- Obsessive Compulsive Behavior
Amantadine (Symmetrel®) Studies of this drug for chorea have given variable results. One study found chorea benefit in a two week trial at 400 mg/day [Verhagen Metman L 2002]. Another study using intravenous drug was also positive [Lucetti C 2003]. However, a later two week placebo controlled study of 24 patients using 300 mg/day found no positive effect for chorea [O'Suilleabhain P 2003].
Amantadine dosage begins at 100 mg per day, and is increased to 300-400 mg total dose. Larger doses should be split and taken twice a day. Side effects most often include low blood pressure, nausea, insomnia, agitation, and headache.
Memantine (Namenda®) One study found benefit for chorea in 12 patients in an open label study [Ondo WG 2007]. Another trial testing memantine in 27 patients demonstrated slowing of disease progression in both cognitive and motor parameters, but did not specifically measure chorea response [Beister A 2004]. A larger placebo controlled trial of this drug for use in Huntington's is presently underway in the Unitied States, but is primarily testing for cognitive benefit.
Memantine dosage starts at 5mg/day for the first week, then increases by 5 mg/day for the next 3 weeks (wait a week to increase each dose). The target dose is 20- 30mg/day taking it twice daily in divided dose. Side effects can include hypertension, dizziness, confusion, headache, constipation and vomiting.
Tetrabenazine (Nitoman® in Canada and some European countries; Xenazine® in the U.S. and some European countries). This drug is now FDA approved for use in the United States. This drug was shown to decrease chorea in a large placebo controlled clinical trial for the short term [Huntington Study Group 2006]. A subsequent study has shown that chorea benefit continues long term. Side effects include sleepiness, insomnia, anxiety, and depression.
Because of the high risk of serious depression, and even suicide with this drug, I recommend the judicious use of antidepressants with tetrabenazine. Antidepressants can restore the levels of serotonin and norepinephrine which are depleted by tetrabenazine.
Tetrabenazine dosing should start at 12.5 mg once or twice a day, and then increased by 12.5 mg per week until chorea decreases, or side effects occur. I have found that with prolonged use, dosage can often be decreased while maintaining desired affect. When on this drug it is important to see your doctor regularly to assess for depression side effects.
Verhagen Metman L, Morris MJ, Farmer C, Gillespie M, Mosby K, Wuu J, Chase TN. Huntington's disease: a randomized, controlled trial using the NMDA-antagonist amantadine. Neurology. 2002 Sep 10;59(5):694-9. PubMed abstract
Lucetti C, Del Dotto P, Gambaccini G, Dell' Agnello G, Bernardini S, Rossi G, Murri L, Bonuccelli U. IV amantadine improves chorea in Huntington's disease: an acute randomized, controlled study. Neurology. 2003 Jun 24;60(12):1995-7. PubMed abstract
O'Suilleabhain P, Dewey RB Jr. A randomized trial of amantadine in Huntington disease. Arch Neurol. 2003 Jul;60(7):996-8. PubMed abstract
Ondo WG, Mejia NI, Hunter CB. A pilot study of the clinical efficacy and safety of memantine for Huntington's disease. Parkinsonism Relat Disord. 2007 Oct;13(7):453-4. Epub 2006 Oct 13. PubMed abstract
Beister A, Kraus P, Kuhn W, Dose M, Weindl A, Gerlach M. The N-methyl-D-aspartate antagonist memantine retards progression of Huntington's disease. J Neural Transm Suppl. 2004;(68):117-22. PubMed abstract
Huntington Study Group. Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial. Neurology. 2006 Feb 14;66(3):366-72. PubMed abstract