Article

Tetrabenazine in the treatment of hyperkinetic movement disorders.

Department of Neurology, Parkinson's disease Center and Movement Disorders Clinic, Baylor College of Medicine, Houston, TX, USA.
Expert Review of Neurotherapeutics (Impact Factor: 2.83). 02/2006; 6(1):7-17. DOI: 10.1586/14737175.6.1.7
Source: PubMed

ABSTRACT Tetrabenazine, a dopamine-depleting agent first synthesized half a century ago, was initially developed for the treatment of schizophrenia. Although psychotic disorders have since been treated more successfully with other neuroleptic medications, many studies have shown this drug to be effective in the treatment of hyperkinetic movement disorders (hyperkinesias). Hyperkinesias are neurologic disorders characterized by abnormal involuntary movements such as chorea associated with Huntington's disease, tics in Tourette's syndrome and stereotypies in tardive dyskinesia. Recently, clinical trials investigating tetrabenazine for the treatment of chorea associated with Huntington's disease found the drug to be safe and efficacious, making approval by the US Food and Drug Administration for this indication a distinct possibility.

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    ABSTRACT: A ABSTRACT BSTRACT OBJECTIVE: To define the offending drugs associated with the occurrence of tardive syndromes in patients referred to a movement disorders clinic. BACKGROUND: Tardive dyskinesia (TD), a hyperkinetic movement disorder causally related to dopamine receptor blocking drugs (DRBD), is a well-recognized iatrogenic disorder. Although published reports on TD mainly focus on patients who have been exposed to DRBD used as anti-psychotics, these medications are also used to treat a wide array of medical, chiefly gastrointestinal, conditions. METHODS: A retrospective chart review was performed on subjects evaluated for TD in the Movement Disorders Clinic at Baylor College of Medicine. RESULTS: We report data on 434 patients listed in our database for whom we have detailed clinical information. The patients (334 female, 77.0%), had a mean age of 63.8 ±14.8 years at their initial evaluation. A causal DRBD was well defined in 411 (94.7%) patients. The most common medications associated with the onset of TD were haloperidol (N=191, 18.4%), metoclopramide (N=171, 16.5%), the combination of Amitriptyline and Perphenazine (N=85, 8.2%), and thioridazine (N=72, 6.9%) [Figure 2]. CONCLUSIONS: TD, a feared and common side effect of DRBD treatment, may be caused by multiple treatment agents other than anti-psychotic medications. Tardive dyskinesia (TD), a hyperkinetic movement disorder temporally and causally related to exposure to dopamine receptor blocking drugs (DRBD), also referred to as neuroleptics, is a well-recognized iatrogenic condition particularly in adults [Stacy and Jankovic, 1991; Rodnitzky, 2005] as well as in children including infants [Mejia and Jankovic, 2005]. Although the literature on TD mainly focuses on patients who have been exposed to DRBD used as anti-psychotics, these medications are also used to treat a wide array of medical, chiefly gastrointestinal, conditions [Tonini, 2004; Paulson, 2005; Pasricha et al, 2006] [Table 1]. Most of the drugs that cause TD are DRBD that block dopamine D2 receptors, but other classes of drugs have the potential to cause TD [Table 2, Table 3]. The reported frequency of TD in patients treated with DRBD has varied greatly, with an average at around 25% of exposed adults, and half that frequency in children [Stacy and Jankovic, 1991; Mejia and Jankovic, 2007]. Risk factors associated with the development of TD include advanced age, female gender, and total cumulative drug exposure [Woerner et al, 1998; van Os et al, 1997; Fernandez et al, 2003; Wonodi et al, 2004]. Chlorpromazine (e.g. Thorazine) Triflupromazine (e.g. Vesprin) Thioridazine (e.g. Mellaril) Mesoridazine (e.g. Serentil) Trifluoperazine (e.g. Stelazine) Prochlorperazine (e.g. Compazine) Perphenazine (e.g. Trilafon) Fluphenazine (e.g. Prolixin) Perazine Thioxanthenes a. Aliphatic b. Piperazine Chlorprothixene (e.g. Tarctan) Thiothixene (e.g. Navane) Butyrophenones Haloperidol (e.g. Haldol) Droperidol (e.g. Inapsine) Diphenylbutylpiperidine Pimozide (e.g. Orap) Dibenzazepine Loxapine (e.g. Loxitane) Dibenzodiazepine Clozapine (e.g. Clozaril) Quetiapine (e.g. Seroquel) Thienobenzodiazepine Olanzapine (e.g. Zyprexa) Pyrimidinone Risperidone (e.g. Risperdal) Benzisothiazole Ziprasidone (e.g. Geodon) Benzisoxazole Iloperidone (e.g. Zomaril) Substituted benzamides Metoclopramide (e.g. Reglan) Tiapride Sulpride Clebopride Remoxipride Veralipride Amisulpride Indolones Molindone (e.g. Moban) Quinolinone Aripiprazole (e.g. Abilify) Tricyclic Amoxapine (e.g. Asendin) Calcium channel blockers Flunarizine (e.g. Sibelium) Cinnarizine (e.g. Stugeron) N-acetyl-4-methoxytryptamine Melatonin TABLE 2. Medications with the potential to cause TD A retrospective chart review was performed on subjects evaluated for TD in the Movement Disorders Clinic at Baylor College of Medicine. We included patients who: 1) exhibited a hyperkinetic movement disorder, 2) had a documented exposure to one or more DRBD for at least 3 months before the onset of symptoms (shorter exposure time to DRBD was accepted if this was clearly related to the development of TD), and 3) the hyperkinetic movement disorder persisted for at least one month after stopping the offending DRBD [Jankovic, 1995]. We excluded patients with drug-induced parkinsonism [Noyes et al, 2006]. Demographic and clinical data were ascertained. We also searched for information about dose, treatment duration, and drug free intervals.