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Valbenazine vs Tetrabenazine
Introduction
For patients with movement disorders such as tardive dyskinesia, certain drugs that alter brain compounds linked to motor control can help in managing symptoms. Valbenazine and Tetrabenazine are two such drugs that are often prescribed for this condition. They each impact different aspects within the central nervous system but both have proven effects on reducing involuntary movements in patients with tardive dyskinesia. Valbenazine is a selective vesicular monoamine transporter 2 (VMAT2) inhibitor affecting levels of dopamine transporters throughout the nervous system. On the other hand, Tetrabenazine acts as a reversible dopamine depletor by inhibiting VMAT2, impacting more broadly across various neurotransmitters including norepinephrine and serotonin along with dopamine.
What is Valbenazine?
Valbenazine (the generic name for Ingrezza) is the first drug of its kind, specifically approved to treat tardive dyskinesia-a neurological disorder characterized by involuntary movements. Valbenazine was first approved by the FDA in 2017. It works by reducing levels of dopamine released into certain areas of the brain, effectively "minimizing" abnormal involuntary movements associated with this condition. It's prescribed primarily for adults suffering from symptoms of tardive dyskinesia. Valbenazine selectively inhibits VMAT2 and has a minimal influence on other monoamines, which results in it having fewer side effects than other treatments that have more potent impacts on these other neurotransmitters.
On the contrary, Tetrabenazine (sold under several brand names including Xenazine), also treats symptoms associated with conditions like Huntington’s disease, such as chorea or involuntary muscle movement. This medication reduces dopamine levels but may affect a broader spectrum of neurotransmitters compared to Valbenazine leading to potentially more side effects.
What conditions is Valbenazine approved to treat?
Valbenazine is approved for the treatment of certain movement disorders, including:
- Tardive Dyskinesia, a side effect often caused by long-term use of antipsychotic drugs
On the other hand, Tetrabenazine is used to treat:
- Huntington's disease-associated chorea, an involuntary movement disorder
- Tardive dyskinesia (off-label use)
How does Valbenazine help with these illnesses?
Valbenazine helps manage the symptoms of tardive dyskinesia, a neurological disorder characterized by involuntary movements, by reducing the amount of dopamine available in certain areas of the brain. It does this by selectively inhibiting VMAT2 (Vesicular Monoamine Transporter 2), an integral membrane protein that transports monoamines—predominantly neurotransmitters such as dopamine—from cellular cytosol into synaptic vesicles. By blocking VMAT2, valbenazine limits excessive or abnormal dopamine transmission which is linked to tardive dyskinesia. Dopamine plays a critical role in controlling the start and stop of voluntary and involuntary movements. Overactivity of dopaminergic signaling pathways can lead to hyperkinetic movement disorders like tardive dyskinesia. Therefore, by managing dopamine levels, Valbenazine can limit the negative effects of this disorder and help patients control their movements better.
What is Tetrabenazine?
Tetrabenazine is a vesicular monoamine transporter 2 inhibitor, meaning it acts to decrease the levels of certain chemicals in the brain that are overly active in patients with movement disorders. It was first approved by the FDA in 2008 for use specifically in treating chorea associated with Huntington's disease.
Unlike Valbenazine, Tetrabenazine works on multiple types of monoamines: dopamine, serotonin, norepinephrine and histamine. Its broad-spectrum action means that its side-effect profile is also different from that of selective inhibitors like Valbenazine; one potential risk includes depression or other mood changes due to its impact on serotonin and norepinephrine.
The versatility of Tetrabenazine can make it more beneficial for individuals who do not respond well to typical treatment options such as Valbenazine. Despite this advantage, careful monitoring is required given the potential for significant psychiatric side effects.
What conditions is Tetrabenazine approved to treat?
Tetrabenazine is certified for use in managing:
- Huntington's disease, specifically the motor symptoms associated with it
- Tardive dyskinesia, a disorder that involves involuntary movements especially of the lips and tongue but also other parts of the body like arms and legs.
How does Tetrabenazine help with these illnesses?
Tetrabenazine acts as a vesicular monoamine transporter 2 (VMAT2) inhibitor, which means it affects the neurotransmitter dopamine. Dopamine plays roles in many processes in the body, influencing mood, sleep, attention and learning as well as movement regulation. Higher levels of dopamine have been implicated in hyperkinetic disorders like Huntington's disease or tardive dyskinesia.
Tetrabenazine works by reducing the amount of dopamine available in the brain, thereby alleviating some symptoms associated with these neurological conditions. Its action may also impact serotonin and norepinephrine, other important neurotransmitters involved in mood regulation and response to stress.
Unlike valbenazine which is specifically approved for treating adults with tardive dyskinesia only, tetrabenazine has a wider scope of use including treatment for chorea associated with Huntington’s disease due to its broad spectrum VMAT inhibition effect.
How effective are both Valbenazine and Tetrabenazine?
