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Risk factors and outcome of mood disorders in epilepsy: a case-control study
Seizure 2003; 12: 121–125
doi:10.1016/S1059–1311(02)00192-9
Risk factors and outcome of mood disorders in epilepsy: a case-control study K. JAGADHEESAN, ASHWANI K. GARG & S. HAQUE NIZAMIE Central Institute of Psychiatry, Kanke (PO), Ranchi-834006, India Correspondence to: Dr S. Haque Nizamie, MD, DPM, Professor of Psychiatry and Director, Central Institute of Psychiatry, Kanke (PO), Ranchi-834006, India. E-mail: [email protected]
Background: This case-control study investigated both the risk factors and outcome of mood disorders in epilepsy. Methods: For this study, 44 patients with both epilepsy and a mood disorder (study group) were compared with 44 randomly selected patients of epilepsy without a mood disorder (control group). Psychiatric diagnosis was made as per ICD-10 Diagnostic Criteria for Research (ICD-10 DCR). International classification for seizure types (1981) was used for classification of seizure types. Results: Of the patients in the study group, a majority were educated up to at least primary level, had later onset of seizures, longer duration of epilepsy and cluster attacks. The outcome of mood disorders in epilepsy was found good in most. Conclusions: Educated patients who develop epilepsy at a later age and patients with poorly controlled epilepsy are more likely to experience mood disorders. In most patients with epilepsy, mood disorders remit completely; notably, in some patients affective symptoms resolve spontaneously. © 2002 BEA Trading Ltd. Published by Elsevier Science Ltd. All rights reserved. Key words: mood disorders; depression; mania; epilepsy; outcome.
INTRODUCTION Mood disorders are one among the psychiatric disorders that are often found in patients with epilepsy. Of the different types of mood disorders, depression is a common one with its incidence rate ranging between 14 and 55%1, 2 . Evidently, depression may occur during peri-ictal period, as a part of ictal phenomenon or immediately after seizures as a post-ictal phenomenon, or interictal period3–6 . And, it may take either neurotic form, suggesting a reaction to having epilepsy7 , or endogenous form5 . In comparison to depression, mania and bipolar disorders are less often observed in relation to epilepsy1, 8, 9 . Additionally, the intensity of manic episodes are found less severe in epilepsy than that for bipolar I disorder10 . A possible reason for the relative rarity of manic mood swings is the antimanic properties of antiepileptic drugs11 . The consequences of unrecognised and untreated mood disorders in epilepsy are many. Suicide is a serious negative consequence linked with depression, and many studies have indicated increased suicidal rate among depressed patients with epilepsy12, 13 . Besides, 1059–1311/02/$35.00
presence of co-morbid mood disorders, particularly depression is documented to be associated with poor quality of life14 in patients with epilepsy. A wide range of psychosocial, illness- and treatment-related factors are linked with the occurrence of psychopathology in patients with epilepsy. Either single or combined effect of these factors could be responsible for psychopathology at an individual level15 . Similar explanations also hold true for mood disorders of epilepsy, e.g. depression might be a reaction to having a chronic illness with its associated life problems, or may represent an endogenous mood disturbance caused directly by epilepsy, or may be just coincidental or may be of iatrogenic (drug-induced) in origin6, 16 . Although mood disorders constitute a significant problem in the management of epilepsy, outcome of the same has not been adequately studied. In view of a few investigators, who have investigated this issue1, 7, 17 , remission occurs suddenly and outcome of mood disorders is favourable. Because only few studies have investigated risk factors of mood disorders in epilepsy and examined the outcome of affective
© 2002 BEA Trading Ltd. Published by Elsevier Science Ltd. All rights reserved.
122
symptoms, the current study was designed. The major aim of this study was to explore the factors that influence the occurrence and outcome of mood disorders of epilepsy.
