title: The impact of side effects on long-term retention in three new antiepileptic drugs.
abstract: OBJECTIVE
  To determine long-term retention, percentage of patients withdrawing because of adverse events, percentage of patients achieving seizure freedom, safety profile of the new anti-epileptic drugs lamotrigine, levetiracetam and topiramate.
  
  
  METHODS
  All patients treated with lamotrigine, levetiracetam or topiramate in the Epilepsy Centre were identified. Each drug was analyzed from introduction of the drug in the Netherlands up to a final assessment point 2 years later.
  
  
  RESULTS
  Data from 1066 patients were included: 336 for lamotrigine, 301 for levetiracetam, 429 for topiramate. Two-year retention rates were 69.2% (lamotrigine), 45.8% (levetiracetam), 38.3% (topiramate); (LTG vs. LEV at p<0.001; LTG vs. TPM at p<0.001; LEV vs. TPM at p=0.005). Seizure freedom rates were lowest for lamotrigine and highest for levetiracetam. Adverse events played a role in drug discontinuation in 154/429 patients (35.9%) on topiramate, 52/336 patients (15.5%) on lamotrigine (p<0.001), 68/301 patients (22.5%) on levetiracetam (p<0.001). Mood and general CNS-effects are common in patients on lamotrigine and levetiracetam, and neurocognitive side effects are most prevalent in patients on topiramate. A positive effect on cognition is frequently noted in patients on lamotrigine.
  
  
  CONCLUSIONS
  A drug that is only modestly efficacious but has a favourable safety profile may look better than a drug that is more efficacious but produces clinically meaningful adverse events. Therefore, a drug's retention rate is mainly determined by its side effect profile. As a consequence, retention rate was highest for lamotrigine and lowest for topiramate. Intermediate retention rates were seen with levetiracetam use.
authors.affiliation: Departments of Neurology, Clinical Neurophysiology, Neuropsychology and Pharmacology of the Epilepsy Centre Kempenhaeghe, Heeze, The Netherlands. BootsmaHP@kempenhaeghe.nl
authors.forename: Hans P
authors.initials: HP
authors.lastname: Bootsma
authors.forename: Lukas
authors.initials: L
authors.lastname: Ricker
authors.forename: Yechiel A
authors.initials: YA
authors.lastname: Hekster
authors.forename: Jacques
authors.initials: J
authors.lastname: Hulsman
authors.forename: Danielle
authors.initials: D
authors.lastname: Lambrechts
authors.forename: Marian
authors.initials: M
authors.lastname: Majoie
authors.forename: Ad
authors.initials: A
authors.lastname: Schellekens
authors.forename: Marc
authors.initials: M
authors.lastname: de Krom
authors.forename: Albert P
authors.initials: AP
authors.lastname: Aldenkamp
mesh_terms: D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use*; D004363:Drug Utilization / Q000706:statistics & numerical data; D004827:Epilepsy / Q000188:drug therapy*; D005632:Fructose / Q000031:analogs & derivatives; D006801:Humans; D000077213:Lamotrigine; D000077287:Levetiracetam; D008137:Longitudinal Studies; D010349:Patient Compliance / Q000523:psychology*; D010889:Piracetam / Q000031:analogs & derivatives; D013997:Time Factors; D000077236:Topiramate; D016896:Treatment Outcome; D014227:Triazines
chemical_list: D000927:Anticonvulsants; D014227:Triazines; D000077236:Topiramate; D005632:Fructose; D000077287:Levetiracetam; D000077213:Lamotrigine; D010889:Piracetam