Psychiatric comorbidity in adult patients with idiopathic generalized epilepsy

Psychiatric comorbidity in adult patients with idiopathic generalized epilepsy

Available online at www.sciencedirect.com Epilepsy & Behavior 13 (2008) 248–251 www.elsevier.com/locate/yebeh Brief Communication Psychiatric comor...

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Available online at www.sciencedirect.com

Epilepsy & Behavior 13 (2008) 248–251 www.elsevier.com/locate/yebeh

Brief Communication

Psychiatric comorbidity in adult patients with idiopathic generalized epilepsy Nozomi Akanuma a,b,c,*, Eriko Hara b,d, Naoto Adachi e, Koichiro Hara f, Michael Koutroumanidis b a Lambeth Rehabilitation Services, South London & Maudsley NHS Foundation Trust, London, UK Department of Clinical Neurophysiology and Epilepsies, Guy’s & St. Thomas’ NHS Foundation Trust, London, UK c Department of Clinical Neuroscience, Institute of Psychiatry, King’s College London, London, UK d Psychiatry and Behavioral Science, Tokyo Medical and Dental University Graduate School, Tokyo, Japan e Adachi Mental Clinic, Sapporo, Japan f Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, London, UK

b

Received 20 September 2007; revised 10 December 2007; accepted 15 January 2008 Available online 18 March 2008

Abstract We reviewed the medical records of 157 adult (P18 years) patients with firmly diagnosed idiopathic generalized epilepsy (IGE) to investigate the extent and the type of psychiatric comorbidity and its relationship to various IGE syndromes and other epilepsy-related neurobiological factors. Forty-one patients (26.1%, 14 men and 27 women, median age: 34.0 years, range: 18–68, mean: 36.5) had comorbid mental disorders according to the 10th revision of the International Classification of Diseases (ICD-10) criteria, with four patients having a dual diagnosis. Mood disorders were the most common comorbid mental disorder (46.7%), followed by anxiety–panic disorder (26.7%). Comorbid psychiatric disorders occurred in all syndromes and in association with all seizure types, and, as in focal epilepsies, seizure control was significantly better in patients without psychiatric comorbidity (40.5% vs 19.5%, v2(1) = 5.873, P = 0.015). Ó 2008 Elsevier Inc. All rights reserved. Keywords: Epilepsy; Idiopathic generalized epilepsy; Psychiatric disorders; Comorbidity; Neuropsychiatry

1. Introduction Patients with idiopathic generalized epilepsy (IGE) are usually considered to have a favorable prognosis without intellectual or behavioral impairment. However, several investigators have reported a variably increased incidence of psychiatric symptoms in patients with IGE [1–4]; for example, up to one-third of patients with adult-onset IGE are diagnosed and treated for mental disorders [1]. Recent reports have shown a high prevalence of psychiatric comorbidity in patients with juvenile myoclonic epilepsy (JME)

[2,3], but there are no reports on other syndromes, including those recognized by the International League Against Epilepsy (ILAE), such as juvenile absence epilepsy (JAE) or IGE with generalized tonic–clonic seizures only [5,6]. To investigate the extent and the type of psychiatric comorbidity, its possible effect on seizure outcome, and its relationship to various IGE syndromes and other epilepsy-related neurobiological factors, such as seizure type and photosensitivity, we carried out an exploratory, retrospective study in a large cohort of patients, in whom the diagnosis of IGE was confirmed on clinical and video/EEG grounds. 2. Patients and methods

*

Corresponding author. Address: Lambeth Rehabilitation Services, South London & Maudsley NHS Foundation Trust, 308/312 Brixton Road, London SW9 6AA, UK. Fax: +44 20 3228 7001. E-mail address: [email protected] (N. Akanuma). 1525-5050/$ - see front matter Ó 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2008.01.006

We reviewed the medical records of all patients with IGE aged 18 years and older, who were consecutively referred to and followed up in the epilepsy clinic of St. Thomas’ Hospital in London between January 1990 and

N. Akanuma et al. / Epilepsy & Behavior 13 (2008) 248–251 December 2004 to find those with a psychiatric diagnosis. The diagnosis of IGE is based on the official clinical and EEG diagnostic criteria set by the ILAE [5,6]. Our clinical and EEG methodology on syndromic diagnosis and classification of IGEs has been detailed elsewhere [7]. When syndromic diagnosis by strict and straightforward electroclinical criteria is not possible, we attempt a seizure symptom categorization and note important neurobiological factors such as photosensitivity, tendency for status, and focal symptoms. Patients are not only prospectively studied, but also retrospectively investigated through old medical notes and past EEG reports or actual tracings to better characterize their epilepsy and understand its natural history. For the purpose of this article, we reviewed and evaluated the age at onset and duration of epilepsy, seizure types, IGE subsyndromes, and outcome of seizure control. Satisfactory seizure control was defined as no seizures of any type for at least 1 year from last follow-up, and such patients were classified as seizure-free. Follow-up periods shorter than 2 years were deemed insufficient for reliable definition of outcome; therefore, patients with IGE falling into this category were excluded from the analysis. Psychiatric diagnoses were made in accordance with the 10th revision of the International Classification of Diseases (ICD-10). For the patients reviewed or seen for the first time during the last 5 years, psychiatric diagnoses were made after clinical interviews with the qualified neuropsychiatrists on our team (N.A. and E.H.), whereas for the few remaining patients whose last clinical follow-up was before 2000, psychiatric diagnoses were based on past medical correspondence and previous hospital or community psychiatric reviews. Data analyses were performed using SPSS 14.0 (SPSS Inc., Chicago, IL, USA). Linear demographic characteristics were compared using the t test. Nominal clinical characteristics were analyzed with the v2 test with Yates’ correction or Fisher’s exact test. Statistical significance was set at P < 0.05.

