- Email: [email protected]
Differential diagnosis and treatment of psychiatric disorders in children and adolescents with epilepsy
Epilepsy & Behavior 5 (2004) S10–S17 www.elsevier.com/locate/yebeh
Differential diagnosis and treatment of psychiatric disorders in children and adolescents with epilepsy David W. Dunna,*, Joan K. Austinb a b
Indiana University School of Medicine, Indianapolis, IN 46202, USA Indiana University School of Nursing, Indianapolis, IN 46202, USA Received 30 June 2004; accepted 30 June 2004 Available online 14 August 2004
Abstract Behavioral problems, such as the inattentive form of attention-deficit hyperactivity disorder (ADHD), anxiety, and depression, are common in children and adolescents with epilepsy and especially associated with central nervous system damage, family dysfunction, and severe seizures. This article discusses the risk factors to be considered when focusing on the prevalence of behavioral problems, the family factors that influence their incidence, as well as the differential diagnosis of behavioral disorders commonly associated with epilepsy. It also considers the assessment of these behavioral disorders and their treatment with psychotherapy, education, and a variety of psychopharmacological agents. Ó 2004 Elsevier Inc. All rights reserved. Keywords: Epilepsy; Childhood seizures; Psychiatric comorbidities; Attention-deficit hyperactivity disorder; Depression; Anxiety; Psychosis; Psychotherapy
1. Introduction In this discussion of the differential diagnosis of psychiatric disorders in children and adolescents with epilepsy, our goal is to address three questions. First, what are the risk factors for behavioral problems in children with epilepsy? Second, what types of behavioral and emotional problems are most prevalent in children with epilepsy? Third, what forms of treatment are available and should be offered to the child with both epilepsy and behavioral problems? Behavioral and emotional problems are a major concern for children with epilepsy. Behavioral problems are quite common in these children. In a classic epidemiological study, Rutter et al. [1] found that 28.6% of children with uncomplicated seizures and 58.3% of children *
Corresponding author. E-mail address: [email protected] (D.W. Dunn).
1525-5050/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2004.06.011
with seizures and additional neurological damage had behavioral problems. In comparison, the prevalence of behavioral problems in the general population of children was 6.6%, and in children with chronic illnesses not involving the central nervous system it was 11.6%. In a more recent national epidemiological study from Great Britain, Davies et al. [2] reported remarkably similar prevalence figures. The rate of psychiatric disorders was 37% in children with epilepsy, 11% in children with diabetes mellitus, and 9% in controls. They found behavioral disorders in 26.2% of children with uncomplicated epilepsy and in 56% of children with complicated epilepsy. These behavioral problems often are not recognized or are not treated. In one study of children with epilepsy and normal intelligence, 61% of the children had a psychiatric diagnosis based on DSM-IV criteria, but only 33% of the children received mental health treatment [3].
D.W. Dunn, J.K. Austin / Epilepsy & Behavior 5 (2004) S10–S17
2. Risk factors 2.1. General Just as epilepsy is a heterogeneous disorder with multiple etiologies, seizure types and syndromes, and variable degrees of seizure control, there are multiple factors that influence the risk of psychopathology in children with epilepsy. Factors to consider in assessing the prevalence of behavioral problems include demographic variables, neurological variables, seizure variables, therapy, and psychosocial variables [4]. Table 1 lists a few of these factors. Let us first consider the factors that have not been shown to be consistently indicative of risk. Demographic variables have been minimally predictive of the likelihood of psychiatric or behavioral problems. Gender is inconsistent as a predictor of problems. As an example, in a study of children with new-onset seizures, we found boys with prior unrecognized seizures to have more behavioral problems than girls [5], but in a study of children with chronic seizures, girls with more severe seizures had the most difficulties [6]. In other studies, Stores [7] found boys at higher risk, and Hoare and Kerley [8] found no difference by gender. Age at onset of seizures is more predictive of cognitive problems than of behavioral difficulties [9]. Lower socioeconomic status, defined by either income or caregiver education, has been associated with behavioral problems [5,10]. A more definite risk factor for behavioral problems is the presence of additional central nervous system damage [1,11]. Standard epidemiological studies from the Isle of Wight showed that 50 to 60% of children with central nervous system damage, i.e., children with cerebral palsy or mental retardation plus epilepsy, demonstrated significant behavioral problems, and a recent national survey from England found that children with
Table 1 Risk factors for behavioral problems in pediatric epilepsy Demographic variables Age Gender Socioeconomic status Neurological variables Additional central nervous system dysfunction Mental handicap Severe epileptic syndromes Intractable epilepsy Early age of seizure onset AED polytherapy Psychosocial variables Family stress and mastery Child response to illness Stigma
S11
complicated epilepsy had twice the prevalence of behavioral problems as children with uncomplicated epilepsy [2]. Scandinavian studies have also confirmed that a combination of neurological damage and epilepsy results in a 50–60% risk of behavioral problems [12]. Quality-of-life studies have shown, not surprisingly, that children with epilepsy plus mental retardation typically have a more impaired quality of life. However, the effect appears to be more than additive in these children [13,14]. Seizure variables have been associated with behavioral problems in children with epilepsy. Seizure type has been inconsistent as a predictor. We found children with partial seizures to have more behavioral problems than children with generalized seizures in a sample of patients with new-onset epilepsy [5]. In comparison, there was no association between seizure type and behavioral difficulties in a study of patients with chronic seizures conducted by our group [15]. Seizure syndrome is probably a more important factor. The children with catastrophic epilepsies such as West syndrome or Lennox–Gastaut syndrome have more behavioral and cognitive troubles [16,17]. Seizure severity and seizure frequency are important variables in predicting behavioral problems [9,15]. Moreover, even in children with new-onset seizures, recurrent seizures were a predictor of behavioral problems [18]. Behavioral problems in this patient population are also associated with some antiepileptic drugs (AEDs). These include the benzodiazepines, phenobarbital, and topiramate [19,20]. This topic has been reviewed recently [21,22], and is discussed further in the article by Dr. Glauser in this supplement. 2.2. Family and child factors Family factors also influence the incidence of behavioral problems. The measure most consistently predictive of behavioral problems is the measure of family mastery (see the article by Austin et al. in this supplement). The families who are able to deal with the childÕs epilepsy, who feel confident that they can handle the problems associated with pediatric epilepsy, are the ones who are able to transfer this confidence to their children, resulting in a better quality of life. Family style seems to be important as well. Overcontrolling families, ones that are intrusive and do not give their children sufficient chance to develop independence, produce children who do more poorly [8,15,23,24]. The childÕs own response to his or her epilepsy is also significantly associated with behavioral problems. Our studies [25] found that children and adolescents worry about their epilepsy and the social impact it has on their lives. Some of them worry about dying and, specifically, about dying from their seizures. It is important to
S12
D.W. Dunn, J.K. Austin / Epilepsy & Behavior 5 (2004) S10–S17
identify these children. Overall, children who have a negative attitude toward their illness develop more problems related to self-concept, and are more likely to develop depression [4,26]. One explanation for the occurrence of depression in children with epilepsy is the learned helplessness model [27]. The children at risk feel they have no control over their epilepsy; this external or unknown locus of control appears to be a risk factor for the development of depression [28]. Though many studies have focused on children with chronic seizures, at least some of the risk factors for behavioral problems in children with epilepsy may predate the occurrence of seizures. There are studies showing that children and families who have had problems before the seizures started were more prone to developing behavioral problems after seizure onset [5,29,30]. Austin et al. [5] found that about one-third of children with new-onset seizures had behavioral problems apparent within the first month of seizure onset. In this sample, approximately one-third of children with new-onset seizures had experienced episodes that in retrospect were probably seizures. These children with prior unrecognized seizures had more behavioral problems when assessed at baseline. This finding suggested that seizures and some of the behavioral problems might be due to an underlying central nervous system dysfunction, rather than the psychosocial reaction to having seizures or the effect of antiepileptic drugs.
