Management of Seizures in Patients with Mood Disorders: Levetiracetam Considerations
For patients with seizure disorders and comorbid mood disorders, levetiracetam (Keppra) should be avoided as first-line therapy due to its significant risk of causing or exacerbating psychiatric symptoms, and alternative anti-seizure medications with mood-stabilizing properties should be preferred. 1, 2
Psychiatric Side Effects of Levetiracetam
- Levetiracetam is associated with significant behavioral and psychiatric adverse effects, including non-psychotic behavioral disorders (reported as aggression and irritability) in 5-11.4% of patients compared to 0-3.6% in placebo groups 3
- Non-psychotic mood disorders (including depressed mood, depression, and mood swings) occur in 6.7-12.7% of levetiracetam-treated patients compared to 3.3-8.3% of placebo patients 3
- Up to 5% of patients require dose reduction or discontinuation due to behavioral or psychiatric events (anxiety, depression, irritability, and nervousness) 3
- In rare cases, levetiracetam can induce psychotic-like behavior, including auditory hallucinations and suicidal thoughts 3, 4
Preferred Alternative Anti-Seizure Medications for Patients with Mood Disorders
- Lamotrigine or oxcarbazepine should be considered first-line therapy for patients with seizures and comorbid mood disorders due to their mood-stabilizing properties 5, 1, 2
- These medications have demonstrated efficacy for seizure control while providing mood-stabilizing benefits, making them ideal for patients with both conditions 1, 2, 6
- For patients with generalized convulsive status epilepticus who continue to have seizures despite benzodiazepines, fosphenytoin, levetiracetam, or valproate may be used with similar efficacy 7, 8
Switching Process for Patients Currently on Levetiracetam
- When switching from levetiracetam due to mood-related side effects, use the overlap method where the new anti-seizure medication is started while maintaining the current levetiracetam dose 5
- Gradually titrate the new medication to an effective dose before slowly tapering levetiracetam to minimize the risk of withdrawal seizures 5, 3
- For severe psychiatric adverse reactions, consider hospitalization for monitoring during the switch 5
- Never stop levetiracetam suddenly as this may precipitate withdrawal seizures 5, 3
Special Considerations
- Patients with a history of psychiatric disorders are at higher risk of developing behavioral adverse effects with levetiracetam 4, 9
- ECT may be considered in patients with severe mood disorders and seizures, as it has been shown to be safe and effective in patients with concurrent seizure disorders 7
- Valproic acid should be avoided in women of childbearing potential due to teratogenicity risks 5
- Schedule follow-up within 2-4 weeks of initiating a new medication to assess for seizure control and new adverse effects 5
Monitoring Recommendations
- Monitor for both seizure control and psychiatric symptoms when initiating or changing anti-seizure medications 5, 2
- Educate patients and families about potential psychiatric side effects of levetiracetam and when to seek medical attention 5
- Consider that mood disorders in epilepsy may present with atypical manifestations that do not meet standard diagnostic criteria 1
- Failure to treat mood disorders in epilepsy may increase suicide risk and worsen quality of life 1, 7
By selecting anti-seizure medications with favorable psychiatric profiles for patients with comorbid mood disorders, clinicians can optimize both seizure control and psychiatric stability while minimizing adverse effects.