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Risk factors and outcome of mood disorders in epilepsy: a case-control study

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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 inepilepsy: 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 ofPsychiatry, Kanke (PO), Ranchi-834006, India.  E-mail :  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 randomlyselected patients of epilepsy without a mood disorder (control group). Psychiatric diagnosis was made as per ICD-10 DiagnosticCriteria for Research (ICD-10 DCR). International classification for seizure types (1981) was used for classification of seizuretypes.  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 morelikely to experience mood disorders. In most patients with epilepsy, mood disorders remit completely; notably, in some patientsaffective 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 disor-ders that are often found in patients with epilepsy. Of the different types of mood disorders, depression is acommon one with its incidence rate ranging between14 and 55% 1,2 . Evidently, depression may occur dur-ing peri-ictal period, as a part of ictal phenomenon orimmediatelyafterseizuresasapost-ictalphenomenon,or interictal period 3–6 . And, it may take either neu-rotic form, suggesting a reaction to having epilepsy 7 ,or endogenous form 5 . In comparison to depression,mania and bipolar disorders are less often observed inrelation to epilepsy 1,8,9 . Additionally, the intensity of manic episodes are found less severe in epilepsy thanthat for bipolar I disorder 10 . A possible reason for therelative rarity of manic mood swings is the antimanicproperties of antiepileptic drugs 11 .The consequences of unrecognised and untreatedmood disorders in epilepsy are many. Suicide is a seri-ous negative consequence linked with depression, andmany studies have indicated increased suicidal rateamong depressed patients with epilepsy 12,13 . Besides,presence of co-morbid mood disorders, particularlydepression is documented to be associated with poorquality of life 14 in patients with epilepsy.A wide range of psychosocial, illness- and treat-ment-related factors are linked with the occurrenceof psychopathology in patients with epilepsy. Ei-ther single or combined effect of these factors couldbe responsible for psychopathology at an individuallevel 15 . Similar explanations also hold true for mooddisorders of epilepsy, e.g. depression might be a reac-tion to having a chronic illness with its associated lifeproblems, or may represent an endogenous mood dis-turbance caused directly by epilepsy, or may be justcoincidental or may be of iatrogenic (drug-induced)in srcin 6,16 .Although mood disorders constitute a significantproblem in the management of epilepsy, outcome of the same has not been adequately studied. In viewof a few investigators, who have investigated thisissue 1,7,17 , remission occurs suddenly and outcome of mood disorders is favourable. Because only few stud-ies have investigated risk factors of mood disordersin epilepsy and examined the outcome of affective 1059–1311/02/$35.00 © 2002 BEA Trading Ltd. Published by Elsevier Science Ltd. All rights reserved.  122  K. Jagadheesan  et al. symptoms, the current study was designed. The majoraim of this study was to explore the factors that influ-ence the occurrence and outcome of mood disordersof epilepsy. METHODS For this case-control study, case notes of patients whohad attended the weekly epilepsy clinic of CentralInstitute of Psychiatry between 1989 and 1999 werescreened and records of patients who had more thantwo unprovoked seizures were identified. Case recordswith inadequate information, and records of patientswho had only febrile, single and acute symptomaticseizures were excluded. Similarly, records of patientswho had a history of mood disorders prior to the onsetof epilepsy were also excluded.After the initial screening, all case records of pa-tients who had been followed up to at least 6 monthswere chosen ( n  =  300). To ensure the reliability of diagnosis and assess outcome, a minimum follow-upperiod of 6 months was considered in this study. Of the total 300 records, about 44 case records of pa-tients diagnosed with an ICD-10 affective disorder 18 were identified (study group). For effective matching,by using a random table, of the case records of 158patients of epilepsy who had no evidence for anothermental disorder, records of 44 patients were selected(control group).Demographic and clinical variables such as ageof onset of epilepsy, sex, marital status, education,employment, family history of psychiatric disor-ders, presence of mental retardation, cluster andstatus attacks, seizure type and frequency, durationof epilepsy, EEG abnormalities, type of antiepilepticdrugs, seizure control and improvement of affectivedisorder were obtained from case notes. Internationalclassification of epilepsies, ILAE-1981 19 , was usedto classify seizure types. Based on clinical grounds,i.e. according to the presence or absence of affec-tive symptoms, patients with mood disorders werecategorised into improved (full remission) and notimproved groups.StatisticalanalysiswasdonewithSPSS-Winversion7.5. To examine the group differences, Chi-square testwith and without Yates’ correction, Fisher’s exact testand Mann–Whitney ‘ U  ’-test were used for categoricaland continuous variables, respectively. The level of significanceof0.05orbelowwasadoptedinthisstudy. RESULTS This study compared 44 patients of epilepsy who hada mood disorder (study group) with 44 patients of  Table 1: Subjects’ characteristics. Variables GroupControl group Study group( n , %) ( n , %)Age of epilepsy onset ** (years; mean  ±  SD)12.19  ±  9.60 21.44  ±  13.58SexMale 29 (65.9) 34 (77.3)Female 15 (34.1) 10 (22.7)Education * Illiterate 15 (34.1) 5 (11.4)Literate 29 (65.9) 39 (88.6)Marital statusSingle 17 (70.8) 19 (46.3)Married 7 (29.2) 22 (53.7)OccupationUnemployed 4 (13.8) 8 (26.7)Employed 25 (86.2) 22 (73.3) * P   ≤ 0 . 