Interventions for ADHD in Children & Adolescents with Epilepsy: A Review and Decision Tree to Guide Clinicians

Abstract

Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common pediatric epilepsy comorbidities. Treating ADHD in the context of epilepsy can be overwhelming for parents and clinicians. Current frontline treatment for ADHD is stimulant medication. However, some parents of pediatric patients with epilepsy have concerns about adding additional medication to their child’s epilepsy regimen and/or about adverse effects of stimulant medication. Non-medication ADHD treatments including psychosocial interventions and ketogenic diet have also shown success in improving ADHD symptoms. Our focused review provides an easy-to-use guide for clinicians on ADHD interventions and combinations of interventions for pediatric patients with epilepsy and ADHD. Our guide includes information from 8 electronic databases for peer-reviewed, English language studies of psychosocial treatments for youth with epilepsy and ADHD. One hundred eight studies were selected based on inclusion criteria (21 systematic reviews, 12 meta-analyses, 8 literature reviews, 6 population surveys, 31 clinical trials, 20 cross-sectional studies, and 10 retrospective reviews). Results indicated that stimulant medication is a frontline treatment for ADHD symptoms in youth with epilepsy, with important caveats and alternatives.

1. Introduction

An estimated 470,000 children and adolescents are living with epilepsy in the US [1] and between 30% and 40% of them are diagnosed with attention-deficit/hyperactivity disorder (ADHD) [2,3,4]. ADHD is defined as a persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development [5,6] with three subtypes, including predominantly inattentive, predominantly hyperactive, and combined inattentive and hyperactive, of which predominantly inattentive type is most common [4,7,8]. In pediatric epilepsy, attention problems often predate seizure onset, suggesting common underlying pathophysiology rather than a causal relationship between seizures and ADHD [9,10]. Multiple studies have found increased incidence of epilepsy in patients with ADHD and increased incidence of ADHD in patients with epilepsy when compared to the general population [4,11]. These findings suggest that attention problems and seizures represent separate manifestations of the same underlying cause, perhaps represented differentially along the developmental course [3]. A possible neurobiological etiology of ADHD in epilepsy has been posited in functional neuroimaging literature, suggesting dysfunction in inhibitory control pathways, including the right inferior prefrontal cortex, supplemental motor area, and anterior cingulate gyrus [12].

Other research has pointed to a mixture of genetic and environmental factors contributing to development of epilepsy-ADHD comorbidity [10] with attention problems identified prior to seizure onset; thus, eliminating anti-seizure medication (ASM) or seizure-related psychosocial stress as causes of ADHD, though they may influence symptoms. Patients on ASMs have been shown to have a higher incidence of ADHD (27.6%) compared to patients who were not treated with ASMs (14.0%), with increasing number of ASMs [13] associated with greater vulnerability to ADHD symptoms. A literature search revealed that some ASMs (i.e., phenobarbital, topiramate, valproic acid) may induce or exacerbate behavioral symptoms (e.g., those associated with ADHD) in patients with epilepsy, whereas other medications (i.e., lacosamide, carbamazepine, lamotrigine) are reported to have beneficial effects on behavior [14].

Both epilepsy and ADHD negatively influence neurodevelopment. Research suggests that patients with comorbid epilepsy and ADHD are at greater risk for poor educational outcome and quality of life and more severe cognitive problems [15,16] compared to children with epilepsy alone [14]. Academically, more than 50% of children and adolescents with comorbid epilepsy and ADHD require support from an Individualized Education Program (IEP), compared to only 15% with epilepsy alone [17].

Neuropsychological testing has indicated that attention and executive function are the most common cognitive domains affected by combined epilepsy and ADHD [18]. Behavioral ratings of executive functioning often implicate abnormalities in impulse control, attentional shifting, planning, initiation, and complex problem solving [17]. These deficiencies suggest frontal subcortical involvement, which is supported by a study that examined quantitative MRI volumetrics in patients with comorbid epilepsy and ADHD and found those patients had abnormalities in frontal lobes and smaller brainstem volumes [19]. The study also found that compared to healthy controls, patients with ADHD had global reductions in gray matter volumes that were robustly localized in the right lentiform nucleus and extended to the caudate nucleus [19].

