Treatment of pseudobulbar affect in ALS with dextromethorphan/quinidine: A randomized trial

University of Wisconsin, 600 Highland Ave., Rm. H6/563 CSC, Madison, WI 53792-5132, USA.
Neurology (Impact Factor: 8.29). 11/2004; 63(8):1364-70. DOI: 10.1212/01.WNL.0000142042.50528.2F
Source: PubMed


Patients with ALS commonly exhibit pseudobulbar affect.
The authors conducted a multicenter, randomized, double-blind, controlled, parallel, three-arm study to test a defined combination of dextromethorphan hydrobromide (DM) and quinidine sulfate (Q) (AVP-923) for the treatment of pseudobulbar affect in ALS. Q inhibits the rapid first-pass metabolism of DM. The effects of AVP-923 (30 mg of DM plus 30 mg of Q) given twice daily for 28 days were compared with those of its components. Patients were evaluated on days 1, 15, and 29. The primary efficacy variable was the change from baseline in the Center for Neurologic Study Lability Scale (CNS-LS) score. Secondary efficacy variables were laughing/crying episode rates and changes in Visual Analog Scales for Quality of Life (QOL) and Relationships (QOR). Efficacy was evaluated in intention-to-treat subjects who were not poor metabolizers of DM (n = 65 for AVP-923, n = 30 for DM, and n = 34 for Q). Safety was assessed in all randomized subjects (n = 140).
AVP-923 patients experienced 3.3-point greater improvements in CNS-LS than DM patients (p = 0.001) and 3.7-point greater improvements than Q patients (p < 0.001). AVP-923 patients exhibited lower overall episode rates, improved QOL scores, and improved QOR scores (p < 0.01 for all endpoints). Adverse effects were mostly mild or moderate; treatment-related discontinuation was 24% for AVP-923, 6% for DM, and 8% for Q.
AVP-923 palliates pseudobulbar affect in ALS. Overall benefits of treatment are reflected in fewer episodes of crying and laughing and improvements in overall quality of life and quality of relationships.

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Available from: Ronald Thisted, Dec 19, 2013
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    • "Le syndrome pseudo-bulbaire, caractérisé par un rire et pleurer spasmodique, est fréquent et peut être amélioré par les tricycliques et les inhibiteurs de la recapture de la sérotonine. L'association de dextrométhorphan et de quinidine (Nuedex- ta W ), déjà utilisée aux États-Unis dans cette indication [9], a reçu en juin 2006 une autorisation de mise sur le marché de la part de l'Agence médicale européenne. "
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    La Presse Médicale 05/2014; 43(5). DOI:10.1016/j.lpm.2014.01.013 · 1.08 Impact Factor
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    • "The medical literature is vague as to what amounts of the substance cause these dangerous conditions, as the individuals seen in the emergency room sometimes do not remember or do not wish to disclose how much DXM they took or whether they took other chemicals as well. The users' CYP2D6 phenotypes are rarely looked at, which could have serious implications related to dosage and negative physical and psychological effects (Gasche et al., 2004). Much of the information comes from users who consumed many doses of OTC cough medicines, which complicates the situation in two ways. "
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    ABSTRACT: Dextromethorphan (DXM), a nonprescription psychoactive drug that may lead to spiritual or transpersonal altered states of consciousness, has legitimate therapeutic applications that are being investigated by clinical researchers. It is easily available in over-the-counter cough medicines, and due to its psychoactive properties, DXM is an increasingly popular drug of abuse. Nonmedical use of DXM can lead to dependence and death. Clinical research related to nonmedical DXM use is limited, but many theories and experience reports have been published on the Internet. Nonmedical DXM users may consist of two types: those who seek recreation and those who want to explore their mind (psychonauts). Given the potential importance of DXM-facilitated transpersonal experiences, this article suggests research be conducted on the chemical. The experiences of others must be taken into account before any adequate theory of DXM can be formulated. Dextromethorphan (DXM) was introduced over-the-counter (OTC) in 1958 (American Medical Association, 1988) as a nonprescription antitussive (cough suppressant). DXM is an opioid, ''the D-isomer of levorphanol, a semisynthetic morphine derivative'' (McFee, Mofenson, & Caraccio, 2000, p. 123). Several fields of medicine have used DXM therapeutically, which is a relatively safe drug when used for medical purposes (Bem & Peck, 1992; Steinberg, Bell, & Yenari, 1996). DXM is primarily of clinical and research interest because of its neuropharmacological properties. DXM binds to four distinct neuron receptor sites; these are most likely the sigma1, PCP2, sigma2, and NMDA receptor sites (Zhou & Musacchio, 1991). DXM also indirectly inhibits the reuptake of serotonin (International Programme on Chemical Safety [IPCS], 1996). Although DXM was derived from the opiate levorphanol, it does not bind to any of the opiate receptors. When individuals ingest doses five or more times the recommended dose, DXM becomes psychoactive and has been classified as a dissociative drug (National Institute on Drug Abuse [NIDA], 2001) and a club drug (Parks & Kennedy, 2004). Occasional clinical case reports appear of individuals ending up in the hospital related to negative side effects of their substance use. DXM, however, does not produce withdrawal symptoms characteristic of physically addictive substances, although tolerance does occur (Wolfe & Caravati, 1995).
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    • "Occasionally, the emotional outbursts are more troubling for the relatives and nursing staff than the patient, and treatment may not be necessary. A randomized controlled trial of a combination of dextrometorphan and quinidine showed this to be effective in improving emotional lability and quality of life (Brooks et al., 2004). Side-effects were experienced by 89% of patients and 24% discontinued treatment during the trial's 4-week duration. "

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