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Monotherapy or Polytherapy for Epilepsy Revisited: A Quantitative Assessment
Author(s) -
Lammers M. W.,
Hekster Y. A.,
Keyser A.,
Meinardi H.,
Renier W. O.,
Lier H.
Publication year - 1995
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1157.1995.tb00484.x
Subject(s) - tolerability , medicine , epilepsy , adverse effect , pediatrics , neurology , pharmacoepidemiology , defined daily dose , cohort , anesthesia , drug , psychiatry , pharmacology , medical prescription
Summary: Some investigators argue that treating epilepsy with several antiepileptic drugs (AEDs) simultaneously (polytherapy) may give rise to more adverse effects than monotherapy, but this argument lacks supporting quantitative data. To reexamine this issue, we recruited a cohort of patients from the outpatients of the Special Centres for Epilepsy in The Netherlands and from the outpatients of the Department of Neurology, Nijmegen University, The Netherlands. Two tools were used for analysis. All daily doses of antiepileptic drugs (AEDs) were standardized by the ratio of prescribed daily dose to defined daily dose (PDD/DDD). The DDD is the assumed average effective daily dose for a drug used for its main indication in adults. The assignment of DDD Values is the task of the World Health Organization (WHO) Collaborating Centre for Drugs Statistics Methodology and Nordic Council on Medicines, which regularly publishes Guidelines for Defined Daily Doses. The severity of adverse effects (AE) was assessed by using the Neurotoxicity Index and the Systemic Toxicity Index as developed by the VA Cooperative Study Group for their recent studies comparing the efficacy and tolerability of AEDs. One hundred sixty‐one patients received monotherapy; all had a PDD/DDD ratio ≤2/day; 128 of 262 patients receiving polytherapy also had ≤2 PDD/DDD ratios/day. The mono‐ and polytherapy groups were stratified according to the PDD/DDD ratio. The prevalence of neurological AE for patients with similar PDD/DDD ratios was 50–80% for monotherapy patients and 50–80% for polytherapy patients. The difference between the mono‐ and polytherapy groups was not significant. The prevalence of neurological AE for patients receiving polytherapy with a PDD/DDD ratio >2.0 was 71–100%, whereas all patients with a PDD/DDD ratio >4.0 had neurological AE. This difference between patients with a PDD/DDD ratio ≤2.0 and those with >2.0 was statistically significant; p < 0.05. The severity of neurological AE also increased with dose, but appeared to peak at ∼3.5 PDD/DDD ratio. Our study underscores the usefulness of applying quantitative methods to the analysis of drug AE. Comparison of monotherapy and polytherapy showed no difference for equipotent doses. Because distribution of the AED doses was uneven between the groups receiving mono‐ and polytherapy, our study permits only a tentative statement that the frequency and severity of AE is independent of the use of either. In addition, frequency and intensity of AE apparently are not very sensitive to changes in dose. An experimental prospective study is planned to verify or refute the conclusions of this observational pilot study.