title: Loss of the initial efficacy of levetiracetam in patients with refractory epilepsy.
abstract: OBJECTIVE
  The efficacy and safety of the anti-convulsive drug levetiracetam (LEV) has been well documented but few clinical studies have investigated tolerance to LEV. The aim of this study was to evaluate the loss of the initial efficacy of LEV in adult patients with refractory partial-onset seizures.
  
  
  METHODS
  We enrolled patients with refractory partial epilepsy who were started on add-on LEV treatment. The efficacy of LEV was evaluated every three months and the seizure frequency was decided by the average number of monthly seizures. A responder was defined as a patient with a ≥50% reduction in seizure frequency from the baseline. Seizure freedom was defined as a seizure-free status from the beginning of LEV treatment to the evaluation period. Loss of the initial efficacy was defined as a shift from responder status during the first three months of LEV treatment to non-responder status during the follow-up period.
  
  
  RESULTS
  A total of 95 epilepsy patients were analyzed. During the first three months of LEV treatment, 50 (52.6%) of the 95 patients were responders with a ≥50% seizure reduction. Nine patients (18.0%) showed a loss of initial efficacy during the second three-month period. In contrast, only two (4.0%) of the non-responders during the first three months became responders during the next three months. However, this difference did not reach statistical significance (P=0.054). Based on Kaplan-Meier survival estimates, 49.2% of the patients who initially responded to LEV treatment during the first three months were predicted to lose this response at 42 months. Loss of the initial efficacy of LEV treatment occurred mostly within 18 months.
  
  
  CONCLUSIONS
  This study suggests that the occurrence of tolerance is more common than late gain of efficacy of treatment although larger prospective studies would have to be carried out to prove this observation.
authors.affiliation: Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, 86 Asanbyeongwon-gil, Songpa-gu, Seoul 138-736, Republic of Korea.
authors.forename: Gha-hyun
authors.initials: GH
authors.lastname: Lee
authors.forename: Bo-mi
authors.initials: BM
authors.lastname: Kim
authors.forename: Joong Koo
authors.initials: JK
authors.lastname: Kang
authors.forename: Sang-Ahm
authors.initials: SA
authors.lastname: Lee
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D010889:Piracetam / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011446:Prospective Studies; D019233:Retreatment; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D000077287:Levetiracetam; D010889:Piracetam