Drugs

, Volume 75, Issue 1, pp 83–90 | Cite as

Dextromethorphan/Quinidine: A Review of Its Use in Adults with Pseudobulbar Affect

Adis Drug Evaluation

Abstract

Fixed-dose dextromethorphan/quinidine capsules (Nuedexta®) utilize quinidine to inhibit the metabolism of dextromethorphan, enabling high plasma dextromethorphan concentrations to be reached without using a larger dose of the drug. The drug combination is the first treatment to be approved for pseudobulbar affect (PBA), a condition of contextually inappropriate/exaggerated emotional expression that often occurs in adults with neurological damage conditions, such as amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, traumatic brain injury, Alzheimer’s disease or Parkinson’s disease. Dextromethorphan/quinidine at the recommended dosages of 20/10 or 30/10 mg twice daily reduced the rate of PBA episodes and improved PBA severity in a 12-week, double-blind, placebo-controlled trial in adults with ALS or MS (STAR), with further improvements in the severity of the condition observed in a 12-week open-label extension phase. Dextromethorphan/quinidine 20/10 mg twice daily also improved PBA secondary to dementia in a cohort of a 12-week noncomparative trial (PRISM II). The drug combination was generally well tolerated in these studies, with no particular safety or tolerability concerns. Although longer-term efficacy and tolerability data for dextromethorphan/quinidine 20/10 or 30/10 mg twice daily would be beneficial, current evidence indicates that it is a useful option in the treatment of adults with PBA.

