Seizure (2007) 16, 586—592
www.elsevier.com/locate/yseiz
Psychiatric events in epilepsy Cesare Maria Cornaggia a, Massimiliano Beghi a, Ettore Beghi b,c,* for the REST-1 Group1 a
Clinical Psychiatry, University of Milano Bicocca, V. Cadore 48, 20052 Monza, Milan, Italy Department of Neuroscience, University of Milano Bicocca, V. Cadore 48, 20052 Monza, Milan, Italy c Institute ‘‘Mario Negri’’, V. Eritrea 62, 20157 Milan, Italy b
Received 15 November 2006; received in revised form 13 April 2007; accepted 26 April 2007
KEYWORDS Psychiatric; Epilepsy; Depression; Anxiety; Case—control
Summary Psychiatric events are thought to be more frequent in people with epileptic seizures than in the general population. However, inter-ictal psychiatric events attributable to epilepsy remain controversial. The aim of the present study was to evaluate the occurrence of psychiatric events in a population of fairly unselected patients with epilepsy and in the general population, and the correlation between psychiatric complaints and selected demographic and disease characteristics. The survey was part of a multicentre prospective cohort study of everyday life risks conducted in eight European countries and comparing referral children and adults with epilepsy referred to secondary/tertiary centers to age- and sex-matched nonepileptic controls. Nine hundred and fifty-one patients with epilepsy and 909 controls were studied. Each patient and his/her control received a diary to record any accident or illness, with severity, circumstances, causes, consequences, and (for the cases) the possible relation to a seizure. The follow-up period ranged between 1 and 2 years. Fifty-eight psychiatric events occurred in 25 patients (2.6%) and 88 in 19 controls (2.1%). Housewives (9.3%) and unemployed persons (4.1%) were mostly affected. No correlation was found between psychiatric events, demographic and disease characteristics. Our results suggest that people with epilepsy if unselected are not at higher risk for psychiatric disorders than the general population. # 2007 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Introduction
* Corresponding author at: Istituto di Ricerche, Farmacologiche ‘‘Mario Negri’’, Via Eritrea 62, 20157 Milano, Italy. Tel.: +39 02 39014542; fax: +39 02 33200231. E-mail address:
[email protected] (E. Beghi). 1 See Appendix A.
Psychiatric events are frequently reported to be more frequent in people with epilepsy than in the general population1—3 and they tend to affect health-related quality of life.4,5 The risk of suicide is supposed to exceed that of the general population.6,7 Psychiatric events in patients with epilepsy are classified taking in account their correlation
1059-1311/$ — see front matter # 2007 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.seizure.2007.04.006
Psychiatric events in epilepsy with seizure timing (pre-ictal, ictal, post-ictal, interictal). The real prevalence of inter-ictal psychiatric events remains controversial and difficult to define for several reasons. The studied populations (mostly recruited in secondary and tertiary centers) are heterogeneous.8 Although the definition of psychiatric illness is uniform,9,10 the diagnostic criteria, whether clinical or instrumental, are not consistent across studies. Psychiatric events may precede, concur with or follow a diagnosis of epilepsy and usually differ between children and adults.5 Depression and anxiety seem to be the most frequent psychiatric events in epilepsy.3,6 Specific childhood comorbidities include attention deficit hyperactivity disorder (ADHD), autism and developmental disabilities. By contrast, psychoses are less common in children than in adults.5 Some comorbid conditions, like depression and anxiety, are evenly distributed in children and adults with epilepsy.2,5,11 Most psychiatric disturbances are predominant in people with drug-resistant epilepsy2,12,13 and temporal lobe epilepsy,12,14 with/without associated neurological or mental abnormalities5,15 and psychosocial problems.16 However, some authors suggest that epilepsy not associated with other relevant disturbance or handicap does not carry a higher risk of psychiatric disorders17 and/or suicide,18 and there are no differences in the psychiatric risk between epilepsy and other chronic conditions.19,20 The aim of the present study was to evaluate the occurrence of psychiatric events in a fairly unselected population of patients with epilepsy compared to the general population, and the correlation between psychiatric comorbidity and patients’ and disease characteristics.
