a randomised, placebo-controlled trial
BACKGROUND: The partial opiate-receptor agonist buprenorphine has been suggested for treatment of heroin dependence, but there
are few long-term and placebo-controlled studies of its effectiveness. We aimed to assess the 1-year efficacy of buprenorphine in
combination with intensive psychosocial therapy for treatment of heroin dependence.

METHODS: 40 individuals aged older than 20 years, who met DSM-IV criteria for opiate dependence for at least 1 year, but did not fulfil
Swedish legal criteria for methadone maintenance treatment were randomly allocated either to daily buprenorphine (fixed dose 16 mg
sublingually for 12 months; supervised daily administration for a least 6 months, possible take-home doses thereafter) or a tapered 6
day regimen of buprenorphine, thereafter followed by placebo. All patients participated in cognitive-behavioural group therapy to
prevent relapse, received weekly individual counselling sessions, and submitted thrice weekly supervised urine samples for analysis to
detect illicit drug use. Our primary endpoint was 1-year retention in treatment and analysis was by intention to treat.

FINDINGS: 1-year retention in treatment was 75% and 0% in the buprenorphine and placebo groups, respectively (p=0.0001; risk ratio
58.7 [95% CI 7.4-467.4]). Urine screens were about 75% negative for illicit opiates, central stimulants, cannabinoids, and
benzodiazepines in the patients remaining in treatment.

INTERPRETATION: The combination of buprenorphine and intensive psychosocial treatment is safe and highly efficacious, and should
be added to the treatment options available for individuals who are dependent on heroin.

Kakko, J., Svanborg, K., Kreek, M., 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 The Lancet  361(9358), 662-668. https://dx.doi.org/ Link to Pubmed
10.1016/s0140-6736(03)12600-1
 Injectable extended-release naltrexone for opioid dependence: a
double-blind, placebo-controlled, multicentre randomised trial


BACKGROUND: Opioid dependence is associated with low rates of treatment-seeking, poor adherence to treatment, frequent relapse, and major societal
consequences. We aimed to assess the efficacy, safety, and patient-reported outcomes of an injectable, once monthly extended-release formulation of the opioid
antagonist naltrexone (XR-NTX) for treatment of patients with opioid dependence after detoxification.

METHODS: We did a double-blind, placebo-controlled, randomised, 24-week trial of patients with opioid dependence disorder. Patients aged 18 years or over who
had 30 days or less of inpatient detoxification and 7 days or more off all opioids were enrolled at 13 clinical sites in Russia. We randomly assigned patients (1:1) to
either 380 mg XR-NTX or placebo by an interactive voice response system, stratified by site and gender in a centralised, permuted-block method. Participants also
received 12 biweekly counselling sessions. Participants, investigators, staff , and the sponsor were masked to treatment allocation. The primary endpoint was the
response profile for confirmed abstinence during weeks 5–24, assessed by urine drug tests and self report of non-use. Secondary endpoints were self-reported
opioid-free days, opioid craving scores, number of days of retention, and relapse to physiological opioid dependence. Analyses were by intention to treat. This trial
is registered at ClinicalTrials.gov, NCT00678418.

FINDINGS: Between July 3, 2008, and Oct 5, 2009, 250 patients were randomly assigned to XR-NTX (n=126) or placebo (n=124). The median proportion of weeks
of confirmed abstinence was 90·0% (95% CI 69·9–92·4) in the XR-NTX group compared with 35·0% (11·4–63·8) in the placebo group (p=0·0002). Patients in the
XR-NTX group self-reported a median of 99·2% (range 89·1–99·4) opioid-free days compared with 60·4% (46·2–94·0) for the placebo group (p=0·0004). The mean
change in craving was –10·1 (95% CI –12·3 to –7·8) in the XR-NTX group compared with 0·7 (–3·1 to 4·4) in the placebo group (p<0·0001). Median retention was
over 168 days in the XR-NTX group compared with 96 days (95% CI 63–165) in the placebo group (p=0·0042). Naloxone challenge confirmed relapse to
physiological opioid dependence in 17 patients in the placebo group compared with one in the XR-NTX group (p<0·0001). XR-NTX was well tolerated. Two patients
in each group discontinued owing to adverse events. No XR-NTX-treated patients died, overdosed, or discontinued owing to severe adverse events.

INTERPRETATION: XR-NTX represents a new treatment option that is distinct from opioid agonist maintenance treatment. XR-NTX in conjunction with
psychosocial treatment might improve acceptance of opioid dependence pharmacotherapy and provide a useful treatment option for many patients.

