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.
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.
Canevini
Maria Paola
MP
Division of Neurology 2, Department of Medicine, Surgery, Dentistry, San Paolo Hospital, University of Milan, Milan, Italy.
De Sarro
Giovambattista
G
Galimberti
Carlo Andrea
CA
Gatti
Giuliana
G
Licchetta
Laura
L
Malerba
Ambra
A
Muscas
Giancarlo
G
La Neve
Angela
A
Striano
Pasquale
P
Perucca
Emilio
E
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
D000927:Anticonvulsants