Introduction
Epilepsy affects over 70 million people worldwide. With the evolving resistance of focal epilepsy, there is need for add-on therapies for better clinical outcomes.
Objectives
To evaluate the effectiveness of levetiracetam as an add-on treatment for people with drug-resistant focal epilepsy.
Search methods
The Cochrane Register of Studies (CRS Web, which includes the Cochrane Epilepsy Group Specialized Register and CENTRAL), MEDLINE Ovid, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) were searched till November 2018.
Selection criteria
Randomized, placebo-controlled trials of add-on levetiracetam treatment in patients with drug-resistant focal epilepsy.
Data collection and analysis
Selected trials for inclusion were independently reviewed by two authors who assessed trials for bias, extracted data and evaluated the overall certainty of the evidence. Outcomes investigated included 50% or greater reduction in focal seizure frequency (response), treatment withdrawal, adverse eDects (including a specific analysis of changes in behaviour), cognitive eDects, and quality of life (QoL). The primary analysis was intention-to-treat. A meta-analysis for all outcomes using a Mantel-Haenszel approach and calculated risk ratios (RR), with 95% confidence intervals (CI) for all estimates apart from adverse effects (99% CIs). The heterogeneity was assessed using a Chi2 test and the I2 statistic.
Results
- The study included 14 trials (2455 participants), predominantly possessing low risks of bias.
- Participants were adults in 12 trials (2159 participants) and children in the remaining two (296 participants).
- The doses of levetiracetam tested were 500 mg/day to 4000 mg/day in adults and 60 mg/kg/day in children.
- Treatment duration ranged from 12 to 24 weeks.
- Levetiracetam at either 500 mg/day or 4000 mg/day did not perform better than placebo for the 50% or greater reduction in seizure frequency outcome (500 mg: RR 1.60, 95% CI 0.71 to 3.62; P = 0.26; 4000 mg: RR 1.64, 95% CI 0.59 to 4.57; P = 0.34).
- Levetiracetam was significantly better than placebo at all other individual doses (1000 mg to 3000 mg).
- RR was significantly in favour of levetiracetam compared to placebo when results were pooled across all doses (RR 2.37, 95% CI 2.02 to 2.78; 14 studies, 2455 participants; moderate-certainty evidence).
- Dose–response analysis demonstrated that with the rise of 1000 mg in levetiracetam the odds of achieving response (50% or greater reduction in seizure frequency) were increased by nearly 40%.
- Participants were not significantly more likely to experience treatment withdrawal with levetiracetam than with placebo.
- Somnolence was the most common adverse effect occurring in 13% of patients and it was significantly associated with levetiracetam compared to placebo (pooled RR 1.62, 99% CI 1.19 to 2.20; 13 studies, 2423 participants; moderate-certainty evidence).
- Changes in behaviour were negligible in adults affecting 1%, but affecting 23% children.
- Levetiracetam had a positive effect on some aspects of cognition and QoL in adults.
- Levetiracetam therapy worsened certain aspects of child behaviour.