Tetrabenazine is a prescription medication used to manage certain hyperkinetic movement disorders. It acts on the central nervous system to help control the involuntary, erratic motions that characterize these conditions. This medication’s function, clinical performance, and safety considerations are important for patients and caregivers. Understanding the balance between the drug’s effectiveness and its potential side effects is key for anyone considering this therapy.
How Tetrabenazine Works and Conditions It Treats
Tetrabenazine functions as a reversible inhibitor of vesicular monoamine transporter 2 (VMAT2). This transporter protein moves neurotransmitters, including dopamine, serotonin, and norepinephrine, into storage vesicles within nerve endings. By blocking VMAT2, the medication limits the amount of these monoamines packaged and released into the synapse.
This action reduces the concentration of neurotransmitters in the synaptic cleft, particularly dopamine, which is heavily involved in motor control. This depletion of dopamine in the basal ganglia helps dampen the excessive signaling that leads to uncontrolled movements.
The primary approved use for Tetrabenazine is treating chorea associated with Huntington’s disease. Chorea is a movement disorder characterized by involuntary, irregular, and rapid movements. The drug addresses these motor symptoms but does not treat the underlying neurodegenerative cause or associated cognitive and psychiatric symptoms. It is also used for other hyperkinetic disorders, such as tardive dyskinesia, which involves involuntary, repetitive movements often affecting the face and tongue.
Measuring Clinical Effectiveness and Dosing
The effectiveness of Tetrabenazine is measured using standardized neurological rating scales. For chorea related to Huntington’s disease, the most common tool is the Unified Huntington’s Disease Rating Scale (UHDRS), specifically the Total Maximal Chorea (TMC) score. Clinical trials show that patients experience a significant reduction in chorea severity compared to placebo. For example, one study reported an average severity reduction of approximately 23.5% as measured by UHDRS units.
Physicians may also use the Clinical Global Impressions (CGI) Improvement Scale, which assesses the overall change in the patient’s condition since starting treatment. Successful treatment can also lead to improvements in functional measures like gait and balance, which are usually noticed within the first few weeks of reaching an effective dose.
Dosing requires a slow and careful process known as titration to find the lowest dose that provides a therapeutic effect while minimizing side effects. Treatment usually begins with a low dose, such as 12.5 mg once daily, and is gradually increased in small increments, often by 12.5 mg per week. The daily dose is typically divided and taken two or three times a day when the total dose exceeds 50 mg. The maximum recommended daily dose for most patients is 100 mg, but this limit may be lower for individuals who are poor metabolizers of the CYP2D6 liver enzyme.
Safety Profile: Common and Serious Adverse Effects
Common Side Effects
The most frequently reported side effects are related to Tetrabenazine’s mechanism of reducing neurotransmitter activity. Sedation and somnolence, or excessive sleepiness, are common adverse events affecting a large percentage of patients. Conversely, some individuals experience insomnia or difficulty sleeping.
Other common effects include psychiatric symptoms such as depression and anxiety, and a general feeling of fatigue. The medication can also cause Parkinsonism-like symptoms, including tremor, muscle stiffness, or difficulty with balance and gait. Gastrointestinal issues like nausea are also reported, which can sometimes be managed by taking the medication with food.
Serious Adverse Effects
While less frequent, certain adverse effects require immediate attention from a healthcare provider. One serious risk is Neuroleptic Malignant Syndrome (NMS), a rare but potentially fatal condition. Symptoms of NMS include very high fever, severe muscle rigidity, altered mental status, and autonomic instability, such as irregular pulse or blood pressure.
The medication can also cause QTc prolongation, an abnormality in the heart’s electrical activity that can lead to dangerous, irregular heartbeats. Patients may also experience orthostatic hypotension, a sudden drop in blood pressure upon standing that can cause dizziness or fainting. Another serious effect is hyperprolactinemia, where an increase in the hormone prolactin can potentially affect bone health or fertility.
Critical Warnings and Drug Interactions
Tetrabenazine carries a specific regulatory warning regarding the risk of depression and suicidal ideation. Due to this recognized risk, patients with untreated or inadequately managed depression should not be prescribed the drug. Close monitoring for any sudden changes in mood, behavior, or the emergence of suicidal thoughts is necessary for all patients taking this medication.
The use of Tetrabenazine is prohibited in several circumstances due to severe health risks. It is contraindicated in patients with impaired liver function, as this could lead to dangerously high drug exposure levels.
The medication must not be used concurrently with Monoamine Oxidase Inhibitors (MAOIs), or within 14 days of stopping an MAOI. Coadministration with reserpine is also strictly avoided; at least 20 days must pass after discontinuing reserpine before starting Tetrabenazine. This precaution is necessary because both drugs deplete monoamines, and combining them can cause an unsafe level of neurotransmitter depletion. Additionally, Tetrabenazine should not be used with other VMAT2 inhibitors, such as deutetrabenazine or valbenazine, due to the risk of additive effects and overdose.
The medication’s metabolism is influenced by the CYP2D6 enzyme. Drugs that inhibit this enzyme, such as certain antidepressants (e.g., fluoxetine or paroxetine), can significantly increase the levels of Tetrabenazine’s active metabolites. In such cases, the dosage of Tetrabenazine must be reduced to avoid toxicity. Furthermore, because of the risk of QTc prolongation, the medication should be avoided in combination with any other drug known to affect the QTc interval, including certain antipsychotics or antiarrhythmic medications.