James P Wymer | PubMed Health

PubMed2006

Randomized, controlled trial of dextromethorphan/quinidine for pseudobulbar affect in multiple sclerosis.

OBJECTIVE: To evaluate the efficacy and safety of DM/Q (capsules containing dextromethorphan [DM] and quinidine [Q]) compared with placebo, taken twice daily, for the treatment of pseudobulbar affect over a 12-week period in multiple sclerosis patients. METHODS: A total of 150 patients were randomized in a double-blind, placebo-controlled study to assess pseudobulbar affect with the validated Center for Neurologic Study-Lability Scale. Each patient also recorded the number of episodes experienced between visits, estimated quality of life and quality of relationships on visual analog scales, and completed a pain rating scale. RESULTS: Patients receiving DM/Q had greater reductions in Center for Neurologic Study-Lability Scale scores than those receiving placebo (p < 0.0001) at all clinic visits (days 15, 29, 57, and 85). All secondary end points also favored DM/Q, including the number of crying or laughing episodes (p <or= 0.0077), quality of life (p < 0.0001), quality of relationships (p = 0.0001), and pain intensity score (p = 0.0271). DM/Q was well tolerated; only dizziness occurred with greater frequency than with placebo. INTERPRETATION: Results in multiple sclerosis patients were similar to those of a previous study in amyotrophic lateral sclerosis, demonstrating that DM/Q may be beneficial in treating potentially disabling pseudobulbar affect in a variety of neurological disorders.

Affect↗

PubMed2006

Dextromethorphan and quinidine in adult patients with uncontrolled painful diabetic peripheral neuropathy: a 29-day, multicenter, open-label, dose-escalation study.

BACKGROUND: Pain associated with diabetic peripheral neuropathy (DPN) has a substantial negative impact on patients' quality of life. OBJECTIVES: The primary objective of this study was to evaluate the tolerability of capsules containing dextromethorphan (DM) and quinidine (Q) in patients with painful DPN. A secondary objective was to perform a preliminary assessment of the efficacy of DM/Q in this patient population. METHODS: This was a multicenter, open-label, dose-escalation study. Eligible patients were aged between 18 and 80 years, had a confirmed diagnosis of diabetes with acceptable glycemic control, had been receiving established diabetic therapy for at least 3 months, and had a clinical diagnosis of distal symmetric sensory neuropathy with daily DPN-associated pain for the previous 3 months. On study entry, patient-rated diabetic pain had to be moderate or greater. Patients who met the inclusion criteria underwent a 2-week washout period during which all analgesics were discontinued, followed by 29 days of treatment with capsules containing DM 30 mg and Q 30 mg (DM30/Q30), beginning with 1 capsule/d and escalating at approximately 1-week intervals, as tolerated, to a maximum dose of 4 capsules/d (DM120/Q120). Tolerability was assessed based on adverse events and changes in clinical and laboratory parameters and nerve conduction velocity. Preliminary efficacy assessments included changes from baseline in scores on the pain intensity rating scale (PIRS), pain relief rating scale (PRRS), peripheral neuropathy quality-of-life instrument, and patients' diary assessments of sleep, present pain intensity, pain, and activity. RESULTS: The study included 36 men and women (mean age, 58 years; mean body mass index, 32.8 kg/m(2)). Of the 33 subjects who completed the study, 23 (69.7%) did so at the highest permitted dose (DM120/Q120). The most commonly reported adverse events (occurring in > or =5% of subjects) were nausea (27.8%), dizziness (25.0%), and headache (25.0%). Three patients experienced 5 serious adverse events, only 1 of which was considered possibly related to study drug. The most commonly occurring laboratory abnormalities (involving glycosylated hemoglobin, serum glucose, triglycerides, and cholesterol) were considered typical of a population with diabetes. Improvements from baseline in scores on the PIRS, PRRS, and other exploratory efficacy measures were noted (P < 0.001). CONCLUSIONS: The results of this open-label study indicated that the combination of DMIQ (dose range, DM30/Q30-DM120/Q120) was well tolerated in patients with pain associated with DPN. Based on the preliminary efficacy results, a randomized, controlled, double-blind trial is warranted to assess the tolerability and efficacy of this combination in patients with DPN.

Adult↗