Generated Narrative: Citation 179637 version: 21; Last updated: 2025-10-13 12:34:35+0000 Profile: JournalArticleCitation ArtifactPublicationStatus: Active url: Citation 18508207 A Phase 3 placebo-controlled, double-blind, multi-site trial of the alpha-2-adrenergic agonist, lofexidine, for opioid withdrawal. identifier: FEvIR Object Identifier/179637, https://pubmed.ncbi.nlm.nih.gov/18508207, <a href="http://terminology.hl7.org/7.0.1/NamingSystem-uri.html" title="As defined by RFC 3986 (http://www.ietf.org/rfc/rfc3986.txt)(with many schemes defined in many RFCs). For OIDs and UUIDs, use the URN form (urn:oid:(note: lowercase) and urn:uuid:). See http://www.ietf.org/rfc/rfc3001.txt and http://www.ietf.org/rfc/rfc4122.txt #xD;#xA;#xD;#xA;This oid is used as an identifier II.root to indicate the the extension is an absolute URI (technically, an IRI). Typically, this is used for OIDs and GUIDs. Note that when this OID is used with OIDs and GUIDs, the II.extension should start with urn:oid or urn:uuid: #xD;#xA;#xD;#xA;Note that this OID is created to aid with interconversion between CDA and FHIR - FHIR uses urn:ietf:rfc:3986 as equivalent to this OID. URIs as identifiers appear more commonly in FHIR.#xD;#xA;#xD;#xA;This OID may also be used in CD.codeSystem.">Uniform Resource Identifier (URI)/urn:oid:2.16.840.1.113883.4.642.40.44.15.3 version: 1.0.0-ballot3 title: 18508207 A Phase 3 placebo-controlled, double-blind, multi-site trial of the alpha-2-adrenergic agonist, lofexidine, for opioid withdrawal. status: Active date: 2026-01-13 11:03:07+0000 author: Computable Publishing®: MEDLINE-to-FEvIR Converter: publisher: HL7 International / Clinical Decision Support contact: HL7 International / Clinical Decision Support: http://www.hl7.org/Special/committees/dss description: This Citation Resource is referenced in an example for the EBMonFHIR Implementation Guide. UseContexts - Code Value[x] * Citation Classification Type: fevir-platform-use (FEvIR Platform Use) Medline Base jurisdiction: World copyright: https://creativecommons.org/licenses/by-nc-sa/4.0/ approvalDate: 2008-12-16 lastReviewDate: 2021-10-20 classification type: Citation Source classifier: MEDLINE classification type: MEDLINE Citation Owner classifier: National Library of Medicine, Index Section currentState: Medline Citation Status of Medline, PubMed PublicationStatus of ppublish statusDate activity: PubMed Pubstatus of Received period: ?? --> 2007-11-22 statusDate activity: PubMed Pubstatus of Revised period: ?? --> 2008-04-08 statusDate activity: PubMed Pubstatus of Accepted period: ?? --> 2008-04-09 statusDate activity: PubMed Pubstatus of Pubmed period: ?? --> 2008-05-30 09:00:00+0000 statusDate activity: PubMed Pubstatus of Medline period: ?? --> 2008-12-17 09:00:00+0000 statusDate activity: PubMed Pubstatus of Entrez period: ?? --> 2008-05-30 09:00:00+0000 statusDate activity: PubMed Pubstatus of PMC release period: ?? --> 2009-09-01 citedArtifact identifier: https://pubmed.ncbi.nlm.nih.gov/18508207, mid/NIHMS61453, https://www.ncbi.nlm.nih.gov/pmc//PMC2613766, https://doi.org/10.1016/j.drugalcdep.2008.04.002, pii/S0376-8716(08)00140-3 Titles - Type Text * Primary title A Phase 3 placebo-controlled, double-blind, multi-site trial of the alpha-2-adrenergic agonist, lofexidine, for opioid withdrawal. Abstracts - Type Text * Primary human use CONTEXT: Lofexidine is an alpha-2-adrenergic receptor agonist that is approved in the United Kingdom for the treatment of opioid withdrawal symptoms. Lofexidine has been reported to have more significant effects on decreasing opioid withdrawal symptoms with less hypotension than clonidine. OBJECTIVE: To demonstrate that lofexidine is well tolerated and effective in the alleviation of observationally defined opioid withdrawal symptoms in opioid dependent individuals undergoing medically supervised opioid detoxification as compared to placebo. DESIGN: