Medical Journal of Dr. D.Y. Patil Vidyapeeth

REVIEW ARTICLE
Year
: 2015  |  Volume : 8  |  Issue : 4  |  Page : 425--430

Psychiatric aspects of pediatric epilepsy: Focus on anxiety disorder


Sujita Kumar Kar 
 Department of Psychiatry, King George's Medical University, Lucknow, Uttar Pradesh, India

Correspondence Address:
Sujita Kumar Kar
Department of Psychiatry, King George«SQ»s Medical University, Lucknow - 226 003, Uttar Pradesh
India

Abstract

Psychiatric co-morbidities are commonly seen with pediatric epilepsy, which can be in the form of cognitive deficits like - inattention and intellectual disability, motor disturbances like - hyperactivity, emotional disturbances like - depression and anxiety disorders and behavioral problems like - impulsivity, aggression and even psychotic behavior. Anxiety disorders like - Obsessive compulsive disorder, posttraumatic stress disorder, social phobia, separation anxiety disorder, agoraphobia and panic attacks are commonly seen with pediatric epilepsy. Presence of co-morbid anxiety disorder in pediatric epilepsy is responsible for scholastic decline, peer maladjustment and poor quality of life. Management of anxiety disorders in children with epilepsy is always a challenge. Until, there is no general consensus regarding management of anxiety disorders in pediatric epilepsy. Despite its enormous impact on an individual«SQ»s life, this area has not been addressed adequately through clinical research. This review focuses on psychiatric aspects of pediatric epilepsy with specific emphasis on anxiety disorders.



How to cite this article:
Kar SK. Psychiatric aspects of pediatric epilepsy: Focus on anxiety disorder.Med J DY Patil Univ 2015;8:425-430


How to cite this URL:
Kar SK. Psychiatric aspects of pediatric epilepsy: Focus on anxiety disorder. Med J DY Patil Univ [serial online] 2015 [cited 2019 Dec 12 ];8:425-430
Available from: http://www.mjdrdypu.org/text.asp?2015/8/4/425/160777


Full Text

 Introduction



Worldwide, more than 50 million people are suffering from epilepsy, out of which approximately 80% belong to countries deprived of resources. [1],[2] Many of these people were unable to receive treatment due to lack of awareness, stigma, poverty, lack of facility and socio-cultural factors. [1] So epilepsy remains a challenge, in these resource poor countries.

Prevalence of epilepsy in India is comparable with other countries including the western counterparts; [3] however, some studies have mentioned about higher prevalence and incidence of epilepsy in developing countries than developed countries. [4] Infection, particularly neurocysticercosis, is an important cause of epilepsy in developing countries. [4] The outcome of epilepsy is almost similar across the globe. [4] Pediatric epilepsy has a close association with psychiatric disorders. [5],[6] In 50-60% of children with epilepsy, the disorder remit completely by the time they reach their adulthood; however, the risk of psychiatric disorder remains high in comparison to normal healthy population. [7] Hence, it is very important to understand pediatric epilepsy and associated psychiatric disorders in children with epilepsy. Extensive online search of literature had been done using the key words - childhood epilepsy/pediatric epilepsy, anxiety disorders (with individual name of anxiety disorders) in websites like - Google Scholar, PubMed and individual journal sites as well as Google books.

 Epilepsy in Pediatric Population



Epilepsy is a common disorder of the pediatric population. In a study (from Spain), the annual incidence of epilepsy in the pediatric population was found to be 626 per every million population, which is quite similar to the data from other western countries. [8] This study revealed that focal epilepsy is more common in the pediatric population than generalized epilepsy. [8] The prevalence of different sub-types epilepsy varies across age. West syndrome, focal symptomatic epilepsy, focal benign epilepsy and focal cryptogenic epilepsies are the most common variant of epilepsy during infancy, early childhood, school going years and adolescence respectively. [8] Across the life span of a child, the incidence of epilepsy is highest during infancy and declines with increasing age. [8]

In Indian pediatric population, prevalence of epilepsy is comparable with that of developed countries. [9] Neurocysticercosis is found to be an important cause of pediatric epilepsy in India. [6] Indian studies mentioned about some key risk factors of intractable pediatric epilepsy, like - onset of epilepsy at an early age, perinatal brain injuries and neuro-developmental abnormalities. [3],[9],[10] Certain subtypes of seizure also turn into intractable epilepsy. [9] Intractable epilepsy may attributes to more management difficulties, increased risk of polypharmacy, increased financial burden, more adverse drug reaction, more co-morbidity and poor quality of life (QOL).

