638
Views
0
CrossRef citations to date
0
Altmetric
Original Article

Sublingual dexmedetomidine (BXCL501) reduces opioid withdrawal symptoms: findings from a multi-site, phase 1b/2, randomized, double-blind, placebo-controlled trial

, , , , , , & show all
Pages 109-122 | Received 13 May 2022, Accepted 03 Nov 2022, Published online: 11 Jan 2023

References

  • Substance Abuse and Mental Health Services Administration. Key substance use and mental health indicators in the United States: results from the 2019 National Survey on Drug Use and Health (HHS Publication No. PEP20-07-01-001, NSDUH Series H-55); 2020 Rockville, MD: Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration. https://www.samhsa.gov/data/
  • American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. The American Psychiatric Association; 2013. doi:10.1176/appi.books.9780890425596
  • Center for Disease Control and Prevention. Wide-ranging online data for epidemiologic research (WONDER); 2020. Atlanta, GA: CDC, National Center for Health Statistics. http://wonder.cdc.gov.
  • National Institute on Drug Abuse. Principles of drug addiction treatment: a research-based guide. 3rd ed. Rockville, MD: National Institute on Drug Abuse; 2012. NIH Publication No. 12-4180. www.drugabuse.gov/publications/principles-drug-addiction-treatment
  • Broers B, Giner F, Dumont P, Mino A. Inpatient opiate detoxification in Geneva: follow-up at 1 and 6 months. Drug Alcohol Depend. 2000;58:85–92. doi:10.1016/S0376-8716(99)00063-0.
  • Mattick RP, Hall W. Are detoxification programmes effective? Lancet. 1996;347:97–100. doi:10.1016/S0140-6736(96)90215-9.
  • Kosten TR, George TP. The neurobiology of opioid dependence: implications for treatment. Sci Pract Perspect. 2002;1:13–20. doi:10.1151/spp021113.
  • Tetrault JM, O’Connor PG. Management of opioid intoxication and withdrawal. In: Ries RK, DA Fiellin, SC Miller R Siatz, editors. Principles of addiction medicine. 4th ed. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins; 2009. pp. 589–606.
  • Gold MS, Redmond DE Jr., Kleber HD. Noradrenergic hyperactivity in opiate withdrawal supported by clonidine reversal of opiate withdrawal. Am J Psychiatry. 1979;136:100–02.
  • Gossop M. The development of a short opiate withdrawal scale (SOWS). Addict Behav. 1990;15:487–90. doi:10.1016/0306-4603(90)90036-W.
  • Maldonado R. Participation of noradrenergic pathways in the expression of opiate withdrawal: biochemical and pharmacological evidence. Neurosci Biobehav Rev. 1997;21:91–104. doi:10.1016/0149-7634(95)00061-5.
  • Doughty B, Morgenson D, Brooks T. Lofexidine: a newly FDA-approved, Nonopioid treatment for opioid withdrawal. Ann Pharmacother. 2019;53:746–53. doi:10.1177/1060028019828954.
  • Gorodetzky CW, Walsh SL, Martin PR, Saxon AJ, Gullo KL, Biswas KA. Phase III, randomized, multi-center, double blind, placebo-controlled study of safety and efficacy of lofexidine for relief of symptoms in individuals undergoing inpatient opioid withdrawal. Drug Alcohol Depend. 2017;176:79–88. doi:10.1016/j.drugalcdep.2017.02.020.
  • Kuszmaul AK, Palmer EC, Frederick EK. Lofexidine versus clonidine for mitigation of opioid withdrawal symptoms: a systematic review. J Am Pharm Assoc. 2003;60:145–52. doi:10.1016/j.japh.2019.10.004.
  • Strang J, Bearn J, Gossop M. Lofexidine for opiate detoxification: review of recent randomised and open controlled trials. Am J Addict. 1999;8:337–48. doi:10.1080/105504999305749.
  • Gerra G, Zaimovic A, Giusti F, Di Gennaro C, Zambelli U, Gardini S, Delsignore R. Lofexidine versus clonidine in rapid opiate detoxification. J Subst Abuse Treat. 2001;21:11–17. doi:10.1016/S0740-5472(01)00178-7.
  • Jones JD, Varshneya NB, Hudzik TJ, Huhn AS. Improving translational research outcomes for opioid use disorder treatments. Cur Addict Rep. 2021;8:109–21. doi:10.1007/s40429-020-00353-5.
  • Lopez LM, Mehta JL. Comparative efficacy and safety of lofexidine and clonidine in mild to moderately severe systemic hypertension. Am J Cardiol. 1984;53:787–90. doi:10.1016/0002-9149(84)90405-3.