An inpatient, Phase 3, placebo-controlled, double-blind, randomized multi-site trial with three phases: (1) opioid agonist stabilization phase (days 1-3), (2) detoxification/medication or placebo phase (days 4-8), and (3) post detoxification/medication phase (days 9-11). SUBJECTS: Sixty-eight opioid dependent subjects were enrolled at three sites with 35 randomized to lofexidine and 33 to placebo. MAIN OUTCOME MEASURE: Modified Himmelsbach Opiate Withdrawal Scale (MHOWS) on study day 5 (second opioid detoxification treatment day). RESULTS: Due to significant findings, the study was terminated early. On the study day 5 MHOWS, subjects treated with lofexidine had significantly lower scores (equating to fewer/less severe withdrawal symptoms) than placebo subjects (least squares means 19.5+/-2.1 versus 30.9+/-2.7; p=0.0019). Lofexidine subjects had significantly better retention in treatment than placebo subjects (38.2% versus 15.2%; Log rank test p=0.01). CONCLUSIONS: Lofexidine is well tolerated and more efficacious than placebo for reducing opioid withdrawal symptoms in inpatients undergoing medically supervised opioid detoxification. relatesTo type: Cites classifier: Journal Article citation: Aghajanian GK. Central noradrenergic neurons: a locus for the functional interplay between alpha-2 adrenoceptors and opiate receptors. J Clin Psychiatry. 1982;43(6 Pt 2):20–24. relatesTo type: Cites classifier: Journal Article citation: Aghajanian GK. Tolerance of locus coeruleus neurones to morphine and suppression of withdrawal response by clonidine. Nature. 1978;276(5684):186–188. relatesTo type: Cites classifier: Journal Article citation: Aigner A, Schmidt U. Lofexidine, a new, antihypertensive imidazoline derivative. Clinical profile of action with single-drug treatment and in combination with hydrochlorothiazide. Arzneimittelforschung. 1982;32(8a):976–983. relatesTo type: Cites classifier: Journal Article citation: Akhurst JS. The use of lofexidine by drug dependency units in the United Kingdom. Eur Addict Res. 1999;5(1):43–49. relatesTo type: Cites classifier: Journal Article citation: Arnsten AF, Cai JX, Goldman-Rakic PS. The alpha-2 adrenergic agonist guanfacine improves memory in aged monkeys without sedative or hypotensive side effects: evidence for alpha-2 receptor subtypes. J. Neurosci. 1998;8(11):4287–4298. relatesTo type: Cites classifier: Journal Article citation: Aston-Jones G, Hirata H, Akaoka H. Local opiate withdrawal in locus coeruleus in vivo. Brain Res. 1997;765(2):331–336. relatesTo type: Cites classifier: Journal Article citation: Bearn J, Gossop M, Strang J. Randomised double-blind comparison of lofexidine and methadone in the in-patient treatment of opiate withdrawal. Drug Alcohol Depend. 1996;43(1–2):87–91. relatesTo type: Cites classifier: Journal Article citation: Bearn J, Gossop M, Strang J. Accelerated lofexidine treatment regimen compared with conventional lofexidine and methadone treatment for in-patient opiate detoxification. Drug Alcohol Depend. 1998;50:227–232. relatesTo type: Cites classifier: Journal Article citation: Buccafusco JJ, Marshall DC. Dorsal root lesions block the expression of morphine withdrawal elicited from the rat spinal cord. Neurosci Lett. 1985;59(3):319–324. relatesTo type: Cites classifier: Journal Article citation: Carnwath T, Hardman J. Randomised double-blind comparison of lofexidine and clonidine in the out-patient treatment of opiate withdrawal. Drug Alcohol Depend. 1998;50(3):251–254. relatesTo type: Cites classifier: Journal Article citation: Freedman JE, Aghajanian GK. Opiate and alpha 2-adrenoceptor responses of rat amygdaloid neurons: co-localization and interactions during withdrawal. J Neurosci. 1985;5(11):3016–3024. relatesTo type: Cites classifier: Journal Article citation: Gold MS, Pottash AC, Sweeney DR, Extein I, Annitto WJ. Opiate detoxification with lofexidine. Drug Alcohol Depend. 