The effectiveness of interventions for young people with illicit drug problems. Claire MacLeod & Catriona Matheson, September 2011 Key Points: 1. Two Cochrane reviews and nine trials were found. Most of the trials were conducted in the USA thus generalisability of findings is limited. One UK trial was found. 2. The evidence base was predominantly focussed on mixed drug problems, but trials focussing on heroin and cannabis usage were also found. 3. No trials of interventions specifically focussed on cocaine, LSD or psychostimulant abuse were found. 4. The evidence from the single UK trial indicated some benefit of one-hour single-session face-to-face motivational interviews for generic drug use in adolescents. 5. There is insufficient evidence around the effectiveness of treatment in opiate dependence and further research is warranted. Background Drug misuse in adolescents is recognised as a growing problem worldwide. This brief topic review looked at the published literature on randomised controlled trials (RCTs), trials and comparative studies of various pharmacological, psychosocial and family interventions for young people with illicit drug problems. Cannabis is often cited as the most commonly used drug by young people, but cocaine, ecstasy, amphetamines, LSD, inhalants, and heroin are also used. Drug misuse often occurs in conjunction with alcohol abuse and is also linked with mental health. Many individuals are also polydrug or multidrug users, consuming more than one illicit substance. Hence, this topic is complex and multifaceted, but of increasing importance in today’s world. Methods PubMed/MEDLINE, Scopus, the CRD, and the Cochrane database were searched from inception to August 2011. Search terms used were ‘substance misuse’ and ‘adolescents’, with various combinations of drug names and limitations to trials and comparative studies to focus the search on comparative studies and reduce the volume of non-relevant literature. The reference lists of relevant articles were also hand searched. Only RCTs, controlled trials and comparative studies were included, and the majority of participants had to be less than 18 years old. Results Two Cochrane reviews and nine trials were identified by the search strategy. Most of the trial literature was undertaken in the USA. One UK trial was found. The included evidence is briefly discussed below, grouped according to drug type. Opiate usage Two Cochrane reviews and three USA trials were found (all of the trials were already included in the Cochrane reviews). Minozzi S, Amato L, Davoli M. Maintenance treatments for opiate dependent adolescents (Review). The Cochrane Library 2009, Issue 2. This Cochrane review searched the literature for published trials of any opioid agonist treatment alone or in combination with psychosocial treatment versus control in opiate dependent adolescents (up to 18 years old). Two USA trials were identified (Lehmann, 1973 and Woody, 2008) that enrolled 187 outpatient heroin addicts aged between 14 and 21 years. Lehmann 1973 studied LAAM maintenance versus methadone maintenance, and Woody 2008 studied shortterm buprenorphine-naloxone (14-day detox) versus maintenance buprenorphine-naloxone (14 weeks). The trial by Lehmann was considered at high risk of bias whilst the Woody trial was considered at low risk of bias. The Lehmann trial reported no difference between interventions. The Woody trial reported statistically significantly lower rates of self-reported use at 12 months (RR 0.73, 95% CI 0.57 to 0.95) and self-reported cocaine use (RR 0.12, 95% CI 0.02 to 0.90) with buprenorphine-naloxone maintenance but no statistically significant differences in the rates of positive urine at the end of treatment, selfreported alcohol use, or self-reported marijuana use. There were no side-effects reported with Lehmann, but the Woody trial reported that head-ache was common (16-21%) with buprenorphine. The review authors concluded that there was a lack of evidence, which could be due to the difficulties in conducting trials in young people. The systematic review was well conducted and the authors’ conclusions appear appropriate. Minozzi S, Amato L, Davoli M. Detoxification treatments for opiate dependent adolescents (Review). The Cochrane Library 2009, Issue 4. This Cochrane review searched the literature for published trials of any pharmacological treatment alone or in combination with psychosocial treatment versus control in opiate dependent adolescents (up to 18 years old). Two USA trials were identified (Marsch, 2005 and Woody, 2008) that enrolled 190 outpatient opiate addicts aged between 13 and 21 years. Marsch 2005 studied buprenorphine sublingual tablets versus clonidine patches and Woody 2008 studied buprenorphine-naloxone maintenance (14 weeks) versus buprenorphine naloxone short-term (14-day detox). Both trials were considered quite good quality. The Marsch trial reported that buprenorphine was associated with a statistically significantly greater likelihood of initiating naltrexone to maintain abstinence compared with clonidine (RR 11.00, 95% CI 1.58 to 76.55). The Woody trial reported statistically significantly higher rates of self-reported use at 12 months (RR 1.36, 95% CI 1.05 to 1.76) and self-reported cocaine use (RR 8.54, 95% CI 1.11 to 65.75) with buprenorphine detox (compared with maintenance) but no statistically significant differences in the rates of positive urine at the end of treatment, self-reported alcohol use, or self-reported marijuana use. The Marsch trial did not report adverse events. There were no serious adverse events reported with the Woody trial, but headache was commonly reported (16-21%) with buprenorphine. The review authors concluded that there was a lack of evidence, especially for methadone, which could be due to the difficulties in conducting trials in young people. The systematic review was well conducted and the authors’ conclusions appear appropriate. Marsch LA, Bickel WK, Basger GJ, et al. Comparison of pharmacological treatments for opioid-dependent adolescents. Archives of General Psychiatry 2005;62:1157-64. This trial was included in the Cochrane detoxification review and is already discussed above. Lehmann WX. The use of 1-alpha-acetyl-methadol (LAAM) as compared to methadone In the maintenance and detoxification of young heroin addicts. NIDA monograph 1973;8:82-3. This trial was included in the Cochrane maintenance review and is already discussed above. Woody GE, Poole SA, Subramanian G, et al. Extended versus short-term buprenorphine-naloxone for treatment of opiate-addicted youth. JAMA 2008; 300(17):2003-11. This trial was included in both the Cochrane reviews and is already discussed above. Cannabis usage One publication was found that that reported on two trials conducted in the USA. Dennis M, Godley SH, Diamond G, et al. The Cannabis Youth Treatment (CYT) Study: Main findings from two randomised trials. J Substance Abuse Treatment 2004; 27:197-213. The first trial studied Motivational Enhancement Treatment/Cognitive Behaviour Therapy 5 sessions (MET/CBT5), versus Motivational Enhancement Treatment/Cognitive Behaviour Therapy 12 sessions (MET/CBT12), versus Family Support Network (FSN) in 300 adolescents aged between 13 and 18 years. The majority of participants had weekly or daily marijuana use, but some participants also reported alcohol use and other drug use. There was no significant difference between interventions in terms of days of abstinence, but there was a trend favouring MET/CBT5 in terms of per cent in recovery. The trial also reported that MET/CBT5 was the least costly programme and thus the most cost-effective programme overall. The trial was reasonably well conducted, using a randomised design, reporting loss to follow-up and patient characteristics, and the trial results seem reliable. The second trial studied MET/CBT5, versus Adolescent Community Reinforcement Approach (ACRA) versus Multidisciplinary Family Therapy (MDFT) in 300 adolescents aged between 13 and 18 years. The majority of participants had weekly or daily marijuana use, but some participants also reported alcohol use and other drug use. There was no significant difference between interventions in terms of days of abstinence or per cent recovery. The trial reported that ACRA was the least costly programme and thus the most cost-effective programme overall. The trial was reasonably well conducted, using a randomised design, reporting loss to follow-up and patient characteristics, and the trial results seem reliable. Non-specific drug misuse and multi-drug misuse Four trials were found, three were conducted in the USA and one was conducted in the UK (McCambridge, 2004). Baer JS, Garrer SB, Beadnell B, et al. Brief motivational interventions with homeless adolescents: evaluating effects on substance use and service utilisation. Psychology of Addictive Behaviours 2007; 21(4):5826. This randomised trial studied 117 homeless adolescents (aged 13-19 years) with drug and/or alcohol abuse problems. The intervention was a brief