Injectable extended-release naltrexone for opioid dependence

Throckmorton, Douglas C.; Temple, Robert; Rappaport, Bob A.; Roca, Rigoberto; Winchell, Celia

doi:10.1016/s0140-6736(11)61332-9

Cited by 1 publication

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“…The suggestion that NI may be associated with inordinate death rates, as has come from certain uncontrolled case series 108,109 has generated significant controversy and has formally been refuted by many authorities. 103,[110][111][112][113][114][115][116][117] As noted above, elevated death rates have not been a feature of any of the randomized trials of NI, nor has it been problematic either in 45,000 US patients treated, nor in the follow-up period after completion of some of the large Russian clinical trials. 103 Moreover the issue has been carefully addressed in at least two clinical reviews of large case series.…”

Section: Mortality Studiesmentioning

confidence: 99%

Epidemiologic and Molecular Pathophysiology of Chronic Opioid Dependence and the Place of Naltrexone Extended-Release Formulations in its Clinical Management

Reece

2012

Subst�Abuse

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Naltrexone implants and depot injections (NI) are a novel form of treatment for opiate dependence (OD). Major questions relate to their absolute and relative efficacy and safety. Opportunely, six recent clinical trial data from several continents have uniformly provided dramatic evidence of the potent, dose-related and highly significant efficacy of NI, with minimal or manageable accompanying toxicity and safety concerns. The opiate-free lifestyle is attained significantly more often with NI adjusted O.R. = 6.00 (95% C.I. 3.86–9.50), P < 10−10. Other drug use and drug craving are also rapidly reduced. The optimum manner in which to commence NI remains to be established. Of particular relevance is the relative safety of NI compared to the chronic opiate agonists (COA) usually employed, as the long-term toxicity of COA is only just being elucidated. Large population-based studies have found elevated rates of cardiovascular disease, six cancers, liver and respiratory disease, and all-cause mortality in COA. Whilst opiates have been shown to trigger numerous molecular pathways, the most interesting is the demonstration that the opiate morphinan’s nucleus binds to the endotoxin groove of the TLR4-MD2 heterodimer. This has the effect of triggering a low grade endotoxaemic-like state, which over time may account for these protean clinical findings, an effect which is reversed by opiate antagonists. This emerging evidence suggests an exciting new treatment paradigm for OD and a corresponding increase in the role of NI in treatment.

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Section: Mortality Studiesmentioning

confidence: 99%

Epidemiologic and Molecular Pathophysiology of Chronic Opioid Dependence and the Place of Naltrexone Extended-Release Formulations in its Clinical Management

Reece

2012

Subst�Abuse

View full text Add to dashboard Cite

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Injectable extended-release naltrexone for opioid dependence

Cited by 1 publication

References 1 publication

Epidemiologic and Molecular Pathophysiology of Chronic Opioid Dependence and the Place of Naltrexone Extended-Release Formulations in its Clinical Management

Epidemiologic and Molecular Pathophysiology of Chronic Opioid Dependence and the Place of Naltrexone Extended-Release Formulations in its Clinical Management

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