Epilepsy severity, including drug-resistant epilepsy, is positively associated with higher risk of ADHD. Several epilepsy-specific factors are associated with poorer attention in youth with the disorder, including tonic-clonic seizures, symptomatic epilepsy, early age of onset, higher seizure frequency, and longer duration of epilepsy [12,20,21], whereas seizure type and presence of an abnormal electroencephalogram (EEG) are not associated with poorer attention [12]. Given the neuropsychological complexity of youth with epilepsy and ADHD, treatment of their ADHD symptoms is often less straightforward than that of their peers with medically uncomplicated ADHD. For this reason, we have written this focused review to provide a user-friendly, stepwise approach to managing problems associated with ADHD in children and adolescents with epilepsy. We have included the most current evidence-based treatments including pharmacological, psychosocial, and diet-related interventions to guide clinicians’ decision-making when treating these patients and provided a table (Table 1) and decision tree (Figure 1) for this purpose.

Figure 1. Decision tree for managing ADHD symptoms in pediatric patients with epilepsy.

^aMethylphenidate and if that is not helpful or has adverse effects, amphetamines may be trialed

^bWell-Established or probably efficacious treatments

• Attention and EF only: Consider Cognitive Remediation
• Behavior: Consider Parent Training and/or Classroom Management Behavioral Therapies
• Social: Consider Peer Intervention Behavioral Therapy

^cConsultation with specialist regarding effectiveness of classic ketogenic (cKG) or modified Atkins (MAD) in managing ADHD symptoms may be helpful.

^dIf atomoxetine or guanfacine are not helpful, less well-studied nonstimulants or modafinil may be trialed.

2. Pharmacological Treatment of ADHD

The aims of pharmacological treatment should follow four general principles: 1) ameliorate behavioral, cognitive, and social interaction problems, 2) avoid adverse effects, 3) minimize interactions with other medications, and 4) improve quality of life. The choice of a pharmacological agent will also depend on a variety of considerations, such as child’s age, weight, ability to swallow pills, desired duration of treatment, and presence of underlying comorbid conditions. Additional considerations should be made regarding history of substance use in the patient or other persons living within the household.

There are currently multiple pharmacological interventions available to treat ADHD, including stimulant and nonstimulant options; however, medications vary in their effectiveness and adverse effects and are not appropriate for all patients (Table 1). Increased scrutiny is necessary when evaluating ADHD-focused treatment options for patients with epilepsy. Despite benefits, some medications used to treat ADHD can increase seizure frequency [22,23]. Studies found that 10-15% of patients with difficult-to-treat epilepsies experienced an increase in seizure frequency when methylphenidate was added to their medication regimen [22,23]. Therefore, these patients require close monitoring for any side effects, including changes in seizure frequency after initiation of ADHD medication. It is important to keep in mind that the underlying etiology for seizures can contribute to ADHD or be a confounding factor in the morbidity, including seizures involving frontal lobes and in recurrent intermittent subclinical seizures, which may have a significant impact on cognition and behavior. As such, when planning pharmacological treatment, consideration of the underlying etiology of ADHD symptoms is a key factor in selecting treatment.

Underlying causes of attention problems in epilepsy patients often differ from those seen in children with ADHD alone and may include ictal and interictal epileptiform discharges, sleep problems, and ASM-related attention difficulties (e.g., benzodiazepines) [24,25,26,27,28]. Thus, evaluation and treatment of attention difficulties in pediatric epilepsy should address those factors first, after which need for ADHD-focused medication may be assessed. If medication management is deemed necessary, guidelines for monitoring its effects on core ADHD symptoms include collecting parent (and teacher, if possible) rating scales of patients’ behavior over multiple time points [29]. The need for dose adjustment and continuation and/or termination of treatment should be discussed with patients and their families. Below we provide specific information on the most prescribed stimulant and nonstimulant medications for ADHD and their effectiveness and known adverse effects when used to treat pediatric patients with comorbid epilepsy and ADHD.