3. The differential diagnosis 3.1. Common disorders Numerous studies have shown that children with epilepsy are at risk for several psychiatric disorders. The British Child and Adolescent Mental Health Survey divided the psychiatric diagnoses of children with epilepsy into broad categories. The percentage of children with complicated epilepsy who had any emotional problem was 16%; conduct disorder (CD) and oppositional defiant disorder (ODD) were seen in 24%; 12% had attention-deficit hyperactivity disorder (ADHD); and the percentage with any pervasive developmental disorder was 16%. The percentage of children with uncomplicated epilepsy who had emotional problems was 17%, and CD and oppositional disorder were present in 17%. None of the children with uncomplicated epilepsy had ADHD or pervasive developmental disorders. To compare, the percentage of healthy children with psychiatric disorders was 4% for emotional disorders, 5% for CD, 2% for ADHD, and 0.2% for pervasive developmental disorders [2]. Steffenburg et al. [12] assessed children with epilepsy and mental retardation. They found autistic disorder
in 27%, autistic spectrum disorder in 11%, ADHD in 7%, and overanxious disorder in 3%. Caplan et al. [31] and Dunn et al. (in preparation) have used standardized measures of psychiatric disorders in children with epilepsy and normal intelligence. Caplan et al. [31] used either the Kiddie Schedule for Affective Disorders and Schizophrenia or the Diagnostic Inventory for Children and Adolescents to establish psychiatric diagnoses. They also divided their sample into children with primary generalized epilepsy (PGE) and those with complex partial epilepsy (CPE). They found disruptive disorders (ADHD, ODD, and CD) in 25% of children with CPE and in 26% of those with PGE; anxiety/mood disorder in 13% of each group; and comorbid disruptive disorder and anxiety/mood disorder in 14% of children with CPE and 16% with PGE. A schizophrenia-like psychosis was noted only in children with CPE (10%). Our study (Dunn et al. (in preparation)) assessed 167 children with chronic seizures. Categorical diagnoses were established using either the Child Symptom Inventory or the Adolescent Symptom Inventory, depending on the age. We used the screening cutoff score method to determine likelihood of a psychiatric diagnosis. With this measure, we found possible diagnoses of ADHD predominantly inattentive type in 22.8%, ADHD predominantly hyperactive–impulsive type in 2.4%, ADHD combined type in 11.4%, ODD in 20.4%, CD in 18%, and depressive disorder and dysthymia in 9.6%. There was evidence of an anxiety disorder in a third of the children and adolescents. Hedderick and Buchhalter [32], in a population-based study in Rochester, Minnesota, found comorbid psychiatric disorder defined by the DSM-IV in 51% of children with epilepsy. When those with mental retardation were excluded, the figure was 40%. The most common disorders were ADHD (17%), mood disorder (12%), and adjustment disorder (10%). 3.2. Assessing disorders The recognition of behavioral disorders in children with epilepsy is dependent on the time and effort expended in the clinic to assess children for psychiatric comorbidity. A history that asks only about number of seizures, change in seizure type, and side effects of antiepileptic medication may overlook many of the psychiatric problems seen in children with epilepsy. Questions about school performance can help with the recognition of ADHD. Asking about anger, irritability, moodiness, and worries can lead to possible diagnosis of mood and anxiety disorders; and questions about confusion, hallucinations, or regression could point to a psychotic disorder. Kanner and Weisbrot [33] have reviewed both the psychiatric evaluation and rating scales available for
D.W. Dunn, J.K. Austin / Epilepsy & Behavior 5 (2004) S10–S17
use in the epilepsy clinic. In a large comprehensive epilepsy clinic, clinical nurse specialists and psychosocial consultants can be helpful [34,35]. 3.3. Problems with attention in children with epilepsy ADHD is defined by a combination of problems with attention, including poor concentration, distractibility, forgetfulness, frequent careless errors, and incomplete work, and hyperactivity and impulsivity characterized by fidgeting, trouble staying seated, excessive talking, interrupting, and inability to wait or take turns. Symptoms are present in multiple settings including home, school, and extracurricular activities [36]. Diagnosis is best made by reports from the parents with corroboration from schoolteachers. Problems with attention can be due to seizures or to antiepileptic medications. Unrecognized absence or partial seizures may present as impaired attention. Williams et al. [37] have found that failure to complete homework and difficulty staying on task were symptoms of ADHD, but were not symptoms evident in children with absence seizures. Nocturnal seizures may disrupt sleep, resulting in excess daytime sleepiness. This may cause inattention and restlessness, which might be classified as a disorder of vigilance as defined by Weinberg and Brumback [38]. The lethargy and attentional problems seen with several antiepileptic drugs should be considered in the differential diagnosis of ADHD in children with epilepsy. Barbiturates and benzodiazepines have been associated with inattention and hyperactivity. There are reports of difficulty concentrating or cognitive slowing in some patients on tiagabine, topiramate, and zonisamide. In children with learning disabilities, gabapentin may cause severe hyperactivity and aggressiveness [19,22]. Even after excluding problems with attention and excess activity levels due to seizures or AEDs, ADHD remains the most common behavioral problem associated with childhood epilepsy. In our review of the literature, we found reports of the prevalence of ADHD in childhood epilepsy ranging from 8 to 77%, with prevalence rates of 30–40% in recent studies using standard measures of ADHD [39,40]. In our studies of children with both new-onset epilepsy and chronic epilepsy [5,41], we have measured behavioral problems with the Child Behavior Checklist, the Child Symptom Inventory, or the Adolescent Symptom Inventory, and have consistently found that the most common behavioral problem is impaired attention. The symptoms of ADHD in a child with epilepsy may or may not be the same as those of ADHD in other, non-epileptic children usually referred to the psychiatric clinics. ADHD as seen by the child and adolescent psychiatrist is most commonly the combined type, which includes inattention plus hyperactivity and impulsivity.
S13
The children with ADHD are predominantly boys in a ratio of 3 to 1, with some studies reporting a ratio of boys to girls as high as 9 to 1 [42]. In contrast, children with epilepsy are more likely to present with an inattentive form of ADHD, and the ratio of boys to girls is 1 [41]. Epilepsy may have a broader impact on multiple attentional networks within the central nervous system. Recent neuropsychological assessments in children with epilepsy have shown below-average verbal and visual attention skills, slowing of psychomotor speed, and impairment in sequential cognitive processing [43–45]. The association between ADHD and childhood epilepsy has additional complexities. Hesdorffer et al. [46] found that ADHD was a risk factor for the development of seizures and speculated that ADHD and epilepsy may be due to a common underlying problem. The increase in the rate of spikes found on the EEGs of children with ADHD supports the theory of a common underlying central nervous system dysfunction [47–49]. On the other hand, Williams et al. [50], in a 4-year follow-up, did not find an increase in the number of children with ADHD developing seizures. 3.4. Depression and epilepsy Depression is a common but often overlooked problem in epilepsy [51]. Ettinger et al. [52] found that in their clinic, though 26% of the children with epilepsy had symptoms of depression, none of these had been identified or treated. In part, this may be the result of differences in symptoms of depression in children versus those seen in adults. Children more often present with irritability, withdrawal, somatic complaints, and trouble sleeping. Difficulties with concentration may lead to school failure. Adolescents may have similar complaints but also develop hopelessness, guilt, and suicidal ideation. A family history of mood disorder may be an important clue to the diagnosis of depression in children with epilepsy [53]. In the differential diagnosis of depression and childhood epilepsy, as with attention disorders, the psychiatric effect of AEDs should be considered. Phenobarbital has been associated with depression and an increased risk of suicide [54,55]. Newer AEDs whose mechanism is GABAergic, such as levetiracetam, topiramate, tiagabine, and zonisamide, have caused depressive symptoms [22,51]. Depression is seen in somewhere between 10 and 30% of children and adolescents with epilepsy. In our study [56], we found that about one-fourth of adolescents with epilepsy had symptoms of depression. Ettinger et al. [52] found symptoms of depression in 26%, Alwash et al. [57] in 23%, and Oguz et al. [58] in 28.6%. In this last study, suicidal ideation was noted in 17%, and more often in adolescents than in children.
S14
D.W. Dunn, J.K. Austin / Epilepsy & Behavior 5 (2004) S10–S17
In adults, there is an association of depression with left temporal lobe discharges, but the same does not hold true for children and adolescents with epilepsy. The depression seen in young epilepsy patients does not seem to be associated with any particular seizure syndrome or seizure type. We did find an association between depression and a negative attitude toward illness and dissatisfaction with family relationships. The adolescents with symptoms of depression more often had an external or unknown locus of control [56].
Table 2 Classification of psychoses of epilepsy (POE)
3.5. Anxiety and epilepsy
wise, there are rare episodes of postictal psychosis, a disorder that usually occurs after a prolonged seizure or a cluster of seizures. The psychotic episode typically follows a lucid interval of 24–48 hours and lasts on average for 4–5 days before spontaneously clearing [64]. AEDinduced psychotic reactions have occurred with phenytoin, ethosuximide, vigabatrin, zonisamide, topiramate, and possibly lamotrigine and felbamate [22,65,66]. Table 2 summarizes the classification of psychoses of epilepsy (POE) described by Kanner in 2000 [65].
The prevalence of anxiety in children and adolescents with epilepsy is harder to estimate, as there have been fewer studies. It probably is in the range of 15–25% [59]. Anxiety is more common in adolescents than in younger children. Anxiety is also more common in children who have intractable seizures and in those who are on multiple AEDs [52,57,58]. The differential diagnosis of anxiety in children and adolescents with epilepsy includes consideration of the effects of both seizures and of AEDs. Anxiety can occur as a preictal premonitory symptom and following a seizure. Ictal fear is associated with complex partial seizures of temporal lobe origin. Panic attacks may mimic complex partial seizures. Motor automatisms and alteration in consciousness may help distinguish seizures from panic attacks [60]. Anxiety or nervousness has been seen with activating drugs such as felbamate and topiramate and with withdrawal of AEDs [59]. 3.6. Psychosis and epilepsy Fortunately, the incidence of interictal psychosis associated with epilepsy is rare in children. Matsuura and Trimble reported a prevalence rate of 0.7% in pediatric epilepsy clinics in Japan [61]. This is probably due to the variable of seizure duration. A number of studies have suggested that seizures, particularly from the temporal lobes, usually have been present for 10 to 14 years prior to the onset of chronic interictal psychosis [62]. As a result, patients have generally passed beyond childhood before onset of psychosis. Early symptoms of possible psychosis in children with complex partial seizures have been reported by Caplan et al. [63]. They found an increase in illogical thinking and hallucinations, but not loose associations, in children with complex partial seizures, but not in children with generalized seizures. In the differential diagnosis, seizures and AEDs should again be considered. Child neurologists do see occasional episodes of ictal psychosis, but this seems more often to be a delirium or a confusional state. Like-
Ictal POE Postictal POE Interictal POE Alternative psychosis AED-related psychosis
Associated with seizure activity Transient psychosis occurring within a week of seizure activity Chronic psychotic symptoms not associated with seizures Forced normalization, symptoms following control of seizures Psychosis as a side effect of AEDs
Source. Reproduced, with permission, from Kanner [65].
3.7. Aggression and epilepsy Aggression in children and adolescents with epilepsy has proved harder to define. Our studies [40], which used the Child Behavior Checklist, the Child Symptom Inventory, and the Adolescent Symptom Inventory, found an increased risk in young people with epilepsy of developing ODD or CD, which ranged from 10 to 35%. Aggressive behavior can occur particularly in association with postictal confusion and during those rare cases of postictal psychosis. There is also an increased association of such behavior with underlying central nervous system damage [67]. Aggression has been associated with barbiturates, felbamate, vigabatrin, and, in children with developmental delay, gabapentin [19,22].
