Levetiracetam, commonly known by brand names such as Keppra, is an antiepileptic drug (AED) that has become a cornerstone in the management of epilepsy. Its role is to help prevent and control seizures by influencing the abnormal electrical activity in the brain that causes them. Unlike many older seizure medications, levetiracetam has a distinct and relatively unique mechanism of action, a favorable safety profile, and fewer drug-drug interactions, making it a preferred option for many patients.
The Mechanism of Action: How Levetiracetam Affects the Brain
While the exact process is not yet fully understood, the primary mechanism through which levetiracetam works is by binding to a protein known as synaptic vesicle glycoprotein 2A (SV2A). SV2A is found on the surface of synaptic vesicles, which are critical for neurotransmitter release in the brain.
- Modulates Neurotransmitter Release: By binding to SV2A, levetiracetam modulates the release of neurotransmitters, the brain's chemical messengers. It is thought to reduce the release of excitatory neurotransmitters, such as glutamate, while potentially restoring the function of inhibitory neurotransmitters like GABA.
- Stabilizes Electrical Activity: The modulation of neurotransmitter release helps to stabilize and normalize the electrical activity within the brain. This reduces the hypersynchronization of neurons that leads to the burst of electrical activity characterizing a seizure.
- Neuroprotective Effects: Some research also suggests that levetiracetam may have neuroprotective properties by limiting damage caused by excessive electrical discharge during seizures.
Clinical Applications of Levetiracetam
Levetiracetam is approved for the treatment of various types of seizures in a broad patient population, including adults, children, and infants.
- Partial-onset seizures: Used as a monotherapy or adjunctive therapy for partial-onset (or focal) seizures, which start in one part of the brain.
- Juvenile myoclonic epilepsy (JME): Approved for adjunctive therapy in treating myoclonic seizures associated with JME.
- Primary generalized tonic-clonic seizures (PGTCS): Used as an adjunctive therapy for the large, generalized seizures that affect the entire body.
Additionally, levetiracetam has gained popularity for off-label uses in managing conditions like status epilepticus, a medical emergency involving prolonged or repeated seizures, and for seizure prophylaxis following traumatic brain injury.
Levetiracetam Dosage and Administration
Levetiracetam is available in several formulations to suit patient needs, including oral tablets (immediate and extended-release), an oral solution, and an intravenous formulation for hospital settings. Dosing is typically started low and gradually increased to achieve the best clinical response while minimizing side effects. Consistency is critical; missing doses can increase seizure frequency. Abruptly stopping the medication is not recommended, as it can worsen seizures. For patients with impaired kidney function, dose adjustments are necessary since levetiracetam is cleared predominantly by the kidneys.
Side Effects and Safety Considerations
While generally well-tolerated, levetiracetam can cause a range of side effects, especially during the initial treatment phase. These include:
- Common Side Effects: Sleepiness, drowsiness, dizziness, fatigue, and general weakness are frequently reported.
- Behavioral Changes: Mood-related side effects such as irritability, aggression, anxiety, and depression can occur. In rare cases, suicidal thoughts or behaviors have been linked to the use of anticonvulsants like levetiracetam.
- Other Potential Effects: Loss of appetite, headache, coordination problems, and upper respiratory tract infections (like rhinitis and pharyngitis) are also possible.
- Serious Skin Reactions: Though rare, severe skin reactions like Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported.
Levetiracetam vs. Other Antiepileptic Drugs
Levetiracetam is often compared to older-generation AEDs due to its distinct pharmacological properties and safety profile. Here is a comparison with phenytoin, a long-established epilepsy medication:
| Feature | Levetiracetam | Phenytoin |
|---|---|---|
| Mechanism of Action | Unique binding to SV2A, modulating neurotransmitter release. | Modulates voltage-dependent sodium channels to reduce neuronal firing. |
| Side Effects | Common side effects include sleepiness, dizziness, mood changes, and fatigue. Fewer serious systemic effects than phenytoin. | Significant adverse effects include sedation, gingival hyperplasia, hirsutism, and potentially fatal cardiovascular issues when administered intravenously. |
| Drug Interactions | Minimal metabolism by liver enzymes (cytochrome P450), resulting in very few significant drug interactions. | Induces liver enzymes, leading to numerous and potentially serious interactions with other medications. |
| Pharmacokinetics | Linear kinetics; serum concentration is proportional to the dose. Broader therapeutic index than phenytoin. | Saturated kinetics; small dose changes can cause large, unpredictable increases in serum concentration. Narrow therapeutic index. |
| Monitoring | Less constant monitoring of serum levels is needed, making management simpler. | Requires constant monitoring of serum levels to prevent toxicity. |
What to Consider During Pregnancy and Breastfeeding
Managing epilepsy during pregnancy requires careful consideration of the risks associated with both seizures and medication exposure. Levetiracetam is frequently used in pregnant women due to a low teratogenic risk compared to older AEDs. However, its pharmacokinetics change significantly during pregnancy, especially in the third trimester, and return to baseline postpartum.
- Pregnancy: Regular therapeutic drug monitoring is essential to guide dose adjustments and ensure optimal seizure control. Studies have found that children exposed prenatally to levetiracetam show normal verbal and cognitive abilities at age six. Women can also enroll in pregnancy registries to help gather more data on AED safety.
- Breastfeeding: Levetiracetam is excreted into breast milk, and while infant serum drug levels are generally low, it can cause sedation in some breastfed infants. Clinicians should monitor exclusively breastfed infants for developmental milestones, drowsiness, and weight gain.
Conclusion
What does levetiracetam do to humans? As an anticonvulsant, it controls and prevents various types of seizures by stabilizing abnormal electrical activity in the brain through its action on the SV2A protein. Its unique mechanism, favorable pharmacokinetic profile, and lower risk of significant drug interactions set it apart from many older antiepileptic drugs. It is a versatile and widely used medication for epilepsy management across different age groups, but as with any potent medication, it requires careful consideration of potential side effects, especially in special populations like pregnant individuals. Patients should always consult their healthcare provider to determine if levetiracetam is the right treatment and to manage their medication regimen appropriately.
