Tetmodis: Uses, Dosage & Side Effects
A VMAT2 inhibitor used to treat hyperkinetic movement disorders in Huntington’s chorea by reducing dopamine levels in the brain
Tetmodis (tetrabenazine) is a prescription medicine used to treat the involuntary, jerky, and uncontrollable movements (chorea) associated with Huntington’s disease. It belongs to a class of drugs known as vesicular monoamine transporter 2 (VMAT2) inhibitors, which work by reducing dopamine levels in the brain. Tetmodis is available as 25 mg tablets and should only be initiated and monitored by physicians experienced in the management of Huntington’s disease. This medicine is approved across the European Economic Area and is marketed under the brand name Tetmodis by AOP Orphan Pharmaceuticals.
Quick Facts: Tetmodis
Key Takeaways
- Tetmodis (tetrabenazine) is specifically approved for treating hyperkinetic movement disorders associated with Huntington’s chorea, helping to reduce involuntary and uncontrollable movements by depleting dopamine in the basal ganglia.
- Depression and suicidal ideation are serious risks; Tetmodis is contraindicated in patients with active depression or suicidal thoughts, and all patients require regular psychiatric monitoring throughout treatment.
- Dosing starts low (12.5 mg one to three times daily) and is gradually increased every 3–4 days to find the optimal balance between chorea reduction and tolerability, up to a maximum of 200 mg per day.
- Tetmodis must never be combined with reserpine or MAO inhibitors, and patients taking CYP2D6 inhibitors (such as fluoxetine or paroxetine) may need lower doses due to increased drug exposure.
- Treatment should not be stopped abruptly due to the risk of neuroleptic malignant syndrome, a potentially life-threatening condition characterized by high fever, muscle rigidity, and altered consciousness.
What Is Tetmodis and What Is It Used For?
Tetmodis contains the active substance tetrabenazine, a medicine that belongs to a group of drugs used for the treatment of nervous system disorders. Specifically, tetrabenazine is classified as a vesicular monoamine transporter 2 (VMAT2) inhibitor. VMAT2 is a protein found on the membranes of synaptic vesicles inside nerve cells. Its primary function is to package neurotransmitters—particularly dopamine, serotonin, and norepinephrine—into these vesicles so they can be released at nerve synapses. By reversibly inhibiting VMAT2, tetrabenazine reduces the amount of dopamine that is loaded into vesicles and subsequently available for release.
The therapeutic value of tetrabenazine in Huntington’s disease is directly linked to its dopamine-depleting action. In Huntington’s disease, progressive degeneration of neurons in the striatum (a key structure within the basal ganglia) leads to an imbalance in neurotransmitter signaling, with a relative excess of dopaminergic activity that contributes to choreiform movements. By reducing the availability of dopamine at striatal synapses, tetrabenazine helps to rebalance this signaling and suppress the involuntary jerking, writhing, and twisting movements characteristic of chorea.
Huntington’s disease is a rare, hereditary neurodegenerative condition caused by an expanded CAG trinucleotide repeat in the huntingtin gene on chromosome 4. The disease typically manifests between the ages of 30 and 50, although juvenile-onset forms exist. Chorea is the most recognizable motor symptom of Huntington’s disease, affecting approximately 90% of patients at some stage of the illness. As the disease progresses, chorea may give way to dystonia, rigidity, and bradykinesia. Cognitive decline and psychiatric symptoms, including depression and behavioral changes, are also hallmarks of Huntington’s disease and complicate treatment decisions.
Tetmodis is approved within the European Economic Area (EEA) for the treatment of hyperkinetic movement disorders associated with Huntington’s chorea. The same active substance, tetrabenazine, is available in the United States under the brand name Xenazine and in various other countries under different trade names. Regulatory approval is based on clinical evidence demonstrating that tetrabenazine significantly reduces chorea severity compared with placebo, as measured by standardized chorea assessment scales such as the Unified Huntington’s Disease Rating Scale (UHDRS) Total Maximal Chorea score.