  • Hsu YW, Cortinez LI, Robertson KM, Keifer J, Sum-Ping S, Moretti E, Young C, Wright D, MacLeod D, Somma J. Dexmedetomidine pharmacodynamics: part I: crossover comparison of the respiratory effects of dexmedetomidine and remifentanil in healthy volunteers. Anesthesiology. 2004;101:1066–76. doi:10.1097/00000542-200411000-00005.
  • Kamibayashi T, Maze M, Weiskopf R, Weiskopf R, Todd M. Clinical uses of α2-adrenergic agonists. Anesthesiol. 2000;93:1345–49. doi:10.1097/00000542-200011000-00030.
  • Kaur M, Singh PM. Current role of dexmedetomidine in clinical anesthesia and intensive care. Anesth Essays Res. 2011;5:128–33. doi:10.4103/0259-1162.94750.
  • IGALMITM. Package insert. BioXcel Therapeutics, Inc.; 2022.
  • Gertler R, Brown HC, Mitchell DH, Silvius EN. Dexmedetomidine: a novel sedative-analgesic agent. Proc Bayl Univ Med Cent. 2001;14:13–21. doi:10.1080/08998280.2001.11927725.
  • Peltonen JM, Pihlavisto M, Scheinin M. Subtype-specific stimulation of [35S] GTPgammaS binding by recombinant alpha2-adrenoceptors. Eur J Pharmacol. 1998;355:275–79. doi:10.1016/S0014-2999(98)00518-4.
  • Ouchi K, Sugiyama K. Dexmedetomidine dose dependently enhances the local anesthetic action of lidocaine in inferior alveolar nerve block: a randomized double-blind study. Reg Anesth Pain Med. 2016;41:348–55. doi:10.1097/AAP.0000000000000380.
  • Zhang X, Bai X, Zhang Q, Wang X, Lu L. The safety and efficacy of intranasal dexmedetomidine during electrochemotherapy for facial vascular malformation: a double-blind, randomized clinical trial. J Oral Maxillofac Surg. 2013;71:1835–42. doi:10.1016/j.joms.2013.06.202.
  • Penttilä J, Helminen A, Anttila M, Hinkka S, Scheinin H. Cardiovascular and parasympathetic effects of dexmedetomidine in healthy subjects. Can J Physiol Pharmacol. 2004;82:359–62. doi:10.1139/y04-028.
  • Wagner DS, Brummett CM. Dexmedetomidine: as safe as safe can be. Sem Anesthesia Perioperative Med Pain. 2006;25:77–83. doi:10.1053/j.sane.2006.02.003.
  • Sobell LC, Sobell MB, Buchan G, Cleland PA, Fedoroff I, Leo GI. The reliability of the timeline followback method applied to drug, cigarette, and cannabis use. Paper presented at the 30th Annual Meeting of the Association for Advancement of Behavior Therapy; 1996 Nov; New York, NY.
  • Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, Currier GW, Melvin GA, Greenhill L, Shen S, et al. The Columbia–suicide severity rating scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry. 2011;168:1266–77. doi:10.1176/appi.ajp.2011.10111704.
  • Wesson DR, Ling W. The clinical opiate withdrawal scale (COWS). J Psychoactive Drugs. 2003;35:253–59. doi:10.1080/02791072.2003.10400007.
  • Wang RI, Wiesen RL, Lamid S, Roh BL. Rating the presence and severity of opiate dependence. Clin Pharmacol Ther. 1974;16:653–58. doi:10.1002/cpt1974164653.
  • Yu E, Miotto K, Akerele E, Montgomery A, Elkashef A, Walsh R, Montoya I, Fischman MW, Collins J, McSherry F, et al. A phase 3 placebo-controlled, double-blind, multi-site trial of the alpha-2-adrenergic agonist, lofexidine, for opioid withdrawal. Drug Alcohol Depend. 2008;97:158–68. doi:10.1016/j.drugalcdep.2008.04.002.
  • Battaglia J, Lindborg SR, Alaka J, Meehan K, Wright P. Calming versus sedative effects of intramuscular olanzapine in agitated patients. Am J Emergency Med. 2003;21:192–98. doi:10.1016/S0735-6757(02)42249-8.
  • Preskorn SH, Risinger R, Kakar R. Sublingual dexmedetomidine vs placebo and acute agitation associated with bipolar disorder-reply. JAMA. 2022;328:214–15. doi:10.1001/jama.2022.8349.
