Skip to main content
SpringerLink
Log in

Dextromethorphan/Quinidine

In Pseudobulbar Affect

  • Adis Drug Profile
  • Published:
CNS Drugs Aims and scope Submit manuscript

Abstract

Pseudobulbar affect is characterized by uncontrollable, inappropriate laughing and/or crying that is either unrelated or out of proportion to the emotions felt by the patient and occurs in patients with neurological disorders, such as amyotrophic lateral sclerosis (ALS), multiple sclerosis or traumatic brain injury.

Dextromethorphan/quinidine is indicated in the US for the treatment of pseudobulbar affect. Dextromethorphan, when its metabolism is inhibited by the coadministration of quinidine, has been shown to have a positive effect on the symptoms of pseudobulbar affect.

Dextromethorphan/quinidine 20 mg/10 mg twice daily was associated with a significantly greater decrease in the rate of pseudobulbar affect episodes per day (primary endpoint) than placebo in the 12-week, randomized, double-blind, placebo-controlled, multicentre STAR trial (Safety, Tolerability, And efficacy Results trial of AVP-923 in PBA [pseudobulbar affect]) involving patients with pseudobulbar affect and ALS or multiple sclerosis.

Moreover, the mean change from baseline in Center for Neurologic Study-Lability Scale score at 12 weeks was significantly greater among recipients of dextromethorphan/quinidine 20mg/10 mg twice daily than those receiving placebo.

Dextromethorphan/quinidine 20mg/10 mg twice daily was generally well tolerated. The drug has been shown to cause dosage-dependent corrected QT interval (QTc) prolongation; however, in the STAR trial, dextromethorphan/quinidine 20mg/10mg twice daily appeared to be well tolerated with regard to QTc prolongation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Table III
Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Rosen HJ, Cummings J. A real reason for patients with pseudobulbar affect to smile. Ann Neurol 2007 Feb; 61(2): 92–6

    Article  PubMed  CAS  Google Scholar 

  2. Miller A. Pseudobulbar affect in multiple sclerosis: toward the development of innovative therapeutic strategies. J Neurol Sci 2006 Jun 15; 245(1–2): 153–9

    Article  PubMed  Google Scholar 

  3. Wortzel HS, Oster TJ, Anderson CA, et al. Pathological laughing and crying: epidemiology, pathophysiology and treatment. CNS Drugs 2008; 22(7): 531–45

    Article  PubMed  CAS  Google Scholar 

  4. Wynn D, Kaye R, Hepner A. Impact of pseudobulbar affect on health and QoL [abstract no. M-38 plus poster]. 135th Annual Meeting of the American Neurological Association; 2010 Sep 12–15; San Fransisco (CA)

  5. Martin CM. It’s nothing to laugh about: understanding disorders of emotional expression. Consult Pharm 2007 Sep; 22(9): 732–42

    Article  PubMed  Google Scholar 

  6. Strowd RE, Cartwright MS, Okun MS, et al. Pseudobulbar affect: prevalence and quality of life impact in movement disorders. J Neurol 2010 Aug; 257(8): 1382–7

    Article  PubMed  Google Scholar 

  7. Rabins PV, Arciniegas DB. Pathophysiology of involuntary emotional expression disorder. CNS Spectr 2007 Apr; 12(4 Suppl. 5): 17–22

    PubMed  Google Scholar 

  8. Avanir Pharmaceuticals, Inc. Nuedexta™ (dextromethorphan hydrobromide and quinidine sulfate capsules) US prescribing information [online]. Available from URL: http://www.nuedexta.com/NUEDEXTA_Full_Prescribing_Information-1.pdf [Accessed 2011 Mar 28]

  9. Panitch HS, Thisted RA, Smith RA, et al. Randomized, controlled trial of dextromethorphan/quinidine for pseudobulbar affect in multiple sclerosis. Ann Neurol 2006 May; 59(5): 780–7

    Article  PubMed  CAS  Google Scholar 

  10. Brooks BR, Thisted RA, Appel SH, et al. Treatment of pseudobulbar affect in ALS with dextromethorphan/ quinidine: a randomized trial. Neurology 2004 Oct 26; 63(8): 1364–70