4. Treatment Having identified a child with epilepsy as at risk for developing psychiatric difficulties, what can be done? Ideally, we would like to prevent these behavioral problems, but as a second goal, early treatment is essential. 4.1. Psychotherapy and education Education should be a standard part of all treatment for pediatric epilepsy patients, particularly those at risk for comorbid psychiatric and behavioral problems. This includes informing parents about exactly what they may expect to happen in the course of
D.W. Dunn, J.K. Austin / Epilepsy & Behavior 5 (2004) S10–S17
the childÕs illness, teaching them how to manage the symptoms of epilepsy, explaining how to handle the medication, and identifying symptoms they should watch for in their children. Both individual and group educational sessions have been studied. Lewis et al. [68] used a large-group education format, instructing parents and children with epilepsy about epilepsy and providing training in coping techniques, decision making, and communication. Follow-up studies found improved knowledge, self-perceived social competency, and behavior. They did have difficulty getting families to participate in the four 1-hour sessions. Tieffenberg et al. [69] conducted educational programs using groups of 8 to 10 families. They concentrated on improving young patientsÕ sense of autonomy and mastery. They were able to demonstrate improved knowledge and behavior in children and more knowledge of epilepsy in parents, and saw fewer emergency room visits for the child with epilepsy. Our group [70] has developed ‘‘focused’’ training for small groups, usually two or three families. The families completed questionnaires that assessed worries and concerns of parents and children. We matched families by child age and types of worries and concerns, and brought together these small groups of families for a conference call. These small-group educational interventions resulted in increased knowledge and decreased need for support and additional information. The goal of our program is to identify worries and concern early in the course of the childÕs epilepsy and to prevent the behavioral problems observed in children and adolescents with epilepsy. Once the child has developed behavioral problems, group therapy and individual therapy may be helpful. Specific therapy for children with epilepsy involves assessment for emotionally based precipitants of seizures and behavioral abnormalities. Psychotherapy addresses some of the stresses that may be associated with epilepsy through the teaching of relaxation techniques and coping skills. These techniques have resulted in improvement in self-concept as well as a significant reduction in seizure frequency [71,72]. 4.2. Psychopharmacology If psychotherapy proves ineffective, psychopharmacology is often effective. There is empirical support that stimulant medication improves the symptoms of ADHD in children with epilepsy and improves their cognitive function as well [73,74]. Additionally, in most children with seizures, there are no data to show that seizure breakthrough occurs as a result of adding stimulant medication to the treatment regimen. Neither Feldman et al. [73] nor Gucuyener et al. [75] found an increase in seizures in children treated with methyl-
S15
phenidate. Gross-Tsur et al. [74] noted no seizure recurrence in children who were seizure-free, but an increase in seizures in three-fifths of the children and no change or a reduction in two-fifths of the children with recurrent seizures when methylphenidate was started. Hemmer et al. [76] showed that an abnormal EEG predicted a risk for seizures in children with ADHD, but did not find seizure occurrence related to stimulant use. In the child with epilepsy and a mood disturbance, antidepressant drugs may be helpful, though there are no double-blind, placebo-controlled trials to prove antidepressants safe and effective in this population. Most authorities recommend starting with selective serotonin reuptake inhibitors (SSRIs) [77]. There are data showing that the SSRIs are effective in children with depressive disorders [78,79]. The SSRIs have not caused a significant lowering of seizure threshold, and sertraline has been used in an open-label study in adults with epilepsy without major problems [80]. Although there has been recent concern about the apparent increase in suicidal ideation associated with certain SSRIs, a reasonable approach is to use the drugs cautiously, monitoring for akathisia, particularly during the first weeks of therapy when the child is most at risk for side effects [81]. Other antidepressants may be considered if SSRIs fail [77]. Although trazodone and nefazodone can be effective, they are often associated with lethargy. Venlafaxine and bupropion have been associated with a moderately increased risk of seizures [82]. The tricyclic antidepressants are effective in adults with depression, but there has never been a double-blind, placebo-controlled trial that has shown their effectiveness in childhood depression. In addition, there is some evidence that the tricyclics are associated with an increased risk of seizures [82]. The use of antipsychotics in children and adolescents with epilepsy should be considered when the child or adolescent develops psychotic symptoms. Agents to be avoided include clozapine and chlorpromazine, both of which lower the seizure threshold. There is a moderate risk of seizures with the use of thioridazine, olanzapine, or quetiapine, and probably a low risk with haloperidol or risperidone [82].
5. Summary Behavioral problems are common in children and adolescents with epilepsy and are especially associated with central nervous system damage, family dysfunction, and severe seizures. The most common behavioral problems in this patient population are the inattentive form of ADHD, anxiety, and depression.
S16
D.W. Dunn, J.K. Austin / Epilepsy & Behavior 5 (2004) S10–S17
Therapy for these young people should involve education, counseling (at least group psychotherapy and, if possible, individual therapy), and, when needed, psychopharmacology.
References [1] Rutter M, Graham P, Yule W. A neuropsychiatric study in childhood. Philadelphia: Lippincott Publishers; 1970. [2] Davies S, Heyman I, Goodman R. A population survey of mental health problems in children with epilepsy. Dev Med Child Neurol 2003;45:292–5. [3] Ott D, Siddarth P, Gurbani S, et al. Behavioral disorders in pediatric epilepsy: unmet psychiatric need. Epilepsia 2003;44:591–7. [4] Dunn DW, Austin JK. Behavioral issues in pediatric epilepsy. Neurology 1999;53:S96–100. [5] Austin JK, Harezlak J, Dunn DW, et al. Behavior problems in children before first recognized seizures. Pediatrics 2001;107:115–22. [6] Austin JK, Huster GA, Dunn DW, Risinger MW. Adolescents with active or inactive epilepsy or asthma: a comparison of quality of life. Epilepsia 1996;37:1228–38. [7] Stores G. School-children with epilepsy at risk for learning and behaviour problems. Dev Med Child Neurol 1978;20:502–8. [8] Hoare P, Kerley S. Psychosocial adjustment of children with chronic epilepsy and their families. Dev Med Child Neurol 1991;33:201–15. [9] Schoenfeld J, Seidenberg M, Woodard A, et al. Neuropsychological and behavioral status of children with complex partial seizures. Dev Med Child Neurol 1999;41:724–31. [10] Hermann BP, Whitman S, Dell J. Correlates of behavior problems and social competence in children with epilepsy aged 6–11. In: Hermann BP, Seidenberg M. editors. Childhood epilepsies: neuropsychological, psychosocial and intervention aspects. New York: Wiley; 1989. p. 143–57. [11] Breslau N, Rasmussen BK. The impact of migraine: epidemiology, risk factors, and co-morbidities. Neurology 2001;56:S4–12. [12] Steffenburg S, Gillberg C, Steffenburg U. Psychiatric disorders in children and adolescents with mental retardation and active epilepsy. Arch Neurol 1996;53:904–12. [13] Hoare P. The quality of life of children with chronic epilepsy and their families. Seizure 1993;2:269–75. [14] Sabaz M, Cairns DR, Lawson JA, Bleasel AF, Bye AM. The health-related quality of life of children with refractory epilepsy: a comparison of those with and without intellectual disability. Epilepsia 2001;42:621–8. [15] Austin JK, Risinger MW, Beckett LA. Correlates of behavior problems in children with epilepsy. Epilepsia 1992;33:1115–22. [16] Riikonen R, Amnell G. Psychiatric disorders in children with earlier infantile spasms. Dev Med Child Neurol 1981;23:747–60. [17] Ferrie CD, Madigan C, Tilling K, et al. Adaptive and maladaptive behaviour in children with epileptic encephalopathies: correlation with cerebral glucose metabolism. Dev Med Child Neurol 1997;39:588–95. [18] Austin JK, Dunn DW, Caffrey HM, Perkins SM, Harezlak J, Rose DF. Recurrent seizures and behavior problems in children with first recognized seizures: a prospective study. Epilepsia 2002;43:1564–73. [19] Bourgeois BF. Antiepileptic drugs, learning, and behavior in childhood epilepsy. Epilepsia 1998;39:913–21. [20] Martin R, Kuzniecky R, Ho S, et al. Cognitive effects of topiramate, gabapentin, and lamotrigine in healthy young adults. Neurology 1999;52:321–7.