Krupitsky, E., Nunes, E., Ling, W., Illeperuma, A., Gastfriend, D., Silverman, B. (2011). Injectable
extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled,
multicentre randomised trial The Lancet  377(9776), 1506-1513. https://dx.doi.org/10.1016/ Link to Pubmed
s0140-6736(11)60358-9
 Effects of medication-assisted treatment on mortality among opioids
users: a systematic review and meta-analysis Molecular Psychiatry


Abstract: Opioid use disorder (OUD) is associated with a high risk of premature death. Medication-assisted treatment (MAT) is the
primary treatment for opioid dependence. We comprehensively assessed the effects of different MAT-related characteristics on mortality
among those with OUD by a systematic review and meta-analysis. The all-cause and overdose crude mortality rates (CMRs) and relative
risks (RRs) by treatment status, different type, period, and dose of medication, and retention time were pooled using random effects,
subgroup analysis, and meta-regression. Thirty cohort studies involving 370,611 participants (1,378,815 person-years) were eligible in
the meta-analysis. From 21 studies, the pooled all-cause CMRs were 0.92 per 100 person-years (95% CI: 0.79-1.04) while receiving
MAT, 1.69 (1.47-1.91) after cessation, and 4.89 (3.54-6.23) for untreated period. Based on 16 studies, the pooled overdose CMRs were
0.24 (0.20-0.28) while receiving MAT, 0.68 (0.55-0.80) after cessation of MAT, and 2.43 (1.72-3.15) for untreated period. Compared with
patients receiving MAT, untreated participants had higher risk of all-cause mortality (RR 2.56 [95% CI: 1.72-3.80]) and overdose mortality
(8.10 [4.48-14.66]), and discharged participants had higher risk of all-cause death (2.33 [2.02-2.67]) and overdose death (3.09
[2.37-4.01]). The all-cause CMRs during and after opioid substitution treatment with methadone or buprenorphine were 0.93 (0.76-1.10)
and 1.79 (1.47-2.10), and corresponding estimate for antagonist naltrexone treatment were 0.26 (0-0.59) and 1.97 (0-5.18), respectively.
Retention in MAT of over 1-year was associated with a lower mortality rate than that with retention ≤1 year (1.62, 1.31-1.93 vs. 5.31,
-0.09-10.71). Improved coverage and adherence to MAT and post-treatment follow-up are crucial to reduce the mortality. Long-acting
naltrexone showed positive advantage on prevention of premature death among persons with OUD.

Ma, J., Bao, Y., Wang, R., Su, M., Liu, M., Li, J., Degenhardt, L., Farrell, M., Blow, F., Ilgen, M.,
Shi, J., Lu, L. (2018). Effects of medication-assisted treatment on mortality among opioids
users: a systematic review and meta-analysis Molecular Psychiatry https://dx.doi.org/10.1038/ Link to Pubmed
s41380-018-0094-5
 Buprenorphine maintenance versus placebo or methadone
maintenance for opioid dependence


BACKGROUND: Buprenorphine maintenance treatment has been evaluated in randomised controlled trials against placebo medication, and separately as an alternative to methadone for
management of opioid dependence.

OBJECTIVES: To evaluate buprenorphine maintenance compared to placebo and to methadone maintenance in the management of opioid dependence, including its ability to retain people in
treatment, suppress illicit drug use, reduce criminal activity, and mortality.

SEARCH METHODS: We searched the following databases to January 2013: Cochrane Drugs and Alcohol Review Group Specialised Register, Cochrane Central Register of Controlled Trials,
MEDLINE, EMBASE, Current Contents, PsycLIT, CORK, Alcohol and Drug Council of Australia, Australian Drug Foundation, Centre for Education and Information on Drugs and Alcohol, Library
of Congress, reference lists of identified studies and reviews. We sought published/unpublished randomised controlled trials (RCTs) from authors.

SELECTION CRITERIA: Randomised controlled trials of buprenorphine maintenance treatment versus placebo or methadone in management of opioid-dependent persons.

DATA COLLECTION AND ANALYSIS: We used Cochrane Collaboration methodology.

