Abstracts

Rationale: It has been suggested that the selection of the appropriate AED should be largely influenced by its tolerability profile. We performed a systematic review and meta-analysis of the most frequent treatment-emergent central nervous system adverse events (CNS-AEs) of new antiepileptic drugs (AEDs) Methods: Searching Medline and journals, we selected all randomised controlled trials, double-blind versus placebo, performed in adult patients with drug-resistant partial or generalised epilepsies in which the experimental drug, or placebo, had been added to a conventional AED treatment and in which adverse effects were clearly reported in a table. Parallel or cross over design studies were included but the minimal duration of each double blind treatment had to be 8 weeks. Outcome was number of patients complaining of treatment-emergent CNS-AEs. Sixteen predefined CNS-AEs were considered. Risk differences (RD) were calculated for individual studies and summary statistics were estimated using the random effect model. Statistical heterogeneity was checked using a Chi-squared test for heterogeneity. In addition I2 was used to describe the percentage of total variation across studies that was due to heterogeneity rather than chance. Predefined CNS-AEs in patients treated with active drug or placebo was extracted and RD (95% CI) for CNS-AEs was calculated. Results: Thirty six suitable studies of adults with drug-resistant partial or generalised epilepsies were identified. As regards oxcarbazepine and tiagabine no meta-analysis was possible since only one study each could be included. In this case, we calculated RDs from single studies. Gabapentin was significantly associated with somnolence and dizziness; lamotrigine with dizziness, ataxia and diplopia; levetiracetam with somnolence; pregabalin with somnolence, dizziness, ataxia and fatigue; topiramate with somnolence, dizziness, cognitive impairment and fatigue; zonisamide with somnolence and dizziness. Conclusions: The analysis of double-blind, placebo controlled studies is certainly the most robust way to identify a causal relationship between treatment with new AEDs and some frequently observed, treatment-emergent CNS-AEs in relatively homogeneous populations of drug-resistant epileptic patients. No comparisons between drugs is possible. In two cases (oxcarbazepine and tiagabine) meta analysis was not possible. All new AEDs except LTG and TGB have sedative properties. Brain stem and cerebellar functions are mildly affected by GBP, TPM, ZNS and, probably, TGB, since these AEDs were found significantly associated only with dizziness. These functions are more heavily affected by LTG, PGB, OXC, for which also diplopia and ataxia were found Only one drug, TPM, was associated with cognitive disturbances. Tremor was caused by OXC. Finally, we noted that LEV was significantly associated only with one CNS-AE, ZNS and GBP were associated with two, LTG was associated with three and both PGB and TPM with four CNS-AEs. (Sources of funding: Ente Cassa di Risparmio di Firenze)