It is important to understand that Tetmodis treats only the motor symptoms (specifically chorea) of Huntington’s disease. It does not slow the underlying neurodegenerative process, prevent disease progression, or improve cognitive or psychiatric symptoms. In fact, because tetrabenazine depletes monoamines broadly (not only dopamine but also serotonin and norepinephrine), it can worsen depression—a particularly important consideration given that depression is already highly prevalent in Huntington’s disease patients. For this reason, treatment with Tetmodis must be carefully individualized and closely monitored by specialists experienced in managing Huntington’s disease.
Tetrabenazine is rapidly metabolized in the liver to its active metabolites, alpha-dihydrotetrabenazine (alpha-HTBZ) and beta-dihydrotetrabenazine (beta-HTBZ). Alpha-HTBZ is the primary active metabolite and is a potent, reversible inhibitor of VMAT2. Unlike reserpine (an older monoamine-depleting agent), tetrabenazine’s binding to VMAT2 is reversible, meaning its effects wear off within hours after stopping the drug. This reversibility provides an important safety advantage: if problematic side effects develop, they can be reversed relatively quickly by dose reduction or discontinuation.
What Should You Know Before Taking Tetmodis?
Before starting treatment with Tetmodis, your doctor will conduct a thorough assessment of your medical history, current medications, and psychiatric status. Tetrabenazine carries significant risks, and certain conditions make its use absolutely contraindicated. Understanding these restrictions is essential for your safety. Additionally, because Huntington’s disease itself is associated with a high rate of depression and suicidal behavior, careful screening for psychiatric symptoms must occur before and throughout treatment.
Contraindications
Tetmodis must not be used in the following situations:
- Allergy to tetrabenazine or any of the other ingredients in the tablet (pregelatinized maize starch, lactose monohydrate, talc, iron oxide yellow E172, magnesium stearate).
- Concurrent use of reserpine: Reserpine is another monoamine-depleting agent used historically for hypertension and psychotic conditions. Combining reserpine with tetrabenazine could lead to dangerously excessive dopamine depletion, causing severe parkinsonism, depression, or other serious neurological effects.
- Concurrent use of MAO inhibitors: Monoamine oxidase (MAO) inhibitors are a class of antidepressants that prevent the breakdown of monoamines. Combining them with tetrabenazine can result in a potentially fatal hypertensive crisis and other dangerous interactions. MAO inhibitor treatment must be stopped at least 14 days before beginning tetrabenazine therapy.
- Hepatic impairment: Tetrabenazine is extensively metabolized in the liver. Impaired liver function can lead to unpredictably high drug levels, increasing the risk of severe side effects.
- Parkinsonism: Because tetrabenazine depletes dopamine, it can severely worsen Parkinson-like symptoms (tremor, rigidity, bradykinesia) in patients who already have these features.
- Depression or suicidal ideation: Tetrabenazine commonly causes or worsens depression and has been associated with suicidal thoughts and behavior. It must not be used in patients who are currently depressed or who have active thoughts of self-harm.
- Breastfeeding: It is not known whether tetrabenazine passes into breast milk. Due to the potential for serious adverse reactions in the nursing infant, breastfeeding is contraindicated during treatment.
- Pheochromocytoma: This is a catecholamine-secreting tumor of the adrenal gland. The interaction between endogenous catecholamine release and tetrabenazine’s monoamine-depleting effects makes this a dangerous combination.
- Prolactin-dependent tumors: Because tetrabenazine can increase prolactin levels (by reducing dopamine’s inhibitory effect on prolactin secretion), it should not be used in patients with prolactin-dependent neoplasms such as pituitary prolactinomas or prolactin-responsive breast cancer.
Warnings and Precautions
Talk to your doctor before taking Tetmodis if any of the following apply to you:
- History of parkinsonism: If you have ever experienced tremor, rigidity, or slowness of movement, your doctor will monitor you closely, as tetrabenazine can trigger or worsen parkinsonian symptoms. Dose adjustment may be necessary.
- Hyperprolactinemia: If you have elevated prolactin levels, tetrabenazine may further increase them, potentially causing symptoms such as menstrual irregularities, galactorrhea, or gynecomastia.
- Orthostatic hypotension: If you tend to experience sudden drops in blood pressure when standing up, tetrabenazine may worsen this tendency, increasing the risk of dizziness, lightheadedness, or fainting.
