title: Naltrexone with or without guanfacine for preventing relapse to opiate addiction in St.-Petersburg, Russia.
abstract: BACKGROUND
  Stress is a key precipitant to discontinuing naltrexone and relapsing to opiate abuse. Alpha-2 adrenergic agonists like guanfacine may reduce stress induced craving and have reduced opiate relapse in small clinical trials.
  
  
  METHODS
  This randomized, double blind double dummy placebo-controlled 6-month trial tested oral naltrexone with or without guanfacine for reducing stress and preventing opiate relapse. We randomized 301 patients to: naltrexone 50 mg/day+guanfacine 1 mg/day (n=75) (N/G), naltrexone+guanfacine placebo (N/P) (n=76), naltrexone placebo+guanfacine (n=75) (P/G), and double placebo (n=75) (P/P).
  
  
  RESULTS
  Among the 75 patients in each group the percentage still retained on naltrexone treatment at six months was: N/G 26.7%, N/P 19.7% (p=0.258 to N/G), P/G 6.7% (p<0.05 to both N groups), and P/P 10.7% (p=0.013 to N+G). Guanfacine reduced the severity of stress particularly at weeks 10 and 18. Adverse events (AE) were infrequent (4.7%) without group differences, with most common AEs: headache, poor appetite, insomnia, and dizziness.
  
  
  CONCLUSIONS
  Adding guanfacine to naltrexone did not improve treatment retention or opiate free urines, but it reduced both stress and craving at later time points in treatment, which may be related to stress-induced craving and the animal model of incubation of reinstatement. During treatment, HIV risk, anxiety, and depression reduced among all patients in treatment, regardless of group.
authors.affiliation: St.-Petersburg State Pavlov Medical University, St. Petersburg, Russia; St.-Petersburg Bekhterev Research Psychoneurological Institute, St. Petersburg, Russia.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Krupitsky
authors.forename: Edwin
authors.initials: E
authors.lastname: Zvartau
authors.forename: Elena
authors.initials: E
authors.lastname: Blokhina
authors.forename: Elena
authors.initials: E
authors.lastname: Verbitskaya
authors.forename: Marina
authors.initials: M
authors.lastname: Tsoy
authors.forename: Valentina
authors.initials: V
authors.lastname: Wahlgren
authors.forename: Andrey
authors.initials: A
authors.lastname: Burakov
authors.forename: Dimitry
authors.initials: D
authors.lastname: Masalov
authors.forename: Tatyana N
authors.initials: TN
authors.lastname: Romanova
authors.forename: Vladimir
authors.initials: V
authors.lastname: Palatkin
authors.forename: Arina
authors.initials: A
authors.lastname: Tyurina
authors.forename: Tatyana
authors.initials: T
authors.lastname: Yaroslavtseva
authors.forename: Rajita
authors.initials: R
authors.lastname: Sinha
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kosten
mesh_terms: D000293:Adolescent; D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage*; D000328:Adult; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D016316:Guanfacine / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D009271:Naltrexone / Q000008:administration & dosage*; D009292:Narcotic Antagonists / Q000008:administration & dosage*; D009293:Opioid-Related Disorders / Q000188:drug therapy* / Q000453:epidemiology*; D012426:Russia / Q000453:epidemiology; D055502:Secondary Prevention; D055815:Young Adult
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D009292:Narcotic Antagonists; D016316:Guanfacine; D009271:Naltrexone
keywords: Clinical trial; Guanfacine; Naltrexone; Opiate dependence; Stress