Use of Tetrabenazine in Huntington Disease Patients on Antidepressants or with Advanced Disease: Results from the TETRA-HD Study.
ABSTRACT The safety and effectiveness of tetrabenazine in different sub-populations of Huntington disease (HD) is not known. In this study, we evaluated the safety of tetrabenazine in individuals on an antidepressant and its effectiveness in advanced HD. Tetrabenazine was not associated with an increased incidence of depressed mood among those taking antidepressants and was effective at reducing chorea in those with advanced HD.
Article: Chorea.[Show abstract] [Hide abstract]
ABSTRACT: Chorea is a relatively common movement disorder that can be caused by a large variety of structural, autoimmune, neurodegenerative, pharmacologic, and metabolic disturbances of basal ganglia function. The diagnosis is rarely indicated by the phenotypic appearance of chorea and can be challenging, with many patients remaining undiagnosed. This review highlights salient features that may be observed or elicited in the case of a person with chorea, which may provide an indication of the diagnosis. Recent advances in genetics have identified genes for new disorders and expanded the phenotype of recognized conditions. New therapies include tetrabenazine, a presynaptic dopamine depleter, and deep brain stimulation. Clues to diagnosis may be found in the patient's family or medical history, on neurologic examination, or upon laboratory testing and neuroimaging. While most therapies at present are supportive, correct diagnosis is essential for appropriate genetic counseling and ultimately for future molecular therapies.Continuum (Minneapolis, Minn.). 10/2013; 19(5, Movement Disorders):1242-1263.
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ABSTRACT: Although tetrabenazine, a drug that depletes presynaptic dopamine by inhibiting vesicular monoamine transporter 2 (VMAT2), was approved by the U.S. Food and Drug Administration in 2008 for the treatment of chorea associated with Huntington's disease (HD), there is a paucity of data on its long-term efficacy and safety. Approximately 2,000 patients with a variety of hyperkinetic movement disorders had been treated with open-label tetrabenazine at the Movement Disorders Clinic, Baylor College of Medicine, since 1979. Tetrabenazine was usually started at 12.5 mg/day, and the dosage was gradually increased (up to 300 mg/day). Responses were rated by the investigator 1-5, with 1 = marked chorea reduction, excellent improvement in function; 2 = moderate chorea reduction, very good improvement in function; 3 = fair chorea improvement, only mild improvement in function; 4 = poor or no response for chorea and function; and 5 = worsening chorea, some functional deterioration. Efficacy and safety were analyzed retrospectively. By 2004, 98 HD chorea patients had received tetrabenazine for a mean of 3.1 years (range ≤1-11.4 years). Of those with valid ratings, 75% had either marked or very good responses (rating 1 or 2) at their optimal dosages. The most common adverse events occurring in ≥5% of the patients were somnolence (39%), insomnia (33%), depression (31%), accidental injury (26%), and dysphagia (19%). Efficacy and safety were comparable to results for non-HD chorea patients. Tetrabenazine treatment was associated with long-term improvement in chorea. Adverse event rates were comparable to those reported from controlled trials.Tremor and other hyperkinetic movements (New York, N.Y.). 01/2013; 3.
Article: Huntington's disease.[Show abstract] [Hide abstract]
ABSTRACT: This review highlights the recent advances in Huntington's disease, with particular focus on clinical characterization of prodromal Huntington's disease, as well as the growing literature regarding pathophysiological mechanisms and their relevance to potential therapeutic targets. Clinical and neuroradiological abnormalities can be demonstrated in gene-positive individuals prior to the onset of manifest Huntington's disease, even as far as 15 years before the disease onset. Although some measures show promise as potential markers of disease progression, further longitudinal studies are required. Several molecular pathways have been implicated in the process of neurodegeneration involved in Huntington's disease and provide potential therapeutic targets. With predictive testing allowing the identification of gene-positive individuals prior to disease onset, the prodromal stage of Huntington's disease provides an ideal period for the use of disease-modifying therapy. A quantifiable and reliable biomarker for monitoring disease progression is crucial for clinical studies of neuroprotection, and this remains an area of active research. Understanding of the underlying pathophysiological mechanisms continues to grow, based mainly on cellular and animal models of Huntington's disease.Current opinion in neurology 08/2012; 25(4):491-8. · 5.73 Impact Factor