The European expert opinion survey, 2007; reached the consensus regarding the treatment choices of different subtypes of epilepsy in the pediatric population. [11] Valproate is the drug of choice for most of the pediatric epilepsies. [11] In status epilepticus (complex partial status as well as generalized status), intravenous benzodiazepines are preferred whereas for neonatal status intravenous phenobarbital is considered as the drug of choice. [11]

 Psychiatric Co-morbidities with Pediatric Epilepsy



Psychiatric disorders are commonly found as co-morbidities in pediatric epileptic patients. [5] Bilgiç et al., in their study found that psychiatric disorders are observed more frequently among males in comparison to females. [5] Plioplys et al., in their review studied psychopathology in pediatric epilepsy and found that about 37-77% pediatric patients with epilepsy had some sort of psychopathology; cognitive deficits being the most common one. [12] Another literature review mentions the prevalence of co-morbid psychiatric disorder in pediatric epilepsy to be around 40-50%. [13] Severe form epilepsy in the pediatric population is associated with developmental delay, hyperactivity and features of autism. [12] Otero, in an extensive review analyzed all published papers between 1966 and 2007 in the domain of "Pediatric epilepsy and psychiatric co-morbidities" and concluded that inattention and hyperactivity as common psychopathology associated with pediatric epilepsy, which may be due to direct insult to the brain or attributable to the antiepileptic medications. [14]

Turky et al., in their study found that severity of seizure had positive correlation with the affective symptoms, whereas the cognitive deficit associated with pediatric epilepsy correlate significantly to features of hyperactivity, inattention, disturbances of conduct and relational problem with peer groups. [15]

Russ et al., studied the clinical profile of more than 90,000 children with childhood epilepsy from the National Survey of Children's Health and found that psychiatric disorders like - attention deficit hyperactivity disorder (ADHD), autism spectrum disorder including autism, anxiety disorders, depression, conduct disorder and developmental delay were more frequently associated with children with epilepsy than those without it. [16]

Several studies highlighted ADHD as one of the common psychiatric co-morbidity in childhood epilepsy. [17],[18],[19],[20],[21] The relationship between epilepsy and ADHD in the pediatric population is bidirectional; one increasing the risk of other. [19] Some of the antiepileptic medications like - topiramate, phenobarbital, vigabatrin and gabapentin also have ADHD like side effects. [19] Children with intellectual disability and epilepsy pose higher risk of development of features of ADHD than those with epilepsy alone. [20] Inattention type of ADHD is more commonly seen in patients with childhood epilepsy. [17],[20] Epilepsy related factors like-duration of epilepsy, frequency of seizure and age of onset of the seizure do not have any correlation with the severity of ADHD symptoms. [17] Some specific types of epilepsy like - frontal lobe epilepsy, rolandic epilepsy, childhood absence epilepsy commonly have co-morbid ADHD. [20]

Studies found higher association of autism including autism spectrum disorder in children with epilepsy. [22],[23],[24] However, it is still questionable whether the epileptic electroencephalogram (EEG) changes have any correlation with autism. [22],[23],[24],[25] It is quite possible that the EEG changes due to epilepsy and features of autism are either co-morbid or causative. [25] One of the epilepsy syndromes - Landau-Kleffner Syndrome is associated with features of autism along with features of hyperactivity and aggression. [22],[26]

Features of autism were also seen in patients with Lennox-Gastaut syndrome and Dravet syndrome. [26] Patients with juvenile myoclonic epilepsy, frequently have behavioral problems which may lead to poor social functioning possibly due to dysfunctional frontal lobe. [26]