- CYP2D6 poor or intermediate metabolizer status: The active metabolite alpha-HTBZ is further metabolized by the liver enzyme CYP2D6. Approximately 5–10% of the Caucasian population are poor metabolizers of CYP2D6, meaning they break down the drug much more slowly. This results in significantly higher blood levels of the active metabolite and a greater risk of side effects. If your CYP2D6 metabolizer status is known to be poor or intermediate, your doctor may prescribe a lower dose.
- Long QT syndrome or cardiac rhythm disorders: Tetrabenazine may prolong the QTc interval on the electrocardiogram, which increases the risk of potentially life-threatening cardiac arrhythmias (torsades de pointes). Patients with a known history of QT prolongation, congenital long QT syndrome, or other significant heart rhythm disorders should use tetrabenazine with extreme caution.
- Neuroleptic malignant syndrome (NMS): If you develop mental status changes (confusion, hallucinations), muscle rigidity, and fever, you may be developing NMS—a rare but potentially fatal condition. Seek immediate medical attention if these symptoms occur. NMS has been reported both during treatment with tetrabenazine and following its abrupt discontinuation.
- Akathisia and movement disturbances: Tetrabenazine may cause a distressing sense of inner restlessness and a compelling need to be in constant motion (akathisia), as well as coordination difficulties and involuntary dystonic postures.
- Melanin binding: Tetrabenazine binds to melanin-containing tissue. Over long-term use, this could theoretically affect the eyes (which contain melanin in the retinal pigment epithelium), although clinical significance has not been established.
Depression and suicidal ideation are among the most serious risks of tetrabenazine therapy. Patients with Huntington’s disease already have a significantly elevated baseline risk of depression and suicide compared with the general population. Tetrabenazine, by depleting serotonin in addition to dopamine, can further increase this risk. All patients must be regularly screened for depression, mood changes, suicidal thoughts, and behavioral changes throughout treatment. Caregivers should be educated to watch for warning signs and report them promptly to the prescribing physician.
Pregnancy and Breastfeeding
Tetmodis should not be used during pregnancy. There are insufficient data on the use of tetrabenazine in pregnant women, and the potential risks to the developing fetus are unknown. Animal studies have not adequately assessed reproductive toxicity. If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor before using this medicine. Your doctor will help you weigh the potential risks and benefits.
Breastfeeding is contraindicated during treatment with Tetmodis. It is not known whether tetrabenazine or its active metabolites are excreted in human breast milk. Given the potential for serious adverse effects in the nursing infant, a decision must be made whether to discontinue breastfeeding or discontinue the drug, taking into account the importance of the medicine to the mother.
Use in Children
Tetmodis is not recommended for use in children. The safety and efficacy of tetrabenazine in pediatric patients have not been established. While juvenile-onset Huntington’s disease does occur, it presents with different symptom patterns (predominantly rigidity and bradykinesia rather than chorea) and the role of tetrabenazine in this population has not been adequately studied.
Driving and Operating Machinery
Tetmodis may cause drowsiness and sedation, which can impair your ability to drive or operate machinery. The degree of impairment varies depending on the dose and individual sensitivity. You should not drive, operate heavy machinery, or engage in activities requiring alertness until you know how Tetmodis affects you. Combining Tetmodis with alcohol significantly increases the sedative effect. Discuss your individual risk with your doctor.
Tetmodis tablets contain lactose monohydrate. If you have been told by your doctor that you have an intolerance to certain sugars, contact your doctor before taking this medicine.
How Does Tetmodis Interact with Other Drugs?
Drug interactions are a critical concern with Tetmodis because tetrabenazine affects multiple neurotransmitter systems and is metabolized by specific liver enzymes. Some interactions are absolute contraindications, while others require dose adjustments or enhanced monitoring. Below is a comprehensive overview of the most clinically important interactions.
