Remacemide for drug-resistant localization related epilepsy.
BACKGROUND
Epilepsy is a common neurological condition, affecting 0.5 to 1% of the population. Nearly 30 per cent of people with epilepsy have seizures that are refractory to currently available drugs. In response to this problem, potential new drugs are being developed. Remacemide is one of these.


OBJECTIVE
To evaluate the effects of add-on treatment with remacemide upon seizures, adverse effects, cognition and quality of life for people with drug-resistant localization related epilepsy.


METHODS
We searched the Cochrane Epilepsy Group trials register (4 July 2002), the Cochrane Controlled Trials Register (The Cochrane Library Issue 2, 2002) and MEDLINE (28 May 2002). In addition, we contacted AstraZeneca (makers of remacemide) and colleagues in the field to see if they were aware of any trials that we had missed.


METHODS
Randomized placebo controlled add-on trials of people of any age with localization related seizures, in which an adequate method of concealment of randomization was used. The studies could be blinded or unblinded and be of parallel or crossover design. They had to have a minimum treatment period of eight weeks.


METHODS
Two reviewers independently selected trials for inclusion and extracted data. Any disagreements were resolved by discussion. Outcomes investigated included 50 per cent or greater reduction in seizure frequency, treatment withdrawal, adverse effects, effects on cognition and quality of life. The primary analyses were by intention-to-treat. Dose response was evaluated in regression models.


RESULTS
Two parallel group trials were included representing 514 individuals. Daily doses of 300, 600, 800 and 1200mg of remacemide were tested. The overall relative risk (RR) for remacemide versus placebo with 95% confidence intervals(CI) for a 50 per cent or greater reduction in seizure frequency was 1.59(95% CI 0.91 to 2.79). Due to differences in response rates among trials, regression models were unable to provide reliable estimates of responses to individual doses. Regression models did however suggest a significant effect for 800-1200mg remacemide per day. Remacemide was more likely to be withdrawn than placebo, the RR for treatment withdrawal was 1.90(95% CI 1.00 to 3.60). The RR for dizziness indicates that it is significantly associated with remacemide 3.08(99% CI 1.37 to 6.95). Effects on cognition and quality of life were not reported.


CONCLUSIONS
Given the modest effect on seizure frequency and significant withdrawal rate it is unlikely that remacemide will be further developed as an antiepileptic drug.
Leach
J P
JP
Institute of Neurology, Southern General Hospital, Glasgow, Scotland, UK, G51 4TF. JPLEACH246@aol.com
Marson
A G
AG
Hutton
J L
JL
D000081:Acetamides / Q000627:therapeutic use*; D000927:Anticonvulsants / Q000627:therapeutic use*; D004351:Drug Resistance; D004827:Epilepsy / Q000188:drug therapy*; D006801:Humans; D016032:Randomized Controlled Trials as Topic
D000081:Acetamides; D000927:Anticonvulsants