TABLE 3.

Evidence for Treatment With Medication for OUD

Study	Study Population	Study Description	Follow-up	Main Outcomes
Buprenorphine
Marsch et al70	Adolescents ages 13–18 y (n = 36)	A double-blind, double-dummy, parallel-groups randomized controlled trial; assigned to a 28-d outpatient detox with buprenorphine or clonidine. Buprenorphine taper: • If ≥70 kg and/or self-reported use >3 bags of heroin or equivalent in opiates, given daily starting dose of 8 mg of buprenorphine; otherwise started on 6 mg • Then tapered down by 2 mg every 7 d	28-d detox only	72% of those in buprenorphine group were retained in treatment versus 39% of those in the clonidine group (P < .05). For those in the buprenorphine group, a significantly higher percentage of scheduled urine test results were opiate negative (64% vs 32%; P = .01).
Woody et al71	Youth ages 15–21 y (n = 152)	Randomized clinical trial at 6 US community programs; assigned to 12 wk of buprenorphine or 14-d taper (detox). Buprenorphine dosing: • 12-wk group: titrated up to max of 24 mg/day with taper starting at week 9 • 14-d detox group: titrated up to max of 14 mg/day and tapered off by day 14.	12 wk	Those in the detox group had significantly higher proportions of opioid-positive urine test results at weeks 4 and 8 but not at week 12. Those in buprenorphine group had less injection drug use and more remained in treatment versus youth in detox group.
Matson et al32	Youth ages 14–25 y (n = 103)	Retrospective chart review of clinic patients seen at an adolescent medicine specialty addiction medicine clinic. Buprenorphine dosing: • Home induction based on protocol; majority were on 8 mg twice daily maintenance.	1 y	Opioid abstinence was high at 85.2% with high adherence at 86.6% during clinic visits; 75% of patients returned for a second visit. Low retention of 45% at 60 d and 9% at 1 y.
Marsch et al72	Youth ages 16–24 y (n = 53 in total; n = 11 under age 18)	Double-blind, placebo, randomized controlled trial (2 sites); assigned to 28-d taper versus 56-d taper of buprenorphine. Buprenorphine taper: Titrated up to max of 16 mg/day.	63 d	Those in longer taper group had a significantly higher percentage of opioid-negative urine test results (35% vs 17%, P = .039).
Extended-release naltrexone
Fishman et al33	Youth ages 16–20 y (n = 16)	Case series in a community-based adolescent substance abuse treatment program in Baltimore, Maryland, offering monthly injection of extended-release naltrexone.	4 mo	85% (12 out of 14 who came back for a second visit) received at least 2 doses. 63% were retained in treatment of at least 4 mo. 56% had either substantially decreased opioid use, improvement in at least 1 psychosocial domain, or no new problems due to substance use.
Vo et al73	Youth ages 17–25 y (n = 14 in home-based delivery group; n = 21 in treatment as usual group receiving naltrexone in clinic)	2-y pilot clinical quality improvement initiative offering home-based delivery of extended-release naltrexone with a convenience sample of youth attending a community-based adolescent substance abuse treatment program in Baltimore, Maryland. Intervention: Naltrexone initially delivered to the treatment center from a pharmacy and then brought to patient’s home by a team consisting of a nurse practitioner and a counselor every 3–4 wk.	16 wk	64% (9 out of 14) received at least 1 dose of extended-release naltrexone at home. Home delivery group had an average of 3.3 doses of the potential 5 monthly doses (including first inpatient dose) versus 2.0 doses for treatment as usual group. 50% of the home delivery group received all 5 doses versus 9% in the treatment-as-usual group.
Methadone
DeAngelis and Lehmann74	Youth using heroin ages 15–24 y (n = 37)	Community-based opioid treatment center in Connecticut. Intervention: “low-dose” methadone maintenance regimen based on individual needs for 2–13 wk, followed by a taper off methadone lasting 3–14 wk.	18 mo	Average methadone dose was 20 mg/day with a range of 10–60 mg/day. Average maintenance phase lasted 7 wk, and average taper phase lasted 7 wk. 35% of youth remained opioid-free and were retained in treatment or were working or in school.
Guarino et al75	Young adults ages 18–23 y (n = 22)	Qualitative study with focus groups consisting of patients (n = 7), staff (n = 6), n/a and parents (n = 3) to better understand components of effective treatment with methadone in a young adult methadone program in New York. Treatment model: outpatient intensive weekly counseling in individual and group settings plus the option of family therapy; patients encouraged to taper off methadone once status is “stabilized.”	n/a	The following themes emerged: (1) youth themselves must be motivated for treatment; (2) engagement in treatment is often challenging given youth’s limited lifetime history with significant negative consequences due to use; (3) youth-centered treatment is desired with variable treatment options; (4) duration of treatment should be dictated by individual youth’s need, goals, and outcomes; (5) effective treatment involves the family of youth; and (6) youth remain hopeful that they will be tapered off methadone.
Comparative effectiveness trials
Bell and Mutch76	Adolescents ages 14–17 y (n = 61)	Retrospective chart review of all youth at first presentation for treatment of opioid dependence in an Australian treatment center: 20 youth received methadone, 25 youth received buprenorphine, and 15 youth received symptomatic medication for withdrawal; 1 received no medication.	Variable	Youth receiving methadone had significantly longer retention in the first treatment episode versus those receiving buprenorphine (mean: 354 vs 58 d; P < .01) and missed fewer days in the first month (mean: 3 vs 8 d; P < .05). However, time to re-entry after first episode of buprenorphine was significantly shorter than after methadone.
Mattick et al61	Adult patients; 31 trials included (n = 5430 total participants with a range of 40–736 participants in each study)	Cochrane Systematic Review comparing buprenorphine to placebo and buprenorphine to methadone for opioid dependence. Quality of evidence varied from high to moderate quality.	Interventions ranged in duration from 2 to 52 wk	High quality of evidence (14 studies) that buprenorphine was superior to placebo in retention of participants at all doses examined (2–16 mg/day). Moderate quality of evidence (3 studies) that high-dose buprenorphine (≥16 mg/day) was more effective than placebo in suppressing illicit opioid use. High quality of evidence (5 studies) that buprenorphine in flexible doses was less effective than methadone in retention; however, no difference was observed in suppression of illicit opioid use with moderate quality of evidence (12 studies).
Lee et al77	Adults ≥18 y (n = 570)	Open-label, randomized controlled, comparative effectiveness trial at 8 US community-based inpatient programs with follow-up in outpatient program. 283 randomly assigned to extended-release naltrexone versus 287 randomly assigned to buprenorphine.	24 wk	Extended-release naltrexone had a substantial induction challenge with only 72% of participants successfully initiated versus 94% of participants successfully initiated onto buprenorphine (P < .0001). Among those with successful induction, there was no significant difference in 24-wk relapse between the 2 groups (P = .44). Among those with successful induction, there was no significant difference in opioid-negative urine test results or opioid-abstinent days between the 2 groups.

n/a, not applicable.