Major Interactions (Contraindicated or Avoid)
| Drug / Drug Class | Interaction | Clinical Recommendation |
|---|---|---|
| Reserpine | Both drugs deplete monoamines; combined use causes excessive dopamine depletion with severe parkinsonism, depression, and hypotension | Absolutely contraindicated. Do not co-administer under any circumstances |
| MAO inhibitors (e.g., phenelzine, tranylcypromine, selegiline, moclobemide) | Risk of hypertensive crisis, serotonin syndrome, and other serious reactions due to impaired monoamine metabolism | Contraindicated. MAO inhibitors must be stopped at least 14 days before starting tetrabenazine |
| Levodopa | Tetrabenazine depletes dopamine while levodopa increases it; pharmacological antagonism reduces efficacy of both treatments | Use with extreme caution. Close monitoring required if combination is unavoidable |
Moderate Interactions (Caution Required)
| Drug / Drug Class | Interaction | Clinical Recommendation |
|---|---|---|
| CYP2D6 inhibitors (fluoxetine, paroxetine, terbinafine, quinidine, moclobemide) | Inhibition of CYP2D6 increases plasma concentrations of the active metabolite alpha-dihydrotetrabenazine, amplifying therapeutic and adverse effects | Dose reduction of Tetmodis may be necessary. Monitor closely for side effects |
| Neuroleptics / Antipsychotics | Additive dopamine-depleting and dopamine-blocking effects; increased risk of parkinsonism, NMS, and excessive sedation | Not recommended unless benefits clearly outweigh risks. Careful monitoring required |
| QT-prolonging drugs (certain antipsychotics, antibiotics such as moxifloxacin, antiarrhythmics such as amiodarone, sotalol) | Additive QTc prolongation; increased risk of torsades de pointes and sudden cardiac death | Use with caution. ECG monitoring recommended. Avoid combination if QTc is already prolonged |
| Antidepressants (SSRIs, SNRIs, TCAs) | Increased risk of serotonin-related effects; some SSRIs (fluoxetine, paroxetine) also inhibit CYP2D6 | Not recommended. If essential, choose antidepressants with minimal CYP2D6 inhibition |
| Beta-blockers and Antihypertensives | Additive hypotensive effects; increased risk of symptomatic low blood pressure, dizziness, and falls | Monitor blood pressure regularly. Adjust doses as needed |
| Sedatives, Opioids, and Alcohol | Additive central nervous system depression; increased drowsiness, sedation, and risk of respiratory depression | Avoid or minimize use. Warn patients about enhanced sedative effects |
Always inform your healthcare provider about all medicines you are taking, including prescription drugs, over-the-counter medications, herbal supplements, and vitamins. Drug interactions with tetrabenazine can range from clinically insignificant to life-threatening, and only a qualified healthcare professional can assess the overall safety of your medication regimen.
The CYP2D6 enzyme plays a crucial role in the metabolism of Tetmodis. Genetic variations in the CYP2D6 gene determine how quickly or slowly an individual metabolizes tetrabenazine. Poor metabolizers (approximately 5–10% of Caucasians, 1–2% of Asians) have significantly higher blood levels of the active metabolite, leading to greater drug exposure and increased risk of side effects. In the United States, CYP2D6 genotyping is required before prescribing doses exceeding 50 mg per day (for the US-marketed formulation Xenazine). Knowing your CYP2D6 status can help your doctor choose the safest and most effective dose.
What Is the Correct Dosage of Tetmodis?
Tetmodis dosing follows a careful titration approach, starting low and gradually increasing to find the optimal dose that provides the best balance between chorea reduction and tolerability. Because individual responses vary considerably, there is no single “correct” dose—each patient’s dose is determined through careful monitoring. Always take Tetmodis exactly as prescribed by your doctor.
Adults with Huntington’s Chorea
Starting Dose
Half a tablet (12.5 mg) one to three times daily. The tablet has a score line that allows it to be divided in half.
Dose Titration
The dose may be increased by half a tablet (12.5 mg) every third or fourth day, based on clinical response and tolerability. Increases should continue until optimal chorea reduction is achieved or until side effects (such as drowsiness, parkinsonism, or depression) become intolerable.