METHODS For this case-control study, case notes of patients who had attended the weekly epilepsy clinic of Central Institute of Psychiatry between 1989 and 1999 were screened and records of patients who had more than two unprovoked seizures were identified. Case records with inadequate information, and records of patients who had only febrile, single and acute symptomatic seizures were excluded. Similarly, records of patients who had a history of mood disorders prior to the onset of epilepsy were also excluded. After the initial screening, all case records of patients who had been followed up to at least 6 months were chosen (n = 300). To ensure the reliability of diagnosis and assess outcome, a minimum follow-up period of 6 months was considered in this study. Of the total 300 records, about 44 case records of patients diagnosed with an ICD-10 affective disorder18 were identified (study group). For effective matching, by using a random table, of the case records of 158 patients of epilepsy who had no evidence for another mental disorder, records of 44 patients were selected (control group). Demographic and clinical variables such as age of onset of epilepsy, sex, marital status, education, employment, family history of psychiatric disorders, presence of mental retardation, cluster and status attacks, seizure type and frequency, duration of epilepsy, EEG abnormalities, type of antiepileptic drugs, seizure control and improvement of affective disorder were obtained from case notes. International classification of epilepsies, ILAE-198119 , was used to classify seizure types. Based on clinical grounds, i.e. according to the presence or absence of affective symptoms, patients with mood disorders were categorised into improved (full remission) and not improved groups. Statistical analysis was done with SPSS-Win version 7.5. To examine the group differences, Chi-square test with and without Yates’ correction, Fisher’s exact test and Mann–Whitney ‘U’-test were used for categorical and continuous variables, respectively. The level of significance of 0.05 or below was adopted in this study.
RESULTS This study compared 44 patients of epilepsy who had a mood disorder (study group) with 44 patients of
K. Jagadheesan et al. Table 1: Subjects’ characteristics. Variables
Group Control group (n, %)
Study group (n, %)
12.19 ± 9.60
21.44 ± 13.58
Sex Male Female
29 (65.9) 15 (34.1)
34 (77.3) 10 (22.7)
Education* Illiterate Literate
15 (34.1) 29 (65.9)
5 (11.4) 39 (88.6)
Marital status Single Married
17 (70.8) 7 (29.2)
19 (46.3) 22 (53.7)
Occupation Unemployed Employed
4 (13.8) 25 (86.2)
8 (26.7) 22 (73.3)
Age of epilepsy onset** (years; mean ± SD)
*
P ≤ 0.05;
**
P ≤ 0.001.
epilepsy who had no history of a mood disorder (control group). Of the 44 patients in the study group, five had mania (11.4%) and the rest had depression (88.6%). Because patients with mania were less, a separate analysis comparing patients with mania and depression was not done. In comparison with control group, patients in study group had later age of onset of epilepsy (Mann–Whitney U-test, Z = −3.42, P ≤ 0.01). A significantly high proportion of patients of the study group were educated at least up to primary level (χ 2 = 5.24, df = 1, P ≤ 0.05). Patients in both study and control groups were found comparable in sex (χ 2 = 0.89, df = 1, P = 0.34), marital status (χ 2 = 2.75, df = 1, P = 0.1) and occupational status (χ 2 = 0.82, df = 1, P = 0.37). Children were excluded while analysing marital status and occupation. Similarly, housewives were excluded while analysing occupational status (Table 1). Notably, patients with mental retardation had a higher representation in the control group (Fisher’s exact test, P ≤ 0.05). Unlike control group, patients of the study group had more frequently cluster attacks (χ 2 = 3.75, df = 1, P ≤ 0.05) and long duration of epilepsy (Mann–Whitney U-test, Z = −2.40, P ≤ 0.05). Groups were found similar in family history of psychiatric disorders (χ 2 = 1.66, df = 1, P = 0.2), status attacks (Fisher’s exact test, P = 1.0), seizure frequency (χ 2 = 2.68, df = 1, P = 0.1) and seizure types (χ 2 = 0.87, df = 1, P = 0.4) (Table 2). Both groups also did not differ with regard to EEG abnormalities (χ 2 = 0.00, df = 1, P = 1.0), EEG focus (Fisher’s exact test, P = 1.0), type of antiepileptic drugs (χ 2 = 0.29, df = 1, P = 0.59) and seizure control (more than 50% reduction in the seizure
Risk factors and outcome of mood disorders in epilepsy
123
Table 2: Differences in clinical profile. Control group (n = 44)
Variables retardation*
Study group (n = 44)
Mental (n, %) Family history of psychiatric disorder (n, %) Cluster attacks* (n, %) Status attacks (n, %)
8 3
18.2 6.8
1 8
2.3 18.2
14 2
31.8 4.5
24 1
54.5 2.3
Seizure frequency (n, %) ≥1/month <1/month
27 17
61.4 38.6
35 9
79.5 20.5
Seizure type (n, %) Primary generalised Secondary generalised
8 36
18.2 81.8
4 40
9.1 90.9
Duration of epilepsy* (years; mean ± SD) *
4.76 ± 5.30
7.58 ± 6.81
P ≤ 0.05.
