title: A common reference-based indirect comparison meta-analysis of intravenous valproate versus intravenous phenobarbitone for convulsive status epilepticus.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Neurological and Movement Sciences. Section of Clinical Neurology, University of Verona, Verona, Department of Neurology, Franz Tappeiner Hospital, Merano, Italy, Authors contributed equally.
authors: Francesco
authors: F
authors: Brigo
authors: Stanley C
authors: SC
authors: Igwe
authors: Raffaele
authors: R
authors: Nardone
authors: Frediano
authors: F
authors: Tezzon
authors: Luigi Giuseppe
authors: LG
authors: Bongiovanni
authors: Eugen
authors: E
authors: Trinka
mesh_terms: D000465:Algorithms; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D015982:Bias; D006801:Humans; D007275:Injections, Intravenous; D015233:Models, Statistical; D010634:Phenobarbital / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D013226:Status Epilepticus / Q000188:drug therapy*; D016896:Treatment Outcome; D014635:Valproic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid; D010634:Phenobarbital