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were seizure-free and 102 were not seizure-free. Fifty patients had a family history of epilepsy. Forty-one patients (26.1%, 14 men and 27 women, median age: 34.0 years, range: 18–68, mean: 36.5) had comorbid mental disorders according to ICD-10 criteria, with four patients having a dual diagnosis (Table 1). Mood disorders were found to be the most common comorbid psychiatric condition (21 of all 157 patients with IGE, 13.4%; 21 of all 41 patients with IGE with mental disorders, 46.7%), with neurotic, stress-related, and somatoform disorders being the second (12/157, 7.6%; 12/41, 26.7%). Psychiatric comorbidity was noted in all IGE syndromes without significant difference between the groups (P = 0.763, exact test) (Table 1 and Fig. 1). Only 17 patients (41.5%) had received psychotropic medication or psychotherapeutic interventions for their psychiatric conditions. The rate of seizure freedom was significantly higher in patients without psychiatric comorbidity (47/116, 40.5%) than in those with psychiatric comorbidity (8/41, 19.5%; v2(1) = 5.873, P = 0.015). There was no association between psychiatric comorbidity and gender, age at epilepsy onset, duration of epilepsy, duration of follow-up, or family history of epilepsy (Table 2). In addition, psychiatric comorbidity was not significantly associated with photosensitivity or different types of seizures such as absence, myoclonus, and generalized tonic–clonic seizures (Table 2).

3. Results 4. Discussion We enrolled 157 patients (52 men and 105 women, median age: 31.0 years, range: 18–72, mean: 35.0) with electroclinically confirmed IGE and complete medical records. Numbers of patients by IGE syndrome are given in Table 1. The median age at epilepsy onset was 12.0 years (range: 1–56, mean: 13.2), median disease duration was 20.0 years (range: 2–55, mean: 21.8), and median follow-up period was 15.0 years (range: 2–52, mean: 18.0). Fifty-five patients

Among 157 patients with an electroclinically confirmed diagnosis of IGE and long follow-up, 41 (26.1%) had comorbid mental disorders; this overall rate is well within the range shown by community-based studies [8] and similar to that of a recent report on adult-onset IGE demonstrating that one-third of patients were diagnosed and treated for mental disorders [1].

Table 1 Numbers of patients diagnosed with mental disorders as a function of IGEa syndrome

N Mental disorders (+) ICD-10 categories F1x. Substance use disorders F2x. Schizophrenia spectrum disorders F3x. Mood disorders F4x. Neurotic disorders F6x. Personality disorders F9x. Behavioral and emotional disorders a

JME

JAE

JMAE

GTCS only

CAE

Phantom absencesb

EMA

PMA

Reflex epilepsy

IGE, un-classified

N

43 10

24 8

3 1

15 4

8 0

19 4

12 4

7 1

7 2

19 7

157 41

1 6c 2d 3c,d 1

1 4e 3e 1

1

3 1

1 1 1 1

1 2f 1f 1

2

4 2 1

1 2 21*1 12*2 7*3 2

IGE, idiopathic generalized epilepsy, ICD-10, the 10th revision of the International Classification of Diseases; JME, juvenile myoclonic epilepsy; JAE, juvenile absence epilepsy; JMAE, juvenile myoclonic and absence epilepsy; GTCS only, IGE with generalized tonic–clonic seizures only; CAE, childhood absence epilepsy; EMA, eyelid myoclonia with absences; PMA; perioral myoclonia with absences. b Reported in Ref. [14]. c–f Individual patients with dual diagnosis: *1: two patients with dual diagnosis, *2: three patients with dual diagnosis, *3: three patients with dual diagnosis.

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N. Akanuma et al. / Epilepsy & Behavior 13 (2008) 248–251

Fig. 1. Numbers of patients with comorbid mental disorders by IGE syndrome (n = 157). Forty-one patients (26.1%) had a comorbid mental disorder, with 4 patients with dual diagnosis. JME, juvenile myoclonic epilepsy; JAE, juvenile absence epilepsy; JMAE, juvenile myoclonic and absence epilepsy; GTCS only, IGE with generalized tonic–clonic seizures only; CAE, childhood absence epilepsy; EMA, eyelid myoclonia with absences; PMA; perioral myoclonia with absences.

