title: Adjunctive therapy versus alternative monotherapy in patients with partial epilepsy failing on a single drug: a multicentre, randomised, pragmatic controlled trial.
abstract: OBJECTIVE
  To evaluate the value of alternative monotherapy versus adjunctive therapy in partial epilepsy refractory to single antiepileptic drug (AED) therapy.
  
  
  METHODS
  In a multicentre, parallel-group, open-label study, patients with cryptogenic or symptomatic partial epilepsy not controlled after single or sequential AED monotherapies were randomised to monotherapy with an alternative AED or to adjunctive therapy with a second AED. The AED to be added/substituted and dose adjustments were determined by the physician's best judgement. Patients were followed up until withdrawal from the allocated treatment or for 12 months, whichever first. Outcome measures included proportion of patients continuing on the assigned treatment strategy, proportion of patients seizure-free after achieving the target maintenance dose, and adverse effects rates. Data were analysed by actuarial life tables, Kaplan-Meier survival analysis and Cox proportional hazard regression model.
  
  
  RESULTS
  Of a total of 157 patients (including 94 previously exposed to only one AED), 76 were randomised to alternative monotherapy and 81 to adjunctive therapy. The two groups were balanced in clinical characteristics. The 12-month cumulative probability of remaining on the assigned treatment was 55% in patients randomised to alternative monotherapy and 65% in those randomised to adjunctive therapy (P=0.74). The 12-month probability of remaining seizure-free was 14 and 16%, respectively (P=0.74). Adverse effects were similar in the two groups. No significant differences in outcome within or between groups were identified based on etiology of epilepsy and previous AED exposure.
  
  
  CONCLUSIONS
  Although these findings should be interpreted with caution due to the low statistical power resulting from the relatively small sample size, alternative monotherapy and adjunctive therapy were associated with similar outcomes. Further work is required to determine whether outcome could be improved through identification of specific AED combinations with synergistic activity.
authors.affiliation: Mario Negri Institute for Pharmacological Research, Milan, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Beghi
authors.forename: Giuliana
authors.initials: G
authors.lastname: Gatti
authors.forename: Clara
authors.initials: C
authors.lastname: Tonini
authors.forename: Elinor
authors.initials: E
authors.lastname: Ben-Menachem
authors.forename: David W
authors.initials: DW
authors.lastname: Chadwick
authors.forename: Marina
authors.initials: M
authors.lastname: Nikanorova
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Gromov
authors.forename: Philip E M
authors.initials: PE
authors.lastname: Smith
authors.forename: Luigi M
authors.initials: LM
authors.lastname: Specchio
authors.forename: Emilio
authors.initials: E
authors.lastname: Perucca
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D016001:Confidence Intervals; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016019:Survival Analysis
chemical_list: D000927:Anticonvulsants