title: Phenobarbitone versus phenytoin monotherapy for partial onset seizures and generalised onset tonic-clonic seizures.
abstract: BACKGROUND
  This is an updated version of the original Cochrane review published in The Cochrane Library 2001, Issue 4.Worldwide, particularly in the developing world, phenytoin and phenobarbitone are commonly used antiepileptic drugs, primarily because they are inexpensive. The aim of this review is to summarise data from existing trials comparing phenytoin and phenobarbitone.
  
  
  OBJECTIVE
  To review the best evidence comparing phenobarbitone and phenytoin when used as monotherapy in participants with partial onset seizures or generalised tonic-clonic seizures with or without other generalised seizure types.
  
  
  METHODS
  We searched the Cochrane Epilepsy Group trials register (31 May 2012), the Cochrane Central Register of Controlled Trials (CENTRAL Issue 5 of 12, The Cochrane Library 2012) and MEDLINE (1946 to May week 4, 2012). We hand-searched relevant journals, contacted pharmaceutical companies, original trial investigators and experts in the field.
  
  
  METHODS
  Randomised controlled trials in children or adults with partial onset seizures or generalised onset tonic-clonic seizures with a comparison of phenobarbitone monotherapy with phenytoin monotherapy.
  
  
  METHODS
  This was an individual participant data (IPD) review. Outcomes were time to (a) treatment withdrawal (b) 12-month remission (c) six-month remission and (d) first seizure post randomisation. Cox proportional hazards regression models were used to obtain study-specific estimates of hazard ratios (HRs) with 95% confidence intervals (CIs) with the generic inverse variance method used to obtain the overall pooled estimate of HRs and 95% CIs.
  
  
  RESULTS
  Data have been obtained for four of eight studies meeting the inclusion criteria, amounting to 599 individuals, or approximately 63% of the potential data.The main overall results (pooled HR, 95% CI) were (a) time to treatment withdrawal 1.62 (1.23 to 2.14); (b) time to 12-month remission 0.90 (0.69 to 1.18) (c) time to six-month remission 0.92 (0.73 to 1.16) and (d) time to first seizure 0.85 (0.68 to 1.05). These results indicate a statistically significant clinical advantage for phenytoin in terms of treatment withdrawal. However, this result may have been confounded by several factors including substantial statistical heterogeneity between studies and lack of blinding in two studies.
  
  
  CONCLUSIONS
  The results of this review show that phenobarbitone was significantly more likely to be withdrawn than phenytoin. Given that no significant differences for seizure outcomes were found, the higher withdrawal rate with phenobarbitone may be due to adverse effects. Several factors may have confounded the results of this review.
authors: Department of Biostatistics, University of Liverpool, Liverpool, UK. sarah.nolan@liv.ac.uk.
authors: Sarah J
authors: SJ
authors: Nolan
authors: Catrin
authors: C
authors: Tudur Smith
authors: Jennifer
authors: J
authors: Pulman
authors: Anthony G
authors: AG
authors: Marson
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D002220:Carbamazepine / Q000627:therapeutic use; D002648:Child; D004828:Epilepsies, Partial / Q000188:drug therapy*; D004830:Epilepsy, Tonic-Clonic / Q000188:drug therapy*; D006801:Humans; D060828:Induction Chemotherapy; D010634:Phenobarbital / Q000009:adverse effects / Q000627:therapeutic use*; D010672:Phenytoin / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D012640:Seizures / Q000188:drug therapy*; D013997:Time Factors; D014635:Valproic Acid / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D002220:Carbamazepine; D014635:Valproic Acid; D010672:Phenytoin; D010634:Phenobarbital