title: Off-label prescribing of antiepileptic drugs in pharmacoresistant epilepsy: a cross-sectional drug utilization study of tertiary care centers in Italy.
abstract: OBJECTIVE
  To assess the extent of off-label prescribing of antiepileptic drugs (AEDs) and associated variables in a large population of patients with pharmacoresistant epilepsy.
  
  
  METHODS
  Descriptive analysis of data recorded from consecutively enrolled patients with pharmacoresistant epilepsy attending 11 tertiary referral centers in Italy. Off-label use was stratified by therapeutic indication, dose, and age. Multivariate logistic regression was used to identify variables associated with off-label prescription.
  
  
  RESULTS
  Of a total of 1,124 patients enrolled between November 2006 and August 2007, 53 % (101/191) of children and 31 % (287/933) of adults were receiving at least one off-label AED prescription. Among adults, off-label use was related primarily to indication and was highest for clobazam (100 %) and ethosuximide (40 %), followed by lamotrigine (25 %), and vigabatrin (25 %). In children, clobazam (100 %), lamotrigine (79 %), vigabatrin (55 %), ethosuximide (46 %), and levetiracetam (43 %) were most frequently used off-label, with indication or age being the main causes depending on the specific AED. Logistic regression analysis indicated that higher rates of off-label use were associated with a polytherapy regimen (odds ratio [OR] 2.50, 95 % confidence interval [95 % CI], 1.55-4.03), pediatric age (2.49, 1.66-3.76), having failed ≥3 AEDs (2.16, 1.04-4.48), a diagnosis of generalized epilepsy with structural/metabolic or unknown etiology (2.97, 1.25-7.04), and increasing seizure frequency (1.07, 1.01-1.14).
  
  
  CONCLUSIONS
  Off-label prescribing of AEDs is common among patients with pharmacoresistant epilepsy and is influenced by demographic and disease-related characteristics. Studies are needed to improve the quality of evidence guiding epilepsy treatment, and to evaluate the risks and benefits of off-label prescribing in epilepsy.
authors: Clinical and Experimental Pharmacology Unit, Department of Internal Medicine and Therapeutics, University of Pavia, Via Ferrata, 9, 27100, Pavia, Italy.
authors: Valentina
authors: V
authors: Franco
authors: Maria Paola
authors: MP
authors: Canevini
authors: Giuseppe
authors: G
authors: Capovilla
authors: Giovambattista
authors: G
authors: De Sarro
authors: Carlo Andrea
authors: CA
authors: Galimberti
authors: Giuliana
authors: G
authors: Gatti
authors: Renzo
authors: R
authors: Guerrini
authors: Angela
authors: A
authors: La Neve
authors: Eleonora
authors: E
authors: Rosati
authors: Luigi Maria
authors: LM
authors: Specchio
authors: Salvatore
authors: S
authors: Striano
authors: Paolo
authors: P
authors: Tinuper
authors: Emilio
authors: E
authors: Perucca
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000627:therapeutic use*; D002648:Child; D003430:Cross-Sectional Studies; D004351:Drug Resistance; D004827:Epilepsy / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007558:Italy; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D056687:Off-Label Use / Q000706:statistics & numerical data*; D010818:Practice Patterns, Physicians' / Q000706:statistics & numerical data*; D062606:Tertiary Care Centers; D055815:Young Adult
chemical_list: D000927:Anticonvulsants