title: 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.
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.
  
  
  BACKGROUND
  #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: Neurology Associates , Lincoln, NE , USA.
authors: Gary L
authors: GL
authors: Pattee
authors: James P
authors: JP
authors: Wymer
authors: Catherine
authors: C
authors: Lomen-Hoerth
authors: Stanley H
authors: SH
authors: Appel
authors: Andrea E
authors: AE
authors: Formella
authors: Laura E
authors: LE
authors: Pope
mesh_terms: D000293:Adolescent; D000328:Adult; D000342:Affective Symptoms / Q000188:drug therapy* / Q000209:etiology; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003448:Crying; D065690:Cytochrome P-450 CYP2D6 Inhibitors / Q000627:therapeutic use*; D003915:Dextromethorphan / Q000627:therapeutic use*; D004338:Drug Combinations; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007845:Laughter; D008297:Male; D008875:Middle Aged; D020828:Pseudobulbar Palsy / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology*; D011802:Quinidine / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D065690:Cytochrome P-450 CYP2D6 Inhibitors; D004338:Drug Combinations; D018691:Excitatory Amino Acid Antagonists; C507057:dextromethorphan - quinidine combination; D003915:Dextromethorphan; D011802:Quinidine
keywords: Dextromethorphan/quinidine; Pseudobulbar affect; Safety; Tolerability