title: Opioid antagonists with minimal sedation for opioid withdrawal.
abstract: BACKGROUND
  Managed withdrawal is a necessary step prior to drug-free treatment or as the end point of long-term substitution treatment.
  
  
  OBJECTIVE
  To assess the effectiveness of opioid antagonists in combination with minimal sedation to manage opioid withdrawal.
  
  
  METHODS
  We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2008), MEDLINE (January 1966-July 2008), EMBASE (January 1985-2008 Week 31), PsycINFO (1967 to 7 August 2008) and reference lists of articles.
  
  
  METHODS
  Controlled studies of interventions involving the use of opioid antagonists in combination with minimal sedation to manage withdrawal in opioid-dependent participants compared with other approaches or different opioid antagonist regimes.
  
  
  METHODS
  One author assessed studies for inclusion and undertook data extraction. Inclusion decisions and the overall process were confirmed by consultation between all authors.
  
  
  RESULTS
  Nine studies (6 randomised controlled trials), involving 837 participants, met the inclusion criteria for the review.The quality of the evidence is low, but suggests that withdrawal induced by opioid antagonists in combination with an adrenergic agonist is more intense than withdrawal managed with clonidine or lofexidine alone, while the overall severity is less. Delirium may occur following the first dose of opioid antagonist, particularly with higher doses (> 25mg naltrexone).In some situations antagonist-induced withdrawal may be associated with significantly higher rates of completion of treatment, comp[ared to withdrawal managed primarily with adrenergic agonists. However, this outcome has not been produced consistently, and the extent of any benefit is highly uncertain.
  
  
  CONCLUSIONS
  The use of opioid antagonists combined with alpha(2)-adrenergic agonists is a feasible approach to the management of opioid withdrawal. However, it is unclear whether this approach reduces the duration of withdrawal or facilitates transfer to naltrexone treatment to a greater extent than withdrawal managed primarily with an adrenergic agonist.A high level of monitoring and support is desirable for several hours following administration of opioid antagonists because of the possibility of vomiting, diarrhoea and delirium.Further research is required to confirm the relative effectiveness of antagonist-induced regimes, as well as variables influencing the severity of withdrawal, adverse effects, the most effective antagonist-based treatment regime, and approaches that might increase retention in subsequent naltrexone maintenance treatment.
authors.affiliation: Discipline of Pharmacology, University of Adelaide, Frome Road, Adelaide, South Australia, Australia, 5005.
authors.forename: Linda
authors.initials: L
authors.lastname: Gowing
authors.forename: Robert
authors.initials: R
authors.lastname: Ali
authors.forename: Jason M
authors.initials: JM
authors.lastname: White
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003000:Clonidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D009270:Naloxone / Q000627:therapeutic use; D009271:Naltrexone / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D009293:Opioid-Related Disorders / Q000534:rehabilitation*; D016032:Randomized Controlled Trials as Topic; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
chemical_list: D000316:Adrenergic alpha-Agonists; D009292:Narcotic Antagonists; D009270:Naloxone; D009271:Naltrexone; D003000:Clonidine