Table 2 Demographic and epilepsy-related characteristics of patients with idiopathic generalized epilepsy with and without comorbid mental disorders

N Gender (men/women) Age at epilepsy onset Duration of epilepsy (years) Duration of follow-up (years) Outcome (seizure-free/non-seizure-free) Family history of epilepsy (presence/absence) Photosensitivity (presence/absence) Absence (presence/absence) Myoclonus (presence/absence) Generalized tonic–clonic seizures (presence/absence) a

Patients with comorbidity

Patients without comorbidity

Statistic

P value

41 14/27 14.0 (9.9)a 22.5 (12.2) 19.4 (11.6) 8/33 16/25 19/22 27/14 18/23 39/2

116 38/78 13.0 (9.8) 21.5 (13.0) 17.5 (11.1) 47/69 34/82 43/73 91/25 48/68 107/9

v2(1) = 0.026 t(155) = 0.584 t(155) = 0.435 t(155) = 0.946 v2(1) = 5.873 v2(1) = 1.317 v2(1) = 1.090 v2(1) = 2.574 v2(1) = 0.079 v2(1) = 0.386

0.871 0.560 0.664 0.346 0.015 0.251 0.296 0.109 0.778 0.535

Mean (SD).

The most significant finding of our study is that psychiatric comorbidity occurs in all IGE syndromes and in association with all seizure types (absences, myoclonic seizures, and generalized tonic–clonic seizures) without any significant correlation with a particular syndrome or seizure type. To our knowledge, this is the first observational study of psychiatric comorbidity across the full range of IGE syndromes diagnosed using clinical and video/EEG studies. Indeed, most prospective and retrospective studies have explored psychiatric comorbidity and relevant psychosocial characteristics in patients with JME, reporting rates ranging from 26.5% [4], a rate certainly close to our own JME rate of 23.3%, to 35–47% [2,3]. Such relatively wide discrepancies in the rates of psychiatric comorbidity in patients with JME may relate to different study designs and psychiatric diagnostic methodologies: prospective versus retrospective design; structured interviews versus clinical interviews and observations; DSM-IV versus ICD-10 criteria. Indeed, different patterns of under- and overdiagnosis of structural interviews against clinicians’ diagnoses have been reported [9]. Investigators’ diagnostic criteria for IGE syndromes may also differ, affecting significantly

syndromic classification and, therefore, the relevant prevalence. Despite the robust and universally accepted ILAE diagnostic criteria for JME (and its 50-year-old continuous presence in the international neurological literature), there may be different interpretations of the same phenotype: for example, patients with brief absences and myoclonic jerks may be classified as having JAE or JME, or even intermediate phenotypes, as we did with some patients in whom neither seizure type clearly predominated. Despite these differences, all studies suggest that psychiatric and psychosocial problems are not uncommon in persons with IGE and its subclassifications. Another important finding of our study is that psychiatric comorbidity was significantly associated with poor seizure control, an association that has been known to exist in focal epilepsies [10,11]. A community-based study in patients with various types of epilepsies also showed that poorly controlled seizures, regardless of seizure type, were associated with an increased rate of comorbid depression, anxiety, and psychosocial dysfunction [12]. Iatrogenic consequences, such as polypharmacy and adverse effects of antiepileptic drugs, and psychosocial factors related to seizure intractabil-

N. Akanuma et al. / Epilepsy & Behavior 13 (2008) 248–251

ity, including unemployment, poor social support, and stigmatization, may lead to the emergence of comorbid mental disorders; on the other hand, psychiatric comorbidity may adversely influence compliance and capability to avoid seizure precipitants through a negative attitude. Among various psychiatric disturbances, mood disorders were found to be the most common comorbid psychiatric disorder (46.7%), with anxiety–panic disorder being the second (26.7%). Some patients with IGE exhibit characteristic personality traits, such as a lack of self-control, impressionability, and emotional lability [13], that may make them prone to mental health and behavioral problems. There are limitations to our study. Our sample size did not allow us to carry out analysis in IGE subclassifications. A selection bias toward patients with intractable, complex IGE in our tertiary epilepsy clinic may not be negligible. A lack of control groups, such as patients with other epilepsies or other chronic neurological conditions, or nonclinical populations, should be noted. Notwithstanding these shortcomings, our retrospective study demonstrates that psychiatric disturbances in patients with IGE are not uncommon, occur in all IGE syndromes and not only in JME, and may be associated with poorer seizure control. Despite the overall relatively more favorable seizure control outcome and the preserved intellectual function, comorbid mental disorders need to be taken into consideration for holistic management and optimal treatment of patients with IGE. References [1] Cutting S, Lauchheimer A, Barr W, Devinsky O. Adult-onset idiopathic generalized epilepsy: clinical and behavioral features. Epilepsia 2001;42:1395–8.

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