Disorders - Opioid Use
Borodovsky, J. T., Levy, S., Fishman, M., Marsch, L. A.
In the past decade, a new cohort of adolescents and young adults with opioid use disorders (OUD) has emerged. While medications and psychosocial treatments are available, few adolescents and young adults with OUD can access and remain in treatment. Effective, practical, and scalable treatment paradigms for this young population are needed. Buprenorphine is a medication with unique pharmacological and regulatory characteristics that make it a promising component of adolescent and young adult OUD treatment models. Three randomized controlled trials and multiple observational studies have evaluated the use of buprenorphine to treat this population. However, data from these studies have not been consolidated into an up-To-date summary that may be useful to clinicians. The objective of this narrative review is to inform clinical practice by summarizing results of primary and secondary analyses from randomized controlled clinical trials and observational studies that have evaluated the use of buprenorphine to treat adolescents and young adults with OUD. Based on results from these studies, we encourage the conceptualization of OUD among youth as a chronic medical condition requiring a long-Term management strategy. This includes treatment with buprenorphine in conjunction with medication-prescribing protocols that do not necessarily require daily clinic attendance for observed medication adherence. However, more study of treatment delivery models, addressing such issues as medication adherence and intensity requirements, is needed to determine practices that optimize outcomes for youth. © Copyright 2018 American Society of Addiction Medicine.
Journal of Addiction Medicine, 12(3) : 170-183
- Year: 2018
- Problem: Opioid Use
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Medications used to treat substance abuse
Law, F. D., Diaper, A. M., Melichar, J. K., Coulton, S., Nutt, D. J., Myles, J. S.
Buprenorphine/naloxone, methadone and lofexidine are medications with utility in the treatment of opiate withdrawal. We report the first randomised controlled trial to compare the effects of these two medications on withdrawal symptoms and outcome during opiate induction/stabilisation and detoxification. A double-blind randomised controlled trial was conducted in an outpatient satellite clinic of a specialist drug service. Eighty opiate dependent individuals meeting DSM-IV criteria for opiate dependence, using 1/2 g heroin smoked/chased or 1/4 g heroin injected or 30mg methadone, with 3 years of opioid dependency, underwent a short-term opiate treatment programme involving induction/stabilisation on methadone 30mg or buprenorphine/naloxone 4mg/1mg, followed by detoxification (where the methadone group was assisted by lofexidine). The main outcome measures were urine drug screens for opiates and withdrawal and craving questionnaires. There were no overall differences in positive urine drug screens and drop-outs during any phase of the study. During induction/stabilisation, withdrawal symptoms subsided more slowly for buprenorphine/naloxone than for methadone, and craving was significantly higher in the buprenorphine/naloxone group (p < 0.05, 95% confidence interval -3.5, -0.38). During detoxification, withdrawal symptoms were significantly greater and the peak of withdrawal was earlier for the methadone/lofexidine group than the buprenorphine/naloxone group (p < 0.01, 95% confidence interval 3.0, 8.3). Methadone/lofexidine and buprenorphine/naloxone had comparable outcomes during rapid outpatient stabilisation and detoxification in low dose opiate users. (PsycINFO Database Record (c) 2019 APA, all rights reserved)
Journal of Psychopharmacology, 31(8) : 1046-1055
- Year: 2017
- Problem: Opioid Use
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Medications used to treat substance abuse, Other biological interventions
Marsch, L. A., Moore, S. K., Borodovsky, J. T., Solhkhah, R., Badger, G. J., Semino, S., Jarrett, K., Condon, K. D., Rossettie, K., Vincent, P., Hajizadeh, N., Ducat, E.
BACKGROUND AND AIMS: Few randomized controlled trials have evaluated buprenorphine treatment interventions for opioid-dependent youth. Consequently, optimal administration strategies for this cohort are unclear. Our aim was to evaluate the relative efficacy of two different buprenorphine taper lengths in promoting abstinence from illicit opioids and treatment retention among opioid-dependent youth.
