Tetrabenazine

Tetrabenazine is used as a treatment, but not as a cure, for hyperkinetic disorders such as: • Huntington's disease – specifically, the chorea associated with it • Tourette syndrome and other tic disorders • Tardive dyskinesia, a serious and sometimes irreversible side effect of long-term use of many antipsychotics, mainly typical antipsychotics • Hemiballismus, spontaneous flinging limb movements due to contra-lateral subthalamic nucleus damage Tetrabenazine has been used as an antipsychotic in the treatment of schizophrenia, both in the past and in modern times. ==Adverse effects==

The most common adverse effects, which have occurred in at least 10% of subjects in studies and at least 5% greater than in subjects who received placebo, have been: sedation or somnolence, fatigue, insomnia, depression, suicidal thoughts, akathisia, anxiety, and nausea. It has also been reported to produce apathy. Black box warning There is a boxed warning associated with the use of tetrabenazine: • Increases the risk of depression and suicidal thoughts and behavior in patients with Huntington's disease • Balance risks of depression and suicidality with the clinical need for control of chorea when considering the use of tetrabenazine • Monitor patients for emergence or worsening of depression, suicidality or unusual changes in behavior • Inform patients, caregivers and families of the risk of depression and suicidality and instruct to report behaviours of concern promptly to the treating physician • Exercise caution when treating patients with a history of depression or prior suicide attempts or ideation • Tetrabenazine is contraindicated in patients who are actively suicidal and in patients with untreated or inadequately treated depression ==Pharmacology==

The precise mechanism of action of tetrabenazine is unknown. Its anti-chorea effect is believed to be due to a reversible depletion of monoamines such as dopamine, serotonin, norepinephrine, and histamine from nerve terminals. Tetrabenazine reversibly inhibits vesicular monoamine transporter 2 (VMAT2), resulting in decreased uptake of monoamines into synaptic vesicles, as well as depletion of monoamine storage. ==Research==

Animal model of motivational dysfunction Tetrabenazine is used in the only animal model of motivational dysfunction. The drug results in selective depletion of dopamine at low doses of 0.25 to 1.0mg/kg and induces a low-effort bias in effort-based decision-making tasks at these doses. In contrast, levels of serotonin and norepinephrine are only reduced by up to 15 to 30% at this dosage. Selegiline shows a complicated U-shaped dose–response curve in its efficacy in the model. ==See also==