    Article  PubMed  CAS  Google Scholar 

  11. Pioro EP, Brooks BR, Cummings J, et al. Dextromethorphan plus ultra low-dose quinidine reduces pseudobulbar affect. Ann Neurol 2010 Nov; 68(5): 693–702

    Article  PubMed  CAS  Google Scholar 

  12. 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 Oct; 29(5): 444–52

    Article  PubMed  CAS  Google Scholar 

  13. 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 Oct; 207(2): 248–57

    Article  PubMed  CAS  Google Scholar 

  14. Werling LL, Lauterbach EC, Calef U. Dextromethorphan as a potential neuroprotective agent with unique mechanisms of action. Neurologist 2007 Sep; 13(5): 272–93

    Article  PubMed  Google Scholar 

  15. Rosen H. Dextromethorphan/quinidine sulfate for pseudobulbar affect. Drugs Today (Barc) 2008 Sep; 44(9): 661–8

    Article  CAS  Google Scholar 

  16. Zawertailo LA, Tyndale RF, Busto U, et al. Effect of metabolic blockade on the psychoactive effects of dextromethorphan. Hum Psychopharmacol 2010 Jan; 25(1): 71–9

    Article  PubMed  CAS  Google Scholar 

  17. Moghadamnia AA, Rostami-Hodjegan A, Abdul-Manap R, et al. Physiologically based modelling of inhibition of metabolism and assessment of the relative potency of drug and metabolite: dextromethorphan vs. dextrorphan using quinidine inhibition. Br J Clin Pharmacol 2003 Jul; 56(1): 57–67

    CAS  Google Scholar 

  18. 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 Sep; 60(3): 295–307

    Article  PubMed  CAS  Google Scholar 

  19. 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 Oct; 44(10): 1132–42

    Article  PubMed  CAS  Google Scholar 

  20. Schadel M, Wu D, Otton SV, et al. Pharmacokinetics of dextromethorphan and metabolites in humans: influence of the CYP2D6 phenotype and quinidine inhibition. J Clin Psychopharmacol 1995 Aug; 15(4): 263–9

    Article  PubMed  CAS  Google Scholar 

  21. Pope L, Kaye R, Hepner A, et al. A study of potential pharmacokinetic (PK) and pharmacodynamic (PD) interactions between dextromethorphan/quinidine and memantine [abstract no. NR3-27]. 163rd Annual Meeting of the American Psychiatric Association; 2010 May 22–26; New Orleans (LA)

  22. 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 Jul; 75(4): 380

    Google Scholar 

  23. Brooks BR, Cummings J, Pioro EP, et al. Star trial: sub-analysis of an international, multi-center, placebo-controlled study of AVP-923 (dextromethorphan/quinidine) for the treatment of pseudobulbar affect (PBA) in amyotrophic lateral sclerosis (ALS) patients [abstract no. C41 plus oral presentation]. 20th International Symposium on Amyotrophic Lateral Sclerosis/Motor Neurone Disease; 2009 Dec 8–12; Berlin

  24. Wynn D, Schiffer R, Brooks BR, et al. Double-blind, placebo-controlled, multinational study of dextromethorphan/ quinidine for psuedobulbar affect in multiple sclerosis [abstract no. S150 plus poster]. 24th Annual Meeting of the Consortium of Multiple Sclerosis Centers; 2010 Jun 2–5; San Antonio (TX)

Download references

Acknowledgements and Disclosures

The manuscript was reviewed by: R.G. Miller, Department of Neurosciences, University of San Francisco Medical School, California Pacific Medical Center, San Francisco, California, USA; E.P. Pioro, Section of ALS & Related Disorders, Neurological Institute, Cleveland Clinic, Cleveland, Ohio, USA; W.A. Sheremata, Department of Neurology, Miller School of Medicine, University of Miami, Miami, Florida, USA.

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Author information

Authors and Affiliations

  1. Adis, a Wolters Kluwer Business, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore 0754, Auckland, New Zealand

    Karly P. Garnock-Jones

Authors
  1. Karly P. Garnock-Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Karly P. Garnock-Jones.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Garnock-Jones, K.P. Dextromethorphan/Quinidine. CNS Drugs 25, 435–445 (2011). https://doi.org/10.2165/11207260-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11207260-000000000-00000

Keywords

Search

Navigation