 Pediatric Epilepsy and Anxiety Disorders



Anxiety and depression are commonly associated with pediatric population with epilepsy and frequently seen in the pubertal age. [16],[27],[28],[29] Russ et al., in their study found the prevalence of anxiety in 17% of patients with childhood epilepsy in contrast to 3% in children without epilepsy. [16] Several studies have highlighted, about the intense effect of anxiety disorders on the QOL in patients with epilepsy. [30],[31],[32] Anxiety disorders in epilepsy can be an ictal, postictal or interictal phenomenon. [30] Ictal anxiety, commonly seen in temporal lobe epilepsy, is a well-understood phenomenon and frequently seen as a part of aura. It may also be seen in frontal lobe epilepsy and may mimic with panic attack. [32] Preictal anxiety is mostly difficult to be diagnosed. [32] Postictal anxiety, commonly presents in the form of worry, apprehension, and may amount to the severity of panic episode. [32] Interictal anxiety is the commonest form of anxiety, which may be explained on the basis of bio-psycho-social model. [32]

The development of anxiety in epilepsy can be explained on the basis of several means like: [30],[31],[32]

Neurobiological factors (epileptic focus causing brain changes, brain damage due to epileptic surgery).Psycho-social factors.Effect of antiepileptic medications.Stevanovic et al., in their study, revealed the enormous impact of depression, generalized anxiety and separation anxiety disorders on the health-related QOL in children and adolescents with epilepsy. [33] Dunn et al., studied the psychopathology in pediatric epilepsy using the tool - Child Symptom Inventory and Adolescent Symptom Inventory; one-third of patients had various anxiety disorders like - specific phobias, obsessions, posttraumatic stress disorder and panic attacks. [34] Some patients also had features suggestive of social phobia, separation anxiety disorder, and generalized anxiety disorder. [34] Rabin et al., in their study on children with epilepsy, explored about different emotional and behavioral problems and concluded that emotional problems are more frequently associated with epilepsy than behavioral problems. [35] In this study, they reported about association of several anxiety disorders (obsessive compulsive disorder [OCD], specific phobia, agoraphobia, separation anxiety disorder and panic disorder) with pediatric epilepsy. [35]

Caplan et al., in their study found that age of the patient, verbal IQ, scholastic problems and type of seizure had a correlation with the diagnosis of anxiety disorder. [29] During clinical exploration, the child may have difficulty in expressing or explaining the anxiety symptoms. Sometimes subjective reporting of anxiety and objective manifestations of restlessness varies. Another difficulty may be due to discrepancy between parental reporting of anxiety with that of child's reporting about anxiety in children with epilepsy as seen in study by Stevanovic et al., which emphasizes to involve both parent and the child in the interview. [36]

Oguz et al., in their study explored about different epilepsy related factors that attribute to anxiety in the pediatric population. [27] They found that factors like - duration of epilepsy, frequency of seizures and numbers of antiepileptic drugs used had positive correlation with anxiety and depression. [27] At the same time, type of seizure, age of onset of seizure and electro-physiologic changes didn't have any correlation with anxiety and depression. [27]

The exact prevalence of different anxiety disorders in children with epilepsy is not known. Williams et al., had studied the prevalence of anxiety symptoms in children with epilepsy and found that mild to moderate anxiety symptoms were associated in about 23% cases of childhood epilepsy. [37] Patients on polypharmacy or having uncontrollable seizure or co-morbid behavioral problems or learning difficulties are likely to manifest more anxiety symptoms. [37],[38] Family stress also contributes to anxiety in children with epilepsy. [38]

Sometimes seizure episodes mimic like panic attacks. Mostly complex partial seizure may simulate an episode of panic attack. [39],[40],[41] Temporal lobe involvement is associated with the panic attacks; [40],[41] the possible reason being - excitation of amygdala, which is an integral part of medial temporal lobe. Amygdala is responsible for processing of fear and anxiety response and is involved in various anxiety disorders. Genton et al., had reported about several cases of epilepsy, who had episodes of panic attacks, which were mistaken as relapse of epilepsy even though the patients had presented with classical panic symptoms. [42] On the contrary, Laidlaw and Khin-Maung-Zaw (1993), had mentioned about misdiagnosis of episode of seizure as panic attack. [43] Hence, clinician must be aware of the co-morbid association of anxiety disorders with epilepsy and should be able to differentiate the panic attack from epilepsy. The focus of clinical evaluation should be on the phenomenology as a whole, rather than an isolated symptom alone, while making the diagnosis.