MAIN RESULTS: We include 31 trials (5430 participants), the quality of evidence varied from high to moderate quality.There is high quality of evidence that buprenorphine was superior to
placebo medication in retention of participants in treatment at all doses examined. Specifically, buprenorphine retained participants better than placebo: at low doses (2 - 6 mg), 5 studies,
1131 participants, risk ratio (RR) 1.50; 95% confidence interval (CI) 1.19 to 1.88; at medium doses (7 - 15 mg), 4 studies, 887 participants, RR 1.74; 95% CI 1.06 to 2.87; and at high doses (≥
16 mg), 5 studies, 1001 participants, RR 1.82; 95% CI 1.15 to 2.90. However, there is moderate quality of evidence that only high-dose buprenorphine (≥ 16 mg) was more effective than
placebo in suppressing illicit opioid use measured by urinanalysis in the trials, 3 studies, 729 participants, standardised mean difference (SMD) -1.17; 95% CI -1.85 to -0.49, Notably, low-dose,
(2 studies, 487 participants, SMD 0.10; 95% CI -0.80 to 1.01), and medium-dose, (2 studies, 463 participants, SMD -0.08; 95% CI -0.78 to 0.62) buprenorphine did not suppress illicit opioid
use measured by urinanalysis better than placebo.There is high quality of evidence that buprenorphine in flexible doses adjusted to participant need,was less effective than methadone in
retaining participants, 5 studies, 788 participants, RR 0.83; 95% CI 0.72 to 0.95. For those retained in treatment, no difference was observed in suppression of opioid use as measured by
urinalysis, 8 studies, 1027 participants, SMD -0.11; 95% CI -0.23 to 0.02 or self report, 4 studies, 501 participants, SMD -0.11; 95% CI -0.28 to 0.07, with moderate quality of
evidence.Consistent with the results in the flexible-dose studies, in low fixed-dose studies, methadone (≤ 40 mg) was more likely to retain participants than low-dose buprenorphine (2 - 6 mg),
(3 studies, 253 participants, RR 0.67; 95% CI: 0.52 to 0.87). However, we found contrary results at medium dose and high dose: there was no difference between medium-dose buprenorphine
(7 - 15 mg) and medium-dose methadone (40 - 85 mg) in retention, (7 studies, 780 participants, RR 0.87; 95% CI 0.69 to 1.10) or in suppression of illicit opioid use as measured by urines, (4
studies, 476 participants, SMD 0.25; 95% CI -0.08 to 0.58) or self report of illicit opioid use, (2 studies, 174 participants, SMD -0.82; 95% CI -1.83 to 0.19). Similarly, there was no difference
between high-dose buprenorphine (≥ 16 mg) and high-dose methadone (≥ 85 mg) in retention (RR 0.79; 95% CI 0.20 to 3.16) or suppression of self-reported heroin use (SMD -0.73; 95% CI
-1.08 to -0.37) (1 study, 134 participants).Few studies reported adverse events ; two studies compared adverse events statistically, finding no difference between methadone and
buprenorphine, except for a single result indicating more sedation among those using methadone.

Mattick RP, Breen C, Kimber J, Davoli M. Buprenorphine maintenance versus placebo or

methadone maintenance for opioid dependence. Cochrane Database of Systematic Reviews
2014, Issue 2. Art. No.: CD002207. https://doi.org/10.1002/14651858.CD002207.pub4 Link to Pubmed
 Methadone maintenance vs 180-day psychosocially enriched detoxification
for treatment of opioid dependence: a randomized controlled trial
CONTEXT: 
 Despite evidence that methadone maintenance treatment (MMT) is effective for opioid dependence, it remains a controversial therapy because of its
indefinite provision of a dependence-producing medication.

OBJECTIVE: To compare outcomes of patients with opioid dependence treated with MMT vs an alternative treatment, psychosocially enriched 180-day
methadone-assisted

detoxification.

DESIGN: Randomized controlled trial conducted from May 1995 to April 1999.

SETTING: Research clinic in an established drug treatment service.

PATIENTS: Of 858 volunteers screened, 179 adults with diagnosed opioid dependence were randomized into the study; 154 completed 12 weeks of follow-up.

INTERVENTIONS: Patients were randomized to MMT (n = 91), which required 2 hours of psychosocial therapy per week during the first 6 months; or detoxification
(n = 88), which required 3 hours of psychosocial therapy per week, 14 education sessions, and 1 hour of cocaine group therapy, if appropriate, for 6 months, and 6
months of (nonmethadone) aftercare services.

MAIN OUTCOME MEASURES: Treatment retention, heroin and cocaine abstinence (by self-report and monthly urinalysis), human immunodeficiency virus (HIV) risk
behaviors (Risk of AIDS Behavior scale score), and function in 5 problem areas: employment, family, psychiatric, legal, and alcohol use (Addiction Severity Index),
compared by intervention group.

RESULTS: Methadone maintenance therapy resulted in greater treatment retention (median, 438.5 vs 174.0 days) and lower heroin use rates than did detoxification.
Cocaine use was more closely related to study dropout in detoxification than in MMT. 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 in a lower severity score for legal status (mean [SD] at 12 months,
0.05 [0.13] vs 0.13 [0.19]). There were no differences between groups in employment or family functioning or alcohol use. In both groups, monthly heroin use rates
were 50% or greater, but days of use per month dropped markedly from baseline.

