Levetiracetam, often known by the brand name Keppra, is a widely used antiepileptic drug (AED) for controlling various types of seizures. Its unique mechanism of action, involving the synaptic vesicle protein SV2A, makes it a valuable treatment option, particularly for patients who have not responded to other medications. However, determining the specific success rate of levetiracetam is complex, as it depends on several factors, including the type of epilepsy, whether it is used alone (monotherapy) or with other drugs (adjunctive therapy), and individual patient characteristics.
Defining 'Success' for Levetiracetam
Success with levetiracetam can be measured in different ways, not just as complete seizure freedom. Researchers and clinicians often consider the following metrics when evaluating the drug's effectiveness:
- Responder Rate: The percentage of patients who achieve a significant reduction in seizure frequency, most commonly a 50% or greater reduction from baseline.
- Seizure Freedom Rate: The percentage of patients who become completely free of seizures for a specified period, such as six months or one year.
- Retention Rate: The percentage of patients who continue taking the medication over the long term, indicating tolerability and sustained benefit.
Efficacy in Adjunctive Therapy
Numerous studies have evaluated levetiracetam as an add-on treatment for patients whose seizures are not well-controlled by other medications. This is often where a patient's treatment journey begins with levetiracetam.
Focal-Onset Seizures
For adults with drug-resistant focal epilepsy, studies show a significant response rate compared to placebo. A Cochrane review found that a responder rate (>= 50% reduction in seizures) was just over 50% for children and 34% for adults receiving levetiracetam, both much higher than the placebo groups. In another review of three pivotal clinical trials, 35.2% to 39.6% of adults achieved a ≥50% reduction in partial seizure frequency when using daily doses of 2000-3000 mg.
Generalized Seizures
Levetiracetam has also proven effective as an add-on therapy for generalized epilepsy syndromes, particularly juvenile myoclonic epilepsy (JME) and idiopathic generalized epilepsy (IGE).
- Generalized Tonic-Clonic Seizures (GTC): A trial demonstrated that 72.2% of patients with IGE achieved a 50% or more reduction in GTC seizure frequency with adjunctive levetiracetam, compared to 45.2% with placebo. The seizure-free rate was also higher (34.2% vs. 10.7%).
- Myoclonic Seizures: In a trial for myoclonic seizures, 58.3% of levetiracetam patients experienced at least a 50% reduction in days with myoclonic seizures, compared to 23.3% of placebo patients. Seizure freedom for myoclonic seizures was reported in 16.7% of levetiracetam patients during the full treatment period.
Effectiveness as Monotherapy
For newly diagnosed epilepsy, levetiracetam has shown good efficacy as a standalone treatment. The goal for these patients is often complete seizure freedom from the outset.
Newly Diagnosed Epilepsy
In a head-to-head trial comparing levetiracetam and controlled-release carbamazepine in newly diagnosed partial or generalized tonic-clonic epilepsy, the drugs showed equivalent efficacy. The study found that 73% of levetiracetam patients and 72.8% of carbamazepine patients remained seizure-free for at least six months. A high percentage of these patients achieved seizure freedom at the lowest initial dose.
Pediatric Epilepsy
For children with newly diagnosed benign epilepsy with centrotemporal spikes (BECTS), a prospective randomized trial found that 90.5% of levetiracetam patients remained seizure-free over a mean follow-up of 18.5 months, suggesting excellent monotherapy potential in this specific syndrome.
Factors Influencing Levetiracetam's Success
The variability in success rates can be attributed to several factors, highlighting the importance of a personalized approach to treatment.
Epilepsy Syndrome
As seen in studies, levetiracetam's effectiveness differs depending on the specific epilepsy syndrome. It demonstrates particularly strong results in juvenile myoclonic epilepsy and newly diagnosed BECTS. Long-term studies also show higher seizure-free rates in patients with generalized epilepsy compared to those with focal epilepsy.
Individual Patient History
- Refractory vs. Newly Diagnosed: Patients with newly diagnosed epilepsy often have a higher chance of achieving seizure freedom with their first AED, including levetiracetam, than those with drug-resistant epilepsy. The success rate can decrease with each failed medication trial.
- Underlying Cause: The cause of epilepsy, such as an underlying brain abnormality, can influence response to treatment. For example, studies in neonatal seizures suggest different outcomes depending on the underlying etiology.
Dosage and Adherence
Dosage plays a role in treatment outcomes. Some studies show a dose-dependent effect, with higher doses increasing the odds of a significant seizure reduction. Adherence to the prescribed regimen is also critical for maintaining control and maximizing therapeutic benefit.
Comparison of Efficacy and Outcome Metrics
| Metric | Adjunctive Therapy (Adults, Drug-Resistant Focal Seizures) | Adjunctive Therapy (Adults, Drug-Resistant GTC Seizures) | Monotherapy (Adults, Newly Diagnosed) | Pediatric (Newly Diagnosed BECTS, Monotherapy) |
|---|---|---|---|---|
| ≥50% Seizure Reduction | 34–50% | ~72% | Not primary endpoint | 90.5% |
| Seizure Freedom | 3–8% (Pivotal trials) | ~34% | 73% (at 6 months, comparable to CBZ) | 90.5% (at 18 months) |
| Long-Term Seizure Freedom | 16–26% (Post-marketing studies) | Data less specific | 56.6% (at 1 year) | 90.5% (at 18 months) |
Conclusion
The success rate of levetiracetam is not a single number but a multifaceted picture influenced by the patient's condition, the specific seizure type, and the treatment approach. As an adjunctive therapy, it has consistently shown efficacy in reducing seizure frequency for many patients with drug-resistant focal and generalized epilepsy. As a monotherapy, it offers a strong potential for complete seizure freedom, especially in newly diagnosed cases, demonstrating comparable efficacy to older drugs like carbamazepine. Patients with newly diagnosed or specific epilepsy syndromes, such as JME or BECTS, tend to have better outcomes. Overall, levetiracetam is a valuable and effective tool in epilepsy management, contributing significantly to seizure control and improved quality of life for a broad range of patients. For more information, the Epilepsy Foundation offers helpful resources.