Maximum Dose
The maximum daily dose is 8 tablets (200 mg per day). If the maximum dose has been taken for seven consecutive days without clinical improvement, the medication is unlikely to be effective and should be reconsidered.
| Patient Group | Starting Dose | Titration | Maximum Dose |
|---|---|---|---|
| Adults | 12.5 mg 1–3 times daily | Increase by 12.5 mg every 3–4 days | 200 mg/day |
| Elderly | 12.5 mg 1–3 times daily | Slower titration recommended; monitor closely for parkinsonism | 200 mg/day (clinical judgment) |
| CYP2D6 poor metabolizers | 12.5 mg 1–3 times daily | More cautious titration; lower doses likely required | Lower than standard maximum (individualized) |
| Children | Not recommended | Not applicable | Not applicable |
| Renal impairment | Not recommended | Not applicable | Not applicable |
| Hepatic impairment | Contraindicated | Not applicable | Not applicable |
Elderly Patients
The standard dose has been given to elderly patients without clearly increased adverse effects. However, parkinsonian effects are more common in elderly patients. Treatment should start at the lowest recommended dose and titration should proceed cautiously with enhanced monitoring for parkinsonism, falls, and cognitive changes. Elderly patients may ultimately require lower maintenance doses than younger adults.
Missed Dose
If you forget to take a dose of Tetmodis, do not take a double dose to compensate. Simply take your next scheduled dose at the usual time. Missing an occasional dose is unlikely to cause significant problems, but try to take the medicine as regularly as possible to maintain stable blood levels. If you frequently forget doses, speak with your doctor or pharmacist about strategies to improve adherence.
Overdose
If you take too much Tetmodis, you may develop drowsiness, sweating, low blood pressure (hypotension), and dangerously low body temperature (hypothermia). In severe cases, overdose can lead to profound sedation, cardiovascular collapse, and respiratory depression. If an overdose is suspected, seek emergency medical attention immediately. There is no specific antidote for tetrabenazine overdose; treatment is supportive and symptomatic, focusing on maintaining vital functions, monitoring cardiac rhythm, and correcting hypotension and hypothermia.
Never stop taking Tetmodis suddenly without medical advice. Abrupt discontinuation of tetrabenazine has been associated with neuroleptic malignant syndrome (NMS), a potentially life-threatening condition characterized by high fever, sweating, blood pressure instability, severe muscle rigidity, and altered consciousness. If treatment needs to be stopped, your doctor will taper the dose gradually.
What Are the Side Effects of Tetmodis?
Like all medicines, Tetmodis can cause side effects, although not everyone experiences them. Many side effects are dose-dependent, meaning they are more likely to occur and more severe at higher doses. Your doctor will aim to find the lowest effective dose to minimize side effects while adequately controlling chorea. If you experience any concerning symptoms, contact your healthcare provider promptly.
The side effects of Tetmodis reflect its pharmacological mechanism of monoamine depletion. By reducing dopamine levels, it can cause parkinsonian symptoms and akathisia. By reducing serotonin levels, it can worsen or trigger depression. By reducing norepinephrine levels, it can contribute to low blood pressure and fatigue. Understanding these pharmacological links helps patients and caregivers recognize and report side effects more effectively.
Very Common
May affect more than 1 in 10 patients
- Drowsiness and sedation (especially at higher doses)
- Depression (including worsening of existing depression)
- Parkinsonism: tremor, rigidity, slowness of movement, uncontrollable movements of hands, arms, legs, and head (especially at higher doses)
Common
May affect up to 1 in 10 patients
- Confusion and disorientation
- Anxiety and nervousness
- Insomnia (difficulty sleeping)
- Low blood pressure (hypotension)
- Difficulty swallowing (dysphagia)
- Nausea and vomiting
- Diarrhea
- Constipation
Uncommon
May affect up to 1 in 100 patients
- Mental status changes including hallucinations
- Muscle rigidity with fever (possible early signs of neuroleptic malignant syndrome)
Rare
May affect up to 1 in 1,000 patients
- Neuroleptic malignant syndrome (NMS): a serious condition characterized by altered consciousness, confusion, hallucinations, muscle rigidity, high fever, sweating, and blood pressure instability. Seek immediate medical attention if these symptoms develop
Very Rare
May affect up to 1 in 10,000 patients
- Rhabdomyolysis (muscle breakdown): can cause muscle pain, weakness, dark urine, and potentially kidney damage
Not Known
Frequency cannot be estimated from available data
- Disorientation and nervousness
- Inability to coordinate movements (ataxia)
- Akathisia (inability to sit or stand still; distressing inner restlessness)
- Dystonia (involuntary muscle contractions causing abnormal postures)
- Dizziness and impaired memory
- Lower heart rate (bradycardia)
- Orthostatic dizziness (dizziness when rising from sitting or lying position)
- Abdominal pain and dry mouth
- Hypothermia (low body temperature)
It is important to report suspected side effects to your healthcare provider or to your national pharmacovigilance authority. Reporting side effects after a medicine has been authorized helps to continuously monitor the benefit-risk balance of the treatment. Healthcare professionals and patients can report suspected adverse reactions through their national reporting systems.
