Parent-reported subjective complaints in children using antiepileptic drugs: what do they mean?

Abstract

We used a parent-completed 20-item “side effect scale” quantifying complaints that parents perceive to be caused by antiepileptic drugs (AEDs) in 108 children with active epilepsy. We studied the associations between parent-reported complaints, severity of seizures, and restrictions due to epilepsy, and clinical data including number and AED load. In 85% of the children at least one complaint was reported, in less than 20% complaints were perceived as a substantial problem. In a multivariate analysis, there was no significant relationship between the “side effect scale” score and AED load, or the number of AEDs. However, complaints were associated with parent-reported frequency and severity of seizures. We conclude that the adverse effects of seizures or parental concern about the severity and intractability of seizures in their children may have influenced the reported complaints.

Introduction

Surveys in The Netherlands and the United States have shown that more than 80% of all children with epilepsy in these countries are treated with antiepileptic drugs (AEDs) [1], [2]. In clinical trials of AEDs in children, subjective complaints, such as fatigue and somnolence, are commonly reported and considered as side effects [3]. Subjective complaints are probably relatively rare when childhood epilepsy is in remission [4], but they might be more prevalent when seizures are drug resistant, because in such cases high dosages or multiple AEDs are used. The use of high dosages and multiple AEDs is generally believed to increase the prevalence and severity of side effects. However, it is not always clear if subjective complaints, despite being attributed to the use of AEDs, really are caused by the AEDs or reflect something else, such as adverse effects of seizures or concern about the epilepsy itself. Complaints attributed to AEDs may influence clinical decisions about AED dosage or combining AEDs and therefore it is important to understand what they mean.

We have previously described a method for a standardized quantification of the prevalence and severity of subjective complaints in children taking AEDs attributed to the medication by their parents, using the Hague Side Effects Scale (HASES) [5]. HASES comprises 20 subjective complaints that were common in a pilot population of children using AEDs. The final content of the scale was based on a psychometric analysis from the pilot sample. Items were included based on parental suggestions during in-depth interviews about side effects, item–total correlations in a pilot version of the scale, and internal consistency of the scale, rather than items based on clinicians’ perceptions or on side effects reported in the literature. It is therefore possible that certain complaints, which parents perceive to be AED-related, are in fact related to other causes, such as ongoing seizures. HASES was reliable in terms of internal consistency (Crohnbach’s α=0.88) and retest stability (Pearson correlation after 14 days=0.91).

We report the prevalence and severity of subjective side effects as measured using HASES in children taking AEDs, and the relationship between HASES score and clinical data. We excluded children with epilepsy in remission, because it has been reported that in these children subjective complaints are limited [4]. We hypothesized that, in a context of ongoing seizures despite treatment, complaints, although attributed by the parents to their childrens’ AEDs, could be an expression of clinical factors other than AED toxicity.