Levetiracetam Side Effects in Neurocysticercosis with Seizures
Levetiracetam is generally well-tolerated with a favorable safety profile compared to older antiepileptic drugs, though neuropsychiatric side effects—particularly behavioral disturbances—represent the most clinically significant concern and most common reason for discontinuation. 1, 2
Common Side Effects
Most Frequent Adverse Events (≥5% incidence)
Based on FDA-approved labeling, the most common side effects in adults include 2:
- Somnolence (15% vs 8% placebo)
- Asthenia/fatigue (15% vs 9% placebo)
- Dizziness (9% vs 4% placebo)
- Infection (13% vs 8% placebo)
- Headache (14% vs 13% placebo)
Neuropsychiatric Effects
The most clinically important side effects are behavioral and psychiatric disturbances, occurring in approximately 13.3% of adults, with severe symptoms (depression, agitation, hostility) in 0.7%. 2, 3 These include:
- Irritability and hostility (2% in adults, higher in children at 10-12%) 2
- Depression (4% in adults) 2
- Anxiety (2%) 2
- Nervousness (4%) 2
- Emotional lability 2
- Psychosis (estimated 1.4% prevalence) 3
Critical caveat: Behavioral symptoms can emerge beyond the initial titration period and may develop acutely even in stable patients, particularly those with pre-existing psychiatric conditions. 3
Comparative Safety Profile
Levetiracetam demonstrates superior tolerability compared to traditional antiepileptic drugs. The American Heart Association and American Academy of Neurology recommend levetiracetam over phenytoin or valproic acid due to lower incidence of adverse effects and better cognitive outcomes. 1
Advantages Over Older AEDs
- Fewer cognitive side effects than phenytoin 1
- Lower hematologic toxicity than valproic acid 4
- No serious cardiac effects at therapeutic doses 5
- Minimal drug interactions 1
In oral loading studies, 89% of patients reported no adverse effects, with only 11% experiencing transient irritability, imbalance, tiredness, or lightheadedness. 4, 1
Specific Considerations for Neurocysticercosis
Efficacy and Safety in NCC
In a randomized study comparing levetiracetam to carbamazepine in newly diagnosed NCC patients 6:
- Seizure control: Trend toward better control with carbamazepine (91.8% vs 78% seizure-free), though not statistically significant (p=0.09) 6
- Side effects: Significantly fewer adverse events with levetiracetam (4% vs 34.6%, p<0.0001) 6
- Drug discontinuation: Zero patients discontinued levetiracetam vs 3 patients (6%) discontinued carbamazepine due to skin rash 6
Important clinical pearl: In the NCC study, 11 patients who failed levetiracetam achieved seizure control after switching to carbamazepine, suggesting carbamazepine may be more effective for NCC-related seizures despite worse tolerability. 6
Discontinuation Rates
In controlled trials, 15% of patients receiving levetiracetam discontinued or required dose reduction due to adverse events (vs 11.6% placebo). 2 The most common reasons for discontinuation were 2:
- Somnolence
- Asthenia
- Dizziness
- Behavioral/psychiatric symptoms
Special Monitoring Requirements
Renal Function
Dose adjustments are necessary in patients with renal dysfunction due to predominant renal elimination. 1 However, in status epilepticus studies using doses up to 2,500 mg IV, only isolated cases of nausea and transient transaminitis were noted. 1
Rapid IV Administration
No serious adverse effects were attributable to rapid infusion at 5 mg/kg per minute in status epilepticus studies. 1 In one safety study, only 1 patient experienced flushing and 1 had unrelated oxygen desaturation among 11 patients receiving 2,500 mg IV over 5 minutes. 7
Time Course of Adverse Events
Asthenia, somnolence, and dizziness predominantly occur during the first 4 weeks of treatment with levetiracetam. 2 This suggests early monitoring is critical, though psychiatric symptoms can emerge later in the treatment course. 3
Clinical Recommendations for NCC Patients
Based on IDSA/ASTMH 2017 guidelines for neurocysticercosis 7:
- Antiepileptic drugs should be used in all NCC patients with seizures (strong recommendation, moderate quality evidence) 7
- Choice of antiepileptic drug should be guided by local availability, cost, drug interactions, and potential side effects 7
- Consider tapering after resolution of cystic lesions if seizure-free for 6 months without risk factors (calcifications, breakthrough seizures, >2 total seizures) 7
Bottom line for NCC: While levetiracetam offers superior tolerability, carbamazepine may provide better seizure control in neurocysticercosis specifically, making it a reasonable first choice despite higher side effect rates, with levetiracetam reserved for patients intolerant of carbamazepine. 6