The combination very low-dose naltrexone-clonidine in the management of opioid withdrawal.
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.


OBJECTIVE
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
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.
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27705, USA. paolo.mannelli@duke.edu
Paolo
P
Mannelli
Kathleen
K
Peindl
Li-Tzy
LT
Wu
Ashwin A
AA
Patkar
David A
DA
Gorelick
D000293:Adolescent; D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D003000:Clonidine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019468:Disease Management; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008691:Methadone / Q000627:therapeutic use; D009271:Naltrexone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D058850:Opiate Substitution Treatment / Q000379:methods; D009293:Opioid-Related Disorders / Q000188:drug therapy; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000517:prevention & control
D058647:Adrenergic alpha-2 Receptor Agonists; D009292:Narcotic Antagonists; D009271:Naltrexone; D003000:Clonidine; D008691:Methadone