1981;8(4):307–315. relatesTo type: Cites classifier: Journal Article citation: Gonzalez G, Oliveto A, Kosten TR. Combating opiate dependence: a comparison among the available pharmacological options. Expert Opin Pharmacother. 2004;5(4):713–725. relatesTo type: Cites classifier: Journal Article citation: Gossop M. Clonidine and the treatment of the opiate withdrawal syndrome. Drug Alcohol Depend. 1988;21(3):253–259. relatesTo type: Cites classifier: Journal Article citation: Gossop M. The development of a short opiate withdrawal scale. Addict Behav. 1990;15(5):487–490. relatesTo type: Cites classifier: Journal Article citation: Gowing LR, Farrell M, Ali RL, White JM. Alpha 2-adrenergic agonists in opioid withdrawal. Addiction. 2002;97(1):49–58. relatesTo type: Cites classifier: Journal Article citation: Gowing L, Farrell M, Ali R, White J. Alpha2 adrenergic agonists for the management of opioid withdrawal. The Cochrane Database of Systematic Reviews CD002024. 2004 relatesTo type: Cites classifier: Journal Article citation: Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD. Two new rating scales for opiate withdrawal. Am J Drug Alcohol Abuse. 1987;13(3):293–308. relatesTo type: Cites classifier: Journal Article citation: Herman BH, Vocci F, Bridge P. The effects of NMDA receptor antagonists and nitric oxide synthase inhibitors on opioid tolerance and withdrawal: medication development issues for opiate addiction. Neuropsychopharmacology. 1995;13:269–294. relatesTo type: Cites citation: Herman BH, O'Brien CP. Clinical medications development for opiate addiction: Focus on nonopioids and opioid antagonists for the amelioration of opiate withdrawal symptoms and relapse prevention. Seminars in Neuroscience. 1997;9:158–172. relatesTo type: Cites classifier: Journal Article citation: Howells C, Allen S, Gupta J, Stillwell G, Marsden J, Farrell M. Prison based detoxification for opioid dependence: a randomised double blind controlled trial of lofexidine and methadone. Drug Alcohol Depend. 2002;67(2):169–176. relatesTo type: Cites classifier: Journal Article citation: Hser YI, Hoffman V, Grella CE, Anglin MD. A 33-year follow-up of narcotics addicts. Arch Gen Psychiatry. 2001;58(5):503–508. relatesTo type: Cites classifier: Journal Article citation: Hughes JR, Hatsukami D. Signs and symptoms of tobacco withdrawal. Arch Gen Psychiatry. 1986;43(3):289–294. relatesTo type: Cites classifier: Journal Article citation: Jarrott B, Louis WJ, Summers RJ. Characterization of central alpha-adrenoceptors using 3H-clonidine and its derivatives. Chest. 1983;83 Suppl 2:S339–S340. relatesTo type: Cites citation: Jasinski DR. Assessment of the abuse potentiality of morphine-like drugs (methods used in man) In: Martin WR, editor. Handbook of Experimental Pharmacology. Vol 45. Berlin: Springer-Verlag; 1977. pp. 197–258. relatesTo type: Cites classifier: Journal Article citation: Kahn A, Mumford JP, Rogers GA, Beckford H. Double-blind study of lofexidine and clonidine in the detoxification of opiate addicts in hospital. Drug Alcohol Depend. 1997;44(1):57–61. relatesTo type: Cites citation: Kalbfleisch JD, Prentice RL. The Statistical Analysis of Failure Time Data. New York: John Wiley & Sons, Inc.; 1980. relatesTo type: Cites classifier: Journal Article citation: Kleber HD, Riordan CE, Rounsaville B, Kosten T, Charney D, Gaspari J, Hogan I, O'Connor C. Clonidine in outpatient detoxification from methadone maintenance. Arch Gen Psychiatry. 1985;42(4):391–394. relatesTo type: Cites citation: Kolb MR, Himmelsbach CK. Clinical studies of drug addiction. III. A critical review of the withdrawal treatments with method of evaluating abstinence syndromes. Amer. J. Psychiatry. 1938;94:759–797. relatesTo type: Cites classifier: Journal Article citation: Lin SK, Strang J, Su LW, Tsai CJ, Hu WH. Double-blind randomised controlled trial of lofexidine versus clonidine in the treatment of heroin withdrawal. Drug Alcohol Depend. 