Table 1.
Randomized controlled trials with levetiracetam.
| Reference | Patient population | Study design | Maintenance doses | Efficacy | Safety |
|---|---|---|---|---|---|
| Shorvon et al.79 | Adults, difficult-to-treat focal epilepsy n = 324 |
Multicenter, randomized, parallel-group, double-blind, placebo-controlled. | 1000 mg LEV/day 2000 mg LEV/day. |
Median reduction of weekly seizures 26.5% for 2000 mg LEV/day, 17.7% for 1000 mg LEV/day and 6.1% for placebo (both LEV doses p ⩽ 0.001). Responder rates 22.8% with 1000 mg LEV/day, 31.6% with 2000 mg LEV / day 10.4% with placebo (p ⩽ 0.001 for 2000 mg LEV, p = 0.019 for 1000 mg LEV). | Most frequent adverse events different from placebo: Somnolence, asthenia, headache. |
| Cereghino et al.80 | Adults, difficult-to-treat epilepsy n = 294 |
Multicenter, randomized, parallel-group, double-blind, placebo-controlled. | 1000 mg LEV/day 3000 mg LEV/day. |
Median seizure reduction 26.1% for 1000 mg LEV/day, 30.1% for LEV 3000 mg/day. Responder rates 37.1% for LEV 1000 mg/day and 39.6% for LEV 3000 mg/day (for both doses and variables p ⩽ 0.001 versus placebo). |
Asthenia, somnolence, dizziness, flu-like symptoms, headache, infection, and rhinitis most frequent adverse events different from placebo. |
| Ben-Menachem and Falter81 | Adults aged 16–70 years old, difficult-to-treat epilepsy n = 286 |
Multicenter, randomized, parallel-group, double-blind, placebo-controlled, optional conversion to monotherapy. | 3000 mg LEV/day. | Responder rate 42.1% for LEV versus 16.7% with placebo (p < 0.001) 49 of 69 patients down-titrated to monotherapy 73.8% median percentage reduction of focal seizures. |
Asthenia was the most frequent adverse event, significantly more common than with placebo (13.8% versus 6.7%). |
| Betts et al.82 | Adults, difficult-to-treat epilepsy n = 119 |
2000 mg LEV/day 4000 mg LEV/day No titration. |
Responder rates 48.1% for LEV 2000 mg/day, 28.6% for LEV 4000 mg/day and 16.1% with placebo (p = 0.01 for LEV 2000 mg/day, not significant for 4000 mg LEV/day). | Most frequent adverse events: Somnolence and asthenia. | |
| Brodie et al.83 | Newly onset focal epilepsies in adults | Monotherapy comparative trial versus controlled-release CBZ. | 1000 mg LEV - 3000 mg LEV daily 400 mg–1200 mg CBZ daily. |
73% seizure-free with LEV at 6 months 72.8% seizure-free with CBZ at 6 months. |
Withdrawal rates due to adverse events: 14.4% with LEV, 19.2% with CBZ. Depression and insomnia occurred more frequently with LEV than with CBZ. |
| Werhahn et al.84 | Newly onset focal epilepsies in elderly patients aged 60 years or older | Monotherapy comparative trial against LTG and control-release CBZ. |
1000 mg LEV daily 100 mg LTG daily 400 mg CBZ daily. |
Retention rate after 58 weeks LEV 61.5% LTG 55.6% (n.s.) CBZ 45.8% (p = 0.02) |
Incidence of adverse events: 88.5% with LEV, 94% with LTG, and 89.3% with CBZ. Most frequent adverse events with LEV: Fatigue, renal failure and seizures. Discontinuation due to adverse events or death: LEV 17.2% LTG 26.3% (n.s.) CBZ 32.2% (p = 0.007). |
| Berkovic et al.85 | 4–65 years old. Idiopathic generalized epilepsy with generalized tonic-clonic seizures n = 164 randomized patients |
Multicenter, randomized, parallel-group, double-blind, placebo-controlled. | 3000 mg LEV/day | Mean weekly reduction of generalized tonic-clonic seizures 56.5% with LEV and 28.2% with placebo (p = 0.004). Responder rates: 72.2% with LEV versus 45.2% with placebo (p < 0.001). Seizure freedom from generalized tonic-clonic seizures 34.2% with LEV and 10.7% with placebo (p < 0.001). |
Withdrawal rates due to adverse events: LEV 1.3%, placebo 4.8%. Somnolence most frequent adverse event. |
| Noachtar et al.86 | 12–65 years old. Idiopathic generalized epilepsy with myoclonic seizures n = 120 randomized patients. |
Multicenter, randomized, parallel-group, double-blind, placebo-controlled. | 3000 mg LEV/day | Reduction of ⩾50% of myoclonic seizures in 58.3% with LEV 23.3% with placebo (p < 0.001). Reduction of ⩾50% of all seizures in 56.7% versus 21.7% (p < 0.001). Seizure freedom from myoclonic seizures 25% versus 5% (p = 0.004). Seizure freedom from all seizures 21.7% versus 1.7% (p < 0.001). |
Most frequent adverse events different from placebo: Somnolence (10%), neck pain (8.3%), pharyngitis (6.7%). |
CBZ, carbamazepine; LEV, levetiracetam; LTG, lamotrigine.