DESIGN: A double-blind, placebo controlled, multicenter randomized controlled trial.
SETTING: Two hospital-based research clinics (Manhattan and Brooklyn) in New York City, USA from 2005 to 2010.
PARTICIPANTS: Volunteer sample of 53 primarily Caucasian participants between the ages of 16 and 24 (n = 11 under age 18) who met DSM-IV opioid dependence criteria.
INTERVENTION: Participants were assigned randomly to either a 28-day buprenorphine taper (n = 28) or 56-day buprenorphine taper (n = 25) via a parallel-groups design during a 63-day period. Both groups received behavioral counseling and opioid abstinence incentives. Both taper conditions had a minimum of 1 week of placebo dosing at the end of the taper.
MEASUREMENTS: The primary outcome was opioid abstinence measured as a percentage of scheduled urine toxicology tests documented to be negative for opioids. The secondary outcome was treatment retention, measured as number of days attended scheduled visits.
FINDINGS: Intent-to-treat analyses revealed that participants who received a 56-day buprenorphine taper had a significantly higher percentage of opioid-negative scheduled urine tests compared with participants who received a 28-day buprenorphine taper [35 versus 17%, P = 0.039; Cohen's d = 0.57, 95% confidence interval (CI) = 0.02, 1.13]. Participants who received a 56-day buprenorphine taper were retained in treatment significantly longer than participants who received a 28-day buprenorphine taper (37.5 versus 26.4 days, P = 0.027; Cohen's d = 0.63, 95% CI = 0.06, 1.19). Daily attendance requirement was associated with decreased abstinence and shorter retention compared with a two to three times weekly attendance requirement, independent of taper duration. Follow-up data were insufficient to report.
CONCLUSION: Longer (56-day) buprenorphine taper produces better opioid abstinence and retention outcomes than shorter (28-day) buprenorphine taper for opioid-dependent youth.
Addiction, 111(8) : 1406-15
- Year: 2016
- Problem: Opioid Use
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Medications used to treat substance abuse, Other biological interventions
Borodovsky, J., Marsch, L. A., Moore, S. K.
Aims: Opioid dependence among adolescents is a significant public health issue; however, few evidence-based treatment programs for opioid-dependent youth exist. Clinical trials have shown buprenorphine (BUP) to be a promising medication for treating this cohort. To better inform treatment strategies, outcome data were compared from three randomized trials evaluating different BUP dosing strategies. Methods: A systematic search of the literature revealed three trials that investigated this issue: Marsch et al. (2005), Woody et al. (2008) and Marsch et al. (2014) (unpublished).BUPduration, dosing strategies, and clinical outcomes were compared. Results: Across the trials, 241 youth aged 15-24 were enrolled in treatment. Prevalence of injecting behavior ranged from 33% to 60% and use of heroin as the primary drug of abuse ranged from 41% to 82% (others primarily used prescription opioids). Two studies compared different taper strategies and one study compared a taper to maintenance. All studies provided behavior therapy. Length of treatment with BUP ranged from 14 to 84 days. BUP dose ranged from 4 to 24 mg. All studies favored either BUP treatment (compared to non-opioid treatment) or longerBUPtreatment (compared to shorter) in promoting retention and abstinence (based on opioid negative urinalysis). Marsch et al. (2005) (n = 36) observed 72% (28 day BUP taper) vs 39% (28 day clonidine taper) retained at 28 days and 64% vs 32% abstinent at 28 days. Woody et al., 2008 (n = 152) found 70% (12 week BUP maintenance) vs 20.5% (14 day BUP taper) retained at 12 weeks and 57% vs 49% abstinent at 12 weeks. Marsch et al. (2014) (n = 53) found 36% (63 day BUP taper) vs 17% (28 day BUP taper) retained at 63 days and 35% vs 17% abstinent at 63 days. Conclusions: Though trial designs differ, these data suggest that longer treatment with BUP improves clinical outcomes for opioid dependent youth. These results may guide clinicians seeking to implement science-based treatment models for this population.
Drug & Alcohol Dependence, 156 : e25
- Year: 2015
- Problem: Opioid Use
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Medications used to treat substance abuse
Connery, H. S.
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 medicationassisted 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-approvedmaintenance therapies for opioid use disorder. The currently unmet challenges in treating opioid use disorder are discussed, as are the directions for future research
Harvard Review of Psychiatry, 23(2) : 63-75
- Year: 2015
- Problem: Opioid Use
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Medications used to treat substance abuse
Gonzalez, G., DiGirolamo, G., Romero-Gonzalez, M., Smelson, D., Ziedonis, D., Kolodziej, M.
Background: Opioid use disorders are considered a serious public health problem among young adults. Current treatment is limited to long-term opioid substitution therapy, with high relapse rates after discontinuation. This study evaluated the co-administration of memantine to brief buprenorphine pharmacotherapy as a treatment alternative.; Methods: 13-week double-blind placebo-controlled trial evaluating 80 young adult opioid dependent participants treated with buprenorphine/naloxone 16-4mg/day and randomized to memantine (15mg or 30mg) or placebo. Primary outcomes were a change in the weekly mean proportion of opioid use, and cumulative abstinence rates after rapid buprenorphine discontinuation on week 9.; Results: Treatment retention was not significantly different between groups. The memantine 30mg group was significantly less likely to relapse and to use opioids after buprenorphine discontinuation. Among participants abstinent on week 8, those in the memantine 30mg group (81.9%) were significantly less likely to relapse after buprenorphine was discontinued compared to the placebo group (30%) (p<0.025). Also, the memantine 30mg group had significantly reduced opioid use (mean=0, SEM±0.00) compared to the placebo group (mean=0.33, SEM±0.35; p<0.004) during the last 2 weeks of study participation.; Conclusions: Memantine 30mg significantly improved short-term treatment with buprenorphine/naloxone for opioid dependent young adults by reducing relapse and opioid use after buprenorphine discontinuation. Combined short-term treatment with buprenorphine/naloxone may be an effective alternative treatment to long-term methadone or buprenorphine maintenance in young adults.; Published by Elsevier Ireland Ltd.
Drug And Alcohol Dependence, 156 : 243-253
- Year: 2015
- Problem: Opioid Use
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
, Relapse prevention
-
Treatment and intervention: Biological Interventions (any)
, Medications used to treat substance abuse, Other biological interventions, Psychological Interventions (any)
, Cognitive & behavioural therapies (CBT)
Karimyar J. M., Mosallanejad, L.
Introduction: Drug dependence is a major problem in our country and in international level. Reality therapy is an internal control system that determines why and how to choose the options that are set for our lives. This study aimed to investigate the effect of reality therapy on metacognition, stress and decline in hope in drug addicts.; Materials& Methods: This study is quasi-experimental study. Samples were chosen convenient among 60 drug addicts in Jahrom in 2012. Samples were randomly divided into two groups (each group = 30) of intervention and control groups. Control group received usual care and experimental group received reality therapy.; Results: Results revealed that there was significant difference between the mean scores of metacognition and hope before and after the intervention of experimental group (p < 0.05). Also, there was statistically significant difference between the two groups from these two variables (p < 0.05).but, Stress level wasn't statistically different in two groups.; Discussion: Reality therapy is a method that emphasizes the accountability and the current behavior of individuals. Setting negative emotions, reality therapy promotes metacognition and, through increasing accountability to self-behavior improves hope.;
Global Journal of Health Science, 6(6) : 281-287
- Year: 2014
- Problem: Opioid Use
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Psychological Interventions (any)
, Other Psychological Interventions
Crowley, D. M., Jones, D. E., Coffman, D. L., Greenberg, M. T.
