Methadone Maintenance Dosing Guideline for Opioid Dependence, a Literature Review

Department of Psychiatry, Emory University, School of Medicine, Decatur, GA 30033, USA.
Journal of Addictive Diseases (Impact Factor: 1.46). 01/2010; 29(1):1-14. DOI: 10.1080/10550880903436010
Source: PubMed


To date, methadone dosing is still an issue of debate and controversy among clinicians who are involved in methadone maintenance programs. The authors conducted a literature review to update clinicians about this issue and provide recommendations for proper methadone dosing. Studies eligible for inclusion in the review were retrieved from the PubMed database by searching for reports published between 1990 and September 2008 using the major medical subject headings Methadone (all fields) and dose. Only articles written in English were included. Additional reports were identified from the reference lists of retrieved articles and by manual review of the tables of contents of journals on drug of abuse included in the psychiatry and substance abuse subject category listing 2008 of the Journal Citation Reports. Abstracts of medical meetings were excluded. Twenty-four articles were included in the review. Twelve are randomized, controlled, or double-blind clinical trials, 10 are non-randomized and observational studies, and 2 are meta-analyses. Currently, the consensus is to have a goal for methadone dosing in the range of 60 to 100 mg daily. For patients who continue to use illicit opiates while prescribed this dose range, clinicians may consider doses greater than 100 mg daily. However, this is not the current consensus but rather is based on the limited promising data the authors have; it could be considered if the benefits outweigh the risks for some patients.

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Available from: Ayman Fareed, Mar 07, 2014
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    • "Another line of evidence that suggests ibogaine does not act as an orthosteric MOR agonist is that dosages equivalent to those used in opioid detoxification does not produce signs of overdose in individuals who lack tolerance to opioids [5,6], as would be expected if it were a MOR agonist. The oral dose of the MOR agonist methadone that is generally recommended in the maintenance treatment of opioid dependence is in the range 60 to 100mg [37], and substantially exceeds the LD50 of methadone in humans who are not pharmacologically tolerant to opioids, which is estimated to be less than 50 mg [38]. However, doses of ibogaine equivalent to those used to detoxify addicts do not produce opioid overdose in non-tolerant individuals such as Bwiti initiates, or those taking ibogaine for substance use indications other than opioid dependence. "
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    ABSTRACT: The iboga alkaloids are a class of small molecules defined structurally on the basis of a common ibogamine skeleton, some of which modify opioid withdrawal and drug self-administration in humans and preclinical models. These compounds may represent an innovative approach to neurobiological investigation and development of addiction pharmacotherapy. In particular, the use of the prototypic iboga alkaloid ibogaine for opioid detoxification in humans raises the question of whether its effect is mediated by an opioid agonist action, or if it represents alternative and possibly novel mechanism of action. The aim of this study was to independently replicate and extend evidence regarding the activation of μ-opioid receptor (MOR)-related G proteins by iboga alkaloids.
    Full-text · Article · Oct 2013 · PLoS ONE
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    • "These findings could be partially explained by the Croatian treatment model: implementation of treatment primarily in non-hospital settings characterized by a high degree of accessibility to care, which had to be balanced with relatively lower methadone doses in order to assure safety of the treatment in the out-patient setting (8). To support this thesis, the endpoint methadone dose in this study was 50 mg for both groups of patients, which was lower than the daily methadone dose required for stable maintenance, which ranges from 60 mg to 100 mg, as recommended in the literature (15,16). "
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    ABSTRACT: Aim To determine the risk factors for fatal outcome in patients with opioid dependence treated with methadone at the primary care level. Methods A group of 287 patients with opioid dependence was monitored prospectively from 1995 to 2007. At the beginning of the study, we collected the data on patient baseline characteristics, treatment characteristics, and living environment. At the annual check-up, we collected the data on daily methadone dose, method of methadone therapy administration, and family physician’s assessment of the patient’s drug use status. Results Out of 287 patients, 8% died. Logistic regression analysis showed that the predictors of fatal outcome were continuation of drug use during previous therapeutic attempts (odds ratio [OR], 19.402; 95% confidence interval [CI], 1.659-226.873), maintenance therapy as the planned treatment modality (OR, 3.738; 95% CI, 1.045-13.370), living in an unstable relationship (OR, 9.275; 95% CI, 2.207-38.984), and loss of continuity of care (OR, 12.643; 95% CI, 3.001-53.253). Conclusion The patients presenting these risk factors require special attention. It is important for family physicians to insist on compliance with the treatment protocol and intervene when they lose contact with the patient to prevent the fatal outcome.
    Full-text · Article · Feb 2013 · Croatian Medical Journal
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    • "Methadone is a synthetic opioid best known for its use in the treatment of opioid dependence and is considered a second-line option in the setting of neuropathic pain in cancer patients.96,97 Methadone occurs in R- and S-enantiomeric forms, with essentially all of its activity due to R-methadone. "
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    ABSTRACT: Translating pharmacogenetics to clinical practice has been particularly challenging in the context of pain, due to the complexity of this multifaceted phenotype and the overall subjective nature of pain perception and response to analgesia. Overall, numerous genes involved with the pharmacokinetics and dynamics of opioids response are candidate genes in the context of opioid analgesia. The clinical relevance of CYP2D6 genotyping to predict analgesic outcomes is still relatively unknown; the two extremes in CYP2D6 genotype (ultrarapid and poor metabolism) seem to predict pain response and/or adverse effects. Overall, the level of evidence linking genetic variability (CYP2D6 and CYP3A4) to oxycodone response and phenotype (altered biotransformation of oxycodone into oxymorphone and overall clearance of oxycodone and oxymorphone) is strong; however, there has been no randomized clinical trial on the benefits of genetic testing prior to oxycodone therapy. On the other hand, predicting the analgesic response to morphine based on pharmacogenetic testing is more complex; though there was hope that simple genetic testing would allow tailoring morphine doses to provide optimal analgesia, this is unlikely to occur. A variety of polymorphisms clearly influence pain perception and behavior in response to pain. However, the response to analgesics also differs depending on the pain modality and the potential for repeated noxious stimuli, the opioid prescribed, and even its route of administration.
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