[21] Ketter TA, Post RM, Theodore WH. Positive and negative psychiatric effects of antiepileptic drugs in patients with seizure disorders. Neurology 1999;53:S53–67. [22] Schmitz B. The effects of antiepileptic drugs on behavior. In: Trimble M, Schmitz B. editors. The neuropsychiatry of epilepsy. Cambridge, UK: Cambridge Univ. Press; 2002. p. 241–55. [23] Mitchell WG, Chavez JM, Lee H, Guzman BL. Academic underachievement in children with epilepsy. J Child Neurol 1991;6:65–72. [24] Lothman DJ, Pianta RC, Clarson SM. Mother–child interaction in children with epilepsy: relations with child competence. J Epilepsy 1990;3:157–63. [25] McNelis A, Musick B, Austin J, Dunn D, Creasy K. Psychosocial care needs of children with new-onset seizures, 2. J Neurosci Nurs 1998;30:161–5. [26] Austin JK, Huberty TJ. Development of the Child Attitude Toward Illness Scale. J Pediatr Psychol 1993;18:467–80. [27] DeVellis RF, DeVellis BM. An evolving psychosocial model of epilepsy. In: Whitman S, Hermann BP. editors. Psychopathology in epilepsy: social dimensions. New York: Oxford Univ. Press; 1986. p. 122–42. [28] Mathews WS, Barabas G. Perceptions of control among children with epilepsy. In: Whitman S, Hermann BP. editors. Psychopathology in epilepsy: social dimensions. New York: Oxford Univ. Press; 1986. p. 162–82. [29] Oostrom KJ, Schouten A, Kruitwagen CL, Peters AC, JennekensSchinkel A. ParentsÕ perceptions of adversity introduced by upheaval and uncertainty at the onset of childhood epilepsy. Epilepsia 2001;42:1452–60. [30] Oostrom KJ, Schouten A, Kruitwagen CL, Peters AC, JennekensSchinkel A. Behavioral problems in children with newly diagnosed idiopathic or cryptogenic epilepsy attending normal schools are in majority not persistent. Epilepsia 2003;44:97–106. [31] Caplan R, Arbelle S, Magharious W, et al. Psychopathology in pediatric complex partial and primary generalized epilepsy. Dev Med Child Neurol 1998;40:805–11. [32] Hedderick E, Buchhalter JR. Comorbidity of child-onset epilepsy and psychiatric and behavioral disorders: a population-based study [abstract E12]. Ann Neurol 2003;54(Suppl):S115. [33] Kanner AM, Weisbrot D. Psychiatric evaluation of the patient with epilepsy: a practical approach for the ‘‘nonpsychiatrist’’. In: Ettinger AB, Kanner AM. editors. Psychiatric issues in epilepsy. Philadelphia: Lippincott Williams & Wilkins; 2001. p. 19–30. [34] Ridsdale L, Kwan I, Cryer C. For the Epilepsy Care Evaluation Group. Newly diagnosed epilepsy: can nurse specialists help? A randomized controlled trial. Epilepsia 2000;41:1014–9. [35] Ziegler RG, Erba G, Holden L, Dennison H. The coordinated psychosocial and neurologic care of children with seizures and their families. Epilepsia 2000;41:732–43. [36] Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association; 2000. [37] Williams J, Sharp GB, DelosReyes E, et al. Symptom differences in children with absence seizures versus inattention. Epilepsy Behav 2002;3:245–8. [38] Weinberg WA, Brumback RA. Primary disorder of vigilance: a novel explanation of inattentiveness, daydreaming, boredom, restlessness, and sleepiness. J Pediatr 1990;116:720–5. [39] Semrud-Clikeman M, Wical B. Components of attention in children with complex partial seizures with and without ADHD. Epilepsia 1999;40:211–5. [40] Dunn DW. Attention-deficit hyperactivity disorder, oppositional defiant disorder, and conduct disorder. In: Ettinger AB, Kanner AM. editors. Psychiatric issues in epilepsy. Philadelphia: Lippincott Williams & Wilkins; 2001. p. 111–26. [41] Dunn DW, Austin JK, Harezlak J, Ambrosius WT. ADHD and epilepsy in childhood. Dev Med Child Neurol 2003;45:50–4.
D.W. Dunn, J.K. Austin / Epilepsy & Behavior 5 (2004) S10–S17 [42] Barkley RA. Attention-deficit hyperactivity disorder. 2nd ed. New York: Guilford Press; 1998. [43] Williams J, Griebel ML, Dykman RA. Neuropsychological patterns in pediatric epilepsy. Seizure 1998;7:223–8. [44] Bailet LL, Turk WR. The impact of childhood epilepsy on neurocognitive and behavioral performance: a prospective longitudinal study. Epilepsia 2000;41:426–31. [45] Haverkamp F, Hanisch C, Mayer H, Noeker M. Evidence of a specific vulnerability for deficient sequential cognitive information processing in epilepsy. J Child Neurol 2001;16:901–5. [46] Hesdorffer DC, Ludvigsson P, Olafsson E, Gudmundsson G, Kjartansson O, Hauser WA. ADHD as a risk factor for incident unprovoked seizures and epilepsy in children. Arch Gen Psychiatry 2004;61:731–6. [47] Hughes JR, DeLeo AJ, Melyn MA. The electroencephalogram in attention deficit-hyperactivity disorder: emphasis on epileptiform discharges. Epilepsy Behav 2000;1:271–7. [48] Richer LP, Shevell MI, Rosenblatt BR. Epileptifom abnormalities in children with attention-deficit-hyperactivity disorder. Pediatr Neurol 2002;26:125–9. [49] Holtmann M, Becker K, Kentner-Figura B, Schmidt MH. Increased frequency of rolandic spikes in ADHD children. Epilepsia 2003;44:1241–4. [50] Williams J, Schulz EG, Griebel ML. Seizure occurence in children diagnosed with ADHD. Clin Pediatr 2001;40:221–4. [51] Kanner AM, Palac S. Depression in epilepsy: a common but often unrecognized comorbid malady. Epilepsy Behav 2000;1: 37–51. [52] Ettinger AB, Weisbrot DM, Nolan EE, et al. Symptoms of depression and anxiety in pediatric epilepsy patients. Epilepsia 1998;39:595–9. [53] Plioplys S. Depression in children and adolescents with epilepsy. Epilepsy Behav 2003;4(Suppl. 3):S39–45. [54] Brent DA, Crumrine PK, Varma R, Brown RV, Allan MJ. Phenobarbital treatment and major depressive disorder in children with epilepsy: a naturalistic follow-up. Pediatrics 1990;85:1086–91. [55] Brent DA. Overrepresentation of epileptics in a consecutive series of suicide attempters seen at a childrenÕs hospital, 1978–1983. J Am Acad Child Adolesc Psychiatry 1986;25:242–6. [56] Dunn DW, Austin JK, Huster GA. Symptoms of depression in adolescents with epilepsy. J Am Acad Child Adolesc Psychiatry 1999;38:1132–8. [57] Alwash RH, Hussein MJ, Matloub FF. Symptoms of anxiety and depression among adolescents with seizures in Irbid, Northern Jordan. Seizure 2000;9:412–6. [58] Oguz A, Kurul S, Dirik E. Relationship of epilepsy-related factors to anxiety and depression scores in epileptic children. J Child Neurol 2002;17:37–40. [59] Vazquez B, Devinsky O. Epilepsy and anxiety. Epilepsy Behav 2003;4(Suppl. 4):S20–25. [60] Scicutella A. Anxiety disorders in epilepsy. In: Ettinger AB, Kanner AM. editors. Psychiatric issues in epilepsy. Philadelphia: Lippincott Williams & Wilkins; 2001. p. 95–109. [61] Matsuura M, Trimble MR. Psychoses in epilepsy: a review of Japanese studies. Epilepsy Behav 2000;1:315–26. [62] Sachdev P. Schizophrenia-like psychosis and epilepsy: the status of the association. Am J Psychiatry 1998;155:325–36. [63] Caplan R, Arbelle S, Guthrie D, et al. Formal thought disorder and psychopathology in pediatric primary generalized and com-
[64] [65] [66] [67]
[68]
[69]
[70]
[71]
[72]
[73]
[74]
[75]
[76]
[77]
[78]
[79]
[80] [81] [82]
S17
plex partial epilepsy. J Am Acad Child Adolesc Psychiatry 1997;36:1286–94. Nissenkorn A, Moldavsky M, Lorberboym M, et al. Postictal psychosis in a child. J Child Neurol 1999;14:818–9. Kanner AM. Psychosis of epilepsy: a neurologistÕs perspective. Epilepsy Behav 2000;1:219–27. Miyamoto T, Kohsaka M, Koyama T. Psychotic episodes during zonisamide treatment. Seizure 2000;9:65–70. Schachter SC. Aggressive behavior in epilepsy. In: Ettinger AB, Kanner AM. editors. Psychiatric issues in epilepsy. Philadelphia: Lippincott Williams & Wilkins; 2001. p. 201–13. Lewis MA, Salas I, de la Sota A, Chiofalo N, Leake B. Randomized trial of a program to enhance the competencies of children with epilepsy. Epilepsia 1990;31:101–9. Tieffenberg JA, Wood EI, Alonso A, Tossutti MS, Vicente MF. A randomized field trial of ACINDES: a child-centered training model for children with chronic illnesses (asthma and epilepsy). J Urban Health 2000;77:280–97. Austin JK, McNelis AM, Shore CP, Dunn DW, Musick B. A feasibility study of a family seizure management program: ÔBe Seizure SmartÕ. J Neurol Neurosci Nurs 2002;34:30–7. Williams DT, Gold AP, Shrout P, Shaffer D, Adams D. The impact of psychiatric intervention on patients with uncontrolled seizures. J Nerv Ment Dis 1979;167:626–31. Dahl J, Melin L, Brorson LO, Schollin J. Effects of a broadspectrum behavior modification treatment program on children with refractory epileptic seizures. Epilepsia 1985;26:303–9. Feldman H, Crumrine P, Handen BL, Alvin R, Teodori J. Methylphenidate in children with seizures and attention-deficit disorder. Am J Dis Child 1989;143:1081–6. Gross-Tsur V, Manor O, van der Meere J, Joseph A, Shalev RS. Epilepsy and attention deficit hyperactivity disorder: is methylphenidate safe and effective?. J Pediatr 1997;130:670–4. Gucuyener K, Erdemoglu AK, Senol S, et al. Use of methylphenidate for attention-deficit hyperactivity disorder in patients with epilepsy or electroencephalographic abnormalities. J Child Neurol 2003;18:109–12. Hemmer SA, Pasternak JF, Zecker SG, Trommer BL. Stimulant therapy and seizure risk in children with ADHD. Pediatr Neurol 2001;24:99–102. Hughes CW, Emslie GJ, Crismon ML, et al. The Texas ChildrenÕs Medication Algorithm Project: report of the Texas Consensus Conference Panel on Medication Treatment of Childhood Major Depressive Disorder. J Am Acad Child Adolesc Psychiatry 1999;38:1442–54. Emslie GJ, Rush AJ, Weinberg WA, et al. A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression. Arch Gen Psychiatry 1997;54:1031–7. Wagner KD, Ambrosini P, Rynn M, et al. Efficacy of sertraline in the treatment of children and adolescents with major depressive disorder: two randomized controlled trials. JAMA 2003;290:1033–41. Kanner AM, Kozak AM, Frey M. The use of sertraline in patients with epilepsy: is it safe?. Epilepsy Behav 2000;1:100–5. Miller M, Bakalar J. Should children take antidepressants?. Harv Ment Health Lett 2003;20:5–7. Alldredge BK. Seizure risk associated with psychotropic drugs: clinical and pharmacokinetic considerations. Neurology 1999;53:S68–75.