Table 3: Differences in treatment-related variables. Control group (n = 44)
Variables EEG abnormalities (n, %)
Study group (n = 44)
29
68.2
30
70.5
6 2
75.0 25.0
7 2
77.8 22.2
Antiepileptic drug (n, %) Monotherapy Polytherapy
37 7
84.1 15.9
34 10
77.3 22.7
Seizure control (n, %; >50%)
31
70.5
32
72.7
EEG focus (n, %) Right side Left side
frequency from the baseline) (χ 2 = 0.00, df = 1, P = 1.0) (Table 3). Due to the limited availability of information, outcome of mood disorders was examined only in 31 of 44 (70%) patients. Of the 31 patients, 29 (93.5%) had clinical improvement and two (6.5%) had no improvement. Among the patients who had improvement, 17 (58.6%) had received psychotropic medications, and 12 (41.4%) did not receive it. Conversely, all the patients in the non-improved group did not receive psychotropic drugs.
DISCUSSION This study agrees with the existing literature1, 2 mentioning that depression is more common than mania in patients with epilepsy. Studies examining the influence of psychosocial factors in mood disorders of epilepsy are less. In an earlier study20 , psychosocial factors— stressful life events in the past 6 months, poor adjustment to epilepsy, financial stress and female gender have been found highly predictive of depression. Unlike Hermann and Whitman’s20 study, one study found men to experience depression more often than that of women21 . However, similar to the findings of a later study22 , the current study failed to replicate the sig-
nificance of gender in the aetiology of mood disorders of epilepsy. In comparison to normal controls, patients with epilepsy have significant adjustment problems20, 23 . These patients less frequently use active coping strategies to handle their difficulties24 . An important psychosocial issue strongly coupled with adjustment problems is stigma associated with epilepsy; and stigma has been found positively correlated with abnormal affective states and negatively linked with self-esteem and life satisfaction25 . An early study has revealed that perceived stigma was appreciably related to perceived employment discrimination, seizure-imposed limitations and years of education26 . Although the degree of adjustment to epilepsy and perceived stigma was not measured in the present study, the fact that significantly more patients with epilepsy were educated up to primary level and above suggests that possibly increased perception of negative consequences among educated patients might be a reason for higher rate of mood disorders in this set of population. Patients with mental retardation had a higher representation in the group without a mood disorder in this study. As psychopathology was not assessed with a structured instrument, the possibility of underestimation of psychopathology in this subset of participants
124
is difficult to rule out. In the current study, the rate of family history of psychiatric illnesses was found comparable between groups suggesting the possibility that familial factors maybe less likely to contribute to affective disorders in epilepsy. This issue needs to be clarified in future studies using a comprehensive family history assessment instrument. Neither age of onset of epilepsy nor duration of epilepsy has been correlated with the incidence of mood disorders of epilepsy21 . Conversely, in the present study, patients with mood disorders had a later age of onset of seizures and longer duration of epilepsy than the control group. Although the reason for such discrepancy between the current study and another study21 is unknown, the present findings indicate that probably the beginning of seizures at later age and longer duration of epilepsy may increase the liability for affective disorders. Frequent seizures are noted to be a cause for adjustment problems23 , depression, anxiety and stigma13 . In this direction, although groups in the present study had a comparable seizure frequency, the evidence that a higher proportion of patients in the study group had cluster attacks (indicative of severity of seizure) hints that possibly direct cerebral changes or psychosocial difficulties caused by cluster attacks might be increasing risk for mood disorders. The results of the studies that examined the association between seizure types and mood disorders are conflicting. Both partial seizures (complex partial seizures), particularly of temporal lobe origin13 and generalised epilepsy27 are reported to be risk factor for depression in epilepsy. However, the present study, agreeing with another study28 , failed to find the relationship between type of seizure and mood disorders. Presently, the significance of EEG focus in relation to affective disorders also seems less clear. Both right27 and left side foci5 , particularly left temporal foci21 , have been connected with mood disorders. The present finding that groups were similar with regard to EEG focus suggests that probably the risk for affective disorders in epilepsy may not be directly linked with the side of EEG abnormality. Polytherapy has been implicated in the pathogenesis of mood disorders29 . However, like another study20 , in the current study, no influence of medication type was seen. Till now only a few studies have examined the outcome of mood disorders in epilepsy, and, like other evidences1, 7, 17 , in the current study, outcome of mood disorders was found to be better. Further, the fact that about half of the patients with mood disorders recovered without addition of a psychotropic agent suggests that in substantial number of patients of epilepsy, mood disorders remits without addition of psychotropic agents (antidepressants/antipsychotics). Whether psychotropic properties of antiepileptic
