Detoxification treatments for opiate dependent adolescents
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To assess the effectiveness of any detoxification treatment alone or in combination with psychosocial intervention compared to no intervention, other pharmacological intervention or psychosocial interventions on completion of treatment, reducing the use of substances and reducing health and social status
Background
Several studies have been demonstrated that the adolescent substance abuse is a serious and growing problem (Altobelli 2005). In Europe, estimate of cumulative use of drugs by young people under eighteen vary greatly by Countries, ranging from 3% to 20% (EMCDDA 2005).
School surveys of adolescents in seven Countries of Latin America, found an estimated 5% of the youths in this region have tried drugs (Dortmizer 2004). In the USA, recent household survey data indicate that drugs are used on estimated 9% of 12‐17 years old (SAMHSA 2002). The most common drugs used by young people worldwide are cannabis and inhalants.
The prevalence of use of heroin and other opioids among adolescents has markedly increased in the last decade, reaching levels not observed since the 1960s. The percentage of young between 13 to 18 years old who have used heroin more than doubled between 0.4% and 0.6% in the early 1990s to 1.0% to 1.6% in the recent years (monitoringthefuture 2006).
In USA opioids are the second most commonly abused class of illicit drugs among adolescents, second only marijuana (Marsch 2005). In Australia opioids are the third most used drug after marijuana and stimulants (ecstasy and amphetamines) (AIHW 2005). In the USA, a total of 1.7%, 3.6% and 4.5% of eighth, 10 th and 12 grades, respectively, reported having recreationally used OxyContin (controlled release oxycodone) in 2003. Additionally, in the same year, 2.8% of eight grades, 7.2%of 10 th graders and 10.5% of 12 th graders reported recreational use of Vicodin (hydrocodone bitartrate and acetaminophen) (monitoringthefuture 2006).
In respect of pure heroin, many adolescents initiate use of such pure heroin by snorting it (SAMHSA 2002); however some then progress to injecting it (Nealgus 1998).
These trends and their potential consequences underscore the importance of identifying effective treatments for this growing cohort of opioid dependent adolescents. Numerous medications have been successfully used in the treatment of adolescents with a broad array of psychiatric disorders (Hunt 1990; Kaminer 1995). In contrast medications have been infrequently used in treating substance abuse disorders among adolescents, nevertheless they have generally been shown to be a promising component of such interventions (Kaminer 1995).
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 when young people must be treated probably is necessary monitoring the interventions in order to adapt them to this specific population. To our knowledge no studies have been published examining systematically how to monitor these interventions in this specific sub‐population. Despite this need, no research has been conducted to systematically characterize or evaluate treatment interventions for adolescent heroin and opioid abusers, (Hopfer 2002). Managed withdrawal, or detoxification, is not in itself a treatment for dependence (Lipton 1983; Mattick 1996) but detoxification remains a required first step for many forms of longer‐ term treatment (Kleber 1982). Withdrawal symptoms, particularly drug craving, may continue to be experienced for weeks and even for months after detoxification, and the period of recovery from dependence is typically influenced by a range of psychological, social and treatment related factors.
Different pharmacological agents have been used as detoxification agents to ameliorate withdrawal symptoms, however, the rate of completion of detoxification tends to be low, and rates of relapse to opioid use following detoxification are high (Gossop 1989; Valliant 1988).
In the published literature we didn't found any review assessing the effectiveness of detoxification treatment for adolescent. Many other Cochrane systematic reviews have been published on the effectiveness of various detoxification treatment: methadone(Amato 2005), buprenorphine (Gowing 2006) , alpha adrenergic (Gowing 2004), opioid antagonists with minimal sedation (Gowing 2006 a) and under heavy sedation (Gowing 2006 b), psychosocial combined with detoxification treatment (Amato 2004) and one review comparing inpatient versus outpatient settings for opioid detoxification (Day 2005) but none address the question of the effectiveness of treatments for adolescents subjects.
