title: Opioid antagonists under heavy sedation or anaesthesia for opioid withdrawal.
abstract: BACKGROUND
  Withdrawal (detoxification) is necessary prior to drug-free treatment or as the end point of long-term substitution treatment.
  
  
  OBJECTIVE
  To assess the effectiveness of opioid antagonists to induce opioid withdrawal with concomitant heavy sedation or anaesthesia, in terms of withdrawal signs and symptoms, completion of treatment and adverse effects.
  
  
  METHODS
  We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2009), Medline (January 1966 to 11 August 2009), Embase (January 1985 to 2009 Week 32), PsycINFO (1967 to July 2009), and reference lists of articles.
  
  
  METHODS
  Controlled studies of antagonist-induced withdrawal under heavy sedation or anaesthesia in opioid-dependent participants compared with other approaches, or a different regime of anaesthesia-based antagonist-induced withdrawal.
  
  
  METHODS
  One reviewer assessed studies for inclusion, undertook data extraction and assessed quality. Inclusion decisions and the overall process were confirmed by consultation between all authors.
  
  
  RESULTS
  Nine studies (eight randomised controlled trials) involving 1109 participants met the inclusion criteria for the review.Antagonist-induced withdrawal is more intense but less prolonged than withdrawal managed with reducing doses of methadone, and doses of naltrexone sufficient for blockade of opioid effects can be established significantly more quickly with antagonist-induced withdrawal than withdrawal managed with clonidine and symptomatic medications. The level of sedation does not affect the intensity and duration of withdrawal, although the duration of anaesthesia may influence withdrawal severity. There is a significantly greater risk of adverse events with heavy, compared to light, sedation (RR 3.21, 95% CI 1.13 to 9.12, P = 0.03) and probably with this approach compared to other forms of detoxification.
  
  
  CONCLUSIONS
  Heavy sedation compared to light sedation does not confer additional benefits in terms of less severe withdrawal or increased rates of commencement on naltrexone maintenance treatment. Given that the adverse events are potentially life-threatening, the value of antagonist-induced withdrawal under heavy sedation or anaesthesia is not supported. The high cost of anaesthesia-based approaches, both in monetary terms and use of scarce intensive care resources, suggest that this form of treatment should not be pursued.
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: D000777:Anesthetics; D006801:Humans; D006993:Hypnotics and Sedatives; D009270:Naloxone / Q000627:therapeutic use; D009271:Naltrexone / Q000031:analogs & derivatives / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D009294:Narcotics / Q000009:adverse effects*; D009293:Opioid-Related Disorders / Q000188:drug therapy* / Q000209:etiology; D016032:Randomized Controlled Trials as Topic; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000209:etiology*
chemical_list: D000777:Anesthetics; D006993:Hypnotics and Sedatives; D009292:Narcotic Antagonists; D009294:Narcotics; D009270:Naloxone; D009271:Naltrexone; C038981:nalmefene