At times, seizure may also simulate agoraphobia, which may be accompanied with panic attacks, hence these conditions may be considered as the differential diagnosis of epilepsy in children and adolescents. [44]

 Management of Co-morbid Anxiety Disorders in Pediatric Epilepsy



Children with epilepsy with co-morbid psychiatric disorders like - ADHD, depression, and anxiety disorders, have significant compromise in academic performance, social skills leading to deterioration in the QOL. [45] Another important risk of ignoring the treatment of co-morbid anxiety or affective disorders in childhood epilepsy is suicide. [46]

The management goals in pediatric epilepsy with anxiety disorders are - adequate seizure control, optimization of the functioning of the child and keeping the patient in best and simple pharmaco-therapeutic regimen. [6] So far as the management of psychiatric disorders is concerned, the goals are to improve the scholastic functioning of children, psychosocial adjustment, as well as the QOL through pharmacological, psychological and social interventions. [47]

Management of anxiety disorders in children is quite similar to that of adults. [48] However, there are certain limitations, when co-morbid conditions are associated. All pharmaco-therapeutic options cannot be applied in the management of anxiety disorders in pediatric epilepsy due to several limiting factors like:

Age-related limitationsLimitations related to organicity (epilepsy)Limitation related to concurrent use of antiepileptic medications (due to potential risk of drug-drug interaction)Children with epilepsy are more likely to receive polypharmacy for their illness, as they have to take prescribed antiepileptic medications along with medication for anxiety disorder. The clinicians have to keep following important things in consideration while prescribing

Potential side effects of antiepileptic medications.Drug-drug interactions (interaction with antiepileptic drugs and medications used to treat anxiety disorder).Other factors that are likely to affect the outcome (coping skills of the patient, intellectual ability, presence of other co-morbidities, caregiver's attitude, family stress; etc.).The clinician should avoid an antiepileptic drug which is having side effects like behavioral problems. [19] In the management of anxiety disorders in epilepsy, there are some good pharmaco-therapeutic options like - benzodiazepines, selective serotonin reuptake inhibitors (SSRIs) and buspirone. [32],[49],[50] However, the risk of withdrawal seizure and dependence potential restricts benzodiazepines for short-term use or acute management. [32],[50] Serotonin partial agonist - buspirone and SSRIs are good alternatives for long-term management of anxiety disorders in epilepsy. [32],[49] Some antiepileptic medications like - pregabalin and gabapentin also pose anxiolytic property, hence may be considered in the management. [32],[51] However, there are a lot of restrictions regarding the use of SSRIs and other antidepressants in the pediatric population. US Food and Drug Administration approves the use of fluoxetine, sertraline, fluvoxamine and Clomipramine for treatment of OCD in the pediatric population. [52],[53],[54],[55] However, risk of lowering the seizure threshold in pediatric epilepsy, limits the use of clomipramine. Other three drugs have potential interaction (as mentioned below) with antiepileptic drugs, hence selection of appropriate SSRI and appropriate antiepileptic drug, always remains a challenge. There is no clear cut guideline or recommendation of medications for treatment of other anxiety disorders in pediatric population; when there is associated co-morbidity like epilepsy, the challenge becomes immense. In some studies, Venlafaxine is found to be effective in the management of anxiety disorder in youth. [52]

Selective serotonin reuptake inhibitors are safe in patients with epilepsy with co-morbid anxiety and depression. [56] The tricyclic antidepressants need to be avoided for treating anxiety disorders in epilepsy as they reduce the seizure threshold and are epileptogenic. [56],[57],[58],[59] SSRIs increase the level of certain antiepileptic medication by inhibiting their metabolism. [56],[57],[58],[59] Among the SSRIs, fluoxetine, fluvoxamine, paroxetine and sertraline commonly increase the serum level of antiepileptic medications like - carbamazepine and phenytoin. [28],[29],[30],[31] Sertaline also increases the level of lamotrigine. [56],[57],[58],[59] At the same time, antiepileptic medications also affect the serum level of medications used to treat anxiety disorders by interfering with their metabolism. Carbamazepine decreases the level of certain SSRIs like - paroxetine, citalopram, sertraline (?) and benzodiazepines which are commonly used to treat anxiety disorders. [56],[57],[58],[59] Phenytoin and phenobarbital also reduce the level of paroxetine and benzodiazepines. [56]

