Both levetiracetam (brand name Keppra) and brivaracetam (brand name Briviact) are widely used antiepileptic drugs (AEDs) for controlling seizures. Despite sharing a similar mechanism of action, they are not identical. The nuances in their pharmacology, efficacy, and side effect profiles are critical considerations for clinicians and patients. Understanding the key distinctions is essential for determining which medication is the more suitable option for a particular individual.
Understanding the Core Mechanism
Both levetiracetam and brivaracetam belong to the pyrrolidine class of AEDs and work by binding to the synaptic vesicle glycoprotein 2A (SV2A) in the brain. This protein is involved in the release of neurotransmitters, and by modulating its function, these drugs help to reduce the hyperexcitability of neurons that leads to seizures.
However, a primary pharmacological difference is brivaracetam's higher selectivity and binding affinity for the SV2A protein. It has been shown to have a 15- to 30-fold greater affinity for this binding site compared to levetiracetam, which may contribute to its different clinical profile. This enhanced affinity is one reason why brivaracetam can potentially offer advantages, particularly regarding tolerability.
Comparing Efficacy: Is newer always better?
While brivaracetam is a newer drug with higher SV2A affinity, studies have not shown a statistically significant difference in efficacy between it and levetiracetam for refractory focal seizures. In fact, an indirect comparison found that levetiracetam might have a slightly higher efficacy with a lower probability of dizziness in this patient group. However, comprehensive head-to-head trials comparing the two medications are limited.
A key advantage of brivaracetam is the rapid onset of action, which is facilitated by its pharmacokinetic properties. Unlike levetiracetam, which often requires a gradual dose titration over several weeks, brivaracetam can be started at a therapeutic dose immediately. This can lead to faster seizure control, which may be a critical factor in certain clinical situations.
Tolerability: A Major Differentiating Factor
For many patients, the choice between levetiracetam and brivaracetam hinges on tolerability and side effects. Levetiracetam is well-known for causing neuropsychiatric adverse events (AEs) in a significant portion of patients, including irritability, aggression, depression, and mood changes. These behavioral side effects are a primary reason why patients may need to switch medications.
Brivaracetam, on the other hand, is associated with fewer and less severe neuropsychiatric side effects. For patients who experience mood-related issues on levetiracetam, switching to brivaracetam has often led to a considerable improvement in these symptoms. This is believed to be due to its higher and more selective binding to SV2A. However, brivaracetam is also associated with its own set of common side effects, such as somnolence, dizziness, and fatigue.
Here are some of the key differences in side effects:
- Neuropsychiatric Side Effects: Levetiracetam has a higher rate of behavioral AEs like aggression and irritability. Brivaracetam is less likely to cause these issues.
- Somnolence and Sedation: Both can cause sleepiness, but some studies have reported higher rates of drowsiness with brivaracetam.
- DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms): The FDA has issued a warning that levetiracetam can cause this rare but life-threatening reaction.
- Skin Reactions: Both medications can, in rare cases, cause severe skin reactions such as Stevens-Johnson syndrome.
Dosage, Formulations, and Titration
- Levetiracetam: Available as immediate-release tablets, extended-release tablets (Keppra XR), oral solution, and an intravenous (IV) solution. It typically requires a slower titration period, taking several weeks to reach the target dose.
- Brivaracetam: Available as oral tablets, oral solution, and IV injection (Briviact). It can be initiated at a therapeutic dose without slow titration, allowing for faster achievement of seizure control.
Cost and Accessibility
Cost is a significant factor in the decision-making process. Generic levetiracetam is widely available and much more affordable than the brand-name brivaracetam (Briviact). While manufacturer savings programs are available for brivaracetam, the cost difference can be substantial for many patients.
Controlled Substance Status
Brivaracetam is classified as a Schedule V controlled substance by the DEA because it has some potential for abuse or dependence. This is an important consideration, particularly for patients with a history of substance abuse. Levetiracetam is not a controlled substance.
Indications and Patient Population
Levetiracetam has a broader range of approved indications from the FDA, including adjunctive therapy for myoclonic seizures in patients with juvenile myoclonic epilepsy and primary generalized tonic-clonic seizures in patients with idiopathic generalized epilepsy. Brivaracetam is currently only approved for partial-onset seizures.
In pediatric patients, studies suggest that brivaracetam may have a more favorable behavioral and emotional side effect profile than levetiracetam, which is an important consideration for a sensitive patient population.
Levetiracetam vs. Brivaracetam: At a Glance
| Feature | Levetiracetam (Keppra) | Brivaracetam (Briviact) |
|---|---|---|
| Mechanism of Action | Binds to SV2A with lower affinity. | Binds to SV2A with 15-30 times higher affinity. |
| Efficacy | Broad indications; often comparable to BRV for focal seizures. | Comparable efficacy to LEV for focal seizures; faster onset due to no titration. |
| Tolerability | Higher incidence of neuropsychiatric side effects (aggression, irritability). | More favorable neuropsychiatric profile; less mood side effects. |
| Titration | Typically requires gradual dose escalation. | Can be initiated at a therapeutic dose immediately. |
| Cost | Significantly lower, available as a generic. | More expensive, brand-name only. |
| Controlled Status | Not a controlled substance. | Schedule V controlled substance. |
| Approved Indications | Broader range, including myoclonic and generalized tonic-clonic seizures. | Primarily for partial-onset seizures. |
| Use in Children | Associated with more behavioral side effects. | Better behavioral side effect profile in pediatric patients. |
Conclusion: Which is the right choice?
The question of which is better, levetiracetam or brivaracetam, has no single answer and depends on individual patient needs. Levetiracetam remains a very effective and widely-used first-line option, particularly due to its low cost and extensive history of use.
Brivaracetam, with its faster dose initiation and improved neuropsychiatric tolerability, is an excellent alternative, especially for patients who experience intolerable behavioral side effects with levetiracetam or require rapid seizure control. However, its higher cost and controlled substance status are important considerations. Ultimately, the decision should be made in consultation with a healthcare professional, weighing the potential benefits and risks in the context of the patient's specific epilepsy type, medical history, and personal circumstances. For many, the ability to switch from levetiracetam to brivaracetam and improve tolerability is a major benefit. For others, the efficacy and affordability of generic levetiracetam make it the ideal choice.
For more information on epilepsy treatments, you can consult resources like the National Institute of Health (NIH).