1997;48(2):127–133. relatesTo type: Cites classifier: Journal Article citation: Marjamaki A, Luomala K, Ala-Uotila S, Scheinen M. Use of recombinant human alpha 2-adrenoceptors to characterize subtype selectively of antagonist binding. Eur J Pharmacol. 1993;246(3):219–226. relatesTo type: Cites classifier: Journal Article citation: National Survey on Drug Use and Health. 2006. [accessed on April 10, 2008]. Availabel at: http://www.oas.samhsa.gov/nsduh/2k6nsduh/2k6Results.cfm. relatesTo type: Cites classifier: Journal Article citation: O’Brien PC, Fleming TR. A multiple testing procedure for clinical trails. Biometrics. 1979;35(3):549–556. relatesTo type: Cites citation: Office of National Drug Control Policy. Heroin Fact Sheet. 2003. [Accessed February 6, 2006]. Available at: http://www.whitehousedrugpolicy.gov/publications/factsht/heroin/index.html. relatesTo type: Cites classifier: Journal Article citation: Preston KL, Bigelow GE. Pharmacological advances in addiction treatment. Int J Addict. 1985;20(6–7):845–867. relatesTo type: Cites classifier: Journal Article citation: Raistrick D, West D, Finnegan O, Thistlethwaite G, Brearley R, Banbery J. A comparison of buprenorphine annd lofexidine for community opiate detoxification: results from a randomized controlled trail. Addict. 2005;100(12):1860–1867. relatesTo type: Cites classifier: Journal Article citation: Shearman GT, Lal H, Ursillo RC. Effectiveness of lofexidine in blocking morphine-withdrawal signs in the rat. Pharmacol Biochem Behav. 1980;12(4):573–575. relatesTo type: Cites citation: Snedecor GW, Cochran WG. Statistical Methods. Ames, IA: Iowa State University Press; 1967. relatesTo type: Cites citation: Substance Abuse and Mental Health Data Archive. National Household Survey on Drug Abuse (NHSDA) series. 2003. [Accessed February 6, 2006]. Available at http://www.icpsr.umich.edu/SAMHDA/ and http://webapp.icpsr.umich.edu/cocoon/SAMHDA-SERIES/00064.xml. relatesTo type: Cites classifier: Journal Article citation: Uhlen S, Wikberg JE. Delineation of three pharmacological subtypes of alpha 2-adrenoceptor in the rat kidney. Br J Pharmacol. 1991;104(3):657–6419. relatesTo type: Cites citation: Vocci FJ. Opiates and addiction. In: Sibley DR, Hanin I, Kuhar M, Skolnick P, editors. Handbook of Contemporary Neuropharmacology Volume 2. John Wiley and Sons publisher; 2007. pp. 691–705. relatesTo type: Cites classifier: Journal Article citation: Washton AM, Resnick RB, Perzel JF, Garwood J. Opiate detoxification using lofexidine. NIDA Res Monogr. 1982;41:261–263. relatesTo type: Cites classifier: Journal Article citation: White R, Alcorn R, Feinmann C. Two methods of community detoxification from opiates: an open-label comparison of lofexidine and buprenorphine. Drug Alcohol Depend. 2001;65(1):77–83. relatesTo type: Cites citation: Yu E, Herman BH, Miotto K, Montgomery A, Fudala PJ, Chiang CN, Fisher C, Kampman K, Dhopesh V, Cornish J, Walsh B, Davies K, Vocci F, Bridge P, Ling W, O’Brien CP. NIDA Research Monograph. Rockville: DHHS/NIH/NIDA; 1999. In-patient safety evaluation of lofexidine (alpha-2 adrenergic agonist) for opiate withdrawal; p. 227. relatesTo type: Cites citation: Yu E, Herman BH, Miotto K, Montgomery A, Fudala PJ, Chiang CN, Fisher C, Kampman K, Dhopesh V, Cornish J, Walsh B, Davies K, Vocci F, Bridge P, Ling W, O’Brien CP. In-patient safety evaluation of lofexidine (alpha-2 adrenergic agonist) for opiate detoxification. Drug Alcohol Depend. 