Differential diagnosis and treatment of psychiatric disorders in children and adolescents with epilepsy David W. Dunna,*, Joan K. Austinb a b
Indiana University School of Medicine, Indianapolis, IN 46202, USA Indiana University School of Nursing, Indianapolis, IN 46202, USA Received 30 June 2004; accepted 30 June 2004 Available online 14 August 2004
Abstract Behavioral problems, such as the inattentive form of attention-deficit hyperactivity disorder (ADHD), anxiety, and depression, are common in children and adolescents with epilepsy and especially associated with central nervous system damage, family dysfunction, and severe seizures. This article discusses the risk factors to be considered when focusing on the prevalence of behavioral problems, the family factors that influence their incidence, as well as the differential diagnosis of behavioral disorders commonly associated with epilepsy. It also considers the assessment of these behavioral disorders and their treatment with psychotherapy, education, and a variety of psychopharmacological agents. Ó 2004 Elsevier Inc. All rights reserved. Keywords: Epilepsy; Childhood seizures; Psychiatric comorbidities; Attention-deficit hyperactivity disorder; Depression; Anxiety; Psychosis; Psychotherapy
1. Introduction In this discussion of the differential diagnosis of psychiatric disorders in children and adolescents with epilepsy, our goal is to address three questions. First, what are the risk factors for behavioral problems in children with epilepsy? Second, what types of behavioral and emotional problems are most prevalent in children with epilepsy? Third, what forms of treatment are available and should be offered to the child with both epilepsy and behavioral problems? Behavioral and emotional problems are a major concern for children with epilepsy. Behavioral problems are quite common in these children. In a classic epidemiological study, Rutter et al. [1] found that 28.6% of children with uncomplicated seizures and 58.3% of children *
Corresponding author. E-mail address: [email protected] (D.W. Dunn).
1525-5050/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2004.06.011
with seizures and additional neurological damage had behavioral problems. In comparison, the prevalence of behavioral problems in the general population of children was 6.6%, and in children with chronic illnesses not involving the central nervous system it was 11.6%. In a more recent national epidemiological study from Great Britain, Davies et al. [2] reported remarkably similar prevalence figures. The rate of psychiatric disorders was 37% in children with epilepsy, 11% in children with diabetes mellitus, and 9% in controls. They found behavioral disorders in 26.2% of children with uncomplicated epilepsy and in 56% of children with complicated epilepsy. These behavioral problems often are not recognized or are not treated. In one study of children with epilepsy and normal intelligence, 61% of the children had a psychiatric diagnosis based on DSM-IV criteria, but only 33% of the children received mental health treatment [3].
D.W. Dunn, J.K. Austin / Epilepsy & Behavior 5 (2004) S10–S17
2. Risk factors 2.1. General Just as epilepsy is a heterogeneous disorder with multiple etiologies, seizure types and syndromes, and variable degrees of seizure control, there are multiple factors that influence the risk of psychopathology in children with epilepsy. Factors to consider in assessing the prevalence of behavioral problems include demographic variables, neurological variables, seizure variables, therapy, and psychosocial variables [4]. Table 1 lists a few of these factors. Let us first consider the factors that have not been shown to be consistently indicative of risk. Demographic variables have been minimally predictive of the likelihood of psychiatric or behavioral problems. Gender is inconsistent as a predictor of problems. As an example, in a study of children with new-onset seizures, we found boys with prior unrecognized seizures to have more behavioral problems than girls [5], but in a study of children with chronic seizures, girls with more severe seizures had the most difficulties [6]. In other studies, Stores [7] found boys at higher risk, and Hoare and Kerley [8] found no difference by gender. Age at onset of seizures is more predictive of cognitive problems than of behavioral difficulties [9]. Lower socioeconomic status, defined by either income or caregiver education, has been associated with behavioral problems [5,10]. A more definite risk factor for behavioral problems is the presence of additional central nervous system damage [1,11]. Standard epidemiological studies from the Isle of Wight showed that 50 to 60% of children with central nervous system damage, i.e., children with cerebral palsy or mental retardation plus epilepsy, demonstrated significant behavioral problems, and a recent national survey from England found that children with
Table 1 Risk factors for behavioral problems in pediatric epilepsy Demographic variables Age Gender Socioeconomic status Neurological variables Additional central nervous system dysfunction Mental handicap Severe epileptic syndromes Intractable epilepsy Early age of seizure onset AED polytherapy Psychosocial variables Family stress and mastery Child response to illness Stigma
S11
complicated epilepsy had twice the prevalence of behavioral problems as children with uncomplicated epilepsy [2]. Scandinavian studies have also confirmed that a combination of neurological damage and epilepsy results in a 50–60% risk of behavioral problems [12]. Quality-of-life studies have shown, not surprisingly, that children with epilepsy plus mental retardation typically have a more impaired quality of life. However, the effect appears to be more than additive in these children [13,14]. Seizure variables have been associated with behavioral problems in children with epilepsy. Seizure type has been inconsistent as a predictor. We found children with partial seizures to have more behavioral problems than children with generalized seizures in a sample of patients with new-onset epilepsy [5]. In comparison, there was no association between seizure type and behavioral difficulties in a study of patients with chronic seizures conducted by our group [15]. Seizure syndrome is probably a more important factor. The children with catastrophic epilepsies such as West syndrome or Lennox–Gastaut syndrome have more behavioral and cognitive troubles [16,17]. Seizure severity and seizure frequency are important variables in predicting behavioral problems [9,15]. Moreover, even in children with new-onset seizures, recurrent seizures were a predictor of behavioral problems [18]. Behavioral problems in this patient population are also associated with some antiepileptic drugs (AEDs). These include the benzodiazepines, phenobarbital, and topiramate [19,20]. This topic has been reviewed recently [21,22], and is discussed further in the article by Dr. Glauser in this supplement. 2.2. Family and child factors Family factors also influence the incidence of behavioral problems. The measure most consistently predictive of behavioral problems is the measure of family mastery (see the article by Austin et al. in this supplement). The families who are able to deal with the childÕs epilepsy, who feel confident that they can handle the problems associated with pediatric epilepsy, are the ones who are able to transfer this confidence to their children, resulting in a better quality of life. Family style seems to be important as well. Overcontrolling families, ones that are intrusive and do not give their children sufficient chance to develop independence, produce children who do more poorly [8,15,23,24]. The childÕs own response to his or her epilepsy is also significantly associated with behavioral problems. Our studies [25] found that children and adolescents worry about their epilepsy and the social impact it has on their lives. Some of them worry about dying and, specifically, about dying from their seizures. It is important to
S12
D.W. Dunn, J.K. Austin / Epilepsy & Behavior 5 (2004) S10–S17
identify these children. Overall, children who have a negative attitude toward their illness develop more problems related to self-concept, and are more likely to develop depression [4,26]. One explanation for the occurrence of depression in children with epilepsy is the learned helplessness model [27]. The children at risk feel they have no control over their epilepsy; this external or unknown locus of control appears to be a risk factor for the development of depression [28]. Though many studies have focused on children with chronic seizures, at least some of the risk factors for behavioral problems in children with epilepsy may predate the occurrence of seizures. There are studies showing that children and families who have had problems before the seizures started were more prone to developing behavioral problems after seizure onset [5,29,30]. Austin et al. [5] found that about one-third of children with new-onset seizures had behavioral problems apparent within the first month of seizure onset. In this sample, approximately one-third of children with new-onset seizures had experienced episodes that in retrospect were probably seizures. These children with prior unrecognized seizures had more behavioral problems when assessed at baseline. This finding suggested that seizures and some of the behavioral problems might be due to an underlying central nervous system dysfunction, rather than the psychosocial reaction to having seizures or the effect of antiepileptic drugs.
