title: Patterns of lamotrigine use in daily clinical practice during the first 5 years after introduction in the Netherlands.
abstract: OBJECTIVE
  Follow-up data on the long-term effectiveness (efficacy and tolerability) of lamotrigine are limited. A useful though crude measure for effectiveness in daily clinical practice is the treatment retention rate determined from drug dispensing data. This study describes the baseline characteristics, the usage patterns and the retention rate of this antiepileptic drug (AED) in a population-based cohort of lamotrigine users in the Netherlands during the first 5 years after its registration in 1995. Data from this cohort are compared with those from the initial randomized clinical trials (RCTs) in patients with refractory epilepsy.
  
  
  METHODS
  This retrospective cohort study used dispensing data from community pharmacies. Baseline characteristics and usage patterns were evaluated for first time users of lamotrigine in this study. Usage patterns were characterized as continued, add-on or discontinued use during the patient observation time window. Cox regression analysis was used to explore possible relationships between baseline characteristics and specific usage patterns defined. The baseline characteristics and discontinuation rates in this cohort study were compared with RCT data reported in medical literature.
  
  
  RESULTS
  A total of 3598 lamotrigine users were identified. The mean age of the population was 39 years and 54% were female. On average, patients used two other AEDs at the start of lamotrigine therapy and approximately 6% of the patients had no history of prior AED use. The discontinuation rate was 25% after 1 year, and approximately 32% at the end of the 5-year study. Addition of another drug or discontinuation was seen in more than half of the population 3 years after the start of therapy. Concurrent use of valproic acid was associated with a better retention rate. Absence of AED history, use of antidepressants, or use of migraine abortive drugs resulted in an increased likelihood of discontinuing lamotrigine. The population from RCTs differed from the study cohort with respect to age, concurrent use of AEDs and length of follow-up.
  
  
  CONCLUSIONS
  Data from RCTs cannot easily be extrapolated to daily clinical practice. In this large, observational study, lamotrigine therapy failed in a considerable number of patients, although the mean retention rate was better than previously reported by others. Population-based linkage of health care records can be used to further clarify the effectiveness of lamotrigine.
authors.affiliation: Department of Clinical Pharmacy, University Medical Centre Nijmegen, Nijmegen, The Netherlands. p.knoester@erasmusmc.nl
authors.forename: P D
authors.initials: PD
authors.lastname: Knoester
authors.forename: S V
authors.initials: SV
authors.lastname: Belitser
authors.forename: C L P
authors.initials: CL
authors.lastname: Deckers
authors.forename: A
authors.initials: A
authors.lastname: Keyser
authors.forename: W O
authors.initials: WO
authors.lastname: Renier
authors.forename: A C G
authors.initials: AC
authors.lastname: Egberts
authors.forename: Y A
authors.initials: YA
authors.lastname: Hekster
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D016208:Databases, Factual; D004363:Drug Utilization; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D010593:Pharmaceutical Services / Q000706:statistics & numerical data; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012107:Research Design; D012189:Retrospective Studies; D012646:Self Administration / Q000706:statistics & numerical data*; D016312:Treatment Refusal / Q000706:statistics & numerical data*; D014227:Triazines / Q000008:administration & dosage*
chemical_list: D000927:Anticonvulsants; D014227:Triazines; D000077213:Lamotrigine