2.1. Stimulant Medication

Several randomized clinical studies over the last four decades have proven the efficacy of stimulants in treating attention problems in pediatric epilepsy populations [30,31,32,33,34,35]. The two most prescribed stimulants are methylphenidate and amphetamine. They come in different forms, including liquid and pill immediate release, capsule intermediate and extended release (long acting), oral disintegrating, and skin patches. Long-acting medications have the advantage of convenience and higher compliance; however, usage in younger children is cautioned due to prolonged medication effects and potential adverse effects. Possible adverse effects of stimulant medications in general include cardiovascular problems, especially in patients with preexisting cardiac issues or family history of cardiovascular disease [36]. Beginning with a small dose is advised, with slow titration every one to three weeks until symptoms of ADHD reduce/remit or adverse effects appear, whichever occurs first. Variability is high when determining the optimum dose for each patient.

Stimulant medications are considered a controlled substance with high risk for misuse/abuse and illegal sharing/selling. During a fourteen-year span, the National Poison Data System reported a 65% increase in calls related to ADHD medication abuse in teenage patients [37] and nearly 30% of adolescents have a friend who has abused prescription stimulants [38]. The National Monitoring of Adolescent Prescription Stimulants Study reported that 52% of youth had engaged in at least one form sharing or selling of stimulants and that this behavior increased with age [39]. Thus, when treating adolescent patients with stimulants, particularly ages 12-18, clinicians should discuss potential problems at each medical visit to assess for risk.

2.1.1. Methylphenidate

Methylphenidate is recommended as the frontline treatment for ADHD in children and adolescents and is considered safe and effective for treating pediatric patients with comorbid epilepsy [30,31,32,33,34,35]. In a recent meta-analysis [34], when compared to other stimulant medications, methylphenidate resulted in the fewest adverse effects when compared to placebo, while being effective in treating ADHD symptoms in pediatric patients. Reported benefits of methylphenidate include improved academic performance, social functioning, mood, and self-esteem [40,41,42]. Common adverse effects include loss of appetite and sleep problems [33]. Rarer problems include cardiovascular and gastrointestinal changes [43,44].

Methylphenidate has previously been reported to exacerbate tic disorders and anxiety; however, a recent metanalysis of controlled medication trials found no association between psychostimulants and new onset or worsening tics [45]. Historically, methylphenidate was not recommended for children under 6 years old due to concerns regarding growth retardation [46] but recent research has found it to be safe and effective with the caveat that it be implemented only if behavioral therapy alone is insufficient. In rare cases, it may increase seizure frequency, especially at higher doses [47,48,49]. Methylphenidate has also been associated with worsening EEG findings [50]. To aid clinicians in screening patients prior to prescribing methylphenidate, a systematic review by Auvin et al. (2018) provides useful information on screening tools, management of ADHD in children with epilepsy, and the possible risks of pharmacological treatments of these patients [30]. In sum, methylphenidate is considered a safe and effective treatment for ADHD symptoms in most pediatric patients with epilepsy [30].

2.1.2. Amphetamines

Amphetamines offer the most robust pharmacological treatment for ADHD; however, they carry a higher risk for adverse effects than methylphenidate, making them a less optimal choice [34]. Adverse effects are like those seen in methylphenidate. Nonetheless, in cases where methylphenidate is not effective at improving ADHD symptoms, amphetamines are considered a safe and effective alternative [30,34].

2.1.3. Modafinil

Modafinil is typically used to treat severe lethargy but is uncommonly used off label to treat ADHD [51]. It is an atypical stimulant in that its mechanism of action on the brain differs from stimulants discussed above and may result in fewer negative side effects [44,52]. There is limited research available on the effectiveness of modafinil in treating ADHD symptoms, but existing literature suggests it may be helpful for some patients [34,44]. Additional research is necessary to better assess modafinil’s efficacy and effectiveness in patients with epilepsy.

