BACKGROUND: Epilepsy is a common neurologic disorder, affecting approximately 50 
million people worldwide; nearly a third of these people are not well controlled 
by a single antiepileptic drug (AED) and usually require treatment with a 
combination of two or more AEDs. In recent years, many newer AEDs have been 
investigated as add-on therapy for partial epilepsy; losigamone is one of these 
drugs and is the focus of this systematic review. This is an update of a 
Cochrane review first published in 2012 (Cochrane Database of Systematic Reviews 
2012, Issue 6).
OBJECTIVES: To investigate the efficacy and safety of losigamone when used as an 
add-on therapy for partial epilepsy.
SEARCH METHODS: We searched the Cochrane Epilepsy Group Specialized Register (16 
February 2015), the Cochrane Central Register of Controlled Trials (CENTRAL, The 
Cochrane Library 16 February 2015) and MEDLINE (Ovid, 1946 to 16 February 2015). 
We searched trials registers and contacted the manufacturer of losigamone and 
authors of included studies for additional information. We did not impose any 
language restrictions.
SELECTION CRITERIA: Randomized controlled, add-on trials comparing losigamone 
with placebo for partial epilepsy.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial 
quality and extracted data. The primary outcomes were 50% or greater reduction 
in seizure frequency and seizure freedom; the secondary outcomes were treatment 
withdrawal and adverse events. Results are presented as risk ratios (RRs) with 
95% confidence intervals (CIs) or 99% CIs (for the individual listed adverse 
events to make an allowance for multiple testing).
MAIN RESULTS: Two trials involving a total of 467 patients, aged over 18 years, 
were eligible for inclusion. Both trials assessed losigamone 1200 mg/day or 1500 
mg/day as an add-on therapy for partial epilepsy. One trial was assessed as 
being of good methodological quality while the other was of uncertain quality. 
For the efficacy outcomes, results did show patients taking losigamone were 
significantly more likely to achieve a 50% or greater reduction in seizure 
frequency (RR 1.76; 95% CI 1.14 to 2.72), but associated with a significant 
increase of treatment withdrawal when compared with those taking placebo (RR 
2.16; 95% CI 1.28 to 3.67). For the safety outcomes, results indicated the 
proportion of patients who experienced adverse events in the losigamone group 
was higher than the placebo group (RR 1.34; 95% CI 1.00 to 1.80), dizziness was 
the only adverse event significantly reported in relation to losigamone (RR 
3.82; 99% CI 1.69 to 8.64). The proportion of patients achieving seizure freedom 
was not reported in either trial report. A subgroup analysis according to 
different doses of losigamone showed that a higher dose of losigamone (1500 
mg/day) was associated with a greater reduction in seizure frequency than lower 
doses, but was also associated with more dropouts due to adverse events.
AUTHORS' CONCLUSIONS: The results of this review showed losigamone did reduce 
seizure frequency but was associated with more treatment withdrawals when used 
as an add-on therapy for people with partial epilepsy. However, trials included 
were of short-term duration and uncertain quality. Future well-designed 
randomized, double-blind, placebo-controlled trials with a longer-term duration 
are needed. No new studies have been found since the last version of this 
review.