Historique
Article de Périodique
Evaluation of the effects of lofexidine and clonidine on naloxone-precipitated withdrawal in opioid-dependent humans (2003)
(Evaluation des effets de la loféxidine et de la clonidine sur le sevrage précipité à la naloxone chez des personnes dépendantes des opioïdes)
Auteur(s) :
WALSH, S. L. ;
STRAIN, E. C. ;
BIGELOW, G. E.
Année
2003
Page(s) :
427-439
Langue(s) :
Anglais
Refs biblio. :
42
Domaine :
Drogues illicites / Illicit drugs
Résumé :
FRANÇAIS :
L'efficacité de la lofexidine et de la clonidine dans le sevrage à la naltrexone est comparée chez 14 patients volontaires. La conclusion principale montre que ni la lofexidine, ni la clonidine ne supprime l'inconfort subjectif du sevrage ou ne réduit significativement des signes du système autonome tels la rhinorhée ou les larmes.
ENGLISH :
Aims: To examine the efficacy of lofexidine, an alpha2 adrenergic agonist, to suppress opioid withdrawal symptoms in opioid-dependent humans under inpatient laboratory conditions by using a naloxone challenge procedure. Design: Randomized, within-subject, cross-over design with drug administration taking place under double-blind and triple-dummy conditions. Setting: A 14-bed in-patient hospital research unit dedicated to the conduct of behavioral pharmacology studies. Participants: Eight healthy adult volunteers (two female/six male) with histories of polysubstance abuse and current physical dependence on opioids. Intervention: Participants were stabilized onto methadone and maintained on 30 mg/day p.o, throughout the study. Oral placebo, lofexidine (0.4, 0.8 and 1.6 mg, p.o.) and clonidine (0.1 and 0.2 mg, p.o.) were each tested as pre-treatments once in combination with each of three intramuscular naloxone doses (0. 0.1 and 0.3 mg, i.m.) during 18 separate experimental sessions. Measurements: An array of physiological indices (e.g. heart rate, blood pressure, pupil diameter) as well as a number of subjective and observer-rating scales sensitive to opioid withdrawal effects. Findings: As expected, lofexidine and clonidine both produced dose-related decreases in blood pressure and heart rate but few subjective effects; naloxone increased opioid withdrawal signs and symptoms in a dose- and time-dependent fashion. Although both lofexidine and clonidine reduced the cardiovascular response to naloxone challenge, close inspection of the data reveal that this occurred only to the extent that baseline physiological parameters were reduced, while neither drug significantly modified the overall magnitude of the response to naloxone. Moreover, neither lofexidine nor clonidine suppressed the subjective discomfort of opioid withdrawal or significantly reduced other autonomic signs of opioid withdrawal, such as lacrimation or rhinorrhea. Conclusions: These data suggest that lofexidine is well tolerated even at supra-therapeutic acute doses. However, its failure to modify most signs and symptoms of opioid withdrawal suggest that its effective use in spontaneous withdrawal will require concomitant medications for improved therapeutic response. (Review' s abstract)
L'efficacité de la lofexidine et de la clonidine dans le sevrage à la naltrexone est comparée chez 14 patients volontaires. La conclusion principale montre que ni la lofexidine, ni la clonidine ne supprime l'inconfort subjectif du sevrage ou ne réduit significativement des signes du système autonome tels la rhinorhée ou les larmes.
ENGLISH :
Aims: To examine the efficacy of lofexidine, an alpha2 adrenergic agonist, to suppress opioid withdrawal symptoms in opioid-dependent humans under inpatient laboratory conditions by using a naloxone challenge procedure. Design: Randomized, within-subject, cross-over design with drug administration taking place under double-blind and triple-dummy conditions. Setting: A 14-bed in-patient hospital research unit dedicated to the conduct of behavioral pharmacology studies. Participants: Eight healthy adult volunteers (two female/six male) with histories of polysubstance abuse and current physical dependence on opioids. Intervention: Participants were stabilized onto methadone and maintained on 30 mg/day p.o, throughout the study. Oral placebo, lofexidine (0.4, 0.8 and 1.6 mg, p.o.) and clonidine (0.1 and 0.2 mg, p.o.) were each tested as pre-treatments once in combination with each of three intramuscular naloxone doses (0. 0.1 and 0.3 mg, i.m.) during 18 separate experimental sessions. Measurements: An array of physiological indices (e.g. heart rate, blood pressure, pupil diameter) as well as a number of subjective and observer-rating scales sensitive to opioid withdrawal effects. Findings: As expected, lofexidine and clonidine both produced dose-related decreases in blood pressure and heart rate but few subjective effects; naloxone increased opioid withdrawal signs and symptoms in a dose- and time-dependent fashion. Although both lofexidine and clonidine reduced the cardiovascular response to naloxone challenge, close inspection of the data reveal that this occurred only to the extent that baseline physiological parameters were reduced, while neither drug significantly modified the overall magnitude of the response to naloxone. Moreover, neither lofexidine nor clonidine suppressed the subjective discomfort of opioid withdrawal or significantly reduced other autonomic signs of opioid withdrawal, such as lacrimation or rhinorrhea. Conclusions: These data suggest that lofexidine is well tolerated even at supra-therapeutic acute doses. However, its failure to modify most signs and symptoms of opioid withdrawal suggest that its effective use in spontaneous withdrawal will require concomitant medications for improved therapeutic response. (Review' s abstract)
Affiliation :
Dept Psychiatry Behaviour Sci., 5510 Nathan Shock Drive, Baltimore, MD 21224
Etats-Unis. United States.
Etats-Unis. United States.