Contact your doctor or go to the nearest emergency department immediately if you experience: confusion or hallucinations with fever and muscle rigidity (possible NMS); severe depression or thoughts of self-harm; difficulty breathing or severe swallowing problems; signs of an allergic reaction (rash, swelling, difficulty breathing); or dark-colored urine with severe muscle pain (possible rhabdomyolysis).
How Should You Store Tetmodis?
Proper storage is essential to maintain the effectiveness and safety of your medication. Tetmodis tablets are supplied in a white container with a screw cap containing 112 tablets. The tablets are light-sensitive, which is why they must be stored in the original packaging. Exposure to excessive heat, light, or moisture can degrade the active ingredient, reducing its potency or potentially forming harmful breakdown products.
Store Tetmodis at or below 25°C (77°F). Do not refrigerate or freeze. Keep the container tightly closed when not in use. Do not transfer tablets to another container, as this removes them from the light-protective packaging. Always check the expiry date on the container and carton before taking a dose; the expiry date refers to the last day of the stated month.
Keep this medicine out of the sight and reach of children. Accidental ingestion by a child could cause serious adverse effects including profound drowsiness, hypotension, and hypothermia, requiring immediate medical attention.
Do not dispose of unused medicines via household waste or through wastewater. Return any unused or expired tablets to your pharmacy for safe disposal. Proper disposal of medicines helps to protect the environment.
What Does Tetmodis Contain?
Understanding the composition of your medication is important, particularly if you have known allergies or intolerances to specific ingredients. Each Tetmodis 25 mg tablet contains the following:
Active Ingredient
Tetrabenazine 25 mg — the pharmacologically active substance responsible for the therapeutic effects of the medicine. Tetrabenazine is a benzoquinolizine derivative that acts as a reversible inhibitor of vesicular monoamine transporter 2 (VMAT2).
Excipients (Inactive Ingredients)
- Pregelatinized maize starch: A binder and disintegrant that helps the tablet maintain its structure and dissolve properly in the gastrointestinal tract.
- Lactose monohydrate: A filler that provides bulk to the tablet. Patients with lactose intolerance should consult their doctor before taking Tetmodis, although the amount of lactose per tablet is generally small.
- Talc: A glidant that prevents ingredients from sticking together and helps ensure uniform tablet weight and content.
- Iron oxide yellow (E172): A coloring agent that gives the tablets their distinctive yellow appearance.
- Magnesium stearate: A lubricant that prevents the tablet mixture from adhering to the manufacturing equipment during compression.
Tablet Description and Packaging
Tetmodis tablets are yellow, round, and have a score line (break line) on one side to allow the tablet to be divided into two equal halves of 12.5 mg each. The other side is engraved with “TE25” for identification. Each container holds 112 tablets in a white plastic bottle with a screw cap.
Tetmodis is manufactured by AOP Orphan Pharmaceuticals GmbH, based in Vienna, Austria, and is approved within the European Economic Area under the brand names Tetmodis, Tetrabenazine AOP Orphan Pharmaceuticals, and Motetis (in Hungary), among others. The medicine is authorized in numerous European countries including Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Greece, Ireland, the Netherlands, Poland, Spain, and the United Kingdom.
Frequently Asked Questions About Tetmodis
Tetmodis (tetrabenazine) is used for the treatment of hyperkinetic movement disorders associated with Huntington’s chorea. Huntington’s disease causes involuntary, jerky, and irregular movements called chorea, which result from progressive brain degeneration. Tetmodis works by reducing dopamine levels in the brain’s movement control centers (basal ganglia), which helps suppress these involuntary movements. It treats only the motor symptoms of chorea and does not slow the progression of Huntington’s disease itself. Treatment should be initiated and supervised by a specialist experienced in managing movement disorders.