Other than pharmacotherapy, attempts should also be taken to reduce stigma and family stress, which may be beneficial in the management. [38] The children with epilepsy with co-morbid anxiety disorders need regular monitoring and proper health education. [38]

Cognitive behavior therapy (CBT) is an effective modality of treatment in various anxiety disorders, irrespective of age. [52] It can be tried in patients with pediatric epilepsy with co-morbid anxiety disorders. Jones et al., in their pilot study on children with epilepsy with co-morbid social phobia found that CBT to be effective in reducing the anxiety, improving the self-concept and social skills. [43] However, cognitive impairment and developmental delay associated with pediatric epilepsy may limit the clinical utility of CBT.

 Conclusion



Though a large percentage of patients with pediatric epilepsy do have some sort of psychiatric disorder, very few of them seek or receive mental health treatment. This gap in the management is not due to any isolated reason, rather due to multiple, inter-influencing factors like - lack of parental education and awareness, lack of resources (drugs and other health related facilities) and lack of financial support. [60] Another recent study also agrees to the fact that psychiatric co-morbidities including anxiety disorders are quite high in children and adolescents with epilepsy, and nearly one-third of those who have a diagnosable psychiatric illness receive treatment for it. [61] The future challenge is to fill this perilous gap in management. There is a need for increased awareness of psychiatric disorders as well as epilepsy in the caregivers. The care providers (physicians) should also be able to identify and treat the psychiatric disorders in collaboration with the mental health professionals, which will give a better outcome perspective to the management. Despite high co-morbid association of anxiety disorders with pediatric epilepsy, it is less well researched. There is lack of definite guideline for management of anxiety disorders in pediatric epilepsy. Important research data are lacking in this area, hence this may be a potential area of future research.

