Methods

Randomised controlled trial. Recruitment modality: self‐referred participants.

Participants

36 adolescents (13‐18 years) who met the DSM‐IV criteria for opioid dependence. Pregnant women and patients with significant psychiatric disorders (e.g. psychosis) or medical illnesses (e.g. cardiovascular disease) were excluded.

Mean age. 17.35 years; 39% male; 97% white. Injection route of opiate use: 36%; other drug dependence alcohol: 17.5%, cannabis: 17%, cocaine: 10%, amphetamine: 6%.

Interventions

(1) Buprenorphine detoxification: sublingual buprenorphine tablets daily with flexible dosing procedure based on weight and self‐reported opiate use at intake (starting dose range: 6 mg‐ 8 mg). Buprenorhine dose that decreased by 2 mg every 7 days. Behavioural therapy 3 one‐hour individual sessions per week. Contingency management approach: participants could earn a voucher on the provision of opioid negative urine samples. At the end of the study, participants were offered naltrexone.

(2) Transdermal clonidine patches 0.1 mg on intake day and day 1; a second patch was added on day 2 and worn until day 6. An optional third patch (depending on the severity of withdrawal symptoms) may have been added on day 4 and worn until day 6. All patches were removed on day 7 and replaced with a 0.2 mg doses. On day 14 the patches were removed again and replaced with a 0.1 mg dose patch. On day 21 the patches were removed again and replaced with a 0 mg dose. Behavioural therapy 3 one‐hour individual session per week. Contingency management approach: participants could earn a voucher on the provision of opioid negative urine samples. At the end of the study, participants were offered naltrexone.

Durattion of the trials: 28 days.

Outcomes

Drop out from treatment measured as the percentage of patients who did not complete the entire detoxification treatment. Time retained in treatment. Opiate abstinence as the percentage of scheduled urine samples opiate negative. Other drug use as percentage of urine samples positives. Acceptability of the treatment: withdrawal effect measured by the Adjective rating scale. Initiation of naltrexone treatment as percentage of patients who initiated.

Notes

Country: USA
Setting: outpatients

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

"participants were randomly assigned to either detoxification with clonidine or with buprenorphine. In this process participants were stratified for sex and past month route of opiate use (injection vs intranasal)"

Allocation concealment (selection bias)

Unclear risk

"participants were randomly assigned to either detoxification with clonidine or with buprenorphine. In this process participants were stratified for sex and past month route of opiate use (injection vs intranasal)"

Blinding (performance bias and detection bias)
objective outcomes (drop out, use of substance measured by urine‐analysis, abstinent at follow‐up, initiation of naltrexone treatment)

Low risk

"The study used a parallel group, double blind, double dummy design". Participants in the clonidine group received placebo buprenorphine tablets and patients in the buprenorphine group received placebo clonidine patches"

COMMENT: the outcomes are unlikely to be influenced by lack of blinding

Blinding (performance bias and detection bias)
Subjective outcome

Low risk

"The study used a parallel group, double blind, double dummy design". Participants in the clonidine group received placebo buprenorphine tablets and patients in the buprenorphine group received placebo clonidine patches"
COMMENT: blinding of participants and personnel. Not specified if research staff members who assessed subjective outcomes were blind but we judge that they probably were.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

"the primary analysis (drop out, time retained, use of substance) included all participants randomised independently to drop out/non compliance, consistent with an intention to treat approach. All secondary outcomes (withdrawals symptoms and signs) were confined to the data from treatment intake to the end of the first week when retention was still high in both condition"

Selective reporting (reporting bias)

Low risk

Methods

Multicentre randomised controlled trial. Recruitment modality described.

Participants

154 participants who met the DSM IV diagnostic criteria for opioid dependence and who sought outpatient treatment.152 randomised. Mean age: 19 years. Only one participant was 15 years old and no participants were 14 years old. Male: 59%. White: 56%.

Interventions

(1) Maintenance group:12 weeks buprenorphine. Naloxone: up to 24 mg/day buprenorphine and 0.5 mg naloxone for 9 weeks and then tapered to week 12. :74 patients.

(2) Detoxification group: 2 weeks buprenorphine. Naloxone: up to 14 mg/day buprenorphine and then tapered to day 14: 78 patients.

Both groups were offered 1 weekly individual and 1 group counselling.

Outcomes

Primary outcome: opioid positive urine test results at weeks 4, 8 and 12.

Secondary outcomes: drop out, self‐reported use, enrolment in addiction treatment outside the assigned condition, other drug use, adverse events. Results at 6,9,12 months follow‐up: self‐reported opioid use, self‐reported other drug use, other addiction treatment received.

Notes

Country: USA

Setting: outpatients

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation occurred through an automated 24‐hour service at the Veterans Affairs Cooperative Studies Program in Perry Point, Maryland, that was programmed
to randomise patients separately by site. At each site, a biased coin randomisation protected against severe imbalance of sex, ethnicity, route of administration, and age across the treatment groups.

Age was dichotomised as 14 to 18 years or 18 to 21 years, ethnicity as the majority ethnic group vs all others within the site, and route of administration as injecting or non injecting.

Allocation concealment (selection bias)

High risk

Balance was assessed by comparing the group sum of the binary indicators as each new patient was randomised. If both groups were balanced when a new patient was being randomised, then each group had an allocation probability of 1/2; if there was an imbalance, then the group with the higher score on the sum of indicators received an allocation probability of 1/3 and the other group a probability of 2/3.

Blinding (performance bias and detection bias)
objective outcomes (drop out, use of substance measured by urine‐analysis, abstinent at follow‐up, initiation of naltrexone treatment)

Low risk

Patients and providers impossible to be blinded for the nature of the intervention (14 days detox vs 12 weeks maintenance).

COMMENT: objective outcomes unlikely to be biased by lack of blinding.

Blinding (performance bias and detection bias)
Subjective outcome

High risk

Patients and providers impossible to be blinded for the nature of the intervention (14 days detox vs 12 weeks maintenance)

Outcome assessor not blinded: "Research assistant likely knew groups assignment because the study was not blinded"

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Number of participants withdrawn from the study reported for each group. Reason for withdrawal given. Analysis on the basis of the Intention‐to‐treat principle: "patients were contacted at all assessment point regardless of whether they remained in treatment".

Selective reporting (reporting bias)

Low risk