Tetmodis works by inhibiting a protein called vesicular monoamine transporter 2 (VMAT2). This protein is responsible for loading dopamine, serotonin, and norepinephrine into storage vesicles inside nerve cells. When VMAT2 is blocked, less dopamine is packaged into vesicles and subsequently released at nerve synapses. Since excessive dopamine signaling in the basal ganglia contributes to chorea, reducing dopamine availability helps suppress involuntary movements. Unlike the older drug reserpine, tetrabenazine binds to VMAT2 reversibly, meaning its effects wear off within hours of stopping the drug.
Yes, depression is a very common side effect of Tetmodis, occurring in more than 1 in 10 patients, and can be serious. Because tetrabenazine depletes serotonin as well as dopamine, it can worsen existing depression or trigger new depressive episodes. This is particularly concerning because patients with Huntington’s disease already have a significantly elevated risk of depression and suicidal behavior. Tetmodis is contraindicated in patients with active depression or suicidal ideation. All patients must be regularly monitored for mood changes, and caregivers should be educated to recognize warning signs and seek prompt medical attention.
Tetmodis must not be taken with reserpine (another monoamine-depleting drug) or with MAO inhibitors (a class of antidepressants). MAO inhibitors must be stopped at least 14 days before starting tetrabenazine. Caution is also needed with CYP2D6 inhibitors (such as fluoxetine, paroxetine, terbinafine, and quinidine), which increase blood levels of the active metabolite and may require dose reduction. Levodopa, neuroleptics, sedatives, opioids, alcohol, beta-blockers, and QT-prolonging drugs all have significant interactions with Tetmodis and should only be used together under careful medical supervision.
Stopping Tetmodis abruptly can be dangerous. Cases of neuroleptic malignant syndrome (NMS) have been reported after sudden discontinuation of tetrabenazine. NMS is a potentially life-threatening condition characterized by high fever, sweating, blood pressure instability, severe muscle rigidity, and altered consciousness (confusion, delirium). If treatment needs to be stopped, your doctor should reduce the dose gradually over time. Never stop taking Tetmodis on your own without medical advice.
Tetmodis should not be used during pregnancy or breastfeeding. There is insufficient data on the safety of tetrabenazine in pregnant women, and the potential risks to the developing fetus are unknown. Animal studies have not adequately evaluated reproductive toxicity. Breastfeeding is also contraindicated, as it is not known whether tetrabenazine or its metabolites pass into breast milk. If you are pregnant, plan to become pregnant, or are breastfeeding, discuss alternative treatment options with your doctor.
References
- European Medicines Agency (EMA). Tetmodis Summary of Product Characteristics. AOP Orphan Pharmaceuticals GmbH. Last revised December 2021.
- U.S. Food and Drug Administration (FDA). Xenazine (tetrabenazine) Prescribing Information. Lundbeck Inc. 2024.
- Huntington Study Group. Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial. Neurology. 2006;66(3):366–372. doi:10.1212/01.wnl.0000198586.85250.13
- Armstrong MJ, Miyasaki JM. Evidence-based guideline: Pharmacologic treatment of chorea in Huntington disease: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2012;79(6):597–603. doi:10.1212/WNL.0b013e318263c443
- Frank S. Treatment of Huntington’s disease. Neurotherapeutics. 2014;11(1):153–160. doi:10.1007/s13311-013-0244-z
- European Huntington’s Disease Network (EHDN). Standards of Care for Huntington’s Disease. 2023.
- World Health Organization (WHO). ATC/DDD Index 2025. N07XX06 – Tetrabenazine.
- British National Formulary (BNF). Tetrabenazine. NICE Evidence Services. Accessed January 2026.
- Kenney C, Hunter C, Jankovic J. Long-term tolerability of tetrabenazine in the treatment of hyperkinetic movement disorders. Mov Disord. 2007;22(2):193–197. doi:10.1002/mds.21222
- Jankovic J, Beach J. Long-term effects of tetrabenazine in hyperkinetic movement disorders. Neurology. 1997;48(2):358–362.
Medical Editorial Team
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Written by iMedic Medical Editorial Team – specialists in neurology and clinical pharmacology
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Last reviewed: January 19, 2026 | Next review: July 2026 | Editorial Standards | Our Medical Team