References

  1. 1.
    Parvizi J, Coburn KL, Shillcutt SD, et al. Neuroanatomy of pathological laughing and crying: a report of the American Neuropsychiatric Association Committee on Research. J Neuropsychiatry Clin Neurosci. 2009;21(1):75–87.PubMedCrossRefGoogle Scholar
  2. 2.
    Miller A, Pratt H, Schiffer RB. Pseudobulbar affect: the spectrum of clinical presentations, etiologies and treatments. Expert Rev Neurother. 2011;11(7):1077–88.PubMedCrossRefGoogle Scholar
  3. 3.
    Parvizi J, Arciniegas DB, Bernardini GL, et al. Diagnosis and management of pathological laughter and crying. Mayo Clin Proc. 2006;81(11):1482–6.PubMedCrossRefGoogle Scholar
  4. 4.
    Werling LL, Keller A, Frank JG, et al. A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder. Exp Neurol. 2007;207(2):248–57.PubMedCrossRefGoogle Scholar
  5. 5.
    Pioro EP. Current concepts in the pharmacotherapy of pseudobulbar affect. Drugs. 2011;71:1193–207.PubMedCrossRefGoogle Scholar
  6. 6.
    Marier JF, Deschenes JL, Hage A, et al. Enhancing the uptake of dextromethorphan in the CNS of rats by concomitant administration of the P-gp inhibitor verapamil. Life Sci. 2005;77(23):2911–26.PubMedCrossRefGoogle Scholar
  7. 7.
    European Medicines Agency. Nuedexta (dextromethorphan/quinidine) oral capsules: EU summary of product characteristics. http://www.ema.europa.eu. Accessed 5 Nov 2014.
  8. 8.
    Avanir Pharmaceuticals Inc. Nuedexta® (dextromethorphan hydrobromide and quinidine sulfate) oral capsules: US prescribing information. 2010. https://www.nuedexta.com. Accessed 5 Nov 2014.
  9. 9.
    Andersen PM, Abrahams S, Borasio GD, et al. EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS): revised report of an EFNS task force. Eur J Neurol. 2012;19(3):360–75.PubMedCrossRefGoogle Scholar
  10. 10.
    Miller RG, Jackson CE, Kasarskis EJ, et al. Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: multidisciplinary care, symptom management, and cognitive/behavioral impairment (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2009;73(15):1227–33.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Codd EE, Shank RP, Schupsky JJ, et al. Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics: structural determinants and role in antinociception. J Pharmacol Exp Ther. 1995;274(3):1263–70.PubMedGoogle Scholar
  12. 12.
    Nguyen L, Robson MJ, Healy JR, et al. Involvement of sigma-1 receptors in the antidepressant-like effects of dextromethorphan. PLoS One. 2014;9(2):e89985.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Haiman G, Pratt H, Miller A. Effects of dextromethorphan/quinidine on auditory event-related potentials in multiple sclerosis patients with pseudobulbar affect. J Clin Psychopharmacol. 2009;29(5):444–52.PubMedCrossRefGoogle Scholar
  14. 14.
    Brooks BR, Bravver E, Desai UG, et al. Bulbar speech-articulation/swallowing rate changes measured in amyotrophic lateral sclerosis (ALS) patients treated with dextromethorphan/quinidine(nuedexta) for pseudobulbar affect (PBA)-determination of treatment effect size for future clinical trials [abstract no. M1408]. Ann Neurol. 2012;72(S16):S65–6.Google Scholar
  15. 15.
    Zawertailo LA, Tyndale RF, Busto U, et al. Effect of metabolic blockade on the psychoactive effects of dextromethorphan. Hum Psychopharmacol. 2010;25(1):71–9.PubMedCrossRefGoogle Scholar
  16. 16.
    European Medicines Agency. Neudexta (dextromethorphan/quinidine): assessment report for an initial marketing authorisation application. 25 Apr 2013. http://www.ema.europa.eu. Accessed 5 Nov 2014.
  17. 17.
    Pioro EP, Brooks BR, Cummings J, et al. Dextromethorphan plus ultra low-dose quinidine reduces pseudobulbar affect. Ann Neurol. 2010;68(5):693–702.PubMedCrossRefGoogle Scholar
  18. 18.
    Pope LE, Khalil MH, Berg JE, et al. Pharmacokinetics of dextromethorphan after single or multiple dosing in combination with quinidine in extensive and poor metabolizers. J Clin Pharmacol. 2004;44(10):1132–42.PubMedCrossRefGoogle Scholar
  19. 19.
    Capon DA, Bochner F, Kerry N, et al. The influence of CYP2D6 polymorphism and quinidine on the disposition and antitussive effect of dextromethorphan in humans. Clin Pharmacol Ther. 1996;60(3):295–307.PubMedCrossRefGoogle Scholar
  20. 20.
    Pope LE, Schoedel KA, Bartlett C, et al. A study of potential pharmacokinetic and pharmacodynamic interactions between dextromethorphan/quinidine and memantine in healthy volunteers. Clin Drug Investig. 2012;32(8):e1–15.PubMedCentralPubMedGoogle Scholar
  21. 21.
    Pioro E, Brooks B, Cummings J, et al. Persistent efficacy of dextromethorphan (DM)/quinidine (Q) for pseudobulbar affect (PBA): results from a 12-week, open-label extension (OLE) study [abstract no. LBS.006]. Neurology. 2010;75(4):380.Google Scholar
  22. 22.
    Doody RS, D’Amico S, Cutler AJ, et al. Safety, tolerability, and effectiveness of dextromethorphan/quinidine for pseudobulbar affect in patients with Alzheimer’s disease/dementia: PRISM II [poster no. M1334WIP]. In: 139th Annual Meeting of the American Neurological Association, Baltimore (MD); 2014.Google Scholar
  23. 23.
    Avanir Pharmaceuticals. Safety and efficacy of AVP-923 in PBA patients with ALS or MS (STAR) [ClinicalTrial.gov identifier NCT00573443]. US National Institutes of Health, ClinicalTrials.gov. 2013. http://www.clinicaltrials.gov. Accessed 5 Nov 2014.
  24. 24.
    Jillapalli D. US FDA center for drug evaluation and research: medical review of Zenvia. 25 Sep 2010. http://www.accessdata.fda.gov. Accessed 30 Aug 2013.
  25. 25.
    Pioro E, Brooks B, Cummings J, et al. Safety and tolerability of dextromethorphan/quinidine for pseudobulbar affect in a 12-week, open-label extension study [abstract no. P06.128]. In: 62nd Annual Meeting of the American Academy of Neurology, Toronto (ON); 2010.Google Scholar
  26. 26.
    Siffert J, Abijo O, Formella A. Dextromethorphan 20 mg/quinidine 10 mg effectiveness and tolerability in treating PBA in patients with stroke, dementia and other neurological conditions: results of a retrospective chart review [abstract]. Consult Pharm. 2013;28(10).Google Scholar
  27. 27.
    Cruz MP. Nuedexta for the treatment of pseudobulbar affect. Drug Forcast. 2013;38(6):325–8.Google Scholar
  28. 28.
    Pattee GL, Wymer JP, Lomen-Hoerth C, et al. An open-label multicenter study to assess the safety of dextromethorphan/quinidine in patients with pseudobulbar affect associated with a range of underlying neurological conditions. Curr Med Res Opin. 2014;30(11):2255–65.PubMedCrossRefGoogle Scholar
  29. 29.
    Cummings JL. Neuropsychiatric inventory: comprehensive assessment of psychopathology in patients with dementia. 2009. http://www.dementia-assessment.com.au/behavioural/index.html. Accessed 5 Nov 2014.

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  1. 1.SpringerAucklandNew Zealand

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