Purpose: Prescription drug abuse has reached epidemic proportions. Nonmedical prescription opioid use carries increasingly high costs. Despite the need to cultivate efforts that are both effective and fiscally responsible, the cost-effectiveness of universal evidence-based-preventive-interventions (EBPIs) is rarely evaluated. This study explores the performance of these programs to reduce nonmedical prescription opioid use.; Methods: Sixth graders from twenty-eight rural public school districts in Iowa and Pennsylvania were blocked by size and geographic location and then randomly assigned to experimental or control conditions (2002-2010). Within the intervention communities, prevention teams selected a universal family and school program from a menu of EBPIs. All families were offered a family-based program in the 6th grade and received one of three school-based programs in 7th-grade. The effectiveness and cost-effectiveness of each school program by itself and with an additional family-based program were assessed using propensity and marginal structural models.; Results: This work demonstrates that universal school-based EBPIs can efficiently reduce nonmedical prescription opioid use. Further, findings illustrate that family-based programs may be used to enhance the cost-effectiveness of school-based programs.; Conclusions: Universal EBPIs can effectively and efficiently reduce nonmedical prescription opioid use. These programs should be further considered when developing comprehensive responses to this growing national crisis.; Copyright © 2014 Elsevier Inc. All rights reserved.
Preventive Medicine, 62 : 71-77
- Year: 2014
- Problem: Opioid Use
- Type: Randomised controlled trials
-
Stage: Universal prevention
-
Treatment and intervention: Psychological Interventions (any)
, Skills training, Other Psychological Interventions
Minozzi, S., Amato, L., Bellisario, C., Davoli, M.
BACKGROUND: The scientific literature examining effective treatments for opioid dependent adults clearly indicates that pharmacotherapy is a necessary and acceptable component of effective treatments for opioid dependence. Nevertheless, no studies have been published that systematically assess the effectiveness of the pharmacological detoxification among adolescents.
OBJECTIVES: To assess the effectiveness of any detoxification treatment alone or in combination with psychosocial intervention compared with no intervention, other pharmacological intervention or psychosocial interventions on completion of treatment, reducing the use of substances and improving health and social status.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (2014, Issue 1), PubMed (January 1966 to January 2014), EMBASE (January 1980 to January 2014), CINHAL (January 1982 to January 2014), Web of Science (1991-January 2014) and reference lists of articles.
SELECTION CRITERIA: Randomised controlled clinical trials comparing any pharmacological interventions alone or associated with psychosocial intervention aimed at detoxification with no intervention, placebo, other pharmacological intervention or psychosocial intervention in adolescents (13 to 18 years).
DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by The Cochrane Collaboration
MAIN RESULTS: Two trials involving 190 participants were included. One trial compared buprenorphine with clonidine for detoxification. No difference was found for drop out: risk ratio (RR) 0.45 (95% confidence interval (CI): 0.20 to 1.04) and acceptability of treatment: withdrawal score mean difference (MD): 3.97 (95% CI -1.38 to 9.32). More participants in the buprenorphine group initiated naltrexone treatment: RR 11.00 (95% CI 1.58 to 76.55), quality of evidence moderate.The other trial compared maintenance treatment versus detoxification treatment: buprenorphine-naloxone maintenance versus buprenorphine detoxification. For drop out the results were in favour of maintenance treatment: RR 2.67 (95% CI 1.85, 3.86), as well as for results at follow-up RR 1.36 [95% CI 1.05to 1.76); no differences for use of opiate, quality of evidence low.
AUTHORS' CONCLUSIONS: It is difficult to draw conclusions on the basis of two trials with few participants. Furthermore, the two studies included did not consider the efficacy of methadone that is still the most frequent drug utilised for the treatment of opioid withdrawal. One possible reason for the lack of evidence could be the difficulty in conducting trials with young people due to practical and ethical reasons.
