Monotherapy or Polytherapy for Epilepsy Revisited: A Quantitative Assessment

Abstract

Summary: Some investigators argue that treating epi lepsy with several antiepileptic drugs (AEDs) simulta neously (polytherapy) may give rise to more adverse ef fects than monotherapy, but this argument lacks support ing 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, Nij megen 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 val ues is the task of the World Health Organization (WHO) Collaborating Centre for Drugs Statistics Methodology and Nordic Council on Medicines, which regularly pub lishes Guidelines for Defined Dally Doses. The severity of adverse effects (AE) was assessed by using the Neu rotoxicity Index and the Systemic Toxicity Index as de veloped by the VA Cooperative Study Group for their recent studies comparing the efficacy and tolerability of AEDs. One hundred sixty-one patients received mono therapy; all had a PDD/DDD ratio ^2/day; 128 of 262 patients receiving poly therapy also had ^2 PDD/DDD ratios/day. The mono-and poly therapy groups were stratified according to the PDD/DDD ratio. The prevalence of neurological AE for patients with similar PDD/DDD ra tios was 50-80% for monotherapy patients and 50-82% for poly therapy patients. The difference between the mono-and polytherapy groups was not significant. The prevalence of neurological AE for patients receiving poly therapy with a PDD/DDD ratio > 2 .0 was 71-100%, whereas all patients with a PDD/DDD ratio > 4.0 had neu rological AE. This difference between patients with a PDD/DDD ratio ^2.0 and those with > 2.0 was statisti cally 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 useful ness of applying quantitative methods to the analysis of drug AE, Comparison of monotherapy and polytherapy showed no difference for equipotent doses. Because dis tribution of the AED doses was uneven between the groups receiving mono-and poly therapy, our study per mits 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 con clusions of this observational pilot study. Key Words: Ep ilepsy-Antiepileptic drugs-Adverse effectsMonotherapy-Polytherapy-Clinimetrics.Remaining seizure-free is sufficiently important for many patients with epilepsy for them to accept the adverse effects (AE) of continual use of antiep ileptic drugs (AEDs). The problem of toxicity of AEDs has been reviewed repeatedly (1-4). There is a long tradition ...

Drug utilization profile in adult patients with refractory epilepsy at a tertiary referral center

“…Age, gender, age at onset of seizures, antiepileptic therapy details, pharmacoresistance grading, con comitant non-AED medications, types of seizure, and epilepsy according to the International League Against Epilepsy (ILAE) classification 8,9 , and spontaneous reports of adverse effects were registered. Evaluation of AED dosages was performed by calculating the ratio of the prescribed daily dose (PDD) over the defined daily dose (DDD) (PDD/DDD) 10 . DDD is a unit of measurement commonly applied in drug utilization researches and is defined as the assumed average maintenance dose per day of a drug used on its main indication in adults 11 .…”

Multimodal MRI Reveals Secondarily Generalized Seizure Related Abnormalities at 1.5 T: Preliminary Findings

“…This threshold value of 20 SGTCS was varied to investigate its influence on the results. Drug load was calculated by standardizing the doses of antiepileptic drugs using the ratio of prescribed daily dose to defined daily dose (Lammers et al, 1995). No SGTCS were reported in the last two weeks before MRIscanning.…”

Commission on Outcome Measurement in Epilepsy, 1994–1997: Final Report

“…39, No. 2, 1998 received increasing attention (89); further research into the development of standardized methodology for quantitative assessment should be encouraged. In some cases, the value of the information for monitoring the course of epilepsy does not justify the effort required to obtain the data; e.g., the Multiple Sleep Latency Test (MSLT) (25) undoubtedly provides accurate and reproducible scores in scoring drowsiness, but the test is very time-consuming.…”