K. Jagadheesan et al.
drugs are responsible for such spontaneous resolution of mood disorders is an issue to be explored in future. Nevertheless, this present finding that there is a possibility of spontaneous resolution indicates that psychotropic drugs to be considered only when a mood disorder is severe and disabling. Although this study is one among the few studies that have investigated predictors and outcome of mood disorders of epilepsy, it has few limitations such as retrospective design, smaller sample size, and lack of detailed assessment of psychosocial variables and psychopathology. Nevertheless, this study indicates that educated patients who develop epilepsy at a later age and patients with poorly controlled epilepsy may be more likely to experience mood disorders. In addition, it also suggests that mood disorders in epilepsy have a better outcome.
REFERENCES 1. McKenna, P. J., Kane, J. M. and Parrish, K. Psychotic syndrome in epilepsy. American Journal of Psychiatry 1985; 142: 895–904. 2. Lishman, W. A. Organic Psychiatry. 3rd ed. Oxford, Blackwell Science Ltd., 1998. 3. Agnihotri, B. R., Teja, J. S., Prabhu, G. G. and Virmani, V. Study of psychiatric, psychologic and social disturbances in epileptics. Indian Journal of Psychiatry 1972; 14: 171–182. 4. Betts, T. A. A follow-up study of a cohort of patients with epilepsy admitted to psychiatric care in an English city. In: Epilepsy: Proceedings of the Hans Berger Centenary Symposium (Eds P. Harris and C. Maudsley). Edinburgh, Churchill Livingstone, 1974: pp. 326–338. 5. Betts, T. A. Depression, anxiety and epilepsy. In: Epilepsy and Psychiatry (Eds E. H. Reynolds and M. R. Trimble). Edinburgh, Churchill Livingstone, 1981. 6. Kanner, A. M. and Nieto, J. C. R. Depressive disorders in epilepsy. Neurology 1999; 53 (Suppl. 2): S26–S32. 7. Mendez, M. F., Cummings, J. L. and Benson, D. F. Depression in epilepsy; significance and phenomenology. Archives of Neurology 1986; 43: 766–770. 8. Blumer, D. Epilepsy and disorders of mood. In: Advances in Neurology, Vol. 55 (Eds D. Smith, E. Treiman and M. Trimble). New York, Raven Press, 1991: pp. 185–195. 9. Wolf, P. Manic episodes in epilepsy. In: Advances in Epileptology: 13th Epilepsy International Symposium (Eds H. Akimoto, H. Kazamatsui, M. Seino and A. A. Ward). New York, Raven Press, 1982: pp. 237–340. 10. Kudo, T., Ishida, S., Kubota, H. and Yagi, K. Manic episode in epilepsy and bipolar I disorder: a comparative analysis of 13 patients. Epilepsia 2001; 42: 1036–1042. 11. Robertson, M. M., Trimble, M. R. and Townsend, H. R. A. The phenomenology of depression in epilepsy. Epilepsia 1987; 28: 364–372. 12. Robertson, M. M. and Trimble, M. R. Depressive illness in patients with epilepsy: a review. Epilepsia 1983; 24 (Suppl. 2): S109–S116. 13. Lambert, M. V. and Robertson, M. M. Depression in epilepsy, etiology, phenomenology and treatment. Epilepsia 1999; 40 (Suppl. 10): S21–S47. 14. Wiegartz, P., Seidenberg, M., Woodard, A., Gidal, B. and Hermann, B. Co-morbid psychiatric disorder in chronic epilepsy: recognition and etiology of depression. Neurology 1999; 53 (Suppl. 2): S3–S8.