2001;63:S175. publicationForm publishedIn type: Periodical identifier: Print ISSN Type/0376-8716, ISOAbbreviation/Drug Alcohol Depend, ISSN Linking/0376-8716, Medline Title Abbreviation/Drug Alcohol Depend, NLM Unique ID/7513587 title: Drug and alcohol dependence publisherLocation: Ireland citedMedium: Print volume: 97 issue: 1-2 articleDate: 2008-09-01 pageString: 158-68 publicationForm citedMedium: Internet without issue articleDate: 2008-05-27 webLocation classifier: Abstract url: https://pubmed.ncbi.nlm.nih.gov/18508207/ webLocation classifier: DOI Based url: https://doi.org/10.1016/j.drugalcdep.2008.04.002 classification type: Publishing Model classifier: Print Electronic classification type: Chemical classifier: Adrenergic alpha-Agonists, Analgesics, Opioid, Clonidine, lofexidine classification type: MeSH heading artifactAssessment: ArtifactAssessment: artifact[x] = this resource classification type: Publication type classifier: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S. classification type: Knowledge Artifact Type classifier: Journal Article artifactAssessment: Classifier added by Computable Publishing LLC classification type: Citation subset classifier: IM contributorship complete: true entry contributor: Yu E forenameInitials: E affiliation: University of Pennsylvania & Philadelphia Veterans Affairs Medical Center, Philadelphia VAMC 116, University & Woodland Avenues, Philadelphia, PA 19104, USA. yu_e@mail.trc.upenn.edu <yu_e@mail.trc.upenn.edu> entry contributor: Miotto K forenameInitials: K entry contributor: Akerele E forenameInitials: E entry contributor: Montgomery A forenameInitials: A entry contributor: Elkashef A forenameInitials: A entry contributor: Walsh R forenameInitials: R entry contributor: Montoya I forenameInitials: I entry contributor: Fischman MW forenameInitials: MW entry contributor: Collins J forenameInitials: J entry contributor: McSherry F forenameInitials: F entry contributor: Boardman K forenameInitials: K entry contributor: Davies DK forenameInitials: DK entry contributor: O'Brien CP forenameInitials: CP entry contributor: Ling W forenameInitials: W entry contributor: Kleber H forenameInitials: H entry contributor: Herman BH forenameInitials: BH Generated Narrative: Practitioner #contributor0 name: Elmer Yu Generated Narrative: Practitioner #contributor1 name: Karen Miotto Generated Narrative: Practitioner #contributor2 name: Evaristo Akerele Generated Narrative: Practitioner #contributor3 name: Ann Montgomery Generated Narrative: Practitioner #contributor4 name: Ahmed Elkashef Generated Narrative: Practitioner #contributor5 name: Robert Walsh Generated Narrative: Practitioner #contributor6 name: Ivan Montoya Generated Narrative: Practitioner #contributor7 name: Marian W Fischman Generated Narrative: Practitioner #contributor8 name: Joseph Collins Generated Narrative: Practitioner #contributor9 name: Frances McSherry Generated Narrative: Practitioner #contributor10 name: Kathy Boardman Generated Narrative: Practitioner #contributor11 name: David K Davies Generated Narrative: Practitioner #contributor12 name: Charles P O'Brien Generated Narrative: Practitioner #contributor13 name: Walter Ling Generated Narrative: Practitioner #contributor14 name: Herbert Kleber Generated Narrative: Practitioner #contributor15 name: Barbara H Herman Generated Narrative: ArtifactAssessment #meshHeading0 artifact: Citation 18508207 A Phase 3 placebo-controlled, double-blind, multi-site trial of the alpha-2-adrenergic agonist, lofexidine, for opioid withdrawal. content type: components (if present) include qualifier codings classifier: Adrenergic alpha-Agonists freeToShare: true component type: qualifier classifier: is not a major topic component type: qualifier classifier: adverse effects Components - 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18508207 A Phase 3 placebo-controlled, double-blind, multi-site trial of the alpha-2-adrenergic agonist, lofexidine, for opioid withdrawal.
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This Citation Resource is referenced in an example for the EBMonFHIR Implementation Guide.
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A Phase 3 placebo-controlled, double-blind, multi-site trial of the alpha-2-adrenergic agonist, lofexidine, for opioid withdrawal.