Material and methods The investigation was conducted in eight European countries: Italy, Germany, Holland, England, Portugal, Russia, Estonia and Slovenia. This collaboration was required to recruit a large sample of patients in a short time and to compare different socio-cultural situations. The participants included university and general hospitals with experience, technology and qualification for the management of children and adults with epilepsy. More details of the study methods and design are given elsewhere and are only summarized here.21 To limit an overrepresentation of more severe epilepsy varieties (most common in secondary and tertiary centers), we recruited mostly subjects with epilepsy diagnosed in the participating centers during the previous 5 years and excluded patients diagnosed >10 years before admission. Age (5 years) and sex-matched
587 controls were selected from the same social class (relatives or friends). Patients and controls were given daily diaries to record details about any medical event (illness or accident) occurring during the study period. Medical events were recorded with type and severity, causes and circumstances, and medical interventions and actions. Patients and controls were invited for monthly telephone contacts and quarterly visits, to check compliance and improve the quality and completeness of the recordings. At the time of each visit, the local investigators completed ad hoc summary forms including demographics and, for patients with epilepsy, the main clinical features and the course of the disease (i.e. seizure recurrence), treatments and any treatment changes, and adverse treatment events. When present, concurrent illnesses and disabilities were recorded both in patients with epilepsy and in matched controls. Disability was defined as a physical or psychological problem receiving help from public or private agencies, including hospital, school and employment. In patients with epilepsy, seizures and underlying syndromes were classified according to standard criteria.22,23 Concurrent illnesses and medical events included psychiatric disorders. Where possible, each psychiatric event was coded with reference to the ICD-9 codes.9 The study started in June 1993; recruitment was completed on 30 June 1996 and the follow-up on 30 June 1997. The follow-up ranged between 1 and 2 years for each individual. The x2-test was used, to compare the demographic characteristics of the cases and controls and the number of psychiatric events in the two groups, and to correlate the events to the main demographic and disease features. The results were processed by using the SPSS statistical package.
Results Population profile A sample of 951 patients with epilepsy and 909 matched controls were recruited. The mean follow-up period was 17.4 months for the cases and 17.2 months for the controls. Eighty-seven cases and 69 controls were from Germany, 128 and 117 from Holland, 18 and 17 from England, 281 and 272 from Italy, 96 and 93 from Portugal, 235 and 236 from Russia, 90 and 90 from Estonia, 16 and 15 from Slovenia. The sample included 498 male and 453 female patients with epilepsy and 463 male and 446 female controls preferably aged 15—24 years (35% of cases
588
C.M. Cornaggia et al.
and 34% of controls); 58% of cases and 60% of controls had a basic education, 41% of cases and 46% of controls were students and 73% of cases and 71% of controls were not married. More controls than cases held a driving license (43% versus 31%). The demographic variables of the sample are summarised in Table 1. The characteristics of the epilepsies are summarised in Table 2: 55% of patients had partial and 37% had generalized epilepsy. The length of illness was 3 years or longer in 70% of cases and seizure frequency was less than one in 6 months in almost one-third of cases.
Psychiatric events Fifty-eight psychiatric events occurred in 25 patients (2.6%) and 88 in 19 controls (2.1%). The Table 1 Demographic characteristics of the sample (951 cases, 909 controls) Variable
Patients with epilepsy
Controls
N
%
N
%
Sex M F
498 453
52 48
463 446
51 49
Age <15 15—24 25—34 35
233 337 174 207
24 35 19 22
231 308 175 195
25 34 19 22
Education No education Basic Pre-university University Special school Not specified
13 553 277 66 42 —
2 58 29 7 4 —
7 545 252 91 13 1
1 60 28 10 1 —
Marital status Not married Married Divorced Widowed
666 260 15 10
70 27 2 1
617 270 18 4
68 30 2 <1
Driving licence Associated illnesses Associated disabilities
298 282 123
31 30 13
395 159 15
43 17 2
Occupation Student Skilled worker Unskilled worker Unemployed Pensioner Housewife Trainee Other
390 176 151 98 59 55 17 5
41 18 16 10 6 6 2 1
413 199 129 72 48 25 5 18
45 22 14 8 5 3 1 2
Table 2
Type of epilepsy in 951 cases
Variable
N
%
Partial Cryptogenic Symptomatic Idiopathic Undetermined
490 184 190 55 61
55 21 21 6 7
Generalized Idiopathic Symptomatic/cryptogenic Undetermined
331 252 42 37
37 28 5 4
Undetermined Special Unclassifiable Seizures in the last 2 years
57 17 4 790
8 — — 83
Disease duration (years) 1 1—2 3—5 6
151 133 330 332
16 14 35 35
Seizure frequency None <1/6 months <1 per month <1 per week <1 per day Daily
161 293 213 158 72 54
17 31 22 17 7 6
Timing Day Night Both
603 130 194
65 14 21
clinical characteristics of these events are summarised in Tables 3a and 3b. The prevalence of psychiatric events was not significantly higher in cases compared to controls. Psychiatric events were often mild; affective or anxiety events were largely predominant. Ten patients (40%) and five controls (26%) did not require medication or psychotheraphy. Hospital admission was required only for one patient (suicide attempt) and one control (depression). Days off work were 462 in six patients with epilepsy (350 for one patient) and 249 in six controls. The frequency of psychiatric events varied among countries (Tables 3a and 3b), Portugal having the highest rates and Eastern European Countries the lowest rates. Most psychiatric events were present in housewives (9.3%) and unemployed persons (4.1%). No correlation was found between psychiatric disturbances, and demographic characteristics both in patients with epilepsy and in controls. The disease characteristics were also unrelated to psychiatric comorbidity.