  • Precedex US Package Insert; 2016. http://labeling.pfizer.com/ShowLabeling.aspx?id=4404
  • Comer SD, Collins ED, MacArthur RB, Fischman MW. Comparison of intravenous and intranasal heroin self-administration by morphine-maintained humans. Psychopharmacology (Berl). 1999;143:327–38. doi:10.1007/s002130050956.
  • Comer SD, Cooper ZD, Kowalczyk WJ, Sullivan MA, Evans SM, Bisaga AM, Vosburg SK. Evaluation of potential sex differences in the subjective and analgesic effects of morphine in normal, healthy volunteers. Psychopharmacology (Berl). 2010;208:45–55. doi:10.1007/s00213-009-1703-4.
  • Comer SD, Sullivan MA, Whittington RA, Vosburg SK, Kowalczyk WJ. Abuse liability of prescription opioids compared to heroin in morphine-maintained heroin abusers. Neuropsychopharmacology. 2008;33:1179–91. doi:10.1038/sj.npp.1301479.
  • Cooper ZD, Johnson KW, Pavlicova M, Glass A, Vosburg SK, Sullivan MA, Manubay JM, Martinez DM, Jones JD, Saccone PA, et al. The effects of ibudilast, a glial activation inhibitor, on opioid withdrawal symptoms in opioid-dependent volunteers. Addict Biol. 2016;21:895–903. doi:10.1111/adb.12261.
  • SAS Proprietary Software Version 9.3. Cary NC: SAS Institute.
  • Cheung CW, Ng KF, Liu J, Yuen MY, Ho MH, Irwin MG. Analgesic and sedative effects of intranasal dexmedetomidine in third molar surgery under local anaesthesia. Br J Anaesth. 2011;107:430–37. doi:10.1093/bja/aer164.
  • Hospira. Approved labeling for precedex (dexmedetomidine hydrochloride) injection for intravenous use. Lake Forest, IL: Hospira, Inc; 2016.
  • Kundra P, Velayudhan S, Krishnamachari S, Gupta SL. Oral ketamine and dexmedetomidine in adults’ burns wound dressing-A randomized double-blind cross over study. Burns. 2013;39:1150–56. doi:10.1016/j.burns.2013.02.012.
  • Nooh N, Sheta SA, Abdullah WA, Abdelhalim AA. Intranasal atomized dexmedetomidine for sedation during third molar extraction. Int J Oral Maxillofac Surg. 2013;42:57–862. doi:10.1016/j.ijom.2013.02.003.
  • Fishman M, Tirado C, Alam D, Gullo K, Clinch T, Gorodetzky CW. Safety and efficacy of lofexidine for medically managed opioid withdrawal: a randomized controlled clinical trial. J Addict Med. 2019;13:169–76. doi:10.1097/ADM.0000000000000474.
  • Gish EC, Miller JL, Honey BL, Johnson PN. Lofexidine, an {alpha}2-receptor agonist for opioid detoxification. Ann Pharmacother. 2010;44:343–51. doi:10.1345/aph.1M347.
  • Rehman SU, Maqsood MH, Bajwa H, Tameez U, Din A, Malik MN. Clinical efficacy and safety profile of lofexidine hydrochloride in treating opioid withdrawal symptoms: a review of literature. Cureus. 2019;11:e4827. doi:10.7759/cureus.4827.
  • Kohli U, Pandharipande P, Muszkat M, Sofowora GG, Friedman EA, Scheinin M, Wood AJ, Ely EW, Tyndale RF, Choi L, et al. CYP2A6 genetic variation and dexmedetomidine disposition. Eur J Clin Pharmacol. 2012;68:937–42. doi:10.1007/s00228-011-1208-z.
  • Centers for Disease Control and Prevention Health Alert Network. Increases in fentanyl drug confiscations and fentanyl-related overdose fatalities; 2015. [accessed 18 Nov 2019]. https://emergency.cdc.gov/han/han00384.asp
  • Martinez S, Jones JD, Brandt L, Campbell AN, Abbott R, Comer SD. The increasing prevalence of fentanyl: a urinalysis-based study among individuals with opioid use disorder in New York City. Am J Addic. 2020;30:65–71. doi:10.1111/ajad.13092.
  • Comer SD, Cahill CM. Fentanyl: receptor pharmacology, abuse potential, and implications for treatment. Neurosci Biobehav Rev. 2019;106:49–57. doi:10.1016/j.neubiorev.2018.12.005.
  • Luba RL. As secondary analysis examining Fentanyl’s impact on opioid withdrawal symptoms and exploring the role of body weight in Fentanyl clearance. College on Problems of Drug Dependence Annual Meeting; 2002 June 15; Minneapolis, MN.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.