Objectives
To assess the effectiveness of any detoxification treatment alone or in combination with psychosocial intervention compared to no intervention, other pharmacological intervention or psychosocial interventions on completion of treatment, reducing the use of substances and reducing health and social status
Methods
Criteria for considering studies for this review
Types of studies
Randomised controlled trials and controlled clinical trials
Types of participants
Opiate dependent adolescents (13‐18 years)
No restriction for subjects with physical or psychological illness
Types of interventions
Experimental intervention:
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Any pharmacological interventions (methadone, buprenorphine, adrenergic agonists, symptomatics) alone or associated with psychosocial intervention aimed at detoxification
Control intervention:
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No intervention,
-
Other pharmacological interventions
-
Psychosocial interventions alone
Types of outcome measures
Primary outcomes
(1) Dropouts measured as number of subjects that did not complete the detoxification treatment
(2) use of primary substance measured as number of subjects with opiate positive urynalisis during and at the end of treatment or self report data
(3) Acceptability of the treatment as a) duration and severity of signs and symptoms of withdrawal, including patient self‐rating, b) side effects;
(4) results at follow up measured as number of subjects relapsed at the end of follow up
Secondary outcomes:
(5) engagement in further treatment measured as number of subjects that are enrolled in any psychosocial or pharmacological treatment
(6) Use of other substances of abuse
(7) Overdose fatal or nonfatal
(8) Criminal activity
(9) Social functioning (integration at school or at work, family relationship)
Types of comparisons foreseen
-
any detoxification treatment vs no treatment
-
any detoxification treatment vs other pharmacological treatment (e.g. methadone versus buprenorphine)
-
any pharmacological treatment plus psychosocial treatment vs any pharmacological treatment alone
-
any detoxification treatment vs any psychosocial treatment
Search methods for identification of studies
Electonic searches
We will undertake a comprehensive search to identify all relevant studies. Relevant trials will be obtained from the following sources:
(1) The Cochrane Central Register of Controlled Trials (CENTRAL‐ The Cochrane Library, most recent)
(2) PubMed (from 1966 ‐ to present)
(3) EMBASE (from 1980 ‐ to present )
(4) CINAHL (1982‐ to present)
We will compile detailed search strategies for each database searched. These will be based on the search strategy developed for PubMed but revised appropriately for each database to take account of differences in controlled vocabulary and syntax rules.
Search strategy for PubMed database:
1. exp opioid‐related disorders/
2. (drug or substance) and (use* or abuse* or misuse* or addict* or dependen* or disorder*)
3. ((opioid*) and (abuse* or addict* or dependen*))
4. (detoxifi* or desintoxi* or disintoxi* or disintossi*)
5. 1 or 2 or 3 or 4
6. exp heroin/
7. heroin.ti,ab
8.( opioid* or opiate*)
9. exp methadone/
10. methadone
11. 6 or 7 or 8 or 9 or 10
combined with the phases 1 & 2 of the Cochrane Sensitive Search Strategy for the identification of RCTs as published in Appendix 5b2, Cochrane Handbook for Systematic Reviews of Interventions:
12.randomized controlled trial.pt.
13.randomized controlled trials/
14.controlled clinical trial.pt.
15.random allocation/
16.double blind method/
17.single blind method/
18. 12 or 13 14 or 15 or 16 or 17
19. clinical trial.pt.
20. exp clinical trials/
21.((singl* or doubl* or trebl* or tripl*) and (blind* or mask*))
22. exp PLACEBOS/
23. placebo*
24. random*
25. exp Research Design/
26. 19 or 20 or 21 or 22 or 23 or 24 or 25
27. 18 or 26
28. adolescent/exp
29. adolescen*
30. teen*
31. (young people)
32. (young adult)
33. (early adult)
34. (youth)
35. 28 or 29 or 30 or 31 or 32 or 33 or 34
36. 5 and 11
37. 36 and 27 and 35
38. limit 37 to Human
References to ongoing and recently finished clinical trials are identified by searching the National Research Register, IFPMA Clinical Trials Database which contains ClinicalTrials.gov, Centerwatch, Current‐Controlled‐Trials and ClinicalStudyResults.gov, Osservatorio Nazionale sulla Sperimentazione Clinica dei Medicinali.
Proceedings are searched from the following meetings on addiction: Annual Scientific Meeting of the College on Problems of Drug Dependence, European College of Neuropsychopharmacology, American Psychiatric Association.
Manual searches
We will search the reference lists of addiction textbooks, review articles and relevant trials. We will also contact investigators seeking information about unpublished or incomplete trials.
