Psychiatric Disorders in Children and Adolescents Who Have Epilepsy

Epilepsy occurs in approximately 1% of the population. It is the third most common neurologic disorder in the United States after Alzheimer disease and stroke. The prevalence of epilepsy is equal to the combined prevalence of cerebral palsy, multiple sclerosis, and Parkinson disease. Epilepsy is the most common childhood neurologic disorder, affecting 0.5% to 1.0% of children younger than age 16 years. (1) More than 326,000 children younger than age 15 years have epilepsy, and approximately 90,000 have seizures that are not controlled completely by treatment. Epilepsy often occurs in conjunction with other conditions, including autism spectrum disorder, cerebral palsy, Down syndrome, and intellectual disability.Although seizures are the most readily identifiable feature of epilepsy, behavior and cognitive functioning also are affected negatively in a substantial number of children. The prevalence of psychiatric comorbidity in epilepsy is significantly higher than in healthy controls or in children who have other chronic health conditions. This article reviews the current knowledge of coexisting psychiatric disorders in children who have epilepsy and discusses diagnostic and treatment issues.Two epidemiologic investigations, conducted in the United Kingdom 3 decades apart, demonstrate that psychiatric comorbidity is overrepresented in pediatric epilepsy. In the classic Isle of Wight study, Rutter and associates (2) reported that 7% of children in the general population exhibited a mental health problem compared with 12% of children who had non-neurologic physical disorders. Significantly higher rates were reported in those having epilepsy, including 29% in children who had uncomplicated (idiopathic and cryptogenic) epilepsy and 58% in those who had complicated epilepsy (seizures in the context of structural central nervous system abnormalities). Strikingly similar findings were reported in a recent United Kingdom epidemiologic investigation by Davies and colleagues. (3) Among children ages 5 to 15 years of age, psychiatric disorders were found in 9.3% of the general population and in 10.6% of those who had a chronic medical disorder (eg, diabetes). However, among children who had epilepsy, rates were much higher, with 26% in uncomplicated epilepsy and 56% in complicated epilepsy. Similar findings have been found in community- and hospital-based samples, with psychiatric comorbidity ranging from 20% to 61%. These studies substantiate the premise that children who have epilepsy are at increased risk of having mental health problems compared with the general population and children who have other chronic non-neurologic conditions.Interictal psychiatric disorders are common among children who have epilepsy and may be identifiable prior to or at some point following the diagnosis. Interictal psychiatric disorders are viewed as being related less directly to seizure activity, although they still may be linked closely to the pathogenesis of epilepsy. The most common psychiatric disorders among children who have epilepsy include attention-deficit/hyperactivity disorder (ADHD) and depressive and anxiety disorders. Albeit infrequent, psychosis may occur in children who have epilepsy.ADHD is a significant problem among school-age children and is the most common psychiatric comorbidity in children who have epilepsy. The high co-occurrence of ADHD and epilepsy may reflect common neurologic pathophysiology affecting cognitive and behavioral function. The disability associated with ADHD can be significant and may extend to the entire educational, social, and psychological development of a child. It is important to address and treat this significant comorbidity to improve the quality of life for children who have epilepsy. The American Academy of Pediatrics developed clinical practice guidelines for the diagnosis and evaluation of ADHD and recommends ADHD-specific questionnaires and scales to facilitate screening (Table 1).The identification of attention problems in children who have epilepsy is not new. In 1955, Ounstead (4) described a “hyperkinetic syndrome” in children who had epilepsy, and the account of this syndrome resembles that of ADHD. Children who have epilepsy are at a relatively high risk for attention problems, hyperactivity, and impulse control problems. Attention problems can be influenced by epileptiform activity, medication effects, long-term impact of repeated seizures, and cognitive dysfunction. However, attention problems have been reported regardless of seizure type, cause, or severity. ADHD appears to be prevalent among children who have received new diagnoses of epilepsy as well as in children who have chronic epilepsy. Attention problems often are present prior to the first seizure. (5) Among studies using the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders criteria, prevalence rates of ADHD in children who have epilepsy range from 15% to 40%. Some studies suggest that children who have epilepsy have a higher rate of predominantly inattentive-type ADHD than the combined-type ADHD. Despite more recent studies reporting higher rates of combined-type ADHD in epilepsy, the overall pattern is opposite of what is described in the general population, in whom the combined-type ADHD is the most common subtype. Among children who have epilepsy, ADHD is represented equally in both boys and girls, which is in contrast to the general population, in which ADHD is much more common in boys. Armed with the evidence that ADHD is more common among children who have epilepsy, it is important to evaluate and screen for ADHD soon after a diagnosis of epilepsy is confirmed.It has been reported that medications used to treat seizures affect attention negatively. Cognitive slowing and difficulty concentrating have been associated with tiagabine, topiramate, and zonisamide. Additionally, gabapentin may cause hyperactivity and aggression in children who have learning problems, and learning problems are common in children who have epilepsy. Barbiturates and benzodiazepines frequently are associated with inattention and hyperactivity.ADHD medications have not been studied adequately using randomized, placebo-controlled trials in children who have epilepsy. Even today, United States Food and Drug Administration labeling for