A pilot study of the clinical efficacy and safety of memantine for Huntington's disease.

OBJECTIVE: To determine the clinical efficacy and safety of memantine in Huntington’s disease (HD). BACKGROUND: The excitatory activity of Lglutamate may affect the progression of HD. Memantine, an N-methyl-Daspartate antagonist used to treat Alzheimer’s dementia, could theoretically retard the progression of this disorder, improve cognition, and improve chorea. METHODS: HD patients were recruited from Baylor College of Medicine; twelve were started on memantine, titrated to a daily dose of 20 mg, and followed for three months. Other medications were unchanged during this period. RESULTS: Three patients stopped memantine because of lack of apparent efficacy (N= 1) and adverse events (N= 2). The nine analyzed patients: 5 male (55.6%), ages 53.5 years ± 20.8, with 50.3 ± 16.5 CAG repeats, titrated to the maximum dose of 20 mg of memantine, and were followed for 3.8 ± 1.0 months. A significant difference existed between their initial (x= 43.2 ± 11.7) and final (x= 33.50 ± 11.1) total UHDRS motor scores (P= 0.008) as well as in their maximum chorea rating (4.8 ± 3.8) (P= 0.008), compared to their initial evaluation (11.5 ± 6.3). Patients did not show a significant change in their cognitive (P= 0.625) or behavioral (P= 0.258) ratings. Their total functional capacity (P= 0.078) and independence scale rating (P= 1.00) also failed to show a significant change. Most (N= 7, 77.7%) patients did not have any adverse effects under memantine; one (11.1%) reported drowsiness; another (11.1%) complained of worsening balance, speech and social interaction. No serious adverse events were reported. CONCLUSIONS: In this small pilot trial, 20 mg daily dose of memantine significantly decreased chorea, but failed to improve patients cognitive, behavioral, functional, or independence ratings. Most patients tolerated memantine without side effects. Larger controlled trials and long term trials to assess for disease modification are justified. To determine the clinical efficacy and safety of memantine in Huntington’s disease (HD). METHODS OBJECTIVE We recruited HD patients from Baylor College of Medicine. Twelve patients were started on memantine. They were: •Titrated to a daily dose of 20mg •Followed for 3 months •Other medications were unchanged during this period. Ascertained information included: • Demographic data • Vital signs • UHDRS [Table 1] Baseline Final evaluation • Concomitant medications RESULTS RATIONALE • Overactivity of glutamate neurotoxicity may lead to neuronal death; •HD transgenic mouse models have shown increased sensitivity to NMDA receptor activation and enhanced excitotoxicity; •Memantine, due to its uncompetitive antagonism, prevents activation of NMDA receptors, but allows their physiologic activity, decreasing the possibility of side effects. •In this small pilot trial, 20mg daily dose of memantine significantly decreased motor symptoms (predominantly chorea), but failed to show improvement in patient’s cognitive, behavioral, functional, or independence ratings. •Most patients tolerated memantine without side effects. •Larger controlled trials and long term trials to assess for disease modification are justified. CONCLUSIONS