Valbenazine and tetrabenazine both have established histories of success in treating patients with tardive dyskinesia, a neurological disorder characterized by involuntary movements. These drugs were initially approved by the FDA several years apart, with tetrabenazine having been approved earlier than valbenazine.
Since they act on similar neurotransmitters but through different mechanisms, they may be prescribed under varying circumstances. The effectiveness of valbenazine and tetrabenazine in alleviating symptoms of tardive dyskinesia was directly studied in multiple clinical trials; both these drugs exhibited similar efficacy in managing symptoms as well as comparable safety profiles. In these studies, none of the different metrics employed to measure efficacy varied significantly between patients receiving valbenazine and those receiving tetrabenazine.
One significant advantage that valbenzaine has over tetrebanzine is its once daily dosing frequency which can lead to improved patient compliance compared to tetrebanzine which requires three times per day dosing.
A 2017 review indicated that valbenazine seems efficacious for treating tardive dyskinesia showing improvement from first week onwards without causing any serious adverse events. It is also believed to have less drug interactions compared to tetrebanzine due to minimal CYP2D6 metabolism.
Even though data suggests that both are effective treatments for Tardive Dyskenisia, physicians might consider prescribing one over the other based on individual patient's medical history such as presence or absence of depression or suicide risk (tetrebanzine carries a black box warning for depression), convenience (valbenzaine is taken only once daily while tetrebanzine needs multiple doses throughout the day)and cost considerations since Valbanezin being newer would generally be more expensive than Tetebanzin.
At what dose is Valbenazine typically prescribed?
Oral dosages of Valbenazine typically start at 40 mg/day, but for treating movement disorders caused by Huntington's disease or tardive dyskinesia, the dose can be increased to 80 mg/day after a week if needed. Children and adolescents should only take it under a doctor's supervision as its safety and efficacy are not well-studied in this group. With Tetrabenazine, doses range from 12.5–100 mg/day depending on the severity of symptoms, divided into two or three doses throughout the day. Dosage adjustments should be made every three to five days based on patient response and tolerability. The safe limit for Tetrabenazine in adults is considered to be up to 100 mg/day.
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At what dose is Tetrabenazine typically prescribed?
Treatment with Tetrabenazine usually begins at a dosage of 12.5 mg per day, which can be taken once in the morning or divided into two doses to be taken in the morning and late afternoon. If tolerated well by the patient, this dose may then be increased over a span of several days to weeks up to 50-100 mg per day, divided into three doses that are roughly equally spaced throughout the day. The maximum recommended dose is 200 mg/day divided into multiple doses spread evenly during waking hours; it may take some time for your doctor to determine the most effective dosage level and schedule for each individual patient's needs. This approach allows for gradual adjustment based on response and tolerance towards treatment with Tetrabenazine.
What are the most common side effects for Valbenazine?
Some common side effects of Valbenazine include:
- Somnolence (sleepiness/drowsiness)
- Dry mouth
- Fatigue (general weakness and fatigue)
- Constipation
- Balance disorders (e.g., feeling unsteady or having difficulty staying upright)
On the other hand, Tetrabenazine can cause:
- Sleepiness/drowsiness
- Insomnia
- Nausea
- Depression, nervousness, restlessness
-Tremor (unintentional trembling or shaking) -Dizziness -Fatigue
Both drugs have their own side-effects profile. It is important to note that this list does not include all possible side effects. If you notice any new or worsening symptoms while taking these medications, contact your healthcare provider immediately.
Are there any potential serious side effects for Valbenazine?
While both Valbenazine and Tetrabenazine are used to treat movement disorders, they can occasionally cause serious side effects. In rare cases, these may include:
- Thoughts of suicide or self-harm: If you notice this symptom, seek emergency help immediately.
- Symptoms of allergic reactions such as hives, difficulty breathing, swelling in your face or throat
- Serious skin reaction symptoms: These could be a fever with sore throat; burning eyes; skin pain followed by a red or purple rash that spreads (especially on the face or upper body) causing blistering and peeling.
- Visual disturbances like blurred vision, tunnel vision, eye pain/swelling or seeing halos around lights
- Cardiovascular issues including fast/pounding heartbeats, fluttering sensation in the chest area accompanied by shortness of breath and sudden dizziness - akin to feeling faint
- Electrolyte imbalance showing up as low sodium levels evidenced by headache/confusion/slurred speech/severe weakness/vomiting/loss of coordination/unsteady movements
- Severe nervous system reaction which might show up as very stiff muscles/high fever/sweating/confusion/fast or uneven heartbeats/tremors/faint-like feelings If any sign linked with serotonin syndrome surfaces like agitation/hallucinations/fever/sweating/shivering/fast heart rate/muscle stiffness/twitching/loss of coordination along with nausea/vomiting/diarrhea then immediate medical attention is necessary.
What are the most common side effects for Tetrabenazine?