Risk factors and outcome of mood disorders in epilepsy 15. Robertson, M. M. Epilepsy and mood. In: Epilepsy, Behavior and Cognitive Function (Eds M. R. Trimble and E. H. Reynolds). New York, John Wiley & Sons, 1988: pp. 145– 157. 16. Hermann, B. P., Whitman, S. and Anton, M. A multietiological model of psychological and social dysfunction in epilepsy. In: The Neuropsychology of Epilepsy (Ed. T. L. Bennett). New York, Plenum Press, 1992: pp. 39–57. 17. Perrine, K. Neurobehavioral problems in epilepsy. Neurology Clinics 1994; 12: 129–152. 18. World Health Organization. The ICD-10 Classification of Mental and Behavioral Disorders: Diagnostic Criteria for Research (DCR-10). Geneva, World Health Organization, 1993. 19. Commission on Classification and Terminology. International classification of seizures based on seizure types and electroencephalographic findings. Epilepsia 1981; 22: 489– 501. 20. Hermann, B. P. and Whitman, S. Neurobiological, psychosocial and pharmacological factors underlying interictal psychopathology in epilepsy. In: Advances in Neurology, Vol. 55 (Eds D. Smith, E. Treiman and M. Trimble). New York, Raven Press, 1991: pp. 439–452. 21. Altshuler, L., Devinsky, O., Post, R. and Theodore, W. Depression, anxiety and temporal epilepsy. Archives of Neurology 1990; 47: 284–288.
125 22. Robertson, M. M., Channon, S. and Baker, J. Depressive symptomatology in a general hospital sample of outpatients with temporal lobe epilepsy: a controlled study. Epilepsia 1994; 35: 771–777. 23. Kemp, S., Morley, S. and Anderson, E. Coping with epilepsy: do illness representations play a role. British Journal of Clinical Psychology 1999; 38: 43–58. 24. Oosterhuis, A. Coping with epilepsy: the effect of coping styles on self-perceived seizure severity and psychological complaints. Seizure 1999; 8: 93–96. 25. Arnston, P. The perceived psychosocial consequences of having epilepsy. In: Epilepsy and Psychiatry (Eds E. H. Reynolds and M. R. Trimble). Edinburgh, Churchill Livingstone, 1981: pp. 60–71. 26. Ryan, R., Kemper, K. and Emlen, A. C. The stigma of epilepsy as a self-concept. Epilepsia 1980; 21: 433–444. 27. Flor-Henry, P. Psychosis and temporal lobe epilepsy: a controlled investigation. Epilepsia 1969; 10: 363–395. 28. Kogeorgos, J., Fonagy, P. and Scott, D. F. Psychiatric symptom patterns of chronic epileptics attending a neurological clinic: a controlled investigation. British Journal of Psychiatry 1982; 140: 236–243. 29. Mendez, M. F., Doss, R. C., Taylor, J. L. and Salguero, P. Depression in epilepsy: relationship to seizures and anticonvulsive therapy. Journal of Nervous Mental Diseases 1993; 181: 444–447.
doi:10.1016/S1059–1311(02)00192-9
Risk factors and outcome of mood disorders in epilepsy: a case-control study K. JAGADHEESAN, ASHWANI K. GARG & S. HAQUE NIZAMIE Central Institute of Psychiatry, Kanke (PO), Ranchi-834006, India Correspondence to: Dr S. Haque Nizamie, MD, DPM, Professor of Psychiatry and Director, Central Institute of Psychiatry, Kanke (PO), Ranchi-834006, India. E-mail: [email protected]
Background: This case-control study investigated both the risk factors and outcome of mood disorders in epilepsy. Methods: For this study, 44 patients with both epilepsy and a mood disorder (study group) were compared with 44 randomly selected patients of epilepsy without a mood disorder (control group). Psychiatric diagnosis was made as per ICD-10 Diagnostic Criteria for Research (ICD-10 DCR). International classification for seizure types (1981) was used for classification of seizure types. Results: Of the patients in the study group, a majority were educated up to at least primary level, had later onset of seizures, longer duration of epilepsy and cluster attacks. The outcome of mood disorders in epilepsy was found good in most. Conclusions: Educated patients who develop epilepsy at a later age and patients with poorly controlled epilepsy are more likely to experience mood disorders. In most patients with epilepsy, mood disorders remit completely; notably, in some patients affective symptoms resolve spontaneously. © 2002 BEA Trading Ltd. Published by Elsevier Science Ltd. All rights reserved. Key words: mood disorders; depression; mania; epilepsy; outcome.