2.2. Nonstimulant Medication

Stimulant medication is not helpful for all patients with ADHD, with as many as 30% experiencing minimal to no benefits from methylphenidate and amphetamines [52]. In cases where stimulant medication is not helpful, not well tolerated, contraindicated, or not acceptable to patients and families, there are non-stimulant alternatives to treating ADHD symptoms that may be helpful, though their efficacy is generally not as robust when compared to stimulant medications [32,34]. Nonstimulant medications are also often used to target hyperactivity and irritability in children under the age of 6 though they are not generally helpful for symptoms of inattention. The most researched of these include atomoxetine, alpha-2 agonists, and antidepressants [32].

2.2.1.1.1. Atomoxetine

Atomoxetine is frequently used to treat ADHD symptoms in patients for whom stimulant medication is not an option. Retrospective studies found that atomoxetine was helpful in managing ADHD symptoms in pediatric patients with epilepsy with minimal adverse effects, including minimal seizure aggravation [53,54]. A recent meta-analysis found atomoxetine to be a beneficial treatment in children and adolescents with ADHD when compared to placebo though the stimulant medications were considered to be more effective [34]. However, other research has shown atomoxetine to be superior to extended-release non-stimulant medications, like guanfacine, in adolescents [55]. Atomoxetine is also often used for patients with comorbid ADHD and anxiety and is favored by cardiologists due to fewer cardiac effects. Common adverse effects of atomoxetine include decreased appetite, gastrointestinal problems, and lethargy [32]. Rare side effects include irritability, suicidality, liver disease, and worsening behavior [32,54].

2.2.2. Less Well Validated Pharmacological Treatments

A limited number of studies have investigated the usefulness of tricyclic antidepressants, bupropion, and alpha-adrenergic agonists (clonidine and guanfacine) as monotherapies in patients with ADHD alone, and existing studies on the effects of these medications in patients with comorbid epilepsy and ADHD are even more limited. Recent review [32] and meta-analysis [34] indicated that interpretability of studies examining the benefits and adverse effects of bupropion, clonidine, and guanfacine on ADHD symptoms was limited due to high degree of variability in results. However, guanfacine has shown success in managing ADHD symptoms in patients without epilepsy when combined with amphetamines or methylphenidate [43]. These medications are not without side effects; tricyclic antidepressants may result in cardiotoxicity [32] and bupropion may aggravate seizures in patients with epilepsy.

Use of cannabidiol (CBD) for ADHD treatment has been gaining popularity in the last several years. Available studies have focused on the efficacy of CBD in reducing symptoms of ADHD in adults [56] and multiple systematic reviews demonstrated the effectiveness of CBD in managing behavioral symptoms (hyperactivity, impulsivity, and inhibition) but not attention or emotional symptoms [56,57,58]. Another systematic review showed no statistically significant effectiveness in treating mental health disorders, including ADHD [59,60]. Research supporting the use of CBD for pediatric patients diagnosed with ADHD remains limited, though some anecdotal data suggests use of cannabis alleviates their symptoms [56]. Further studies are necessary to establish the effect of CBD on symptoms of ADHD in pediatric patients.

In summary, a wide variety of effective pharmacological options are available to treat ADHD symptoms in pediatric patients with epilepsy with limited adverse effects. However, these patients may not receive ADHD medication because of parents’ reluctance to add new medication to their children’s ASM regime. Further, benefits of ADHD medications have not been found to endure following termination of use [61], at least not in the short term. Thus, when discussing treatment options, parents should be educated regarding possible negative and positive outcomes.