CONCLUSIONS: Our results confirm the usefulness of MMT in reducing heroin use and HIV risk behaviors. Illicit opioid use continued in both groups, but frequency
was reduced. Results do not provide support for diverting resources from MMT into long-term detoxification.

Sees, K., Delucchi, K., Masson, C., Rosen, A., Clark, H., Robillard, H., Banys, P., Hall, S. (2000).
Methadone Maintenance vs 180-Day Psychosocially Enriched Detoxification for Treatment of
Opioid Dependence: A Randomized Controlled Trial JAMA  283(10), 1303-1310. https:// Link to Pubmed
dx.doi.org/10.1001/jama.283.10.1303
 Buprenorphine maintenance treatment in a primary care
setting: outcomes at 1 year


Abstract: The purposes of this study were to assess outcomes of patients prescribed buprenorphine at a
primary care practice and to identify factors associated with favorable outcomes. All 255 patients given at
least one prescription for buprenorphine between August 2003 and September 1, 2007, at a primary care
practice in Baltimore were included. Data regarding demographics and comorbidities were collected
retrospectively. Patients were classified as "opioid-positive" or "opioid-negative" each month based on
patient report, urine toxicology, and provider assessment. After 12 months, 145 (56.9%) patients remained in
treatment, and 64.7% of their months were opioid-negative. Patients using heroin were less likely to be
opioid-negative, whereas those using prescription opioids were more likely to be opioid-negative.
Polysubstance use was associated with increased treatment retention. The prescription of buprenorphine for
opioid dependence treatment can be incorporated into primary care practice, and many patients, including
polysubstance users, benefit from this treatment.

Soeffing, J., Martin, L., Fingerhood, M., Jasinski, D., Rastegar, D. (2009). Buprenorphine
maintenance treatment in a primary care setting: Outcomes at 1 year Journal of Substance
Abuse Treatment  37(4), 426-430. https://dx.doi.org/10.1016/j.jsat.2009.05.003
Link to Pubmed
 Initiating buprenorphine treatment for opioid use disorder during
short-term in-patient 'detoxification': a randomized clinical trial
BACKGROUND AND AIMS: The effectiveness of linking people from short-term in-patient managed withdrawal programs ('detoxification') to long-term, primary
care-based buprenorphine is unknown. We tested whether buprenorphine initiation during an opioid withdrawal program and linkage to office-based buprenorphine
(LINK) after discharge would increase engagement with office-based buprenorphine and decrease illicit opioid use during the ensuing 6 months compared with
standard withdrawal management (WM).

DESIGN: Single-site randomized controlled trial.

SETTING: Short-term in-patient detoxification program in Massachusetts, USA.

PARTICIPANTS: People with opioid use disorder (n = 115) who averaged 32.4 years of age, 68.2% male, 79.1% white, using illicit opioids on 27.3 of the last
30 days, were randomly assigned to WM (n = 59) versus LINK (n = 56).

INTERVENTION AND COMPARATOR: Intervention was buprenorphine induction, in-patient dose stabilization and post-discharge transition to maintenance
buprenorphine at an affiliated primary care clinic (LINK). Comparator was 5-day buprenorphine managed withdrawal protocol (WM).

MEASUREMENTS: Mean 30-day rate of use of illicit opioids (primary aim) and prescribed buprenorphine (secondary aim) at 1, 3 and 6 months.

FINDINGS: Compared with WM, participants in the LINK condition had lower illicit opioid use rates at days 12 [b = -6.81, 95% confidence interval (CI) = -9.69;
-3.92, P < 0.001], 35 (b = -8.55, 95% CI - 11.63; -5.47, P < 0.001), 95 (b = -7.34, 95% CI = -10.59; -4.11, P < 0.001) and 185 (b = -3.52, 95% CI = -7.07; 0.27,
P = 0.052). The LINK arm had higher prescription buprenorphine use rates (P < 0.001) at all assessments.

CONCLUSIONS: Among people with opioid use disorder, initiation of, and linkage to, office-based buprenorphine treatment post-discharge reduced illicit opioid
use and increased days of buprenorphine treatment for up to 6 months post-discharge compared with an in-patient detoxification protocol.

Stein, M., Herman, D., Conti, M., Anderson, B., Bailey, G. (2019). Initiating buprenorphine
treatment for opioid use disorder during short‐term in‐patient ‘detoxification’: a randomized
clinical trial Addiction https://dx.doi.org/10.1111/add.14737
Link to Pubmed