Levetiracetam and Anxiety in Seizure Patients
Levetiracetam 750mg is appropriate for seizure management in this patient, but it carries significant risk of worsening or inducing anxiety and other behavioral symptoms, particularly in patients with pre-existing psychiatric conditions. The medication should be used with caution and close monitoring for neuropsychiatric adverse effects.
Key Safety Concerns with Levetiracetam and Anxiety
Levetiracetam is strongly associated with behavioral and psychiatric adverse effects, including anxiety, which occur in 13.3% of adult patients, with anxiety specifically reported in 1.8% of levetiracetam-treated patients versus 1.1% of placebo patients. 1
Behavioral Side Effect Profile
Non-psychotic behavioral disorders (including aggression, irritability, nervousness, and anxiety) occur significantly more frequently with levetiracetam treatment. In controlled trials, nervousness was reported in 9.9% of pediatric patients on levetiracetam versus 2.1% on placebo, and anxiety occurred in 1.8% versus 1.1% in adults 1
Patients with epilepsy experience behavioral events significantly more often than patients with cognitive or anxiety disorders treated with levetiracetam (P=0.022), suggesting epilepsy itself may predispose to these effects 2
The most serious adverse effects are behavioral in nature and are more common in patients with a history of psychiatric and neurobehavioral problems 3
Clinical Decision Algorithm
If Patient Has Pre-existing Anxiety Disorder:
Consider alternative antiepileptic medications first, as levetiracetam carries increased risk in this population. If levetiracetam must be used:
- Start with close psychiatric monitoring for worsening anxiety, agitation, or mood changes 1, 4
- Behavioral symptoms can emerge beyond the initial titration period and may be the most common reason for drug discontinuation 4
- In one case report, a patient on 750mg twice daily developed severe behavioral symptoms that reversed with cessation of levetiracetam 4
If Patient Needs Anxiety Treatment While on Levetiracetam:
- Treat the underlying anxiety disorder with appropriate anxiolytic therapy while maintaining seizure control 3
- Monitor closely for additive sedation, as somnolence occurs in 15-22.8% of levetiracetam-treated patients 1
- Consider dose reduction if behavioral symptoms emerge (occurred in 10.9% of pediatric patients versus 6.2% on placebo) 1
Dosing Considerations for Seizure Management
For seizure control, the 750mg dose is within the therapeutic range, though loading doses for acute seizures are typically higher:
- For status epilepticus, the recommended loading dose is 30 mg/kg IV at 5 mg/kg per minute 5, 6, 7
- For maintenance therapy in known seizure patients, 750mg represents a standard dose 1
- Lower doses (20 mg/kg or less) show reduced efficacy (38-67%) for acute seizure termination 7, 8
Critical Monitoring Parameters
Establish baseline psychiatric status and monitor for:
- Depression, anxiety, irritability, hostility, or agitation (occur in 37.6% of pediatric patients versus 18.6% on placebo) 1
- Psychotic symptoms (occur in 0.7% of patients, typically within first week of treatment) 1
- Suicidal ideation or behavior 4
- Behavioral symptoms typically occur within the first 4 weeks but can emerge later 1, 4
When to Discontinue or Adjust
Discontinue levetiracetam if:
- Severe behavioral symptoms develop (occurred in 3.0% of pediatric patients requiring discontinuation) 1
- Psychotic symptoms emerge 1, 4
- Withdraw gradually to minimize risk of increased seizure frequency 1
Consider dose reduction if: