Licensed in 2008 to treat Chorea, a neurological condition that causes involuntary, unpredictable movements in the face, hands, and feet. Also used in the treatment of Hemiballismus, a rare neurological disorder that causes involuntary, forceful movements of the limbs on one side of the body, Tardive Dyskinesia, a chronic movement disorder that causes involuntary muscle movements in the face, body, and limbs, and Tourette Syndrome which is a is a neurological disorder that causes involuntary movements and sounds called tics. While medications help control diseases, they can worsen the conditions or create new issues if not administered properly. While doctors start small and gradually increase the doses to learn the least working dose, the FDA-approved drug label states that an accurate Tetrabenazine dose above 50mg per day needs to be genotyped based, in other words, based on your genome (DNA). Any drug you consume is metabolized by a specific enzyme in the body, in the case of Tetrabenazine, CYP2D6 is responsible for the metabolization.

Tetrabenazine Administration

Tetrabenazine is available in tablet form for oral administration and can be taken with or without food. The initial recommended dose is 12.5 mg once daily. Based on patient response and tolerance, the dosage may be increased by 12.5 mg every week. Typically, the dose is increased to 25 mg per day in the second week, administered as 12.5 mg twice daily. Further adjustments can be made, with the total daily dose divided into two or three administrations, not exceeding a maximum of 100 mg per day. Dose adjustments should be individualized, taking into account factors such as the severity of symptoms, patient response, and the presence of any adverse effects.

According to the FDA label, “Patients requiring doses above 50 mg per day should be genotyped for the drug metabolizing enzyme CYP2D6 to determine if the patient is a poor metabolizer (PM) or an extensive metabolizer.”

Chorea and its Symptoms

Chorea is a movement disorder characterized by involuntary, unpredictable body movements. Some of the symptoms include:

• Restlessness (fidgeting): Individuals may exhibit twitching, jerking, or twisting movements of the arms, legs, and face that are not purposeful.
• Milkmaid’s grip: This refers to the involuntary squeezing and releasing of the hands repeatedly when attempting to maintain a firm grip, resembling the motion of milking a cow.
• Difficulty swallowing: Some individuals may experience challenges in swallowing.
• Difficulty talking: Speech may be affected, leading to trouble speaking.
• Abnormal gait: Walking patterns may become irregular, and maintaining balance can be challenging.
• Muscle rigidity or contracture: Some individuals may experience muscle stiffness or contractures.

Common Age of Onset

The age of onset for chorea varies depending on its underlying cause. For instance, in Huntington’s disease, a common cause of chorea, symptoms typically begin between the ages of 30 and 50. However, chorea can manifest at any age, depending on the specific etiology.

Dose for Treating Chorea

The dosing of tetrabenazine for chorea is individualized based on factors such as the severity of symptoms, patient response, and tolerance. The initial dose is typically 12.5 mg once daily, with gradual increases by 12.5 mg each week. The total daily dose is divided into two or three administrations, with a maximum recommended dose of 100 mg per day. Regular monitoring is essential to adjust the dose appropriately and to manage any potential side effects.

Hemiballismus and its Symptoms

Hemiballismus is a rare movement disorder characterized by involuntary, violent, and wide-amplitude movements, typically affecting one side of the body. These movements are more intense than those seen in chorea and can significantly impair daily functioning.

Common Age of Onset

Hemiballismus can occur at any age but is more commonly observed in older adults. It often results from lesions in the subthalamic nucleus, frequently due to cerebrovascular events such as strokes.

Dose for Treating Hemiballismus

Tetrabenazine has been used off-label for the treatment of hemiballismus. The dosing regimen is similar to that used for chorea, starting with a low dose and gradually titrating based on patient response and tolerance. Given the limited specific studies on tetrabenazine for hemiballismus, treatment should be closely monitored by a healthcare professional experienced in managing movement disorders.

Tardive Dyskinesia and its Symptoms

Tardive dyskinesia (TD) is a movement disorder characterized by repetitive, involuntary movements, primarily affecting the face, lips, tongue, and extremities. Symptoms include:

• Facial grimacing: Uncontrolled facial expressions.
• Tongue movements: Protrusion or rolling of the tongue.
• Lip smacking or puckering: Involuntary lip movements.
• Rapid blinking: Increased frequency of eye blinking.
• Movements of the arms, legs, or trunk: Jerking or twisting motions.