methylphenidate (MPH) and other stimulant medications includes a strong precaution that if seizures are present, the medication should be discontinued. This warning has led to hesitation among clinicians and researchers to study stimulants extensively in children who have epilepsy and ADHD. A few open-label trials and two small placebo-controlled studies have involved the use of MPH. (6)(7) MPH appears to have efficacy for ADHD, and the studies did not identify negative effects on the seizure threshold in children whose seizures were well-controlled. Amphetamine compounds also can be considered, although little evidence is available to guide treatment in children who have epilepsy. A new norepinephrine reuptake inhibitor, atomoxetine, reduces symptoms of ADHD in children in the general population. Only a few small open-label trials of atomoxetine have involved children who had epilepsy, but there are no reports of increases in seizure frequency. In conjunction with medications, behavioral and parental interventions should be considered a key component of treatment.Depression in children and adolescents often has a recurrent course, with the risk of suicide increased and resulting significant psychosocial impairment. The American Academy of Child and Adolescent Psychiatry (AACAP) provides practice parameters to guide practitioners in diagnosing and treating children and adolescents who are depressed (www.aacap.org). Symptoms of depression are characterized in Table 2. Irritability, anger, and difficulties in school may be indicators of depression in children and adolescents. Affected children may have trouble making and keeping friends, leading to increased isolation and poor self-esteem. Children may demonstrate behavioral regression, such as the appearance of separation anxiety, due to immature and maladaptive coping mechanisms. A family history of depression is a significant risk factor for depression. In addition, approximately 20% of children who have depression develop mania or hypomania within 5 years. Depression is a serious and significant problem in childhood that can affect development adversely well beyond childhood.Depression frequently is underrecognized and undertreated in children who have epilepsy. Physicians, individuals who have epilepsy, and their families often view depression as expected because having seizures can affect one's life negatively. However, untreated depression is more likely to be chronic. The literature indicates that depression affects the quality of life more than seizure frequency or severity. The prevalence of depression ranges from 10% to 30% in children and adolescents who have epilepsy. The psychiatric adverse effects of antiepileptic medications (AEDs) always should be considered when assessing depression in children who have epilepsy because changes in medications or dosage can alter mood negatively. Phenobarbital, levetiracetam, topiramate, tiagabine, and zonisamide all have been noted to cause depressive symptoms.Depression does not appear to be linked to seizure type, syndrome, or severity in youth who have epilepsy. Depression in children who have epilepsy has been associated strongly with negative attitudes toward epilepsy and problems in the family. Interestingly, depression has been identified as a risk factor for seizures. In a study in Iceland, children and adults who had epilepsy were 1.7 times more likely to have a history of major depression prior to the first unprovoked seizure. (9) In other words, depression appears to be a risk factor for the onset of seizures as well as a significant comorbidity after the seizure disorder manifests.The average length of a depressive episode in children and adolescents ranges from 7 to 9 months; within 2 years, 40% relapse. Because many individuals have a long course involving multiple relapses, it is important for the child, family, and physician to be aware that treatment may be needed until remission is achieved. A pediatrician can manage an initial episode of depression that has no comorbidities or complications. However, a pediatric psychiatrist should be consulted if the depression is resistant to treatment, if there is suicidal ideation or an attempt, or if other psychiatric disorders also are present.Very few randomized, placebo-controlled trials have been conducted in children who are depressed, and children who have epilepsy typically are excluded from such studies. Selective serotonin reuptake inhibitors (SSRIs) are first-line treatments for children and adolescents who have depression with or without epilepsy. SSRIs have fewer adverse effects and minimal overdose risks compared with other antidepressants. In addition, SSRIs are less likely to lower the seizure threshold. Tricyclic antidepressants are not recommended for children who have depression and rarely are used because they lower the seizure threshold and have significant cardiac effects. A note of caution is appropriate regarding the potential interaction between SSRIs and AEDs. Certain SSRIs inhibit certain CYP450 enzymes, resulting in adverse interactions with hepatically metabolized AEDs, including fluoxetine, paroxetine, and fluvoxamine. Sertraline and citalopram frequently are recommended due to their minimal pharmacokinetic interactions with AEDs.Psychotherapy can be used independently or in conjunction with pharmacologic treatments. Cognitive behavior therapy (CBT) is recommended for the treatment of depression in children and adolescents. CBT focuses on solving problems, developing coping mechanisms, and addressing cognitive distortions. Research indicates that CBT is efficacious in the treatment of major depression. However, only a few randomized, controlled studies of CBT have been conducted to determine the effectiveness of this treatment in children who have coexistent depression and epilepsy. Additional research is needed in both psychotherapeutic and pharmacologic treatments.Anxiety disorders are the most common psychiatric disorders in the general population. Table 3 includes the recommendations from the AACAP for the assessment and treatment of children and adolescents who have anxiety disorders.Separation anxiety disorder is a condition in which the affected person exhibits a developmentally inappropriate fear that results in distress when separating from attachment figures. Specific phobia is characterized