3. The differential diagnosis 3.1. Common disorders Numerous studies have shown that children with epilepsy are at risk for several psychiatric disorders. The British Child and Adolescent Mental Health Survey divided the psychiatric diagnoses of children with epilepsy into broad categories. The percentage of children with complicated epilepsy who had any emotional problem was 16%; conduct disorder (CD) and oppositional defiant disorder (ODD) were seen in 24%; 12% had attention-deficit hyperactivity disorder (ADHD); and the percentage with any pervasive developmental disorder was 16%. The percentage of children with uncomplicated epilepsy who had emotional problems was 17%, and CD and oppositional disorder were present in 17%. None of the children with uncomplicated epilepsy had ADHD or pervasive developmental disorders. To compare, the percentage of healthy children with psychiatric disorders was 4% for emotional disorders, 5% for CD, 2% for ADHD, and 0.2% for pervasive developmental disorders [2]. Steffenburg et al. [12] assessed children with epilepsy and mental retardation. They found autistic disorder
in 27%, autistic spectrum disorder in 11%, ADHD in 7%, and overanxious disorder in 3%. Caplan et al. [31] and Dunn et al. (in preparation) have used standardized measures of psychiatric disorders in children with epilepsy and normal intelligence. Caplan et al. [31] used either the Kiddie Schedule for Affective Disorders and Schizophrenia or the Diagnostic Inventory for Children and Adolescents to establish psychiatric diagnoses. They also divided their sample into children with primary generalized epilepsy (PGE) and those with complex partial epilepsy (CPE). They found disruptive disorders (ADHD, ODD, and CD) in 25% of children with CPE and in 26% of those with PGE; anxiety/mood disorder in 13% of each group; and comorbid disruptive disorder and anxiety/mood disorder in 14% of children with CPE and 16% with PGE. A schizophrenia-like psychosis was noted only in children with CPE (10%). Our study (Dunn et al. (in preparation)) assessed 167 children with chronic seizures. Categorical diagnoses were established using either the Child Symptom Inventory or the Adolescent Symptom Inventory, depending on the age. We used the screening cutoff score method to determine likelihood of a psychiatric diagnosis. With this measure, we found possible diagnoses of ADHD predominantly inattentive type in 22.8%, ADHD predominantly hyperactive–impulsive type in 2.4%, ADHD combined type in 11.4%, ODD in 20.4%, CD in 18%, and depressive disorder and dysthymia in 9.6%. There was evidence of an anxiety disorder in a third of the children and adolescents. Hedderick and Buchhalter [32], in a population-based study in Rochester, Minnesota, found comorbid psychiatric disorder defined by the DSM-IV in 51% of children with epilepsy. When those with mental retardation were excluded, the figure was 40%. The most common disorders were ADHD (17%), mood disorder (12%), and adjustment disorder (10%). 3.2. Assessing disorders The recognition of behavioral disorders in children with epilepsy is dependent on the time and effort expended in the clinic to assess children for psychiatric comorbidity. A history that asks only about number of seizures, change in seizure type, and side effects of antiepileptic medication may overlook many of the psychiatric problems seen in children with epilepsy. Questions about school performance can help with the recognition of ADHD. Asking about anger, irritability, moodiness, and worries can lead to possible diagnosis of mood and anxiety disorders; and questions about confusion, hallucinations, or regression could point to a psychotic disorder. Kanner and Weisbrot [33] have reviewed both the psychiatric evaluation and rating scales available for
D.W. Dunn, J.K. Austin / Epilepsy & Behavior 5 (2004) S10–S17
use in the epilepsy clinic. In a large comprehensive epilepsy clinic, clinical nurse specialists and psychosocial consultants can be helpful [34,35]. 3.3. Problems with attention in children with epilepsy ADHD is defined by a combination of problems with attention, including poor concentration, distractibility, forgetfulness, frequent careless errors, and incomplete work, and hyperactivity and impulsivity characterized by fidgeting, trouble staying seated, excessive talking, interrupting, and inability to wait or take turns. Symptoms are present in multiple settings including home, school, and extracurricular activities [36]. Diagnosis is best made by reports from the parents with corroboration from schoolteachers. Problems with attention can be due to seizures or to antiepileptic medications. Unrecognized absence or partial seizures may present as impaired attention. Williams et al. [37] have found that failure to complete homework and difficulty staying on task were symptoms of ADHD, but were not symptoms evident in children with absence seizures. Nocturnal seizures may disrupt sleep, resulting in excess daytime sleepiness. This may cause inattention and restlessness, which might be classified as a disorder of vigilance as defined by Weinberg and Brumback [38]. The lethargy and attentional problems seen with several antiepileptic drugs should be considered in the differential diagnosis of ADHD in children with epilepsy. Barbiturates and benzodiazepines have been associated with inattention and hyperactivity. There are reports of difficulty concentrating or cognitive slowing in some patients on tiagabine, topiramate, and zonisamide. In children with learning disabilities, gabapentin may cause severe hyperactivity and aggressiveness [19,22]. Even after excluding problems with attention and excess activity levels due to seizures or AEDs, ADHD remains the most common behavioral problem associated with childhood epilepsy. In our review of the literature, we found reports of the prevalence of ADHD in childhood epilepsy ranging from 8 to 77%, with prevalence rates of 30–40% in recent studies using standard measures of ADHD [39,40]. In our studies of children with both new-onset epilepsy and chronic epilepsy [5,41], we have measured behavioral problems with the Child Behavior Checklist, the Child Symptom Inventory, or the Adolescent Symptom Inventory, and have consistently found that the most common behavioral problem is impaired attention. The symptoms of ADHD in a child with epilepsy may or may not be the same as those of ADHD in other, non-epileptic children usually referred to the psychiatric clinics. ADHD as seen by the child and adolescent psychiatrist is most commonly the combined type, which includes inattention plus hyperactivity and impulsivity.
S13
The children with ADHD are predominantly boys in a ratio of 3 to 1, with some studies reporting a ratio of boys to girls as high as 9 to 1 [42]. In contrast, children with epilepsy are more likely to present with an inattentive form of ADHD, and the ratio of boys to girls is 1 [41]. Epilepsy may have a broader impact on multiple attentional networks within the central nervous system. Recent neuropsychological assessments in children with epilepsy have shown below-average verbal and visual attention skills, slowing of psychomotor speed, and impairment in sequential cognitive processing [43–45]. The association between ADHD and childhood epilepsy has additional complexities. Hesdorffer et al. [46] found that ADHD was a risk factor for the development of seizures and speculated that ADHD and epilepsy may be due to a common underlying problem. The increase in the rate of spikes found on the EEGs of children with ADHD supports the theory of a common underlying central nervous system dysfunction [47–49]. On the other hand, Williams et al. [50], in a 4-year follow-up, did not find an increase in the number of children with ADHD developing seizures. 3.4. Depression and epilepsy Depression is a common but often overlooked problem in epilepsy [51]. Ettinger et al. [52] found that in their clinic, though 26% of the children with epilepsy had symptoms of depression, none of these had been identified or treated. In part, this may be the result of differences in symptoms of depression in children versus those seen in adults. Children more often present with irritability, withdrawal, somatic complaints, and trouble sleeping. Difficulties with concentration may lead to school failure. Adolescents may have similar complaints but also develop hopelessness, guilt, and suicidal ideation. A family history of mood disorder may be an important clue to the diagnosis of depression in children with epilepsy [53]. In the differential diagnosis of depression and childhood epilepsy, as with attention disorders, the psychiatric effect of AEDs should be considered. Phenobarbital has been associated with depression and an increased risk of suicide [54,55]. Newer AEDs whose mechanism is GABAergic, such as levetiracetam, topiramate, tiagabine, and zonisamide, have caused depressive symptoms [22,51]. Depression is seen in somewhere between 10 and 30% of children and adolescents with epilepsy. In our study [56], we found that about one-fourth of adolescents with epilepsy had symptoms of depression. Ettinger et al. [52] found symptoms of depression in 26%, Alwash et al. [57] in 23%, and Oguz et al. [58] in 28.6%. In this last study, suicidal ideation was noted in 17%, and more often in adolescents than in children.
S14
D.W. Dunn, J.K. Austin / Epilepsy & Behavior 5 (2004) S10–S17
In adults, there is an association of depression with left temporal lobe discharges, but the same does not hold true for children and adolescents with epilepsy. The depression seen in young epilepsy patients does not seem to be associated with any particular seizure syndrome or seizure type. We did find an association between depression and a negative attitude toward illness and dissatisfaction with family relationships. The adolescents with symptoms of depression more often had an external or unknown locus of control [56].
Table 2 Classification of psychoses of epilepsy (POE)
3.5. Anxiety and epilepsy
wise, there are rare episodes of postictal psychosis, a disorder that usually occurs after a prolonged seizure or a cluster of seizures. The psychotic episode typically follows a lucid interval of 24–48 hours and lasts on average for 4–5 days before spontaneously clearing [64]. AEDinduced psychotic reactions have occurred with phenytoin, ethosuximide, vigabatrin, zonisamide, topiramate, and possibly lamotrigine and felbamate [22,65,66]. Table 2 summarizes the classification of psychoses of epilepsy (POE) described by Kanner in 2000 [65].
The prevalence of anxiety in children and adolescents with epilepsy is harder to estimate, as there have been fewer studies. It probably is in the range of 15–25% [59]. Anxiety is more common in adolescents than in younger children. Anxiety is also more common in children who have intractable seizures and in those who are on multiple AEDs [52,57,58]. The differential diagnosis of anxiety in children and adolescents with epilepsy includes consideration of the effects of both seizures and of AEDs. Anxiety can occur as a preictal premonitory symptom and following a seizure. Ictal fear is associated with complex partial seizures of temporal lobe origin. Panic attacks may mimic complex partial seizures. Motor automatisms and alteration in consciousness may help distinguish seizures from panic attacks [60]. Anxiety or nervousness has been seen with activating drugs such as felbamate and topiramate and with withdrawal of AEDs [59]. 3.6. Psychosis and epilepsy Fortunately, the incidence of interictal psychosis associated with epilepsy is rare in children. Matsuura and Trimble reported a prevalence rate of 0.7% in pediatric epilepsy clinics in Japan [61]. This is probably due to the variable of seizure duration. A number of studies have suggested that seizures, particularly from the temporal lobes, usually have been present for 10 to 14 years prior to the onset of chronic interictal psychosis [62]. As a result, patients have generally passed beyond childhood before onset of psychosis. Early symptoms of possible psychosis in children with complex partial seizures have been reported by Caplan et al. [63]. They found an increase in illogical thinking and hallucinations, but not loose associations, in children with complex partial seizures, but not in children with generalized seizures. In the differential diagnosis, seizures and AEDs should again be considered. Child neurologists do see occasional episodes of ictal psychosis, but this seems more often to be a delirium or a confusional state. Like-
Ictal POE Postictal POE Interictal POE Alternative psychosis AED-related psychosis
Associated with seizure activity Transient psychosis occurring within a week of seizure activity Chronic psychotic symptoms not associated with seizures Forced normalization, symptoms following control of seizures Psychosis as a side effect of AEDs
Source. Reproduced, with permission, from Kanner [65].
3.7. Aggression and epilepsy Aggression in children and adolescents with epilepsy has proved harder to define. Our studies [40], which used the Child Behavior Checklist, the Child Symptom Inventory, and the Adolescent Symptom Inventory, found an increased risk in young people with epilepsy of developing ODD or CD, which ranged from 10 to 35%. Aggressive behavior can occur particularly in association with postictal confusion and during those rare cases of postictal psychosis. There is also an increased association of such behavior with underlying central nervous system damage [67]. Aggression has been associated with barbiturates, felbamate, vigabatrin, and, in children with developmental delay, gabapentin [19,22].