References

1Radhakrishnan K. Challenges in the management of epilepsy in resource-poor countries. Nat Rev Neurol 2009;5:323-30.
2Diop AG, de Boer HM, Mandlhate C, Prilipko L, Meinardi H. The global campaign against epilepsy in Africa. Acta Trop 2003;87:149-59.
3Bharucha NE. Epidemiology of epilepsy in India. Epilepsia 2003;44 Suppl 1:9-11.
4Carpio A, Hauser WA. Epilepsy in the developing world. Curr Neurol Neurosci Rep 2009;9:319-26.
5Bilgiç A, Yilmaz S, Tiras S, Deda G, Kiliç EZ. Depression and anxiety symptom severity in a group of children with epilepsy and related factors. Turk Psikiyatri Derg 2006;17:165-72.
6Pellock JM. Understanding co-morbidities affecting children with epilepsy. Neurology 2004;62:S17-23.
7Camfield PR, Camfield CS. What happens to children with epilepsy when they become adults? Some facts and opinions. Pediatr Neurol 2014;51:17-23.
8Durá Travé T, Yoldi Petri ME, Gallinas Victoriano F. Incidence of epilepsy in 0-15 year-olds. An Pediatr (Barc) 2007;67:37-43.
9Udani V. Pediatric epilepsy - An Indian perspective. Indian J Pediatr 2005;72:309-13.
10Gadgil P, Udani V. Pediatric epilepsy: The Indian experience. J Pediatr Neurosci 2011;6:S126-9.
11Wheless JW, Clarke DF, Arzimanoglou A, Carpenter D. Treatment of pediatric epilepsy: European expert opinion, 2007. Epileptic Disord 2007;9:353-412.
12Plioplys S, Dunn DW, Caplan R. 10-year research update review: Psychiatric problems in children with epilepsy. J Am Acad Child Adolesc Psychiatry 2007;46:1389-402.
13Pellock JM. Defining the problem: Psychiatric and behavioral comorbidity in children and adolescents with epilepsy. Epilepsy Behav 2004;5 Suppl 3:S3-9.
14Otero S. Psychopathology and psychological adjustment in children and adolescents with epilepsy. World J Pediatr 2009;5:12-7.
15Turky A, Beavis JM, Thapar AK, Kerr MP. Psychopathology in children and adolescents with epilepsy: An investigation of predictive variables. Epilepsy Behav 2008;12:136-44.
16Russ SA, Larson K, Halfon N. A national profile of childhood epilepsy and seizure disorder. Pediatrics 2012;129:256-64.
17Sherman EM, Slick DJ, Connolly MB, Eyrl KL. ADHD, neurological correlates and health-related quality of life in severe pediatric epilepsy. Epilepsia 2007;48:1083-91.
18Dunn DW, Austin JK, Harezlak J, Ambrosius WT. ADHD and epilepsy in childhood. Dev Med Child Neurol 2003;45:50-4.
19Hamoda HM, Guild DJ, Gumlak S, Travers BH, Gonzalez-Heydrich J. Association between attention-deficit/hyperactivity disorder and epilepsy in pediatric populations. Expert Rev Neurother 2009;9:1747-54.
20Reilly CJ. Attention deficit hyperactivity disorder (ADHD) in childhood epilepsy. Res Dev Disabil 2011;32:883-93.
21Parisi P, Moavero R, Verrotti A, Curatolo P. Attention deficit hyperactivity disorder in children with epilepsy. Brain Dev 2010;32:10-6.
22Rapin I. Autistic regression and disintegrative disorder: How important the role of epilepsy? Semin Pediatr Neurol 1995;2:278-85.
23Nass R, Gross A, Devinsky O. Autism and autistic epileptiform regression with occipital spikes. Dev Med Child Neurol 1998;40:453-8.
24Deonna T, Roulet E. Autistic spectrum disorder: Evaluating a possible contributing or causal role of epilepsy. Epilepsia 2006;47 Suppl 2:79-82.
25Levisohn PM. The autism-epilepsy connection. Epilepsia 2007;48 Suppl 9:33-5.
26Besag FM. Behavioral aspects of pediatric epilepsy syndromes. Epilepsy Behav 2004;5 Suppl 1:S3-13.
27Oguz 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.
28Franks RP. Psychiatric issues of childhood seizure disorders. Child Adolesc Psychiatr Clin N Am 2003;12:551-65.
29Caplan R, Siddarth P, Gurbani S, Hanson R, Sankar R, Shields WD. Depression and anxiety disorders in pediatric epilepsy. Epilepsia 2005;46:720-30.
30Beyenburg S, Mitchell AJ, Schmidt D, Elger CE, Reuber M. Anxiety in patients with epilepsy: Systematic review and suggestions for clinical management. Epilepsy Behav 2005;7:161-71.
31Beyenburg S, Schmidt D. Patients with epilepsy and anxiety disorders. Diagnosis and treatment. Nervenarzt 2005;76:1077-8, 1081.
32Kimiskidis VK, Valeta T. Epilepsy and anxiety: Epidemiology, classification, aetiology, and treatment. Epileptic Disord 2012;14:248-56.
33Stevanovic D, Jancic J, Lakic A. The impact of depression and anxiety disorder symptoms on the health-related quality of life of children and adolescents with epilepsy. Epilepsia 2011;52:e75-8.