2.2.3. Interactions between ADHD and Antiseizure Medication

Understanding interactions between ASMs and ADHD medication, as well as awareness of which ASMs may exacerbate attention and/or behavior problems are imperative for clinicians prescribing ADHD medications for pediatric patients with epilepsy and ADHD [62]. For example, research suggests that stimulant medication and atomoxetine when used in conjunction with ASMs typically do not affect quality of seizure control in pediatric epilepsy patients [62]. Although ASMs can be used safely and effectively in pediatric patients diagnosed with ADHD, rapid titration can increase risk of ADHD symptoms, and ASMs at high dosages may negatively affect attention and behavior [62,63,64]. Among first generation ASMs, Masur et al. (2013) reported attention deficits in 49% of patients treated with valproic acid, 32% treated with ethosuximide, and 24% treated with lamotrigine [64].

3. Ketogenic Diet Treatment for ADHD

In addition to being helpful with seizure reduction in some patients [65,66,67,68,69,70], the ketogenic diet (KD) and modified Atkins diet (MAD) have resulted in cognitive improvements as a secondary treatment outcome [65,71]. In the classic version of KD (cKD), initial treatment requires an inpatient stay, with a fat-to-carbohydrate-plus-protein ratio of 3-4:1. The cKD results in a metabolic state that causes the body to use ketone bodies rather than carbohydrates as the primary energy source (i.e., ketosis). MAD is a less restrictive regimen than cKD in which individuals are encouraged to eat a fat-to-carbohydrate-plus-protein ratio of 1:1 or 2:1, but in contrast to cKD there are no calorie restrictions, and it can be initiated in an outpatient setting [65].

Animal studies evaluating cognitive changes related to ketogenic diet have found attentional improvements in alertness [72,73], attention [74,75], and concentration [76,77,78,79]. For example, a 6-month prospective, randomized, double blinded, placebo-controlled, crossover dietary trial compared the effects of ketogenic medium chain triglyceride diet (MCTD) and standardized placebo diet on behavior in 21 dogs with ADHD and idiopathic epilepsy. The MCTD resulted in significant improvement in the ADHD-related behavioral factor (chasing) and a reduction in stranger-directed fear (p<0.05) compared with the placebo diet [80].

Research on the effects of KD treatment on cognition in humans is limited. Results from a randomized, controlled trial examining the behavioral and cognitive impact of the KD in 50 children and adolescents with medication-refractory epilepsy [73] suggested positive cognitive and behavioral effects of KD, with reduction in parent reported hyperactivity (Strength and Difficulties Questionnaire), and attention deficit and hyperactivity (Social Emotional Questionnaire) following 4 months of completing the KD. Limitations included high dropout rate, variability between control and test group on level of cognitive functioning, and a large age range in the assessment group (1 to 16 years old).

These findings offer some support for use of KD as a potential treatment for ADHD in pediatric patients with epilepsy whose symptoms cannot be treated using medication; however, more research is needed. Clinicians should be aware that KD is contraindicated in certain metabolic disorders and compliance may be more challenging for pediatric patients with ADHD.

4. Psychosocial Treatments for Youth with ADHD and Epilepsy

Psychosocial treatments are more widely accepted and established as alternatives or adjunctive treatments to pharmacological interventions for ADHD symptoms compared to the ketogenic diet [81] and are expected to work well for children with and without epilepsy [31]. Recent reviews of evidence-based psychosocial treatments by Evans et al. (2018) [82], Dekkers et al. (2022) [83], and Groenman et al. (2022) [84] rated existing treatments as well established, possibly efficacious, questionably effective, or experimental. These are described briefly below.

4.1. Well Established Treatments

Behavioral strategies including parent training, classroom management, and peer interventions used in isolation or combination are considered well established for children from preschool to elementary-school age [81,82,83,84]. Parent training involves intensive instruction for parents on how to use effective rules, structure, and communication to reduce their children’s undesirable behaviors and increase desirable behaviors [82,83,84]. Behavioral peer intervention involves coaching parents and teachers in utilizing motivational incentives and positive reinforcements to improve children’s social interactions [82,83,84]. Behavior classroom management interventions incorporate classroom rules and reward and penalty systems to manage problem behaviors and encourage preferable behaviors [82,83,84]. For adolescents, organization training, including managing time and materials is a well-established treatment. However, behavior therapy in adolescents can be challenging due to parent-child conflict, increased want of independence, and decreased supervision. Behavior therapy for adolescents should honor personal treatment goals, form collaboration between parent and child, and promote independence and autonomy while achieving goals.