INTRODUCTION Mood disorders are one among the psychiatric disorders that are often found in patients with epilepsy. Of the different types of mood disorders, depression is a common one with its incidence rate ranging between 14 and 55%1, 2 . Evidently, depression may occur during peri-ictal period, as a part of ictal phenomenon or immediately after seizures as a post-ictal phenomenon, or interictal period3–6 . And, it may take either neurotic form, suggesting a reaction to having epilepsy7 , or endogenous form5 . In comparison to depression, mania and bipolar disorders are less often observed in relation to epilepsy1, 8, 9 . Additionally, the intensity of manic episodes are found less severe in epilepsy than that for bipolar I disorder10 . A possible reason for the relative rarity of manic mood swings is the antimanic properties of antiepileptic drugs11 . The consequences of unrecognised and untreated mood disorders in epilepsy are many. Suicide is a serious negative consequence linked with depression, and many studies have indicated increased suicidal rate among depressed patients with epilepsy12, 13 . Besides, 1059–1311/02/$35.00
presence of co-morbid mood disorders, particularly depression is documented to be associated with poor quality of life14 in patients with epilepsy. A wide range of psychosocial, illness- and treatment-related factors are linked with the occurrence of psychopathology in patients with epilepsy. Either single or combined effect of these factors could be responsible for psychopathology at an individual level15 . Similar explanations also hold true for mood disorders of epilepsy, e.g. depression might be a reaction to having a chronic illness with its associated life problems, or may represent an endogenous mood disturbance caused directly by epilepsy, or may be just coincidental or may be of iatrogenic (drug-induced) in origin6, 16 . Although mood disorders constitute a significant problem in the management of epilepsy, outcome of the same has not been adequately studied. In view of a few investigators, who have investigated this issue1, 7, 17 , remission occurs suddenly and outcome of mood disorders is favourable. Because only few studies have investigated risk factors of mood disorders in epilepsy and examined the outcome of affective
© 2002 BEA Trading Ltd. Published by Elsevier Science Ltd. All rights reserved.
122
symptoms, the current study was designed. The major aim of this study was to explore the factors that influence the occurrence and outcome of mood disorders of epilepsy.
METHODS For this case-control study, case notes of patients who had attended the weekly epilepsy clinic of Central Institute of Psychiatry between 1989 and 1999 were screened and records of patients who had more than two unprovoked seizures were identified. Case records with inadequate information, and records of patients who had only febrile, single and acute symptomatic seizures were excluded. Similarly, records of patients who had a history of mood disorders prior to the onset of epilepsy were also excluded. After the initial screening, all case records of patients who had been followed up to at least 6 months were chosen (n = 300). To ensure the reliability of diagnosis and assess outcome, a minimum follow-up period of 6 months was considered in this study. Of the total 300 records, about 44 case records of patients diagnosed with an ICD-10 affective disorder18 were identified (study group). For effective matching, by using a random table, of the case records of 158 patients of epilepsy who had no evidence for another mental disorder, records of 44 patients were selected (control group). Demographic and clinical variables such as age of onset of epilepsy, sex, marital status, education, employment, family history of psychiatric disorders, presence of mental retardation, cluster and status attacks, seizure type and frequency, duration of epilepsy, EEG abnormalities, type of antiepileptic drugs, seizure control and improvement of affective disorder were obtained from case notes. International classification of epilepsies, ILAE-198119 , was used to classify seizure types. Based on clinical grounds, i.e. according to the presence or absence of affective symptoms, patients with mood disorders were categorised into improved (full remission) and not improved groups. Statistical analysis was done with SPSS-Win version 7.5. To examine the group differences, Chi-square test with and without Yates’ correction, Fisher’s exact test and Mann–Whitney ‘U’-test were used for categorical and continuous variables, respectively. The level of significance of 0.05 or below was adopted in this study.