34Dunn DW, Austin JK, Perkins SM. Prevalence of psychopathology in childhood epilepsy: Categorical and dimensional measures. Dev Med Child Neurol 2009;51:364-72.
35Rabin F, Mullick SI, Nahar JS, Bhuiyan SI, Haque MA, Khan MH, et al. Emotional and behavioral disorders in children with epilepsy. Mymensingh Med J 2013;22:313-9.
36Stevanovic D, Jancic J, Topalovic M, Tadic I. Agreement between children and parents when reporting anxiety and depressive symptoms in pediatric epilepsy. Epilepsy Behav 2012;25:141-4.
37Williams J, Steel C, Sharp GB, DelosReyes E, Phillips T, Bates S, et al. Anxiety in children with epilepsy. Epilepsy Behav 2003;4:729-32.
38Adewuya AO, Ola BA. Prevalence of and risk factors for anxiety and depressive disorders in Nigerian adolescents with epilepsy. Epilepsy Behav 2005;6:342-7.
39Stolle M, Sieben C, Püst B. Panic attacks simulated by occipital lobe seizures. Z Kinder Jugendpsychiatr Psychother 2009;37:203-7.
40Pegna C, Perri A, Lenti C. Panic disorder or temporal lobe epilepsy: A diagnostic problem in an adolescent girl. Eur Child Adolesc Psychiatry 1999;8:237-9.
41Scalise A, Placidi F, Diomedi M, De Simone R, Gigli GL. Panic disorder or epilepsy? A case report. J Neurol Sci 2006;246:173-5.
42Genton P, Bartolomei F, Guerrini R. Panic attacks mistaken for relapse of epilepsy. Epilepsia 1995;36:48-51.
43Laidlaw JD, Khin-Maung-Zaw. Epilepsy mistaken for panic attacks in an adolescent girl. BMJ 1993;306:709-10.
44Lee DO, Helmers SL, Steingard RJ, DeMaso DR. Case study: Seizure disorder presenting as panic disorder with agoraphobia. J Am Acad Child Adolesc Psychiatry 1997;36:1295-8.
45Jones JE. Treating anxiety disorders in children and adolescents with epilepsy: What do we know? Epilepsy Behav 2014;39:137-42.
46Ekinci O, Titus JB, Rodopman AA, Berkem M, Trevathan E. Depression and anxiety in children and adolescents with epilepsy: Prevalence, risk factors, and treatment. Epilepsy Behav 2009;14:8-18.
47Bujoreanu IS, Ibeziako P, Demaso DR. Psychiatric concerns in pediatric epilepsy. Pediatr Clin North Am 2011;58:973-88, xii.
48Taylor D, Paton C, Kapur S. The Maudsley Prescribing Guidelines in Psychiatry. 11 th ed. UK: Wiley-Blackwell; 2012. p. 327-8.
49Harden CL, Goldstein MA, Ettinger AB. Anxiety disorders in epilepsy. In: Ettinger AB, Kanner AM, editors. Psychiatric Issues in Epilepsy: A Practical Guide to Diagnosis and Treatment. Philadelphia: Wolters Kluwer-Lippincott Williams & Wilkins; 2007. p. 248-63.
50Gaitatzis A, Trimble MR, Sander JW. The psychiatric comorbidity of epilepsy. Acta Neurol Scand 2004;110:207-20.
51Mula M, Pini S, Cassano GB. The role of anticonvulsant drugs in anxiety disorders: A critical review of the evidence. J Clin Psychopharmacol 2007;27:263-72.
52Kodish I, Rockhill C, Varley C. Pharmacotherapy for anxiety disorders in children and adolescents. Dialogues Clin Neurosci 2011;13:439-52.
53Rynn M, Puliafico A, Heleniak C, Rikhi P, Ghalib K, Vidair H. Advances in pharmacotherapy for pediatric anxiety disorders. Depress Anxiety 2011;28:76-87.
54Ipser JC, Stein DJ, Hawkridge S, Hoppe L. Pharmacotherapy for anxiety disorders in children and adolescents. Cochrane Database Syst Rev 2009;Jul 8;(3):CD005170.
55Questions and Answers on Antidepressant Use in Children, Adolescents, and Adults. U.S. Food and Drug Administration. Available from: http://www.fda.gov/drugs/drugsafety/informationbydrugclass/ucm096305.htm. [Last accessed on 2015 Jan 31].
56Taylor D, Paton C, Kapur S. The Maudsley Prescribing Guidelines in Psychiatry. 11 th ed. UK: Wiley-Blackwell; 2012. p. 420-30.
57BMJ Group & Pharmaceutical. British National Formulary. 61 st ed. London: BMJ Group & Pharmaceutical Press; 2011.
58Schmitz B. Antidepressant drugs: Indications and guidelines for use in epilepsy. Epilepsia 2002;43 Suppl 2:14-8.
59Stockley's Drug Interactions. Available from: http://www.medicinescomplete.com. [Last accessed on 2014 Nov 12].
60Ott D, Siddarth P, Gurbani S, Koh S, Tournay A, Shields WD, et al. Behavioral disorders in pediatric epilepsy: Unmet psychiatric need. Epilepsia 2003;44:591-7.
61Caplan R, Siddarth P, Stahl L, Lanphier E, Vona P, Gurbani S, et al. Childhood absence epilepsy: Behavioral, cognitive, and linguistic comorbidities. Epilepsia 2008;49:1838-46.