These movements can interfere with daily activities and may persist even after discontinuation of the causative medication.

Common Age of Onset

TD can develop at any age but is more prevalent in older adults. The risk increases with prolonged use of antipsychotic medications, particularly typical antipsychotics.

Dose for Treating Tardive Dyskinesia

Tetrabenazine has been used in the treatment of TD, although it is not specifically approved for this indication. The dosing strategy involves starting at a low dose and gradually increasing based on patient response and tolerance. Close monitoring is essential due to the potential for side effects, including depression and parkinsonism.

Tourette Syndrome and its Symptoms

Tourette syndrome is a neurological disorder characterized by repetitive, involuntary movements and vocalizations called tics. Symptoms include:

• Motor tics: Sudden, brief, repetitive movements such as eye blinking, facial grimacing, shoulder shrugging, or head jerking.
• Vocal tics: Unintended sounds, including throat clearing, grunting, or uttering words or phrases.

The severity and frequency of tics can vary over time and may be exacerbated by stress or excitement.

Common Age of Onset

Tourette syndrome typically manifests in childhood, with the average onset between ages 5 and 7. Males are more commonly affected than females.

Dose for Tourette Syndrome

Tetrabenazine has been used off-label to manage tics in Tourette syndrome.

How Does Tetrabenazine Work?

Tetrabenazine works by reducing the activity of specific neurotransmitters in the brain, particularly dopamine. Its primary mechanism involves inhibiting the vesicular monoamine transporter 2 (VMAT2), a protein that regulates the storage and release of dopamine in nerve cells. By depleting dopamine levels, tetrabenazine helps control abnormal movements associated with disorders like chorea, hemiballismus, and tardive dyskinesia.

Active Ingredient:

Tetrabenazine itself is the active ingredient, and its metabolites (dihydrotetrabenazine) contribute to its pharmacological effects. CYP2D6 metabolizes Tetrabenazine in the body.

Effects on the Brain:

Decreases dopamine levels: This reduces hyperactive neural signaling, which is implicated in movement disorders.

Impact on other neurotransmitters: Tetrabenazine also influences serotonin and norepinephrine, though its effects on these systems are less pronounced than on dopamine.

Potential risks: Dopamine depletion may lead to symptoms of depression or parkinsonism in some individuals.

Potential Side Effects of Tetrabenazine

Tetrabenazine may cause side effects, varying by individual and influenced by dosage. Potential side effects include:

Common Side Effects:

• Fatigue or drowsiness
• Nausea
• Anxiety or restlessness
• Insomnia
• Depressed mood

Less Common but Serious Side Effects:

Suicidal thoughts or behaviors

Parkinsonism-like symptoms (shaky or vibrating movements in the body), slowed movements, and stiffness).
Hypotension (low blood pressure)
Increased risk of QT prolongation, leading to potential heart rhythm issues

Gender-Specific Effects:

• Men: Tend to report parkinsonism-like symptoms more frequently due to higher muscle mass.
• Women: May experience higher rates of depression and anxiety, potentially linked to hormonal interactions.
• Monitoring and Mitigation: Close monitoring of mental health and physical symptoms is essential, particularly in individuals with a history of depression or cardiac conditions.

Pharmacogenomics and Optimal Tetrabenazine Doses:

Pharmacogenomic testing often known as PGx testing shows how an individual may respond to certain medications. This gives you insights into your DNA that help doctors analyze what type of metabolizer you are, based on which they can tailor your medication accordingly. A non-invasive and at home PGx test by RPH LABS shows how your body may respond to 250+ medications. Tetrabenazine is metabolized by CYP2D6 and our report shall clearly show what type of CYP2D6 metabolizer you are.

Unsure how to book a PGx test or how this works? Here we have a step-wise process for you.

References:

https://pubmed.ncbi.nlm.nih.gov/19381278/
https://my.clevelandclinic.org/health/symptoms/21192-chorea
https://pubmed.ncbi.nlm.nih.gov/28965423/

Disclaimer: This blog is only for informational purposes. Always consult a doctor before taking any medical action.