The combination very low-dose naltrexone-clonidine in the management of opioid withdrawal.
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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.We investigated the effects of a VLNTX-clonidine combination in a secondary analysis of data from a double-blind, randomized opioid detoxification trial.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.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.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.
Substance Withdrawal Syndrome
Drug Therapy, Combination
Dose-Response Relationship, Drug
Adrenergic alpha-2 Receptor Agonists
Opiate Substitution Treatment
Published Version (Please cite this version)10.3109/00952990.2011.644003
Publication InfoMannelli, Paolo; Peindl, Kathleen; Wu, Li-Tzy; Patkar, Ashwin A; & Gorelick, David A (2012). The combination very low-dose naltrexone-clonidine in the management of opioid withdrawal. The American journal of drug and alcohol abuse, 38(3). pp. 200-205. 10.3109/00952990.2011.644003. Retrieved from https://hdl.handle.net/10161/20048.
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Associate Professor of Psychiatry and Behavioral Sciences
Professor of Psychiatry and Behavioral Sciences
Assistant Consulting Professor in the Department of Psychiatry and Behavioral Sciences
Professor in Psychiatry and Behavioral Sciences
Education/Training: Pre- and post-doctoral training in mental health service research, psychiatric epidemiology (NIMH T32), and addiction epidemiology (NIDA T32) from Johns Hopkins University School of Public Health (Maryland); Fellow of the NIH Summer Institute on the Design and Conduct of Randomized Clinical Trials.Director: Duke Community Based Substance Use Disorder Research Program.Research interests: COVID-19, Opioid misuse, Opioid overdose, Opioid use disorder
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