title: Relationship between adverse effects of antiepileptic drugs, number of coprescribed drugs, and drug load in a large cohort of consecutive patients with drug-refractory epilepsy.
abstract: OBJECTIVE
  To evaluate the adverse effects (AEs) of antiepileptic drugs (AEDs) in adults with refractory epilepsy and their relationship with number of coprescribed AEDs and AED load.
  
  
  METHODS
  Patients with refractory epilepsy were enrolled consecutively at 11 tertiary referral centers. AEs were assessed through unstructured interview and the Adverse Event Profile (AEP) questionnaire. AED loads were calculated as the sum of prescribed daily dose (PDD)/defined daily dose (DDD) ratios for each coprescribed AED.
  
  
  RESULTS
  Of 809 patients enrolled, 709 had localization-related epilepsy and 627 were on polytherapy. AED loads increased with increasing number of AEDs in the treatment regimen, from 1.2 +/- 0.5 for patients on monotherapy to 2.5 +/- 1, 3.7 +/- 1.1, and 4.7 +/- 1.1 for those on two, three, and > or =4 AEDs, respectively. The number of spontaneously reported AEs correlated with the number of AEs identified by the AEP (r = 0.27, p < 0.0001). AEP scores did not differ between patients with monotherapy and patients with polytherapy (42.8 +/- 11.7 vs. 42.6 +/- 11.2), and there was no correlation between AEP scores and AED load (r = -0.05, p = 0.16).
  
  
  CONCLUSIONS
  AEs did not differ between monotherapy and polytherapy patients, and did not correlate with AED load, possibly as a result of physicians' intervention in individualizing treatment regimens. Taking into account the limitations of a cross-sectional survey, these findings are consistent with the hypothesis that AEs are determined more by individual susceptibility, type of AEDs used, and physicians' skills, than number of coprescribed AEDs and AED load.
authors.affiliation: Division of Neurology 2, Department of Medicine, Surgery, Dentistry, San Paolo Hospital, University of Milan, Milan, Italy.
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Canevini
authors.forename: Giovambattista
authors.initials: G
authors.lastname: De Sarro
authors.forename: Carlo Andrea
authors.initials: CA
authors.lastname: Galimberti
authors.forename: Giuliana
authors.initials: G
authors.lastname: Gatti
authors.forename: Laura
authors.initials: L
authors.lastname: Licchetta
authors.forename: Ambra
authors.initials: A
authors.lastname: Malerba
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Muscas
authors.forename: Angela
authors.initials: A
authors.lastname: La Neve
authors.forename: Pasquale
authors.initials: P
authors.lastname: Striano
authors.forename: Emilio
authors.initials: E
authors.lastname: Perucca
mesh_terms: D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D002983:Clinical Competence / Q000706:statistics & numerical data; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004334:Drug Administration Schedule; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions / Q000139:chemically induced* / Q000453:epidemiology; D004828:Epilepsies, Partial / Q000188:drug therapy; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010818:Practice Patterns, Physicians' / Q000706:statistics & numerical data
chemical_list: D000927:Anticonvulsants