05;  ** P   ≤ 0 . 001. epilepsy who had no history of a mood disorder (con-trol 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, aseparate analysis comparing patients with mania anddepression was not done.In comparison with control group, patients instudy group had later age of onset of epilepsy(Mann–Whitney  U  -test,  Z  = − 3 . 42,  P   ≤  0 . 01). Asignificantly high proportion of patients of the studygroup were educated at least up to primary level( χ 2 =  5 . 24, df   =  1,  P   ≤  0 . 05). Patients in bothstudy and control groups were found comparable insex ( 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 ex-cluded while analysing marital status and occupation.Similarly, housewives were excluded while analysingoccupational status (Table 1).Notably, patients with mental retardation had ahigher representation in the control group (Fisher’sexact test,  P   ≤  0 . 05). Unlike control group, patientsof 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), seizurefrequency ( χ 2 =  2 . 68, df   =  1,  P   =  0 . 1) and seizuretypes ( χ 2 =  0 . 87, df   =  1,  P   =  0 . 4) (Table 2). Bothgroups also did not differ with regard to EEG abnor-malities ( χ 2 =  0 . 00, df   =  1,  P   =  1 . 0), EEG focus(Fisher’s exact test,  P   =  1 . 0), type of antiepilepticdrugs ( χ 2 =  0 . 29, df   =  1,  P   =  0 . 59) and seizurecontrol (more than 50% reduction in the seizure  Risk factors and outcome of mood disorders in epilepsy  123Table 2: Differences in clinical profile. Variables Control group ( n  = 44) Study group ( n  = 44)Mental retardation * ( n , %) 8 18.2 1 2.3Family history of psychiatricdisorder ( n , %)3 6.8 8 18.2Cluster attacks * ( n , %) 14 31.8 24 54.5Status attacks ( n , %) 2 4.5 1 2.3Seizure frequency ( n , %) ≥ 1/month 27 61.4 35 79.5 < 1/month 17 38.6 9 20.5Seizure type ( n , %)Primary generalised 8 18.2 4 9.1Secondary generalised 36 81.8 40 90.9Duration of epilepsy * (years; mean  ±  SD)4.76  ±  5.30 7.58  ±  6.81 * P   ≤ 0 . 05. Table 3: Differences in treatment-related variables. Variables Control group ( n  = 44) Study group ( n  = 44)EEG abnormalities ( n , %) 29 68.2 30 70.5EEG focus ( n , %)Right side 6 75.0 7 77.8Left side 2 25.0 2 22.2Antiepileptic drug ( n , %)Monotherapy 37 84.1 34 77.3Polytherapy 7 15.9 10 22.7Seizure control ( n , %; >50%) 31 70.5 32 72.7 frequency from the baseline) ( χ 2 =  0 . 00, df   =  1, P   = 1 . 0) (Table 3).Due to the limited availability of information, out-come of mood disorders was examined only in 31 of 44 (70%) patients. Of the 31 patients, 29 (93.5%) hadclinical improvement and two (6.5%) had no improve-ment. Among the patients who had improvement, 17(58.6%) had received psychotropic medications, and12 (41.4%) did not receive it. Conversely, all the pa-tients in the non-improved group did not receive psy-chotropic drugs. DISCUSSION This study agrees with the existing literature 1,2 men-tioning that depression is more common than mania inpatientswithepilepsy.Studiesexaminingtheinfluenceof psychosocial factors in mood disorders of epilepsyare less. In an earlier study 20 , psychosocial factors—stressful life events in the past 6 months, poor adjust-ment to epilepsy, financial stress and female genderhave been found highly predictive of depression. Un-likeHermannandWhitman’s 20 study,onestudyfoundmen to experience depression more often than that of women 21 . However, similar to the findings of a laterstudy 22 , the current study failed to replicate the sig-nificance of gender in the aetiology of mood disordersof epilepsy.In comparison to normal controls, patients withepilepsy have significant adjustment problems 20,23 .These patients less frequently use active copingstrategies to handle their difficulties 24 . An importantpsychosocial issue strongly coupled with adjustmentproblems is stigma associated with epilepsy; andstigma has been found positively correlated with ab-normal affective states and negatively linked withself-esteem and life satisfaction 25 . An early studyhas revealed that perceived stigma was apprecia-bly related to perceived employment discrimination,seizure-imposed limitations and years of education 26 .Although the degree of adjustment to epilepsy andperceived stigma was not measured in the presentstudy, the fact that significantly more patients withepilepsy were educated up to primary level and abovesuggests that possibly increased perception of nega-tive consequences among educated patients might bea reason for higher rate of mood disorders in this setof population.Patients with mental retardation had a higher repre-sentation in the group without a mood disorder in thisstudy. As psychopathology was not assessed with astructured instrument, the