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Epileptic Disord. 2013 Sep;15(3):314-23. doi: 10.1684/epd.2013.0601.

A common reference-based indirect comparison meta-analysis of intravenous valproate versus intravenous phenobarbitone for convulsive status epilepticus.

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  • 1Department of Neurological and Movement Sciences. Section of Clinical Neurology, University of Verona, Verona, Department of Neurology, Franz Tappeiner Hospital, Merano, Italy, Authors contributed equally.



To compare intravenous valproate (IV-VPA) with intravenous phenobarbitone (IV-PB) in the treatment of established generalised convulsive status epilepticus (GCSE). Efficacy and safety were estimated using a common-reference based indirect comparison meta-analysis (CRBMA) methodology.


Randomised controlled trials (RCTs) investigating the use of IV-VPA or IV-PB versus intravenous phenytoin (IV-PHT) for GCSE were identified by a systematic search of the literature. A random effects model was used to estimate Mantel-Haenszel odds ratios (ORs) for efficacy and safety of IV-VPA or IV-PB versus IV-PHT in a standard meta-analysis. Adjusted indirect comparisons were then made between VPA and PB using the obtained results.


CRBMA showed that VPA does not lead to significantly higher seizure cessation (OR 1.00; 95% CI: 0.36-2.76) compared to PB, although it exhibits fewer adverse effects (OR 0.17; 95% CI: 0.04-0.71). Results of this CRBMA are consistent with results of a recently published head-to-head comparison of IV-VPA and IV-PB.


There is insufficient evidence to demonstrate superiority of IV-VPA over IV-PB for the treatment of GCSE in terms of efficacy. Some direct and indirect comparisons suggest that VPA has a better safety profile than PB. However, the limited numbers of underpowered RCTs included in this meta-analysis are not sufficient to justify a change in clinical practice. More rigorous and appropriately powered RCTs are therefore required to definitively determine the efficacy and tolerability of VPA for the treatment of GCSE.

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