Levetiracetam, commonly sold under the brand name Keppra, is a widely used antiepileptic drug prescribed for various seizure types. While often considered to have a favorable overall side-effect profile compared to older medications, it is particularly known for causing neuropsychiatric and behavioral adverse effects. These side effects can manifest differently among individuals, with incidence rates varying across studies.
Common Behavioral Side Effects
Many patients experience mood and behavior changes, especially during the initial weeks of treatment or following dose adjustments. These reactions can range from mild to moderate and may improve over time, though they can be significant enough to warrant a change in medication.
- Irritability and Agitation: Many users report feeling more irritable, short-tempered, or agitated. This can be particularly noticeable to family members and caregivers, even if the individual taking the medication is less aware of the change.
- Anxiety: Feelings of anxiety, nervousness, or restlessness are frequently reported. For those with a pre-existing anxiety disorder, levetiracetam may exacerbate their symptoms.
- Depression: Some individuals may experience symptoms of depression, such as feeling sad, empty, or having a loss of interest in activities they once enjoyed. Suicidal ideation, though rare, has also been reported, and patients should be monitored for any signs of worsening mood or self-harming thoughts.
- Mood Swings: Rapidly changing moods, or emotional lability, can occur. This can involve unpredictable shifts between emotions like anger, sadness, and happiness.
Severe Psychiatric Side Effects
While less common, levetiracetam can also cause severe psychiatric symptoms that require immediate medical attention. These are particularly concerning and can lead to hospitalization or discontinuation of the medication.
- Aggression and Hostility: Outbursts of anger, hostility, and aggressive behavior can occur, sometimes without a clear trigger. This has been documented in both adult and pediatric populations.
- Psychotic Symptoms: Rare instances of psychosis have been linked to levetiracetam, characterized by symptoms such as hallucinations and delusions. In a study of 1,412 patients, 7.8% experienced severe psychiatric symptoms, with hallucinations and delusions being common manifestations.
- Suicidal and Self-Harm Behaviors: Some patients have reported suicidal thoughts or engaged in self-harm while on levetiracetam. Close monitoring is crucial, especially for those with a history of depression or other mental health conditions.
Risk Factors for Behavioral Changes
Several factors can increase a person's risk of experiencing behavioral side effects from levetiracetam.
- Pre-existing psychiatric conditions: Individuals with a history of mental health issues, such as depression or anxiety, are at a higher risk.
- Pediatric patients: Behavioral issues, including aggression and irritability, are reported more frequently in children and adolescents.
- Rapid dose titration: Increasing the levetiracetam dose too quickly can trigger or worsen behavioral problems.
- Higher doses: Some studies suggest higher doses may be associated with an increased risk, though it's not always a dose-dependent relationship.
Levetiracetam vs. Other Antiepileptic Drugs: Behavioral Side Effects
Comparing levetiracetam with other antiepileptic drugs (AEDs) can provide context for its behavioral side-effect profile.
| Feature | Levetiracetam (Keppra) | Perampanel | Carbamazepine | Lamotrigine |
|---|---|---|---|---|
| Incidence of Psychiatric Side Effects | Higher than some other AEDs. In one study, psychiatric and behavioral side effects were reported in 22% of patients. | Can induce aggression, but may be more overt. | Lower rate of certain psychiatric side effects compared to levetiracetam. | Subgroup analysis showed higher global mood, anger, and depression compared to levetiracetam in one meta-analysis. |
| Aggression | Higher incidence reported in some studies. Can be more subjectively felt (inward-directed). | Can induce visible outward-directed aggression. | Lower incidence of aggression reported compared to levetiracetam. | Potentially higher incidence of depression compared to levetiracetam, though data varies. |
| Irritability | Significantly higher rates of irritability reported. | Lower hostility scores reported compared to levetiracetam. | Some reports suggest fewer behavioral issues. | Variable effects, but not typically associated with high rates of irritability compared to levetiracetam. |
| Psychosis | Less common, with a reported frequency of less than 1-1.4%. | Reported but with varying opinions on prevalence. | Psychosis is a recognized but less common side effect. | Psychosis can occur, but specific incidence varies. |
Managing Behavioral Side Effects of Levetiracetam
Managing levetiracetam-induced behavioral changes involves close monitoring and working with a healthcare provider to find the right approach.
- Dose Adjustment: Often, a reduction in the levetiracetam dose can help resolve or mitigate behavioral symptoms. Symptoms may improve rapidly after the dose is lowered.
- Discontinuation: If side effects are severe or intolerable, stopping the medication entirely may be necessary. In such cases, a gradual taper is usually recommended to prevent withdrawal seizures.
- Supplementation with Vitamin B6: Some anecdotal and retrospective reports suggest that supplementation with pyridoxine (vitamin B6) may help reduce irritability and other neuropsychiatric side effects, especially in children and some adult populations. However, stronger evidence from controlled studies is still needed.
- Adjunctive Therapy: For severe psychiatric symptoms like psychosis, adding an antipsychotic medication might be part of the treatment regimen.
Conclusion
While levetiracetam is an effective medication for controlling seizures, its potential for behavioral and psychiatric side effects, including irritability, aggression, anxiety, and in rare cases, psychosis, is a significant consideration. Pediatric patients and those with a history of mental health conditions may be at a higher risk. Careful monitoring and communication with a healthcare provider are essential for managing these adverse effects and ensuring both seizure control and overall well-being. By understanding the risks and available management options, patients and their families can work with their clinical team to make informed treatment decisions. You can learn more about medication side effects by consulting resources like the FDA website. [https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-rare-serious-drug-reaction-antiseizure-medicines-levetiracetam-keppra-keppra-xr-elepsia-xr]