4.2. Probably Efficacious Treatments

The Challenging Horizons Program is a school-based intervention aimed at augmenting adolescents’ skills necessary for independent academic and school success. It includes both group and individual interventions, as well as parent education and training [85,86].

4.3. Possibly Efficacious Treatments

Neurofeedback uses audio or visual feedback on brainwave patterns to teach patients how to better self-regulate cognition, emotions, and behaviors [87].

4.4. Experimental Treatments

Cognitive training programs may include computer-based or non-computer (e.g., clinician directed, paper and pencil) games or activities, which aim to improve attention, working memory, and/or other executive functioning skills. Computer-based training is an attractive option because it can be done in the absence of a clinician and in the home or school setting; however, there are trade-offs for this convenience. Computerized cognitive training programs (e.g., CogMed, BrainGame Brian) have led to the most consistent and strongest improvement in working memory, but there is limited evidence that these skills transfer to other domains (e.g., academics, behavior at home and school) [80,85,86,88,89]. The implementation of clinician-directed cognitive training with parent coaching and daily practice shows more promise in the way of improved parent- and clinician-rated symptoms of executive functioning and/or inattention [89].

4.5. Promising Up-and-Coming Treatments

4.5.1. Cognitive Remediation

Because cognitive training programs – especially computer-based programs – show limited generalizability of executive functions to other tasks or skills, they may be less effective in improving children’s and adolescent’s adaptive, learning, and social functioning skills. These broader, more complex constructs pose challenges for pediatric patients with cognitive deficits, such as those seen in ADHD and other neurodevelopmental disorders, as adaptive success is moderated by executive functioning deficits [90].

Cognitive remediation (CR) is a promising alternative to computerized cognitive training programs. CR’s approach incorporates metacognitive or compensatory strategies with cognitive training to address attention, executive functioning, and memory deficits and improve adaptive, learning, and social skill more broadly. The efficacy of CR has most often been studied in brain injury and lesion rehabilitation populations (i.e., traumatic brain injury [TBI], acquired brain injury [ABI]) [91] and has been adapted for pediatric rehabilitation populations [92]. Although outcomes on neuropsychological measures following metacognitive training after brain injury have been mixed, there is promising evidence for ratings of executive functioning, adaptive skill, and daily life improvement for adults [93] and improved academic achievement, use of metacognitive strategies, and parent-rated attention in children [92]. Metacognitive strategy training in adults was found to be most effective when combined with real-life practice or homework, ecologically relevant tasks (e.g., planning, goal setting), and consideration of reinforcement/motivation [93].

There is emerging support for the efficacy of a similar approach to CR in children and adolescents with neurodevelopmental disorders and neurological conditions. Recent studies have demonstrated that use of metacognitive strategy-training that includes daily practice and external structure (e.g., behavioral strategies, reinforcement, parent training) can lead to improvements in attention, executive functioning, behavior, functional academics, and adaptive skills, and can improve performance in youth with ADHD [89,94,95,96,97], autism spectrum disorder (ASD) fetal alcohol spectrum disorder (FASD) [98], and other neurological disorders [99]. More targeted research is needed to understand the efficacy of CR for pediatric patients with epilepsy and ADHD, but CR shows promise.

Other potentially helpful interventions for patients with ADHD with and without comorbid epilepsy include mind-body practices [100], but these require additional investigation before they can be considered efficacious. Yoga, for example, has been successful at reducing some symptoms of ADHD [100,101,102] and decreasing seizure frequency and improving EEG findings in pediatric patients with epilepsy without adverse effects [101].

