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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 Nov; 30(11):2255-65.CM

Abstract

BACKGROUND

Pseudobulbar affect (PBA) is associated with neurological disorders or injury affecting the brain, and characterized by frequent, uncontrollable episodes of crying and/or laughing that are exaggerated or unrelated to the patient's emotional state. Clinical trials establishing dextromethorphan and quinidine (DM/Q) as PBA treatment were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). This trial evaluated DM/Q safety in patients with PBA secondary to any neurological condition affecting the brain.

OBJECTIVE

To evaluate the safety and tolerability of DM/Q during long-term administration to patients with PBA associated with multiple neurological conditions.

METHODS

Fifty-two-week open-label study of DM/Q 30/30 mg twice daily. Safety measures included adverse events (AEs), laboratory tests, electrocardiograms (ECGs), vital signs, and physical examinations.

CLINICAL TRIAL REGISTRATION

#NCT00056524.

RESULTS

A total of 553 PBA patients with >30 different neurological conditions enrolled; 296 (53.5%) completed. The most frequently reported treatment-related AEs (TRAEs) were nausea (11.8%), dizziness (10.5%), headache (9.9%), somnolence (7.2%), fatigue (7.1%), diarrhea (6.5%), and dry mouth (5.1%). TRAEs were mostly mild/moderate, generally transient, and consistent with previous controlled trials. Serious AEs (SAEs) were reported in 126 patients (22.8%), including 47 deaths, mostly due to ALS progression and respiratory failure. No SAEs were deemed related to DM/Q treatment by investigators. ECG results suggested no clinically meaningful effect of DM/Q on myocardial repolarization. Differences in AEs across neurological disease groups appeared consistent with the known morbidity of the primary neurological conditions. Study interpretation is limited by the small size of some disease groups, the lack of a specific efficacy measure and the use of a DM/Q dose higher than the eventually approved dose.

CONCLUSIONS

DM/Q was generally well tolerated over this 52 week trial in patients with PBA associated with a wide range of neurological conditions.

Authors+Show Affiliations

Neurology Associates , Lincoln, NE , USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25062507

Citation

Pattee, Gary L., 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." Current Medical Research and Opinion, vol. 30, no. 11, 2014, pp. 2255-65.
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.
Pattee, G. L., Wymer, J. P., Lomen-Hoerth, C., Appel, S. H., Formella, A. E., & Pope, L. E. (2014). 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. Current Medical Research and Opinion, 30(11), 2255-65. https://doi.org/10.1185/03007995.2014.940040
Pattee GL, 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. PubMed PMID: 25062507.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Pattee,Gary L, AU - Wymer,James P, AU - Lomen-Hoerth,Catherine, AU - Appel,Stanley H, AU - Formella,Andrea E, AU - Pope,Laura E, Y1 - 2014/07/28/ PY - 2014/7/26/entrez PY - 2014/7/26/pubmed PY - 2015/5/29/medline KW - Dextromethorphan/quinidine KW - Pseudobulbar affect KW - Safety KW - Tolerability SP - 2255 EP - 65 JF - Current medical research and opinion JO - Curr Med Res Opin VL - 30 IS - 11 N2 - BACKGROUND: Pseudobulbar affect (PBA) is associated with neurological disorders or injury affecting the brain, and characterized by frequent, uncontrollable episodes of crying and/or laughing that are exaggerated or unrelated to the patient's emotional state. Clinical trials establishing dextromethorphan and quinidine (DM/Q) as PBA treatment were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). This trial evaluated DM/Q safety in patients with PBA secondary to any neurological condition affecting the brain. OBJECTIVE: To evaluate the safety and tolerability of DM/Q during long-term administration to patients with PBA associated with multiple neurological conditions. METHODS: Fifty-two-week open-label study of DM/Q 30/30 mg twice daily. Safety measures included adverse events (AEs), laboratory tests, electrocardiograms (ECGs), vital signs, and physical examinations. CLINICAL TRIAL REGISTRATION: #NCT00056524. RESULTS: A total of 553 PBA patients with >30 different neurological conditions enrolled; 296 (53.5%) completed. The most frequently reported treatment-related AEs (TRAEs) were nausea (11.8%), dizziness (10.5%), headache (9.9%), somnolence (7.2%), fatigue (7.1%), diarrhea (6.5%), and dry mouth (5.1%). TRAEs were mostly mild/moderate, generally transient, and consistent with previous controlled trials. Serious AEs (SAEs) were reported in 126 patients (22.8%), including 47 deaths, mostly due to ALS progression and respiratory failure. No SAEs were deemed related to DM/Q treatment by investigators. ECG results suggested no clinically meaningful effect of DM/Q on myocardial repolarization. Differences in AEs across neurological disease groups appeared consistent with the known morbidity of the primary neurological conditions. Study interpretation is limited by the small size of some disease groups, the lack of a specific efficacy measure and the use of a DM/Q dose higher than the eventually approved dose. CONCLUSIONS: DM/Q was generally well tolerated over this 52 week trial in patients with PBA associated with a wide range of neurological conditions. SN - 1473-4877 UR - https://www.unboundmedicine.com/medline/citation/25062507/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_ L2 - http://www.tandfonline.com/doi/full/10.1185/03007995.2014.940040 DB - PRIME DP - Unbound Medicine ER -