PMID- 25062507
OWN - NLM
STAT- MEDLINE
DCOM- 20150528
LR  - 20211021
IS  - 1473-4877 (Electronic)
IS  - 0300-7995 (Print)
IS  - 0300-7995 (Linking)
VI  - 30
IP  - 11
DP  - 2014 Nov
TI  - 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.
PG  - 2255-65
LID - 10.1185/03007995.2014.940040 [doi]
AB  - 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.
FAU - Pattee, Gary L
AU  - Pattee GL
AD  - Neurology Associates , Lincoln, NE , USA.
FAU - Wymer, James P
AU  - Wymer JP
FAU - Lomen-Hoerth, Catherine
AU  - Lomen-Hoerth C
FAU - Appel, Stanley H
AU  - Appel SH
FAU - Formella, Andrea E
AU  - Formella AE
FAU - Pope, Laura E
AU  - Pope LE
LA  - eng
SI  - ClinicalTrials.gov/NCT00056524
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20140728
PL  - England
TA  - Curr Med Res Opin
JT  - Current medical research and opinion
JID - 0351014
RN  - 0 (Cytochrome P-450 CYP2D6 Inhibitors)
RN  - 0 (Drug Combinations)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (dextromethorphan - quinidine combination)
RN  - 7355X3ROTS (Dextromethorphan)
RN  - ITX08688JL (Quinidine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Affective Symptoms/*drug therapy/etiology
MH  - Aged
MH  - Aged, 80 and over
MH  - Cohort Studies
MH  - Crying
MH  - Cytochrome P-450 CYP2D6 Inhibitors/*therapeutic use
MH  - Dextromethorphan/*therapeutic use
MH  - Drug Combinations
MH  - Excitatory Amino Acid Antagonists/*therapeutic use
MH  - Female
MH  - Humans
MH  - Laughter
MH  - Male
MH  - Middle Aged
MH  - Pseudobulbar Palsy/*drug therapy/etiology/*psychology
MH  - Quinidine/*therapeutic use
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC4743597
OTO - NOTNLM
OT  - Dextromethorphan/quinidine
OT  - Pseudobulbar affect
OT  - Safety
OT  - Tolerability
EDAT- 2014/07/26 06:00
MHDA- 2015/05/29 06:00
PMCR- 2016/02/05
CRDT- 2014/07/26 06:00
PHST- 2014/07/26 06:00 [entrez]
PHST- 2014/07/26 06:00 [pubmed]
PHST- 2015/05/29 06:00 [medline]
PHST- 2016/02/05 00:00 [pmc-release]
AID - 940040 [pii]
AID - 10.1185/03007995.2014.940040 [doi]
PST - ppublish
SO  - Curr Med Res Opin. 2014 Nov;30(11):2255-65. doi: 10.1185/03007995.2014.940040. 
      Epub 2014 Jul 28.