4. Treatment Having identified a child with epilepsy as at risk for developing psychiatric difficulties, what can be done? Ideally, we would like to prevent these behavioral problems, but as a second goal, early treatment is essential. 4.1. Psychotherapy and education Education should be a standard part of all treatment for pediatric epilepsy patients, particularly those at risk for comorbid psychiatric and behavioral problems. This includes informing parents about exactly what they may expect to happen in the course of
D.W. Dunn, J.K. Austin / Epilepsy & Behavior 5 (2004) S10–S17
the childÕs illness, teaching them how to manage the symptoms of epilepsy, explaining how to handle the medication, and identifying symptoms they should watch for in their children. Both individual and group educational sessions have been studied. Lewis et al. [68] used a large-group education format, instructing parents and children with epilepsy about epilepsy and providing training in coping techniques, decision making, and communication. Follow-up studies found improved knowledge, self-perceived social competency, and behavior. They did have difficulty getting families to participate in the four 1-hour sessions. Tieffenberg et al. [69] conducted educational programs using groups of 8 to 10 families. They concentrated on improving young patientsÕ sense of autonomy and mastery. They were able to demonstrate improved knowledge and behavior in children and more knowledge of epilepsy in parents, and saw fewer emergency room visits for the child with epilepsy. Our group [70] has developed ‘‘focused’’ training for small groups, usually two or three families. The families completed questionnaires that assessed worries and concerns of parents and children. We matched families by child age and types of worries and concerns, and brought together these small groups of families for a conference call. These small-group educational interventions resulted in increased knowledge and decreased need for support and additional information. The goal of our program is to identify worries and concern early in the course of the childÕs epilepsy and to prevent the behavioral problems observed in children and adolescents with epilepsy. Once the child has developed behavioral problems, group therapy and individual therapy may be helpful. Specific therapy for children with epilepsy involves assessment for emotionally based precipitants of seizures and behavioral abnormalities. Psychotherapy addresses some of the stresses that may be associated with epilepsy through the teaching of relaxation techniques and coping skills. These techniques have resulted in improvement in self-concept as well as a significant reduction in seizure frequency [71,72]. 4.2. Psychopharmacology If psychotherapy proves ineffective, psychopharmacology is often effective. There is empirical support that stimulant medication improves the symptoms of ADHD in children with epilepsy and improves their cognitive function as well [73,74]. Additionally, in most children with seizures, there are no data to show that seizure breakthrough occurs as a result of adding stimulant medication to the treatment regimen. Neither Feldman et al. [73] nor Gucuyener et al. [75] found an increase in seizures in children treated with methyl-
S15
phenidate. Gross-Tsur et al. [74] noted no seizure recurrence in children who were seizure-free, but an increase in seizures in three-fifths of the children and no change or a reduction in two-fifths of the children with recurrent seizures when methylphenidate was started. Hemmer et al. [76] showed that an abnormal EEG predicted a risk for seizures in children with ADHD, but did not find seizure occurrence related to stimulant use. In the child with epilepsy and a mood disturbance, antidepressant drugs may be helpful, though there are no double-blind, placebo-controlled trials to prove antidepressants safe and effective in this population. Most authorities recommend starting with selective serotonin reuptake inhibitors (SSRIs) [77]. There are data showing that the SSRIs are effective in children with depressive disorders [78,79]. The SSRIs have not caused a significant lowering of seizure threshold, and sertraline has been used in an open-label study in adults with epilepsy without major problems [80]. Although there has been recent concern about the apparent increase in suicidal ideation associated with certain SSRIs, a reasonable approach is to use the drugs cautiously, monitoring for akathisia, particularly during the first weeks of therapy when the child is most at risk for side effects [81]. Other antidepressants may be considered if SSRIs fail [77]. Although trazodone and nefazodone can be effective, they are often associated with lethargy. Venlafaxine and bupropion have been associated with a moderately increased risk of seizures [82]. The tricyclic antidepressants are effective in adults with depression, but there has never been a double-blind, placebo-controlled trial that has shown their effectiveness in childhood depression. In addition, there is some evidence that the tricyclics are associated with an increased risk of seizures [82]. The use of antipsychotics in children and adolescents with epilepsy should be considered when the child or adolescent develops psychotic symptoms. Agents to be avoided include clozapine and chlorpromazine, both of which lower the seizure threshold. There is a moderate risk of seizures with the use of thioridazine, olanzapine, or quetiapine, and probably a low risk with haloperidol or risperidone [82].
5. Summary Behavioral problems are common in children and adolescents with epilepsy and are especially associated with central nervous system damage, family dysfunction, and severe seizures. The most common behavioral problems in this patient population are the inattentive form of ADHD, anxiety, and depression.
S16
D.W. Dunn, J.K. Austin / Epilepsy & Behavior 5 (2004) S10–S17
Therapy for these young people should involve education, counseling (at least group psychotherapy and, if possible, individual therapy), and, when needed, psychopharmacology.
References [1] Rutter M, Graham P, Yule W. A neuropsychiatric study in childhood. Philadelphia: Lippincott Publishers; 1970. [2] Davies S, Heyman I, Goodman R. A population survey of mental health problems in children with epilepsy. Dev Med Child Neurol 2003;45:292–5. [3] Ott D, Siddarth P, Gurbani S, et al. Behavioral disorders in pediatric epilepsy: unmet psychiatric need. Epilepsia 2003;44:591–7. [4] Dunn DW, Austin JK. Behavioral issues in pediatric epilepsy. Neurology 1999;53:S96–100. [5] Austin JK, Harezlak J, Dunn DW, et al. Behavior problems in children before first recognized seizures. Pediatrics 2001;107:115–22. [6] Austin JK, Huster GA, Dunn DW, Risinger MW. Adolescents with active or inactive epilepsy or asthma: a comparison of quality of life. Epilepsia 1996;37:1228–38. [7] Stores G. School-children with epilepsy at risk for learning and behaviour problems. Dev Med Child Neurol 1978;20:502–8. [8] Hoare P, Kerley S. Psychosocial adjustment of children with chronic epilepsy and their families. Dev Med Child Neurol 1991;33:201–15. [9] Schoenfeld J, Seidenberg M, Woodard A, et al. Neuropsychological and behavioral status of children with complex partial seizures. Dev Med Child Neurol 1999;41:724–31. [10] Hermann BP, Whitman S, Dell J. Correlates of behavior problems and social competence in children with epilepsy aged 6–11. In: Hermann BP, Seidenberg M. editors. Childhood epilepsies: neuropsychological, psychosocial and intervention aspects. New York: Wiley; 1989. p. 143–57. [11] Breslau N, Rasmussen BK. The impact of migraine: epidemiology, risk factors, and co-morbidities. Neurology 2001;56:S4–12. [12] Steffenburg S, Gillberg C, Steffenburg U. Psychiatric disorders in children and adolescents with mental retardation and active epilepsy. Arch Neurol 1996;53:904–12. [13] Hoare P. The quality of life of children with chronic epilepsy and their families. Seizure 1993;2:269–75. [14] Sabaz M, Cairns DR, Lawson JA, Bleasel AF, Bye AM. The health-related quality of life of children with refractory epilepsy: a comparison of those with and without intellectual disability. Epilepsia 2001;42:621–8. [15] Austin JK, Risinger MW, Beckett LA. Correlates of behavior problems in children with epilepsy. Epilepsia 1992;33:1115–22. [16] Riikonen R, Amnell G. Psychiatric disorders in children with earlier infantile spasms. Dev Med Child Neurol 1981;23:747–60. [17] Ferrie CD, Madigan C, Tilling K, et al. Adaptive and maladaptive behaviour in children with epileptic encephalopathies: correlation with cerebral glucose metabolism. Dev Med Child Neurol 1997;39:588–95. [18] Austin JK, Dunn DW, Caffrey HM, Perkins SM, Harezlak J, Rose DF. Recurrent seizures and behavior problems in children with first recognized seizures: a prospective study. Epilepsia 2002;43:1564–73. [19] Bourgeois BF. Antiepileptic drugs, learning, and behavior in childhood epilepsy. Epilepsia 1998;39:913–21. [20] Martin R, Kuzniecky R, Ho S, et al. Cognitive effects of topiramate, gabapentin, and lamotrigine in healthy young adults. Neurology 1999;52:321–7.