possibility of underestima-tion of psychopathology in this subset of participants  124  K. Jagadheesan  et al. is difficult to rule out. In the current study, the rateof family history of psychiatric illnesses was foundcomparable between groups suggesting the possibil-ity that familial factors maybe less likely to contributeto affective disorders in epilepsy. This issue needs tobe clarified in future studies using a comprehensivefamily history assessment instrument.Neither age of onset of epilepsy nor duration of epilepsy has been correlated with the incidence of mood disorders of epilepsy 21 . Conversely, in thepresent study, patients with mood disorders had alater age of onset of seizures and longer duration of epilepsy than the control group. Although the reasonfor such discrepancy between the current study andanother study 21 is unknown, the present findings in-dicate that probably the beginning of seizures at laterage and longer duration of epilepsy may increasethe liability for affective disorders. Frequent seizuresare noted to be a cause for adjustment problems 23 ,depression, anxiety and stigma 13 . In this direction, al-though groups in the present study had a comparableseizure frequency, the evidence that a higher propor-tion of patients in the study group had cluster attacks(indicative of severity of seizure) hints that possiblydirect cerebral changes or psychosocial difficultiescaused by cluster attacks might be increasing risk formood disorders.The results of the studies that examined the asso-ciation between seizure types and mood disordersare conflicting. Both partial seizures (complex partialseizures), particularly of temporal lobe srcin 13 andgeneralised epilepsy 27 are reported to be risk factorfor depression in epilepsy. However, the present study,agreeing with another study 28 , failed to find the rela-tionship between type of seizure and mood disorders.Presently, the significance of EEG focus in relationto affective disorders also seems less clear. Bothright 27 and left side foci 5 , particularly left temporalfoci 21 , have been connected with mood disorders.The present finding that groups were similar withregard to EEG focus suggests that probably the risk for affective disorders in epilepsy may not be directlylinked with the side of EEG abnormality. Polyther-apy has been implicated in the pathogenesis of mooddisorders 29 . However, like another study 20 , in the cur-rent study, no influence of medication type was seen.Till now only a few studies have examined the out-come of mood disorders in epilepsy, and, like otherevidences 1,7,17 , in the current study, outcome of mood disorders was found to be better. Further, thefact that about half of the patients with mood dis-orders recovered without addition of a psychotropicagent suggests that in substantial number of patientsof epilepsy, mood disorders remits without addition of psychotropic agents (antidepressants/antipsychotics).Whether psychotropic properties of antiepilepticdrugs are responsible for such spontaneous resolu-tion of mood disorders is an issue to be explored infuture. Nevertheless, this present finding that thereis a possibility of spontaneous resolution indicatesthat psychotropic drugs to be considered only when amood disorder is severe and disabling.Although this study is one among the few studiesthat have investigated predictors and outcome of mooddisorders of epilepsy, it has few limitations such asretrospective design, smaller sample size, and lack of detailed assessment of psychosocial variables and psy-chopathology. Nevertheless, this study indicates thateducated patients who develop epilepsy at a later ageand patients with poorly controlled epilepsy may bemore likely to experience mood disorders. In addition,it also suggests that mood disorders in epilepsy havea better outcome. REFERENCES 1. McKenna, P. J., Kane, J. M. and Parrish, K. Psychotic syn-drome in epilepsy.  American Journal of Psychiatry  1985;  142 :895–904.2. Lishman, W. A.  Organic Psychiatry . 3rd ed. Oxford, Black-well Science Ltd., 1998.3. Agnihotri, B. R., Teja, J. S., Prabhu, G. G. and Virmani, V.Study of psychiatric, psychologic and social disturbances inepileptics.  Indian Journal of Psychiatry  1972;  14 : 171–182.4. Betts, T. A. A follow-up study of a cohort of patients withepilepsy admitted to psychiatric care in an English city. In:  Epilepsy: Proceedings of the Hans Berger Centenary Sympo-sium  (Eds P. Harris and C. Maudsley). Edinburgh, ChurchillLivingstone, 1974: pp. 326–338.5. Betts, T. A. Depression, anxiety and epilepsy. In:  Epilepsyand Psychiatry  (Eds E. H. Reynolds and M. R. Trimble).Edinburgh, Churchill Livingstone, 1981.6. Kanner, A. M. and Nieto, J. C. R. Depressive disorders inepilepsy.  Neurology  1999;  53  (Suppl. 2): S26–S32.7. Mendez, M. F., Cummings, J. L. and Benson, D. F. Depres-sion in epilepsy; significance and phenomenology.  Archivesof Neurology  1986;  43 : 766–770.8. Blumer, D. Epilepsy and disorders of mood. In:  Advancesin 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 Epilep-tology: 13th Epilepsy International Symposium  (Eds H. Aki-moto, 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 episodein 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 inpatients 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. andHermann, B. 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