Systematic review of the screening, diagnosis, and management of ADHD in children with epilepsy. Consensus paper of the Task Force on Comorbidities of the ILAE Pediatric Commission

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a common and challenging comorbidity affecting many children with epilepsy. A working group under the International League Against Epilepsy (ILAE) Pediatric Commission identified key questions on the identification and management of ADHD in children with epilepsy. Systematic reviews of the evidence to support approaches to these questions were collated and graded using criteria from the American Academy of Neurology Practice Parameter. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) requirements were followed, with PROSPERO registration (CRD42018094617). No increased risk of ADHD in boys with epilepsy compared to girls with epilepsy was found (Level A). Valproate use in pregnancy is associated with inattentiveness and hyperactivity in offspring (1 class I study), and children with intellectual and developmental disabilities are at increased risk of ADHD (Level A). Impact of early seizure onset on development of ADHD was unclear (Level U), but more evident with poor seizure control (Level B). ADHD screening should be performed from 6 years of age, or at diagnosis, and repeated annually (Level U) and reevaluated after change of antiepileptic drug (AED) (Level U). Diagnosis should involve health practitioners with expert training in ADHD (Level U). Use of the Strength and Difficulties Questionnaire screening tool is supported (Level B). Formal cognitive testing is strongly recommended in children with epilepsy who are struggling at school (Level U). Behavioral problems are more likely with polytherapy than monotherapy (Level C). Valproate can exacerbate attentional issues in children with childhood absence epilepsy (Level A). Methylphenidate is tolerated and effective in children with epilepsy (Level B). Limited evidence supports that atomoxetine is tolerated (Level C). Multidisciplinary involvement in transition and adult ADHD clinics is essential (Level U). In conclusion, although recommendations could be proposed for some of the study questions, this systematic review highlighted the need for more comprehensive and targeted large-population prospective studies.

Individualization of attention-deficit/hyperactivity disorder treatment: pharmacotherapy considerations by age and co-occurring conditions

“…The Task Force on Comorbidities of the International League Against Epilepsy Pediatric Commission recommends methylphenidate as the first-choice treatment because there is a 65% to 83% improvement in ADHD symptoms without significantly increasing the frequency or severity of seizures. 207 Atomoxetine has also shown efficacy in treating ADHD in this population, but there is limited evidence regarding safety. 207…”

“…207 Atomoxetine has also shown efficacy in treating ADHD in this population, but there is limited evidence regarding safety. 207…”

What are the challenges with the pharmacological management of epilepsy in patients with Attention Deficit Hyperactivity Disorder (ADHD)?

“…More recently, another open-label study that enrolled 30 epilepsy patients and ADHD showed that only one out of these 30 patients withdrew methylphenidate after seizure worsening [10]. Auvin A et al, in 2018 [11], reported in a systematic review the screening tools, diagnosis, and management of ADHD in children with epilepsy and underlined the risks and difficulties of pharmacological treatments of these patients: as the underdiagnosis of ADHD, possible attention and behavioral worsening due to AEDs and, on the other hand, the false myth that stimulants may lower the seizure threshold.…”

“…Among the first generation AEDs, the most documented association of AEDs with behavioral disturbances and hyperactivity is about phenobarbital [PB] that can induce symptoms of ADHD, followed by valproic acid [VPA] and topiramate [TPM] [6,13]. A double-blind, randomized controlled trial that evaluated short term effects on attention skills of ethosuximide [ETS], VPA and lamotrigine [LTG], showed attention deficit in 49% of patients treated with VPA, 32% of those receiving ETS, and 24% of those receiving LTG [13] [11,14] The behavioral effects (in terms of hyperactivity disturbances, irritability, and disinhibition) of the main AEDs are reported in Table 1.…”

Education, Marriage, and Employment in People with Epilepsy: The Barriers that Patients Perceive

“…Considering the high prevalence of functional disabilities (e.g., learning difficulties) among PWE, routine screening of all PWE for early detection and appropriate management of any cognitive dysfunction and functional disability would be a reasonable approach. 15,16 However, these findings should be seen and interpreted in the context of sociocultural backgrounds. For example, in 2019, Iran's unemployment rate was estimated to be 12% of the total labor force 17 ; this is much lower than the 53% rate in PWE in the current study.…”