The Combination Very Low-Dose Naltrexone–Clonidine in the Management of Opioid Withdrawal

Abstract

Background: The management of withdrawal absorbs substantial clinical efforts in opioid dependence (OD). The real challenge lies in improving current pharmacotherapies. Although widely used, clonidine causes problematic adverse effects and does not alleviate important symptoms of opioid withdrawal, alone or in combination with the opioid antagonist naltrexone. Very low-dose naltrexone (VLNTX) has been shown to attenuate withdrawal intensity and noradrenaline release following opioid agonist taper, suggesting a combination with clonidine may result in improved safety and efficacy. Objectives: We investigated the effects of a VLNTX–clonidine combination in a secondary analysis of data from a double-blind, randomized opioid detoxification trial. Methods: Withdrawal symptoms and treatment completion were compared following VLNTX (.125 or .25 mg/day) and clonidine (.1–.2 mg q6h) in 127 individuals with OD undergoing 6-day methadone inpatient taper at a community program. Results: VLNTX was more effective than placebo or clonidine in reducing symptoms and signs of withdrawal. The use of VLNTX in combination with clonidine was associated with attenuated subjective withdrawal compared with each medication alone, favoring detoxification completion in comparison with clonidine or naltrexone placebo. VLNTX/clonidine was effective in reducing symptoms that are both undertreated and well controlled with clonidine treatment and was not associated with significant adverse events compared with other treatments. Conclusions and Scientific Significance: Preliminary results elucidate neurobiological mechanisms of OD and support the utility of controlled studies on a novel VLNTX + low-dose clonidine combination for the management of opioid withdrawal.

Portions of this article were presented at the American Society of Addiction Medicine, 42nd Annual Medical Scientific Conference, April 14–17, 2011, in Washington, DC.

• addiction
• detoxification
• antagonist
• adrenergic
• pharmacotherapies

ACKNOWLEDGEMENTS

This research was supported by grant DA15469 from the NIH, National Institute on Drug Abuse (Dr. Mannelli). Dr. Gorelick is supported by the Intramural Research Program, NIH, National Institute on Drug Abuse. The ID number of this study in clintrials.gov is NCT00135759.

Declaration of Interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Notes

Portions of this article were presented at the American Society of Addiction Medicine, 42nd Annual Medical Scientific Conference, April 14–17, 2011, in Washington, DC.