5. Medication and Psychosocial Treatment Combinations

Although findings from research examining the effectiveness of combined interventions in treating ADHD symptoms have been mixed [37,103], it is generally accepted that the combination of medication and evidence-based psychosocial treatments is best practice when compared to use of these treatments in isolation [104,105]. In fact, in some cases beginning with a psychosocial treatment with the intention of adding medication at a later stage if symptoms do not improve has been found to be more effective at managing ADHD symptoms and more cost effective for families [106]. Further, based on our clinical experience some children with ADHD and epilepsy may not be able to access the behavior skills they are learning due to severe ADHD symptomatology, and may require stimulant/nonstimulant medication support to able to implement those skills.

Parent, and where appropriate, patient education about ADHD in the context of epilepsy should be combined with whichever therapy is selected by the clinician. Clinicians may be able to help improve adherence and persistence to ADHD treatment by educating caregivers [107]. Clinicians can help parents understand that, like epilepsy, ADHD is a chronic condition and discuss with them different options, including pharmacologic, behavioral, or combination therapy. This process should also include information about brain development as it relates to ADHD symptoms, and provide resources for families, such as community supports, school resources, selected readings, videos, and credible educational websites. Clinicians should regularly follow up with patients to verify that medications continue to be effective and well tolerated.

6. Other Considerations (Complex ADHD)

Complex ADHD is a term increasingly used to describe patients with ADHD combined with other neurodevelopmental and/or behavior disorders, including epilepsy, for whom diagnosis and treatment is often more challenging. Complex ADHD includes patients who exhibit moderate to severe functional impairment, diagnostic uncertainty, and/or inadequate response to treatment. These patients are often affected more severely across a variety of settings including home, school, with peers, and in the community, which can have a negative effect on their outcome.

The Society for Developmental and Behavioral Pediatrics has developed a clinical practice guideline for these patients which includes: (1) comprehensive assessment and development of a multimodal treatment plan, (2) evaluation for newly or previously diagnosed coexisting conditions, (3) initiation of psychoeducation regarding ADHD and coexisting conditions at time of diagnosis and throughout treatment, (4) treatment with evidence-based interventions (behavioral, educational, and pharmacological) that focuses on functional impairment, and (5) ongoing, scheduled monitoring of patients due to the chronicity of ADHD[104]. Despite goals to obtain clinician expertise, many specialists are often unavailable due to limited resources, long waitlists, and/or decreased access given sociodemographic disadvantages. Thus, many patients will need management started while waiting on referrals.

7. Conclusion

The vast amount of research regarding pharmacological treatment of ADHD symptoms in pediatric patients with epilepsy has indicated there are a variety of effective medications with minimal adverse effects. However, medication management for ADHD symptoms is not helpful or possible for all children and many parents are reluctant to add medication to their children’s ASM regimen. Given these complexities, it is often difficult for parents and clinicians to decide the best therapeutic option in managing ADHD symptoms in the context of epilepsy. Therefore, we conducted a comprehensive review of available treatments for children and adolescents diagnosed with both epilepsy and ADHD that spans medication, diet, and psychosocial interventions in the hope of providing clinicians with a relatively simple, brief, stepwise process for making treatment decisions for these complex patients. In addition, we provide a table (Table 1) and decision tree (Figure 1) to aid in this process.

Appendix

Table 1.

Advantages, disadvantages, and precautions of medications used to treat ADHD[108].

		Advantages	Disadvantages	Precautions
Stimulants	Short acting	Rapid absorption Rapid action Generally safe Can be used as initial treatment in children weighing less than 16 kg	Must be taken 2-3 times a day	Monitor growth Monitor blood pressure and heart rate before and during treatment
	Long acting	Once daily dosing Sprinkles can be used for children who have difficulty swallowing pills	Costly Side effects last longer
Non stimulant	Atomoxetine	Lower potential for abuse Once daily dosing	Less effective than stimulants Risk of suicidal ideation	Taking it with food avoids side effects Dose adjustments needed if used with drugs that inhibit the cytochrome P450 2D6 (CYP2D6) enzyme
	Alpha Agonists	Can be useful for coexisting conditions (e.g., sleep and tic disorders)	Can lead to orthostasis