Research project DR/17 (Research action DR)
1. Problematic.
Treatment of opiate dependence is no longer limited to abstinence or its management, but is also based on substitution or maintenance treatments (Reggers et al., 2000). There substitution treatments are numerous and aim at different goals. Many substitution drugs, complete or partial agonists, are available for opiates dependence treatments: methadone, buprenorphine – specially in France – , LAAM (levo-alpha acetyl methadol), but also codeine (or dihydrocodeine) particularly used in Germany. Furthermore, other agents were used in a limited fashion such as dextromoramide, morphine (oral or intravenous), burgodin, etc.
For each of these drugs, there is a variability in dosage (Faggiano et al., 2003), in treatment length (Amato et al., 2003), but there are also noticeable differences in their objective and subjective effects.Clarck et al., 2003; Mattick et al., 2003).
Even if methadone is the main substitution treatment, used since decades worldwide, with a demonstrated clinical effectiveness and a relative inocuity in different settings (Bertschy, 1995; Parrino, 1994), it is not clear whether methadone is more efficient than other available agnonists whoever the patient or whatever the support might be. It has furthermore to be noted that methadone substitution treatment holds a number of negative characteristics that potentially influence its effectiveness (Mattick, 2003), the least being the persistence of a substance dependence.
Providing evidence-based datawith the highest level of current evidence on each substitution treatment efficacy is a necessity.
Therefore, available controlled trials will be analysed with the rigorous meta analytical methods described by Cucherat (1997). This strategy will allow to assess the efficacy of these treatments. A less quantitative but structured literature review, will highlight the literature data that do not match with meta analysis applicable standards. This will allow to stick to the best practical reality in the application of substitution treatments and their effectiveness.
2. Aims.
2.1. Main aim.
To compare the relative efficacy of substitution treatments: with no other treatment; with other treatments; with other substitution treatment
2.2. Secondary aim.
To define efficient dosages for each substance (mainly methadone and buprenorphine); to assess the advantages as well as the negative aspects of their use ; to distinguish their efficacy (their effects in controlled studies) from their effectiveness (their effects in clinical practice).
3. Methodology
3.1. Trials selection.
This work will start with a systematic search in the available informatic databases (COCHRANE, MEDLINE, PSYchinfo, EMBASE) of randomised controlled trials (RCT’s) on substitution treatments. Retained trials will be systematically reviewed in order to be includedif they meet underneath defined criteria. Non-randomised studies or randomised controlled trials presenting much too differences with the majority of other ones will be included in the qualitative analysis.
2.2. Outcome.
The judgement criteria taken into account will be binary or continuous. All come from a study by Clarck et al. (2003) that define them as the most frequently used in RCT’s on substitution treatments.
Among binary criteria will be found: treatment, continuous abstinence from opiates, secondary use of another drug.
Following continuous judgement criteria will be gathered: reduction of the opiates use; functioning in various domain of life (social, employment, etc.); quality of life measures.
In summary, the investigation will follow the following methodology:
1. Trials search.
2. Trials selection.
2. Trials methodologic quality quantification.
3. Quantitative and qualitative analyses.
4. Sensitivity analyses.
5. Discussion, conclusions, perspectives and recommandations.
3. Conclusion.
In the approach of opiate dependence treatments, substitution treatments, prior to withdrawal, have an important place. Their objectives, multiple, aim notably at reducing the severity of medico-psycho-social disabilities associated with dependence, which is a fundamental predictive element of a good long-term outcome (NIH, 1998). Therefore a systematic study of the place of substitution in the global strategy, of the substances that can serve this approach, of the needed dosages and lengths of treatments and of the characteristics of patients who can be included are as many parameters that have to be quantified in order to obtain no more a unimodal but a plural approach that may fit better to various patients problems.
4. References.
Amato et al. (2003). Methadone at tapered... Cochrane Database of Systematic Reviews. 3.
Bertschy, G. (1995) pratique des traitements à la méthadone. Paris : Masson.
Clark et al. (2003). LAAM maintenance vs methadone maintenance... Cochrane,Database 3
Cucherat, M. (1997). Méta-analyse des essais thérapeutiques. Paris : Masson.
Faggiano et al. (2003). Methadone maintenance at different dosages... Cochrane Database 3
Mattick et al. (2003). Buprenorphine maintenance vs placebo or... Cochrane DataBase 3
Parino, M. (1994). Traitement à la méthadone. Genève : Editions Médecine et Hygiène.
Reggers et al. (2000). Recommandations dans le traitement... Rev. Med. Liege ; 55 :409-416
Intérêt des traitements de substitution dans la dépendance aux opiacés : rapport final
Reggers, Jean - Somers, Laurent - Richy, Florent ... et al Gent : Academia Press, 2006 (PB6177)
Efficacité et efficience des molécules substitutives dans le traitement de la dépendance aux opiacés : résumé
Reggers, Jean - Somers, Laurent - Richy, Florent ... et al Bruxelles : Politique scientifique fédérale, 2012 (SP2514)
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Effectiviteit en efficiëntie van medicamenten gebruikt voor substitutie : samenvatting
Reggers, Jean - Somers, Laurent - Richy, Florent ... et al Brussel : Federaal Wetenschapsbeleid, 2012 (SP2515)
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Effectiveness and efficiency of substitutive drugs in opiates addiction treatment : summary
Reggers, Jean - Somers, Laurent - Richy, Florent ... et al Brussels : Federal Science Policy, 2012 (SP2516)
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