Psychiatric events in epilepsy
589
Table 3a Demographic and clinical characteristics of patients with epilepsy with psychiatric illness No.
Sex
Age
Country
Psychiatric event
1
M
36
Holland
Insomnia
2
F
29
Holland
Depression Anxiety
3 4 5 6 7 8 9 10 11 12 13 14 15 16
M F F M M F F M F F F F F F
44 27 44 42 72 23 16 30 20 8 32 28 61 52
England Italy Italy Italy Italy Italy Italy Italy Italy Italy Italy Portugal Portugal Portugal
17
M
27
18 19 20 21 22 23
M F F F F M
24 25
Episodes N
Specific therapy
Hospital admission
Days off-work
Type of epilepsy
3
Yes
—
25
P crypt
15 1
Yes Yes
— —
350 —
P ns
Anxiety Depression Depression Insomnia Depression Panic attack Depression Depression Anxiety Anxiety Anxiety Anxiety Anxiety Depression
1 1 1 1 1 1 2 1 1 1 1 3 5 6
No Yes Yes No Yes No No No Yes No No Yes Yes Yes
— — — — — — — — — — — — — —
— — — — — — 1 — — — — — — 60
P ns P symp P idiop G ns P symp P crypt G idiop P crypt P ns G idiop P ns P crypt U P crypt
Portugal
Depression Anxiety
1 1
Yes Yes
— —
— —
G idiop
46 34 20 26 17 15
Portugal Portugal Portugal Portugal Portugal Portugal
Anxiety Depression Anxiety Anxiety Anxiety Anxiety
1 2 1 1 1 1
Yes Yes Yes No No Yes
— — — — — —
— 21 — — — —
ns P symp P crypt P symp ns G idiop
F
15
Russia
Depression Suicide attempt
1 1
Yes
+ (60 days)
? ?
U
M
6
Estonia
Aggressiveness
2
No
—
15
Special
P: partial, G: generalized, crypt: cryptogenic, idiop: idiopathic, symp: sympthomatic, ns: not specified, U: undetermined, M: male, F: female.
Discussion In several reports, the prevalence of psychiatric disorders is significantly higher in people with epilepsy than in the general population.1—3 However, when people with epilepsy associated with mental or neurological handicaps are excluded, this difference tends to decrease significantly. In our sample, subjects with psychiatric events were fewer than usually reported in the general population,10,24 and in most cases they tended to be mild, as hospital admission and work abstention were recorded only in rare instances. The difference may be partly explained by the different definitions of psychiatric complaints. Here, we considered only patients requiring medical attention for their psychiatric discomfort. Psychiatric events were only based on self-reports in diaries: therefore, depressive episodes might be underreported and underestimated, although the underestimation
is expected to be equally distributed among both groups. By contrast, others screened psychiatric comorbidity with validated questionnaires and/or rating scales, which specificity, where assessed, is fairly low25,26 and complaints having doubtful clinical significance may have been included. Another possible interpretation of our findings is the study population. In contrast to other series (focusing on fairly selected referral populations) we tried to enroll patients who could better represent the patients with epilepsy usually seen in clinical practice. On this basis, our results may be more reasonably applied to people with epilepsy from the general population. Although the number of cases with psychiatric events was higher in patients than in controls (25 versus 19), this difference was not statistically significant. On the other hand, the total number of events was higher in the controls than in the cases
590
C.M. Cornaggia et al.
Table 3b Demographic and clinical characteristics of controls with psychiatric illness No.