Cochrane Database of Systematic Reviews, 4 : CD006749
- Year: 2014
- Problem: Opioid Use
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Medications used to treat substance abuse
Minozzi, S., Amato, L., Bellisario, C., Davoli, M.
BACKGROUND: The scientific literature examining effective treatments for opioid-dependent adults clearly indicates that pharmacotherapy is a necessary and acceptable component. Nevertheless, no reviews have been published that systematically assess the effectiveness of pharmacological maintenance treatment in adolescents.
OBJECTIVES: To assess the effectiveness of any maintenance treatment alone or in combination with psychosocial intervention compared to no intervention, other pharmacological intervention or psychosocial interventions for retaining adolescents in treatment, reducing the use of substances and improving health and social status.
SEARCH METHODS: We searched the Cochrane Drugs and Alcohol Group's Trials Register (January 2014), the Cochrane Central Register of Controlled Trials (2014, Issue 1), PubMed (January 1966 to January 2014), EMBASE (January 1980 to January 2014), CINAHL (January 1982 to January 2014), Web of Science (1991 to January 2014) and reference lists of articles.
SELECTION CRITERIA: Randomised and controlled clinical trials of any maintenance pharmacological interventions either alone or associated with psychosocial intervention compared with no intervention, placebo, other pharmacological intervention, pharmacological detoxification or psychosocial intervention in adolescents (13 to 18 years).
DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by The Cochrane Collaboration.
MAIN RESULTS: We included two trials involving 189 participants. One study, with 35 participants, compared methadone with levo-alpha-acetylmethadol (LAAM) for maintenance treatment lasting 16 weeks, after which patients were detoxified. The other study, with 154 participants, compared maintenance treatment with buprenorphine-naloxone and detoxification with buprenorphine. We did not perform meta-analysis because the two studies assessed different comparisons.In the study comparing methadone and LAAM, the authors declared that there was no difference in the use of a substance of abuse or social functioning (data not shown). The quality of the evidence was very low. No side effects, such as nausea, vomiting, constipation, weakness or fatigue, were reported by study participants.In the comparison between buprenorphine maintenance and buprenorphine detoxification, maintenance treatment appeared to be more efficacious in retaining patients in treatment (drop-out risk ratio (RR) 0.37; 95% confidence interval (CI) 0.26 to 0.54), but not in reducing the number of patients with a positive urine test at the end of the study (RR 0.97; 95% CI 0.78 to 1.22). Self reported opioid use at one-year follow-up was significantly lower in the maintenance group, even though both groups reported a high level of opioid use (RR 0.73; 95% CI 0.57 to 0.95). More patients in the maintenance group were enrolled in other addiction treatment programmes at 12-month follow-up (RR 1.33; 95% CI 0.94 to 1.88). The quality of the evidence was low. No serious side effects attributable to buprenorphine-naloxone were reported by study participants and no patients were removed from the study due to side effects. The most common side effect was headache, which was reported by 16% to 21% of patients in both groups
AUTHORS' CONCLUSIONS: It is difficult to draft conclusions on the basis of only two trials. One of the possible reasons for the lack of evidence could be the difficulty of conducting trials with young people for practical and ethical reasons.There is an urgent need for further randomised controlled trials comparing maintenance treatment with detoxification treatment or psychosocial treatment alone before carrying out studies that compare different pharmacological maintenance treatments. These studies should have long follow-up and measure relapse rates after the end of treatment and social functioning (integration at school or at work, family relationships).
Cochrane Database of Systematic Reviews, 6 : CD007210
- Year: 2014
- Problem: Opioid Use
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Medications used to treat substance abuse
Veilleux, Jennifer C., Colvin, Peter J., Anderson, Jennifer, York, Catherine, Heinz, Adrienne J.
