Review question
We reviewed the evidence about the effect of maintenance treatment 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).
Background
Substance abuse among adolescents (13 to 18 years old) is a serious and growing problem. It is important to identify effective treatments for those who are opioid-dependent. The most common drugs used by young people worldwide are cannabis and inhalants. Psychostimulants (ecstasy and amphetamines), cocaine, LSD, heroin and other opioids are also used. Many adolescents who use heroin start by snorting it but some progress to injection. Heroin is used sporadically by the majority who use it, but it can become an addictive disorder. In adults, pharmacotherapy is a necessary and acceptable part of effective treatment for opioid dependence. Among adolescents, medications have been used infrequently and a choice has to be made between detoxification and maintenance treatment. Among maintenance treatment methadone and buprenorphine are the most frequently used drugs. Methadone needs daily doses, while LAAM (levomethadyl acetate hydrochloride) must be taken every two or three days. LAAM has been withdrawn from the market because of concerns about life-threatening effects on the heart .
Psychosocial interventions are interventions that use psychological or social strategy to achieve a therapeutic benefit in inpatient. The most common used approaches are: Cognitive-behavioural therapy,methods based on the assumption that since substance abuse among adolescents is a learned behaviour it can be unlearned as well; contingency management ,which uses reinforcement and punishment contingencies to enhance motivation: family therapy which is based on the conceptualisation that adolescent substance abuse stem from maladaptive family interactions; drug counselling which includes a strong emphasis on abstinence, assistance with social, family and legal problems. It focuses on behaviours and external events rather than intrapsychic processes; therapeutic community and motivational approach which rather than confront the patient's resistance to abstinence in a direct and sometimes aggressive manner, "rolls with resistance". At he same time, he tries to help the patient develop more self-motivation to stop using via specified techniques
Study characteristics
The review authors searched the literature and identified two controlled trials from the USA that involved 187 heroin addicts, aged 14 to 21 years; the participants were treated as outpatients. One study of 37 participants compared methadone with levo-alpha-acetylmethadol (LAAM) for maintenance treatment. After 16 weeks of maintenance treatment the adolescents were detoxified. The second trial of 150 adolescents compared buprenorphine and naloxone as maintenance treatment for nine weeks followed by tapered doses for up to 12 weeks with buprenorphine detoxification over 14 days.
Key results
In the first trial methadone and LAAM led to similar improvements in social functioning. No side effects were reported.
In the second trial the maintenance treatment seemed to be more effective in retaining patients in treatment but not in reducing the use of drugs of abuse. At one-year follow-up, self reported opioid use was clearly less in the maintenance group and more adolescents were enrolled in other addiction programmes. The most common side effect in both groups was headache. No participants left the study because of side effects.
It is difficult to draw conclusions about the use of maintenance pharmacological interventions from only two trials. Conducting trials with young people may be difficult for both practical and ethical reasons.
Quality of the evidence
This review was limited by the very low number of trials retrieved. The quality of the evidence was very low for the comparison between methadone and LAAM and low for the comparison between buprenorphine detoxification and buprenorphine maintenance. The evidence is current to January 2014.
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).
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.
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.
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.
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).
We used the standard methodological procedures expected by The Cochrane Collaboration.
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