**CONTEXT:** Lofexidine is an alpha-2-adrenergic receptor agonist that is approved in the United Kingdom for the treatment of opioid withdrawal symptoms. Lofexidine has been reported to have more significant effects on decreasing opioid withdrawal symptoms with less hypotension than clonidine. **OBJECTIVE:** To demonstrate that lofexidine is well tolerated and effective in the alleviation of observationally defined opioid withdrawal symptoms in opioid dependent individuals undergoing medically supervised opioid detoxification as compared to placebo. **DESIGN:** An inpatient, Phase 3, placebo-controlled, double-blind, randomized multi-site trial with three phases: (1) opioid agonist stabilization phase (days 1-3), (2) detoxification/medication or placebo phase (days 4-8), and (3) post detoxification/medication phase (days 9-11). **SUBJECTS:** Sixty-eight opioid dependent subjects were enrolled at three sites with 35 randomized to lofexidine and 33 to placebo. **MAIN OUTCOME MEASURE:** Modified Himmelsbach Opiate Withdrawal Scale (MHOWS) on study day 5 (second opioid detoxification treatment day). **RESULTS:** Due to significant findings, the study was terminated early. On the study day 5 MHOWS, subjects treated with lofexidine had significantly lower scores (equating to fewer/less severe withdrawal symptoms) than placebo subjects (least squares means 19.5+/-2.1 versus 30.9+/-2.7; p=0.0019). Lofexidine subjects had significantly better retention in treatment than placebo subjects (38.2% versus 15.2%; Log rank test p=0.01). **CONCLUSIONS:** Lofexidine is well tolerated and more efficacious than placebo for reducing opioid withdrawal symptoms in inpatients undergoing medically supervised opioid detoxification.
Aghajanian GK. Central noradrenergic neurons: a locus for the functional interplay between alpha-2 adrenoceptors and opiate receptors. J Clin Psychiatry. 1982;43(6 Pt 2):20–24.
Aghajanian GK. Tolerance of locus coeruleus neurones to morphine and suppression of withdrawal response by clonidine. Nature. 1978;276(5684):186–188.
Aigner A, Schmidt U. Lofexidine, a new, antihypertensive imidazoline derivative. Clinical profile of action with single-drug treatment and in combination with hydrochlorothiazide. Arzneimittelforschung. 1982;32(8a):976–983.
Akhurst JS. The use of lofexidine by drug dependency units in the United Kingdom. Eur Addict Res. 1999;5(1):43–49.
Arnsten AF, Cai JX, Goldman-Rakic PS. The alpha-2 adrenergic agonist guanfacine improves memory in aged monkeys without sedative or hypotensive side effects: evidence for alpha-2 receptor subtypes. J. Neurosci. 1998;8(11):4287–4298.
Aston-Jones G, Hirata H, Akaoka H. Local opiate withdrawal in locus coeruleus in vivo. Brain Res. 1997;765(2):331–336.
Bearn J, Gossop M, Strang J. Randomised double-blind comparison of lofexidine and methadone in the in-patient treatment of opiate withdrawal. Drug Alcohol Depend. 1996;43(1–2):87–91.
Bearn J, Gossop M, Strang J. Accelerated lofexidine treatment regimen compared with conventional lofexidine and methadone treatment for in-patient opiate detoxification. Drug Alcohol Depend. 1998;50:227–232.
Buccafusco JJ, Marshall DC. Dorsal root lesions block the expression of morphine withdrawal elicited from the rat spinal cord. Neurosci Lett. 1985;59(3):319–324.
Carnwath T, Hardman J. Randomised double-blind comparison of lofexidine and clonidine in the out-patient treatment of opiate withdrawal. Drug Alcohol Depend. 1998;50(3):251–254.
Freedman JE, Aghajanian GK. Opiate and alpha 2-adrenoceptor responses of rat amygdaloid neurons: co-localization and interactions during withdrawal. J Neurosci. 1985;5(11):3016–3024.
Gold MS, Pottash AC, Sweeney DR, Extein I, Annitto WJ. Opiate detoxification with lofexidine. Drug Alcohol Depend. 1981;8(4):307–315.
Gonzalez G, Oliveto A, Kosten TR. Combating opiate dependence: a comparison among the available pharmacological options. Expert Opin Pharmacother. 2004;5(4):713–725.
Gossop M. Clonidine and the treatment of the opiate withdrawal syndrome. Drug Alcohol Depend. 1988;21(3):253–259.