[21] Ketter TA, Post RM, Theodore WH. Positive and negative psychiatric effects of antiepileptic drugs in patients with seizure disorders. Neurology 1999;53:S53–67. [22] Schmitz B. The effects of antiepileptic drugs on behavior. In: Trimble M, Schmitz B. editors. The neuropsychiatry of epilepsy. Cambridge, UK: Cambridge Univ. Press; 2002. p. 241–55. [23] Mitchell WG, Chavez JM, Lee H, Guzman BL. Academic underachievement in children with epilepsy. J Child Neurol 1991;6:65–72. [24] Lothman DJ, Pianta RC, Clarson SM. Mother–child interaction in children with epilepsy: relations with child competence. J Epilepsy 1990;3:157–63. [25] McNelis A, Musick B, Austin J, Dunn D, Creasy K. Psychosocial care needs of children with new-onset seizures, 2. J Neurosci Nurs 1998;30:161–5. [26] Austin JK, Huberty TJ. Development of the Child Attitude Toward Illness Scale. J Pediatr Psychol 1993;18:467–80. [27] DeVellis RF, DeVellis BM. An evolving psychosocial model of epilepsy. In: Whitman S, Hermann BP. editors. Psychopathology in epilepsy: social dimensions. New York: Oxford Univ. Press; 1986. p. 122–42. [28] Mathews WS, Barabas G. Perceptions of control among children with epilepsy. In: Whitman S, Hermann BP. editors. Psychopathology in epilepsy: social dimensions. New York: Oxford Univ. Press; 1986. p. 162–82. [29] Oostrom KJ, Schouten A, Kruitwagen CL, Peters AC, JennekensSchinkel A. ParentsÕ perceptions of adversity introduced by upheaval and uncertainty at the onset of childhood epilepsy. Epilepsia 2001;42:1452–60. [30] Oostrom KJ, Schouten A, Kruitwagen CL, Peters AC, JennekensSchinkel A. Behavioral problems in children with newly diagnosed idiopathic or cryptogenic epilepsy attending normal schools are in majority not persistent. Epilepsia 2003;44:97–106. [31] Caplan R, Arbelle S, Magharious W, et al. Psychopathology in pediatric complex partial and primary generalized epilepsy. Dev Med Child Neurol 1998;40:805–11. [32] Hedderick E, Buchhalter JR. Comorbidity of child-onset epilepsy and psychiatric and behavioral disorders: a population-based study [abstract E12]. Ann Neurol 2003;54(Suppl):S115. [33] Kanner AM, Weisbrot D. Psychiatric evaluation of the patient with epilepsy: a practical approach for the ‘‘nonpsychiatrist’’. In: Ettinger AB, Kanner AM. editors. Psychiatric issues in epilepsy. Philadelphia: Lippincott Williams & Wilkins; 2001. p. 19–30. [34] Ridsdale L, Kwan I, Cryer C. For the Epilepsy Care Evaluation Group. Newly diagnosed epilepsy: can nurse specialists help? A randomized controlled trial. Epilepsia 2000;41:1014–9. [35] Ziegler RG, Erba G, Holden L, Dennison H. The coordinated psychosocial and neurologic care of children with seizures and their families. Epilepsia 2000;41:732–43. [36] Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association; 2000. [37] Williams J, Sharp GB, DelosReyes E, et al. Symptom differences in children with absence seizures versus inattention. Epilepsy Behav 2002;3:245–8. [38] Weinberg WA, Brumback RA. Primary disorder of vigilance: a novel explanation of inattentiveness, daydreaming, boredom, restlessness, and sleepiness. J Pediatr 1990;116:720–5. [39] Semrud-Clikeman M, Wical B. Components of attention in children with complex partial seizures with and without ADHD. Epilepsia 1999;40:211–5. [40] Dunn DW. Attention-deficit hyperactivity disorder, oppositional defiant disorder, and conduct disorder. In: Ettinger AB, Kanner AM. editors. Psychiatric issues in epilepsy. Philadelphia: Lippincott Williams & Wilkins; 2001. p. 111–26. [41] Dunn DW, Austin JK, Harezlak J, Ambrosius WT. ADHD and epilepsy in childhood. Dev Med Child Neurol 2003;45:50–4.
D.W. Dunn, J.K. Austin / Epilepsy & Behavior 5 (2004) S10–S17 [42] Barkley RA. Attention-deficit hyperactivity disorder. 2nd ed. New York: Guilford Press; 1998. [43] Williams J, Griebel ML, Dykman RA. Neuropsychological patterns in pediatric epilepsy. Seizure 1998;7:223–8. [44] Bailet LL, Turk WR. The impact of childhood epilepsy on neurocognitive and behavioral performance: a prospective longitudinal study. Epilepsia 2000;41:426–31. [45] Haverkamp F, Hanisch C, Mayer H, Noeker M. Evidence of a specific vulnerability for deficient sequential cognitive information processing in epilepsy. J Child Neurol 2001;16:901–5. [46] Hesdorffer DC, Ludvigsson P, Olafsson E, Gudmundsson G, Kjartansson O, Hauser WA. ADHD as a risk factor for incident unprovoked seizures and epilepsy in children. Arch Gen Psychiatry 2004;61:731–6. [47] Hughes JR, DeLeo AJ, Melyn MA. The electroencephalogram in attention deficit-hyperactivity disorder: emphasis on epileptiform discharges. Epilepsy Behav 2000;1:271–7. [48] Richer LP, Shevell MI, Rosenblatt BR. Epileptifom abnormalities in children with attention-deficit-hyperactivity disorder. Pediatr Neurol 2002;26:125–9. [49] Holtmann M, Becker K, Kentner-Figura B, Schmidt MH. Increased frequency of rolandic spikes in ADHD children. Epilepsia 2003;44:1241–4. [50] Williams J, Schulz EG, Griebel ML. Seizure occurence in children diagnosed with ADHD. Clin Pediatr 2001;40:221–4. [51] Kanner AM, Palac S. Depression in epilepsy: a common but often unrecognized comorbid malady. Epilepsy Behav 2000;1: 37–51. [52] Ettinger AB, Weisbrot DM, Nolan EE, et al. Symptoms of depression and anxiety in pediatric epilepsy patients. Epilepsia 1998;39:595–9. [53] Plioplys S. Depression in children and adolescents with epilepsy. Epilepsy Behav 2003;4(Suppl. 3):S39–45. [54] Brent DA, Crumrine PK, Varma R, Brown RV, Allan MJ. Phenobarbital treatment and major depressive disorder in children with epilepsy: a naturalistic follow-up. Pediatrics 1990;85:1086–91. [55] Brent DA. Overrepresentation of epileptics in a consecutive series of suicide attempters seen at a childrenÕs hospital, 1978–1983. J Am Acad Child Adolesc Psychiatry 1986;25:242–6. [56] Dunn DW, Austin JK, Huster GA. Symptoms of depression in adolescents with epilepsy. J Am Acad Child Adolesc Psychiatry 1999;38:1132–8. [57] Alwash RH, Hussein MJ, Matloub FF. Symptoms of anxiety and depression among adolescents with seizures in Irbid, Northern Jordan. Seizure 2000;9:412–6. [58] Oguz A, Kurul S, Dirik E. Relationship of epilepsy-related factors to anxiety and depression scores in epileptic children. J Child Neurol 2002;17:37–40. [59] Vazquez B, Devinsky O. Epilepsy and anxiety. Epilepsy Behav 2003;4(Suppl. 4):S20–25. [60] Scicutella A. Anxiety disorders in epilepsy. In: Ettinger AB, Kanner AM. editors. Psychiatric issues in epilepsy. Philadelphia: Lippincott Williams & Wilkins; 2001. p. 95–109. [61] Matsuura M, Trimble MR. Psychoses in epilepsy: a review of Japanese studies. Epilepsy Behav 2000;1:315–26. [62] Sachdev P. Schizophrenia-like psychosis and epilepsy: the status of the association. Am J Psychiatry 1998;155:325–36. [63] Caplan R, Arbelle S, Guthrie D, et al. Formal thought disorder and psychopathology in pediatric primary generalized and com-
[64] [65] [66] [67]
[68]
[69]
[70]
[71]
[72]
[73]
[74]
[75]
[76]
[77]
[78]
[79]
[80] [81] [82]
S17
plex partial epilepsy. J Am Acad Child Adolesc Psychiatry 1997;36:1286–94. Nissenkorn A, Moldavsky M, Lorberboym M, et al. Postictal psychosis in a child. J Child Neurol 1999;14:818–9. Kanner AM. Psychosis of epilepsy: a neurologistÕs perspective. Epilepsy Behav 2000;1:219–27. Miyamoto T, Kohsaka M, Koyama T. Psychotic episodes during zonisamide treatment. Seizure 2000;9:65–70. Schachter SC. Aggressive behavior in epilepsy. In: Ettinger AB, Kanner AM. editors. Psychiatric issues in epilepsy. Philadelphia: Lippincott Williams & Wilkins; 2001. p. 201–13. Lewis MA, Salas I, de la Sota A, Chiofalo N, Leake B. Randomized trial of a program to enhance the competencies of children with epilepsy. Epilepsia 1990;31:101–9. Tieffenberg JA, Wood EI, Alonso A, Tossutti MS, Vicente MF. A randomized field trial of ACINDES: a child-centered training model for children with chronic illnesses (asthma and epilepsy). J Urban Health 2000;77:280–97. Austin JK, McNelis AM, Shore CP, Dunn DW, Musick B. A feasibility study of a family seizure management program: ÔBe Seizure SmartÕ. J Neurol Neurosci Nurs 2002;34:30–7. Williams DT, Gold AP, Shrout P, Shaffer D, Adams D. The impact of psychiatric intervention on patients with uncontrolled seizures. J Nerv Ment Dis 1979;167:626–31. Dahl J, Melin L, Brorson LO, Schollin J. Effects of a broadspectrum behavior modification treatment program on children with refractory epileptic seizures. Epilepsia 1985;26:303–9. Feldman H, Crumrine P, Handen BL, Alvin R, Teodori J. Methylphenidate in children with seizures and attention-deficit disorder. Am J Dis Child 1989;143:1081–6. Gross-Tsur V, Manor O, van der Meere J, Joseph A, Shalev RS. Epilepsy and attention deficit hyperactivity disorder: is methylphenidate safe and effective?. J Pediatr 1997;130:670–4. Gucuyener K, Erdemoglu AK, Senol S, et al. Use of methylphenidate for attention-deficit hyperactivity disorder in patients with epilepsy or electroencephalographic abnormalities. J Child Neurol 2003;18:109–12. Hemmer SA, Pasternak JF, Zecker SG, Trommer BL. Stimulant therapy and seizure risk in children with ADHD. Pediatr Neurol 2001;24:99–102. Hughes CW, Emslie GJ, Crismon ML, et al. The Texas ChildrenÕs Medication Algorithm Project: report of the Texas Consensus Conference Panel on Medication Treatment of Childhood Major Depressive Disorder. J Am Acad Child Adolesc Psychiatry 1999;38:1442–54. Emslie GJ, Rush AJ, Weinberg WA, et al. A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression. Arch Gen Psychiatry 1997;54:1031–7. Wagner KD, Ambrosini P, Rynn M, et al. Efficacy of sertraline in the treatment of children and adolescents with major depressive disorder: two randomized controlled trials. JAMA 2003;290:1033–41. Kanner AM, Kozak AM, Frey M. The use of sertraline in patients with epilepsy: is it safe?. Epilepsy Behav 2000;1:100–5. Miller M, Bakalar J. Should children take antidepressants?. Harv Ment Health Lett 2003;20:5–7. Alldredge BK. Seizure risk associated with psychotropic drugs: clinical and pharmacokinetic considerations. Neurology 1999;53:S68–75.