title: Lamotrigine adjunctive therapy for refractory generalized tonic-clonic seizures.
abstract: BACKGROUND
  Primary generalized tonic-clonic seizures are one of a number of generalized seizure types which also includes absence, myoclonic and atonic seizures. Effective control of tonic-clonic seizures is required to reduce the risk of injury and death and to improve quality of life. While most people achieve seizure control with one antiepileptic drug, around 30% do not and usually take a combination of antiepileptic drugs.
  
  
  OBJECTIVE
  To assess the effectiveness of adjunctive lamotrigine for refractory primary generalized tonic-clonic seizures.
  
  
  METHODS
  We searched the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE (Ovid) 1950 to June 2010. No language restrictions were imposed. We also contacted GlaxoSmithKline, manufacturers of lamotrigine.
  
  
  METHODS
  Randomised parallel or cross-over add-on trials of add-on lamotrigine for refractory primary generalized tonic-clonic seizures.
  
  
  METHODS
  Outcome measures were: proportion of people (1) with 50% or greater reduction in frequency; (2) with cessation of seizures; (3) who had treatment withdrawn; (4) with adverse effects; and (5) cognitive effects; (6) quality of life outcome measures. Data were independently extracted by review authors.
  
  
  RESULTS
  Two small trials were found that met the inclusion criteria. Due to differences in study design we decided not to undertake a meta-analysis. One placebo controlled cross-over trial (26 participants) showed a significant 50% reduction in tonic-clonic seizure frequency with lamotrigine. Rash was the only adverse effect causing discontinuation (N = 7). A placebo controlled parallel trial comparing 117 participants found a significant median percent reduction in tonic-clonic seizure frequency of 66.5% with lamotrigine compared with 34.2% with placebo (P = 0.006). The most common adverse events were dizziness, somnolence and nausea.
  
  
  CONCLUSIONS
  Two short term trials indicate that lamotrigine has efficacy against primary generalized tonic-clonic seizures; however, this evidence is insufficient to inform clinical practice and longer term active controlled trials are required.
authors.affiliation: Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool, UK, L9 7AL.
authors.forename: Eugene
authors.initials: E
authors.lastname: Tjia-Leong
authors.forename: Kevin
authors.initials: K
authors.lastname: Leong
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Marson
mesh_terms: D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant / Q000379:methods; D003875:Drug Eruptions / Q000209:etiology; D004830:Epilepsy, Tonic-Clonic / Q000188:drug therapy*; D005076:Exanthema / Q000139:chemically induced; D006801:Humans; D000077213:Lamotrigine; D016032:Randomized Controlled Trials as Topic; D014227:Triazines / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D014227:Triazines; D000077213:Lamotrigine