RESULTS This study compared 44 patients of epilepsy who had a mood disorder (study group) with 44 patients of
K. Jagadheesan et al. Table 1: Subjects’ characteristics. Variables
Group Control group (n, %)
Study group (n, %)
12.19 ± 9.60
21.44 ± 13.58
Sex Male Female
29 (65.9) 15 (34.1)
34 (77.3) 10 (22.7)
Education* Illiterate Literate
15 (34.1) 29 (65.9)
5 (11.4) 39 (88.6)
Marital status Single Married
17 (70.8) 7 (29.2)
19 (46.3) 22 (53.7)
Occupation Unemployed Employed
4 (13.8) 25 (86.2)
8 (26.7) 22 (73.3)
Age of epilepsy onset** (years; mean ± SD)
*
P ≤ 0.05;
**
P ≤ 0.001.
epilepsy who had no history of a mood disorder (control group). Of the 44 patients in the study group, five had mania (11.4%) and the rest had depression (88.6%). Because patients with mania were less, a separate analysis comparing patients with mania and depression was not done. In comparison with control group, patients in study group had later age of onset of epilepsy (Mann–Whitney U-test, Z = −3.42, P ≤ 0.01). A significantly high proportion of patients of the study group were educated at least up to primary level (χ 2 = 5.24, df = 1, P ≤ 0.05). Patients in both study and control groups were found comparable in sex (χ 2 = 0.89, df = 1, P = 0.34), marital status (χ 2 = 2.75, df = 1, P = 0.1) and occupational status (χ 2 = 0.82, df = 1, P = 0.37). Children were excluded while analysing marital status and occupation. Similarly, housewives were excluded while analysing occupational status (Table 1). Notably, patients with mental retardation had a higher representation in the control group (Fisher’s exact test, P ≤ 0.05). Unlike control group, patients of the study group had more frequently cluster attacks (χ 2 = 3.75, df = 1, P ≤ 0.05) and long duration of epilepsy (Mann–Whitney U-test, Z = −2.40, P ≤ 0.05). Groups were found similar in family history of psychiatric disorders (χ 2 = 1.66, df = 1, P = 0.2), status attacks (Fisher’s exact test, P = 1.0), seizure frequency (χ 2 = 2.68, df = 1, P = 0.1) and seizure types (χ 2 = 0.87, df = 1, P = 0.4) (Table 2). Both groups also did not differ with regard to EEG abnormalities (χ 2 = 0.00, df = 1, P = 1.0), EEG focus (Fisher’s exact test, P = 1.0), type of antiepileptic drugs (χ 2 = 0.29, df = 1, P = 0.59) and seizure control (more than 50% reduction in the seizure
Risk factors and outcome of mood disorders in epilepsy
123
Table 2: Differences in clinical profile. Control group (n = 44)
Variables retardation*
Study group (n = 44)
Mental (n, %) Family history of psychiatric disorder (n, %) Cluster attacks* (n, %) Status attacks (n, %)
8 3
18.2 6.8
1 8
2.3 18.2
14 2
31.8 4.5
24 1
54.5 2.3
Seizure frequency (n, %) ≥1/month <1/month
27 17
61.4 38.6
35 9
79.5 20.5
Seizure type (n, %) Primary generalised Secondary generalised
8 36
18.2 81.8
4 40
9.1 90.9
Duration of epilepsy* (years; mean ± SD) *
4.76 ± 5.30
7.58 ± 6.81
P ≤ 0.05.
Table 3: Differences in treatment-related variables. Control group (n = 44)
Variables EEG abnormalities (n, %)
Study group (n = 44)
29
68.2
30
70.5
6 2
75.0 25.0
7 2
77.8 22.2
Antiepileptic drug (n, %) Monotherapy Polytherapy
37 7
84.1 15.9
34 10
77.3 22.7
Seizure control (n, %; >50%)
31
70.5
32
72.7
EEG focus (n, %) Right side Left side
frequency from the baseline) (χ 2 = 0.00, df = 1, P = 1.0) (Table 3). Due to the limited availability of information, outcome of mood disorders was examined only in 31 of 44 (70%) patients. Of the 31 patients, 29 (93.5%) had clinical improvement and two (6.5%) had no improvement. Among the patients who had improvement, 17 (58.6%) had received psychotropic medications, and 12 (41.4%) did not receive it. Conversely, all the patients in the non-improved group did not receive psychotropic drugs.