All searches will include non‐English language literature and studies with English abstracts will be assessed for inclusion. When considered likely to meet inclusion criteria, studies will be translated.
Data collection and analysis
Study selection:
One reviewer (SM) will inspect the search hits by reading titles and abstracts. Each potentially relevant study located in the search will be obtained in full text and assessed for inclusion independently by three reviewers (SM, LA, EP). Doubts will be solved by discussion between the reviewers.
Assessment of the methodological quality:
Study quality will be assessed according to the criteria indicated in Cochrane Reviews Handbook 4.2 (Cochrane Handboook);
Two reviewers (SM, EP) will assess the quality of included studies. Any doubt about how to rate the studies will be resolved by discussion between the reviewers.
Selection bias: empirical research has shown that lack of adequate allocation concealment is associated with bias (Chalmers 1993; Moher 1998; Moher 1999; Schulz 1995). Indeed, concealment has been found to be more important in preventing bias than other components of allocation, such as the generation of the allocation sequence.
Performance bias: systematic differences in the care provided to the participants in the comparison groups and the placebo effect could effectively take place in the addiction field. Blinding of providers avoids co intervention whereas blinding of participants avoids contamination, systematic differences in compliance, systematic differences in the placebo effect and detection bias.
Attrition bias: loss of follow up and drop out from the study is one of the bigger problem in the field of addiction; in fact the retention in treatment is very often the primary outcome measure in these trials; for these reason the information on people who left the study will not used as a validity criterion.
Detection bias: t o keep blind the people who will assess outcomes is particularly important when subjective outcome measures are used, but this is not the case for these studies, where the primary outcomes are the retention in treatment rate or the use of substances measured by Bioanalysis.
Selection bias and performance bias will be assessed and rated as follow:
(1) Selection bias: allocation concealment
A: adequate allocation concealment, central randomizations (e.g. allocation by a central office unaware of subject characteristics), pre‐numbered or coded identical bottles or containers which are administered serially to participants, drug prepared by the pharmacy, serially numbered, opaque, sealed envelopes, on‐site computer system combined with allocations kept in a locked unreadable; computer file that can be accessed only after the characteristics of an enrolled participant have been entered or other description that contained elements convincing of concealment.;
B: unclear allocation concealment: when the authors either did not report an allocation concealment approach at all or report an approach that did not fall in the category A or C.
C: inadequate allocation concealment: alternation or reference to case numbers, dates of birth, day of the week. Any procedure that is entirely transparent before allocation, such as an open list of random numbers or other description that contained elements convincing of not concealment
(2) Performance bias: blinding of those providing and receiving the intervention
A: double blind
B: single blind (blinding of participants)
C: unclear
D: no blinding
Studies with adequate allocation concealment will be classified as A: low risk of bias, studies with unclear allocation concealment will be classified as B: moderate risk of bias and studies with inadequate allocation concealment will be classified as C: high risk of bias
The methodological quality will not be used as a criterion for inclusion; in order to assess the effect of the low quality studies we will perform a sensitivity analysis, either including or excluding the classes C ones from meta‐analysis.
Data extraction:
Data will be extracted independently by two reviewers (SM, EP). Any disagreement will be discussed. Key findings will be summarized narratively in the first instance and assessed for meta‐analysis where possible.
Data synthesis:
Dichotomous outcomes will be analysed calculating the Relative risk (RR) for each trial with the uncertainty in each result being expressed by their confidence intervals. . Continuous outcomes will be analysed calculating the WMD with 95%CI. The RR or the WMD from the individual trials will be combined through meta‐analysis where possible (comparability of intervention and outcomes between trials) using a fixed effect model unless there will be significant heterogeneity, in which case a random effect model will be used. A P‐value of the chi‐square test less than 0.05 indicates a significant heterogeneity. We will not use data presented as number of positive urine tests over total number of tests in the experimental and control group as measure of substance abuse. This is because using tests instead of the participants as the unit of analysis violates the hypothesis of independence among observations. In fact, the results of tests done in each participant are not independent.
Funnel plots (plots of the effect estimate from each study against the sample size or effect standard error) will be used to assess the potential for bias related to the size of the trials, which could indicate possible publication bias.