Gossop M. The development of a short opiate withdrawal scale. Addict Behav. 1990;15(5):487–490.
Gowing LR, Farrell M, Ali RL, White JM. Alpha 2-adrenergic agonists in opioid withdrawal. Addiction. 2002;97(1):49–58.
Gowing L, Farrell M, Ali R, White J. Alpha2 adrenergic agonists for the management of opioid withdrawal. The Cochrane Database of Systematic Reviews CD002024. 2004
Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD. Two new rating scales for opiate withdrawal. Am J Drug Alcohol Abuse. 1987;13(3):293–308.
Herman BH, Vocci F, Bridge P. The effects of NMDA receptor antagonists and nitric oxide synthase inhibitors on opioid tolerance and withdrawal: medication development issues for opiate addiction. Neuropsychopharmacology. 1995;13:269–294.
Herman BH, O'Brien CP. Clinical medications development for opiate addiction: Focus on nonopioids and opioid antagonists for the amelioration of opiate withdrawal symptoms and relapse prevention. Seminars in Neuroscience. 1997;9:158–172.
Howells C, Allen S, Gupta J, Stillwell G, Marsden J, Farrell M. Prison based detoxification for opioid dependence: a randomised double blind controlled trial of lofexidine and methadone. Drug Alcohol Depend. 2002;67(2):169–176.
Hser YI, Hoffman V, Grella CE, Anglin MD. A 33-year follow-up of narcotics addicts. Arch Gen Psychiatry. 2001;58(5):503–508.
Hughes JR, Hatsukami D. Signs and symptoms of tobacco withdrawal. Arch Gen Psychiatry. 1986;43(3):289–294.
Jarrott B, Louis WJ, Summers RJ. Characterization of central alpha-adrenoceptors using 3H-clonidine and its derivatives. Chest. 1983;83 Suppl 2:S339–S340.
Jasinski DR. Assessment of the abuse potentiality of morphine-like drugs (methods used in man) In: Martin WR, editor. Handbook of Experimental Pharmacology. Vol 45. Berlin: Springer-Verlag; 1977. pp. 197–258.
Kahn A, Mumford JP, Rogers GA, Beckford H. Double-blind study of lofexidine and clonidine in the detoxification of opiate addicts in hospital. Drug Alcohol Depend. 1997;44(1):57–61.
Kalbfleisch JD, Prentice RL. The Statistical Analysis of Failure Time Data. New York: John Wiley & Sons, Inc.; 1980.
Kleber HD, Riordan CE, Rounsaville B, Kosten T, Charney D, Gaspari J, Hogan I, O'Connor C. Clonidine in outpatient detoxification from methadone maintenance. Arch Gen Psychiatry. 1985;42(4):391–394.
Kolb MR, Himmelsbach CK. Clinical studies of drug addiction. III. A critical review of the withdrawal treatments with method of evaluating abstinence syndromes. Amer. J. Psychiatry. 1938;94:759–797.
Lin SK, Strang J, Su LW, Tsai CJ, Hu WH. Double-blind randomised controlled trial of lofexidine versus clonidine in the treatment of heroin withdrawal. Drug Alcohol Depend. 1997;48(2):127–133.
Marjamaki A, Luomala K, Ala-Uotila S, Scheinen M. Use of recombinant human alpha 2-adrenoceptors to characterize subtype selectively of antagonist binding. Eur J Pharmacol. 1993;246(3):219–226.
National Survey on Drug Use and Health. 2006. [accessed on April 10, 2008]. Availabel at: http://www.oas.samhsa.gov/nsduh/2k6nsduh/2k6Results.cfm.
O’Brien PC, Fleming TR. A multiple testing procedure for clinical trails. Biometrics. 1979;35(3):549–556.
Office of National Drug Control Policy. Heroin Fact Sheet. 2003. [Accessed February 6, 2006]. Available at: http://www.whitehousedrugpolicy.gov/publications/factsht/heroin/index.html.
Preston KL, Bigelow GE. Pharmacological advances in addiction treatment. Int J Addict. 1985;20(6–7):845–867.
Raistrick D, West D, Finnegan O, Thistlethwaite G, Brearley R, Banbery J. A comparison of buprenorphine annd lofexidine for community opiate detoxification: results from a randomized controlled trail. Addict. 2005;100(12):1860–1867.
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