Sex
Age
Country
Psychiatric event
Episodes N
Specific therapy
Hospital admission
Days off-work
1 2 3 4
F M F F
34 53 56 21
Holland Holland Holland Holland
Depression Depression Behavioural disorder Depression
6 2 1 13
Yes Yes No Yes (psychotherapy)
— — — +
30 — 10 131
5
F
40
England
Depression Panic attack
Yes Yes
—
—
6 7 8 9 10
M F M F F
54 29 47 21 44
Italy Italy Italy Italy Italy
Depression Depression Anxiety Anxiety Anxiety
1 1 17 1 6
No Yes Yes (psychotherapy) No Yes
— — — — —
30 — — — —
11
F
27
Italy
Anxiety Insomnia
17 1
No No
—
—
12
F
34
Portugal
Depression
1
Yes
—
—
13
F
59
Portugal
Psychosis Depression Anxiety
1 1 6
Yes Yes Yes
—
46
14
F
36
Portugal
Anxiety
1
Yes
—
—
15
M
41
Portugal
Anxiety Manic episode
1 1
Yes Yes
—
—
16 17 18 19
F F F F
37 18 32 37
Portugal Portugal Portugal Portugal
Depression Anxiety Anxiety Anxiety
1 1 1 5
Yes Yes No Yes
— — — —
— — 2 —
1 1
M: male, F: female.
(88 versus 58), but the difference can be attributed to three individuals reporting a high number of events (18, 17 and 13). The psychiatric events were predominantly mood disorders, which were treated by family doctors in almost all cases, without further diagnostic investigations nor hospitalization. In agreement with previous studies,27,28 a correlation was found here between psychiatric complaints and no paid occupation, which confirms the socio-economic basis of several psychiatric disturbances. It is important to note that in some countries psychiatric events seem more frequent than in others. For example, in Russia (where 235 cases and 236 controls were recruited) only one case and no controls reported psychiatric events; this is in contrast with the reports of a higher prevalence of psychiatric disorders in Eastern European countries, where the observation may be explained by the fairly low socio-economic conditions.29,30 One can assume that in these countries, depression and other psychiatric disorders, if mild, do not require
medical attention and are not self-reported by the patients. The study has a number of limitations. First of all, this is not an epidemiological survey and, despite our attempts to obtain a fairly unselected study population, the sample may be flawed by an excess of chronic and different-to-treat cases. An even lower risk of psychiatric complaints may be thus expected in a fully representative sample of patients with epilepsy in the general population. Second, there were no a-priori criteria for a correct psychiatric diagnosis. This may cast doubts on the correctness of the diagnosis. However, this study was not designed to screen psychiatric comorbidity but rather to record relevant medical events (including psychiatric). Third, our aim was to identify events requiring medical intervention during a fairly short follow-up. Rare and long-term psychiatric complications may thus have escaped. However, this was beyond the scopes of the study. Last, this was a multicenter study. Heterogeneous approaches were perhaps adopted to register patients’ complaints. However, we exclude the possibility of a reporting bias because
Psychiatric events in epilepsy the same error, where present, involved both cases and controls from the same center. In summary, our study seems to support the belief that uncomplicated epilepsy carries only a modest risk of psychiatric comorbidity, which is generally mild and is unrelated to the main disease characteristics.
591
Acknowledgements The study was supported by the European Union (contract Biomed I, No. BMH1-CT93-1428) and was conducted under the auspices of the International Bureau of Epilepsy.
Appendix A. Rest-1 Group Members EEC Project Leader Study Chairman Steering Committee Italy
Germany The Netherlands United Kingdom Portugal Estonia Slovenia Russia
E Beghi (Monza) CM Cornaggia (Monza) WA Hauser (New York), JN Loeber, H De Boer (Heemstede), R Thorbecke (Bielefeld), AEH Sonnen (Breda) S Severi, P Zolo (Arezzo), LM Specchio, N Specchio (Bari), MP Pasolini, L Antonini (Brescia), U Aguglia, C Russo, A Gambardella (Catanzaro), S Giubergia, PG Zagnoni (Cuneo), M Cosottini, G Zaccara (Firenze), R Trio, F Pisani, M Russo, G Oteri (Messina), CE Cavestro, C Tonini, G Avanzini, F Arienti, CA Defanti (Milano), L Airoldi, M Beghi, G Bogliun, E Brambilla, E Fiordelli, A Mascarini, L Moltrasio, C Primati (Monza), A Tartara, R Manni, G Castelnuovo, R Murelli, CA Galimberti, N Zanotta (Pavia), P Di Viesti, M Zarrelli, F Apollo (San Giovanni Rotondo) E Steuernagel, P Wolf (Bielefeld), U Runge (Greifswald) MCTFM de Krom, C van Heijden, J Griet (Maastricht) SW Brown, H Coyle (Cheshire) JM Lopez Lima, P Beleza, E Ferreira (Porto) T Talvik, A Beilmann (Tartu) E Belousova, T Levart, N Zupancic (Ljubljana) S Gromov, LV Lipatova, V Mikhailov (St. Petersburg)
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