DISCUSSION This study agrees with the existing literature1, 2 mentioning that depression is more common than mania in patients with epilepsy. Studies examining the influence of psychosocial factors in mood disorders of epilepsy are less. In an earlier study20 , psychosocial factors— stressful life events in the past 6 months, poor adjustment to epilepsy, financial stress and female gender have been found highly predictive of depression. Unlike Hermann and Whitman’s20 study, one study found men to experience depression more often than that of women21 . However, similar to the findings of a later study22 , the current study failed to replicate the sig-
nificance of gender in the aetiology of mood disorders of epilepsy. In comparison to normal controls, patients with epilepsy have significant adjustment problems20, 23 . These patients less frequently use active coping strategies to handle their difficulties24 . An important psychosocial issue strongly coupled with adjustment problems is stigma associated with epilepsy; and stigma has been found positively correlated with abnormal affective states and negatively linked with self-esteem and life satisfaction25 . An early study has revealed that perceived stigma was appreciably related to perceived employment discrimination, seizure-imposed limitations and years of education26 . Although the degree of adjustment to epilepsy and perceived stigma was not measured in the present study, the fact that significantly more patients with epilepsy were educated up to primary level and above suggests that possibly increased perception of negative consequences among educated patients might be a reason for higher rate of mood disorders in this set of population. Patients with mental retardation had a higher representation in the group without a mood disorder in this study. As psychopathology was not assessed with a structured instrument, the possibility of underestimation of psychopathology in this subset of participants
124
is difficult to rule out. In the current study, the rate of family history of psychiatric illnesses was found comparable between groups suggesting the possibility that familial factors maybe less likely to contribute to affective disorders in epilepsy. This issue needs to be clarified in future studies using a comprehensive family history assessment instrument. Neither age of onset of epilepsy nor duration of epilepsy has been correlated with the incidence of mood disorders of epilepsy21 . Conversely, in the present study, patients with mood disorders had a later age of onset of seizures and longer duration of epilepsy than the control group. Although the reason for such discrepancy between the current study and another study21 is unknown, the present findings indicate that probably the beginning of seizures at later age and longer duration of epilepsy may increase the liability for affective disorders. Frequent seizures are noted to be a cause for adjustment problems23 , depression, anxiety and stigma13 . In this direction, although groups in the present study had a comparable seizure frequency, the evidence that a higher proportion of patients in the study group had cluster attacks (indicative of severity of seizure) hints that possibly direct cerebral changes or psychosocial difficulties caused by cluster attacks might be increasing risk for mood disorders. The results of the studies that examined the association between seizure types and mood disorders are conflicting. Both partial seizures (complex partial seizures), particularly of temporal lobe origin13 and generalised epilepsy27 are reported to be risk factor for depression in epilepsy. However, the present study, agreeing with another study28 , failed to find the relationship between type of seizure and mood disorders. Presently, the significance of EEG focus in relation to affective disorders also seems less clear. Both right27 and left side foci5 , particularly left temporal foci21 , have been connected with mood disorders. The present finding that groups were similar with regard to EEG focus suggests that probably the risk for affective disorders in epilepsy may not be directly linked with the side of EEG abnormality. Polytherapy has been implicated in the pathogenesis of mood disorders29 . However, like another study20 , in the current study, no influence of medication type was seen. Till now only a few studies have examined the outcome of mood disorders in epilepsy, and, like other evidences1, 7, 17 , in the current study, outcome of mood disorders was found to be better. Further, the fact that about half of the patients with mood disorders recovered without addition of a psychotropic agent suggests that in substantial number of patients of epilepsy, mood disorders remits without addition of psychotropic agents (antidepressants/antipsychotics). Whether psychotropic properties of antiepileptic
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drugs are responsible for such spontaneous resolution of mood disorders is an issue to be explored in future. Nevertheless, this present finding that there is a possibility of spontaneous resolution indicates that psychotropic drugs to be considered only when a mood disorder is severe and disabling. Although this study is one among the few studies that have investigated predictors and outcome of mood disorders of epilepsy, it has few limitations such as retrospective design, smaller sample size, and lack of detailed assessment of psychosocial variables and psychopathology. Nevertheless, this study indicates that educated patients who develop epilepsy at a later age and patients with poorly controlled epilepsy may be more likely to experience mood disorders. In addition, it also suggests that mood disorders in epilepsy have a better outcome.
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