Parent-reported subjective complaints in children using antiepileptic drugs: what do they mean?
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.
Section snippets
Design
Children were consecutively recruited from the child neurology departments of three university hospitals, a pediatric hospital, and a general hospital. Eight child neurologists provided patients. Children with epilepsy were eligible when they were aged 4–16 years, were treated with at least one AED, and had not been seizure-free for more than 1 year. The neurologists selected children whose parents had sufficient written Dutch language skills to be able to complete a questionnaire. Most
Subjects and clinical data
One hundred and seventeen children were eligible for the study; 115 parents completed and returned the questionnaire. The mother completed the questionnaire in 52, the father in 6, both parents in 54, and other primary caretakers in 3 cases. We excluded 7 children because their parents considered more than 10 items of the HASES “not applicable;” these were children with severe encephalopathies and multiple impairments. In 12 other cases, fewer than 5 items were left open and these were scored
Discussion
In our sample of children with many drug-resistant cases, parents reported subjective complaints attributed to the AEDs in more than 80% of their children. However, in less than 20% of our sample high scores on the HASES were found, indicating that only a minority of the parents attributed severe complaints to the AEDs used in their children. After 1 year, a repeated HASES score was highly correlated with the first, indicating persistence of complaints despite expert neurological care, albeit
Acknowledgements
These investigations were supported by the Dutch National Epilepsy Fund, Project A 108. The authors are indebted to the following child neurologists for providing patients and clinical information: C.E. CatsmanBerrevoets, L.A.E.M. Laan, O. van Nieuwenhuizen, and R.J.H.M. Gooskens.
References (19)
- et al.
Randomized comparative monotherapy trial of phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed childhood epilepsy
Lancet
(1996) - et al.
Standardisation of a self–report questionnaire for use in evaluating cognitive, affective and behavioural side-effects of anti-epileptic drug treatments
Epilepsy Res.
(1996) - et al.
The A–B neuropsychological assessment schedule (ABNAS): the further refinement of a patient-based scale of patient-perceived cognitive functioning
Epilepsy Res.
(2001) - et al.
Epilepsy in childhood: an audit of clinical practice
Arch. Neurol.
(1998) - et al.
Treatment of newly diagnosed pediatric epilepsy: a community-based study
Arch. Pediatr. Adolesc. Med.
(1999) - et al.
The paediatric EPITEG collaborative group: a multicentre comparative trial of sodium valproate and carbamazepine in paediatric epilepsy
Dev. Med. Child Neurol.
(1995) - et al.
Antiepileptic drugrelated cognitive complaints in seizure-free children with epilepsy before and after drug discontinuation
Epilepsia
(1998) - et al.
Parent-completed scales for measuring severity of seizures and side effects of antiepileptic drugs in childhood epilepsy: development and psychometric analysis
Epilepsy Res.
(1996) - et al.
Seizure severity in children with epilepsy: a parent-completed scale compared with clinical data
Epilepsia
(1997)
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