Opioid dependence is a problem of national concern, especially with dramatically increased rates of abuse and dependence of prescription opioids. The current article provides an up-to-date review of the literature on opioid dependence treatment, with a focus on conclusions drawn by experts in the field (e.g., Cochrane reviews and meta-analyses) and methodologically rigorous studies (e.g., randomized controlled trials). We describe the major classes of drug treatments available, including opioid agonist (e.g., methadone, buprenorphine, LAAM), antagonist (e.g., naltrexone) and non-opioid pharmacotherapies (e.g., alpha2 adrenergic agonists). These treatments are discussed in the context of detoxification and long term treatment options such as abstinence-based and maintenance strategies. We review the state of the literature as to prevention of opioid overdose and discuss the widespread problem of comorbidity among opioid-dependent populations. We also focus prominently on evidence for inclusion of psychosocial approaches in treatment regimens, either as stand-alone or in conjunction with psychopharmacological options.
Copyright 2009 Elsevier Ltd. All rights reserved.
Clinical Psychology Review, 30(2) : 155-166
- Year: 2010
- Problem: Opioid Use
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
, Relapse prevention
-
Treatment and intervention: Biological Interventions (any)
, Medications used to treat substance abuse
Woody, G.E., Poole, S.A., Subramaniam, G., Dugosh, K., Bogenschutz, M., Abbott, P., Patkar, A., et-al
Context The usual treatment for opioid-addicted youth is detoxification and counseling.
Extended medication-assisted therapy may be more helpful.
Objective To evaluate the efficacy of continuing buprenorphine-naloxone for 12
weeks vs detoxification for opioid-addicted youth.
Design, Setting, and Patients Clinical trial at 6 community programs from July
2003 to December 2006 including 152 patients aged 15 to 21 years who were randomized
to 12 weeks of buprenorphine-naloxone or a 14-day taper (detox).
Interventions Patients in the 12-week buprenorphine-naloxone group were prescribed
up to 24 mg per day for 9 weeks and then tapered to week 12; patients in the
detox group were prescribed up to 14 mg per day and then tapered to day 14. All
were offered weekly individual and group counseling.
Main Outcome Measure Opioid-positive urine test result at weeks 4, 8, and 12.
Results The number of patients younger than 18 years was too small to analyze separately,
but overall, patients in the detox group had higher proportions of opioidpositive
urine test results at weeks 4 and 8 but not at week 12 ( 2
2=4.93, P=.09). At
week 4, 59 detox patients had positive results (61%;95%confidence interval [CI]=47%-
75%) vs 58 12-week buprenorphine-naloxone patients (26%; 95% CI=14%-38%).
At week 8, 53 detox patients had positive results (54%; 95% CI=38%-70%) vs 52
12-week buprenorphine-naloxone patients (23%; 95% CI=11%-35%). At week 12,
53 detox patients had positive results (51%; 95% CI=35%-67%) vs 49 12-week buprenorphine-
naloxone patients (43%; 95% CI=29%-57%). By week 12, 16 of 78
detox patients (20.5%) remained in treatment vs 52 of 74 12-week buprenorphinenaloxone
patients (70%; 2
1=32.90, P .001). During weeks 1 through 12, patients
in the 12-week buprenorphine-naloxone group reported less opioid use ( 2
1=18.45,
P .001), less injecting ( 2
1=6.00, P=.01), and less nonstudy addiction treatment
( 2
1=25.82, P .001). High levels of opioid use occurred in both groups at follow-up.
Four of 83 patients who tested negative for hepatitis C at baseline were positive for
hepatitis C at week 12.
Conclusions Continuing treatment with buprenorphine-naloxone improved outcome
compared with short-term detoxification. Further research is necessary to assess
the efficacy and safety of longer-term treatment with buprenorphine for young
individuals with opioid dependence.
JAMA, 300(17) : 2003-2011
- Year: 2008
- Problem: Opioid Use
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Medications used to treat substance abuse, Medication dose reduction/discontinuation