by a fear of an object or situation. Generalized anxiety disorder involves chronic and excessive worry. It is difficult for children to stop the worries, which are present most of the time. Social phobia is a fear or uncomfortable feeling in social or unfamiliar situations. Panic disorder (with or without agoraphobia) is characterized by episodes of intense fear that occur suddenly, with no warning or predictability. Posttraumatic stress disorder occurs after experiencing a terrifying event or ordeal (eg, car accident, war, assault). Obsessive compulsive disorder is characterized by recurrent, unwanted thoughts or obsessions that may be accompanied by repetitive behaviors (compulsions). Specific phobia and social phobia are the anxiety disorders occurring most commonly. Generalized anxiety disorder frequently is comorbid with depression. Panic disorder is rare in children and may appear in late adolescence. Children and adolescents who have anxiety disorders are at risk for developing new anxiety disorders, depression, and substance abuse.Only a few studies have examined the prevalence of anxiety disorders in children who have epilepsy. Rates of anxiety disorders in children who have epilepsy range from 13% to 49%. Children who have complex partial seizures and absence seizures have been reported to be five times more likely to have a depressive or anxiety disorder compared with controls. (11) In one report, 63% of children who had complex partial or absence epilepsy had a depressive or anxiety disorder. In addition, children afflicted with depression had a coexisting anxiety disorder, and those who had anxiety disorder had more than one form of anxiety disorder. (11)Notably, interictal anxiety should be distinguished from ictal fear, which occurs in the context of a complex partial seizure or a seizure with secondary generalization. Ictal fear is common in individuals who have seizures localized in the temporal lobe or in structures in the limbic system. The ictal fear can last for a few seconds to a few minutes, and descriptions can range from feeling tension or apprehension to experiencing horror or dread. Fear can occur in the context of other physical symptoms, including nausea and increased respirations or heart rate. Fear also can be the only symptom of a simple partial seizure or aura. Moreover, panic attacks can be confused easily with seizures because some seizure types have similar autonomic phenomena (eg, palpitations and piloerection). Automatisms and alterations in consciousness may help to distinguish seizures and panic attacks. Nervousness or anxiety has been associated with AEDs, including felbamate and topiramate. A withdrawal or change in dosage also may result in symptoms of anxiety. It is important to obtain a thorough history from the child and parents to identify any factors that may be influencing the appearance of symptoms of anxiety.SSRIs are the first line of treatment in childhood anxiety disorders. Recent randomized, placebo-controlled trials have demonstrated the efficacy of SSRIs in the treatment of childhood anxiety disorders, including social phobia, generalized anxiety disorder, and seasonal affective disorder. There is no evidence that a particular SSRI is more effective than another for treating childhood anxiety disorders. (10) Currently, there are no dosing guidelines for SSRIs in children and adolescents who have anxiety disorders. (10) Buspirone, a partial serotonin agonist, has been used in the treatment of generalized anxiety disorder in youths, but there are no published controlled trials. No randomized, placebo-controlled trials have investigated the pharmacologic treatment of anxiety disorders in children who have epilepsy.Randomized, controlled trials of CBT have demonstrated that this therapy is efficacious in reducing symptoms of anxiety in children and adolescents, with treatment gains maintained at 1-year and 3-year follow-up visits. However, psychotherapeutic interventions in the treatment of anxiety disorders among children and adolescents who have epilepsy have not been examined systematically. (12) As in depression, more research is needed in psychotherapeutic and pharmacologic treatments for children and adolescents who have epilepsy and comorbid anxiety disorders.The incidence of interictal psychosis appears to be rare in children who have epilepsy. An increase in illogical thinking and hallucinations without apathy or negative affect has been reported in children who have chronic epilepsy and complex partial seizures. Ictal and postictal psychosis can occur but rarely. A postictal psychotic episode may occur after a prolonged seizure or a cluster of seizures. The psychotic episode can last several days and typically resolves spontaneously. If psychotic symptoms occur during seizures, they typically are stereotyped, and children may be unable to recall the content of the hallucination. This pattern is in contrast to children who have psychosis, who generally are able to describe the hallucination, which can vary from episode to episode. Changes in AEDs always should be considered when evaluating psychosis in children who have epilepsy. AED-induced psychotic reactions have been reported with the following medications: phenytoin, ethosuximide, vigabatrin, zonisamide, topiramate, lamotrigine, and felbamate.Antipsychotic medications are appropriate for children and adolescents who have epilepsy if psychotic symptoms develop. Clozapine and chlorpromazine should not be used because they lower the seizure threshold. There appears to be a relatively low risk of seizures with the use of haloperidol and risperidone.Psychiatric disorders are common in children and adolescents who have epilepsy. They appear to be more prevalent among children who have epilepsy than children and adolescents in the general population or children who have other chronic conditions. ADHD, depression, and anxiety disorders appear to be the most common psychiatric disorders in epilepsy; psychotic disorders occur rarely. It is important to screen for these disorders in children who have epilepsy. Early recognition and treatment of psychiatric disorders can reduce their lifelong negative impact. Finally, future study will be important to identify the most efficacious treatments for ADHD, depression, and anxiety in children and adolescents who have epilepsy.