motivational intervention (BMI) which was compared with usual care in an outpatient setting. Randomisation was unbalanced during the study, which may have introduced bias into the trial. There was no difference in drug use outcomes but participants in the BMI group had an increase in service utilisation during the trial which returned to baseline during follow-up. Participants reported overall reductions in drug use over time. The authors concluded that BMI for homeless people is not robust and further research is needed, which appears appropriate. Liddle HA, Dakof GA, Parker K, et al. Multidimensional family therapy for adolescent drug abuse: results of a randomised clinical trial. American Journal of Drug and Alcohol Abuse 2001;27(4):651-88. This trial randomly assigned 182 marijuana and alcohol abusing adolescents (mean age =15.9 years) to one of three treatments: multidimensional family therapy (MDFT), adolescent group therapy (AGT), or multidimensional education intervention (MEI). Interventions were delivered on an out-patient basis by community therapists, and follow-up was 12 months. The results indicated that all of the interventions were beneficial, but MDFT was superior in terms of prosocial school/academic performance, family functioning and drug use. The authors noted limitations in terms of a lack of data on co-morbid conditions, differences in the sample in terms of gender and ethnicity, and potential generalizability problems due to a lack of diagnostic criteria. The authors concluded that family based interventions are most effective. Given the small sample sizes in the intervention groups, together with the limitations identified by the authors, the reliability of results is uncertain. The generalizability to UK clinical practice is also questionable. McCambridge J and Strang J. The efficacy of single session motivational interviewing in reducing drug consumption and perceptions of drug related risk and harm among young people: results from a multi-cluster randomised trial. Addiction 2004;99:39-52. This was the only UK trial identified. It was a cluster randomised trial that enrolled 200 adolescents from further education colleges (aged 16-20 years) to either motivational interviewing or non-intervention education as usual. The included participants were nearly all cannabis users (ranging from daily to monthly), but many were also users of stimulants and some were users of other illicit drugs. Many participants were also users of alcohol and tobacco. The motivational intervention was a one-hour single-session face-to-face structured interview. Data on drug use was collected through interview at recruitment and three months later. The follow up rate was good at 89%. Compared to baseline, the motivational intervention had a 66% reduction in cannabis usage (control arm had a 27% increase in usage), a 39% decrease in alcohol consumption (12% increase in control group), and a 21% decrease in cigarette smoking (12% increase in control group). For both alcohol and cannabis users the effect was greatest in the heavier users. There was no difference in the use of other drugs. The trial also reported other behavioural outcomes such as decisions to cut-down and stop, and selling of drugs. The authors concluded that the trial supports the use of targeting multi-drug use in a generic fashion among adolescents. The trial was generally well conducted but the authors noted the potential for a Hawthorn effect, the lack of statistical powering and the fact that results were self-reported. Overall, the trial provides promising results in a UK setting with a complex population of adolescents with multi-drug use. Morral AR, McCaffrey DF and Ridgeway G. Effectiveness of communitybased treatments for substance abusing adolescents: 12-month outcomes of youths entering Phoenix Academy or alternative probation dispositions. Psychology of Addictive Behaviour 2004;18(3):257-68. This trial studied 449 adolescent participants (aged 13-17 years) recruited to either Phoenix Academy (a specialist drug abuse programme) or control facilities. All participants were detainees, and were followed-up for 12 months. The trial found that Phoenix Academy was associated with superior substance use and psychological functional outcomes. No difference in crime was detected. The authors noted several limitations such as the use of case-mix approach in place of randomisation, the use of self-reported outcomes, and the uncertainty that the programme is specifically better than other programmes. The