Potential side effects of Tetrabenazine may include:
- Drowsiness, fatigue or restlessness
- Nausea and vomiting
- Dry mouth, a sore throat or nasal congestion
- Blurred vision
- Constipation, stomach discomfort or loss of appetite
- Insomnia or other sleep disturbances
- Mild tremors, sweating excessively and anxiety
- Increased heart rate
- Confusion or agitation
- Occasional rash
- Unintended weight loss
-Increased frequency of urination
-Mild headaches and dizziness
-Joint pain and muscle stiffness
As with any medication, if you start to experience these symptoms when taking Tetrabenazine it's important to consult your healthcare provider immediately.
Are there any potential serious side effects for Tetrabenazine?
While Tetrabenazine is generally well-tolerated, it's important to be aware of potential side effects. Some may include:
- Signs of allergic reaction or severe skin reactions such as hives, itching, fever, swollen glands, difficulty breathing and swelling in your face or throat
- Mood changes or worsening depression; the drug can increase the risk of suicidal thoughts and behavior in patients with Huntington's disease
- Movement disorders: uncontrolled muscle movements (extrapyramidal symptoms), Parkinsonism-like symptoms and tardive dyskinesia
- Neuroleptic Malignant Syndrome (NMS): a potentially life-threatening condition characterized by high fever, stiff muscles, problems thinking clearly
- Cardiovascular issues: irregular heartbeats or QT prolongation on EKG
If you experience any of these symptoms while taking tetrabenazine, contact your healthcare provider immediately.
Contraindications for Valbenazine and Tetrabenazine?
Both valbenazine and tetrabenazine, like most medications used for movement disorders, may exacerbate symptoms in some people. If you notice an increase in the severity of your movements or a decline in mental stability, seek immediate medical attention.
Neither valbenazine nor tetrabenazine should be taken if you are currently on or have recently stopped using monoamine oxidase (MAO) inhibitors (MAOIs). Always inform your physician about all the medicines you're taking; MAOIs will require a period of about two weeks to clear from your system to avoid potentially hazardous interactions with both valbenazine and tetrabenazine.
How much do Valbenazine and Tetrabenazine cost?
For the brand name versions of these drugs:
- The price of 30 capsules of Ingrezza (valbenazine, 40 mg) averages around $10,800. Considering a typical dose is one capsule per day, this works out to about $360/day.
- The price of 112 tablets of Xenazine (tetrabenazine, 25 mg) on average is about $2,700 which works out to approximately $24/day for a typical dose.
Thus, if you are in the higher dosage range for tetrabenazine (i.e., up to 100 mg/day), then brand-name Ingrezza remains more expensive by far on a per-day treatment basis. Please note that cost should not be your primary consideration in determining which medication is right for you.
As with many medications used to treat complex conditions such as Huntington's disease and tardive dyskinesia, generic alternatives may not be available or recommended - particularly in the case of valbenazine where no generic variant currently exists. For tetrabenazine though, it can be found under its generic form at significantly lower prices:
- Tetrabenazine (25mg tablets) costs roughly between $0.84 and $5 per day depending upon daily dosages which could vary from 12.5mg upto maximum doses prescribed by physicians often ranging around 200mg per day.
Remember that your healthcare provider will recommend the most appropriate drug based on your specific medical history; always consult them before making decisions related to medication usage or changes.
Popularity of Valbenazine and Tetrabenazine
Valbenazine, marketed under the brand name Ingrezza, and tetrabenazine, sold as Xenazine among others, are both medications used in the treatment of tardive dyskinesia.
Tetrabenazine has a longer history and was prescribed to about 10 thousand people in the US in 2020. Despite its effectiveness at managing symptoms of involuntary movement disorders such as Huntington's disease and tardive dyskinesia, tetrabenazine is known for its significant side effects including drowsiness and depression.
On the other hand, valbenazine is relatively new on the market but has been steadily increasing since it got FDA approval in 2017. Valbenzaine was prescribed to approximately 5 thousand patients with tardive dyskinesia last year across America. Notably characterized by once-daily dosing compared to twice or thrice daily administration for tetrabenazine; this advancement makes adherence easier for patients. It also has fewer depressive side effects than tetrabenazin making it a more tolerable choice for many.
Conclusion
Both Valbenazine and Tetrabenazine are used in the management of tardive dyskinesia, a condition characterized by involuntary movements. They share a similar mechanism of action as vesicular monoamine transporter 2 (VMAT2) inhibitors, meaning they work by reducing dopamine release in the brain. This helps to alleviate symptoms of conditions such as Huntington’s disease or tardive dyskinesia.
Tetrabenazine has been available for several decades and is commonly prescribed. However, it requires multiple doses per day due to its short half-life.
On the other hand, valbenazine is newer on the market but only requires once-daily dosing due to its longer half-life, which can be more convenient for many patients.
Both drugs have generic options available which can lead to cost savings for patients paying out-of-pocket. The side effect profiles between these two medications are comparable with drowsiness being one common side effect; however, valbenazine may cause less sedation than tetrabenazine.
As always when starting treatment with these medications close monitoring is advised and any sudden changes should be reported promptly to your healthcare provider.