authors concluded that further research is needed, which seems appropriate. Methodological Points Most of the trials were conducted in the USA so the generalizability of finding to a UK setting is questionable. The single UK trial was generally well conducted and provides evidence that is directly transferable to UK practice. The UK trial was cluster randomised, reported good follow-up rates (89.5%), and had similar baseline participant characteristics. Intervention Features The type of intervention varied from pharmacological to psychosocial and family interventions. Delivery of interventions was generally by trained personnel, and most interventions were provided on an outpatient basis. The UK trial was based on a single-session one-hour face-to-face motivational interview, which will likely be reproducible in clinical practice, albeit with some training requirements for staff providing the interview. Gaps in Knowledge There are a number of unknown factors in treating adolescents with substance misuse problems: Most of the trial literature came from the USA; hence, the applicability of results to UK practice is uncertain. No evidence was found for interventions specifically targeted at adolescent users of cocaine, psychostimulants, or LSD. Most outcomes were self-reported, which are prone to bias and may overestimate benefits of treatments. The components and factors of the interventions which are most effective are not clear. Many of the interventions were delivered in very controlled conditions with trained personnel, which may not reflect the reality of drug intervention services in practice. There are likely to be subgroups of adolescent drug users that are liable to derive the greatest benefit from interventions, but currently the available literature does not identify these groups. Conclusion The evidence base for interventions targeted at adolescent drug users is sparse; most of the trials were conducted in the USA, only one UK trial was found. The trials were predominantly focussed on mixed drug using populations, but some trials included participants with specific heroin or cannabis usage problems. No trials of interventions exclusively focussed on cocaine, LSD or psychostimulant abuse were found. The evidence from the single UK trial is the most transferable to UK clinical practice and indicates the benefits of a one-hour single-session face-to-face motivational interview for generic drug use in adolescents. There are a number of evidence gaps and further research is warranted. References Baer JS, Garrer SB, Beadnell B, et al. Brief motivational interventions with homeless adolescents: evaluating effects on substance use and service utilisation. Psychology of Addictive Behaviours 2007; 21(4):582-6. Dennis M, Godley SH, Diamond G, et al. The Cannabis Youth Treatment (CYT) Study: Main findings from two randomised trials. J Substance Abuse Treatment 2004; 27:197-213. Lehmann WX. The use of 1-alpha-acetyl-methadol (LAAM) as compared to methadone In the maintenance and detoxification of young heroin addicts. NIDA monograph 1973;8:82-3. Liddle HA, Dakof GA, Parker K, et al. Multidimensional family therapy for adolescent drug abuse: results of a randomised clinical trial. American Journal of Drug and Alcohol Abuse 2001;27(4):651-88. Marsch LA, Bickel WK, Basger GJ, et al. Comparison of pharmacological treatments for opioid-dependent adolescents. Archives of General Psychiatry 2005;62:1157-64. McCambridge J and Strang J. The efficacy of single session motivational interviewing in reducing drug consumption and perceptions of drug related risk and harm among young people: results from a multi-cluster randomised trial. Addiction 2004;99:39-52. Minozzi S, Amato L, Davoli M. Maintenance treatments for opiate dependent adolescents (Review). The Cochrane Library 2009, Issue 2. Minozzi S, Amato L, Davoli M. Detoxification treatments for opiate dependent adolescents (Review). The Cochrane Library 2009, Issue 4. Morral AR, McCaffrey DF and Ridgeway G. Effectiveness of community-based treatments for substance abusing adolescents: 12-month outcomes of youths entering Phoenix Academy or alternative probation dispositions. Psychology of Addictive Behaviour 2004;18(3):257-68. Woody GE, Poole SA, Subramanian G, et al. Extended versus short-term buprenorphine-naloxone for treatment of opiate-addicted youth. JAMA 2008; 300(17):2003-11. Key contact for further information: Dr Catriona Matheson, Centre of Academic Primary Care, University of Aberdeen. e mail: c.i.math@abdn.ac.uk