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1 원저접수번호 :09-029(2 차 -0710) 가천의과학대학교의학전문대학원, 가천의과학대학교길병원신경과학교실 a 허선희박현미 a Depression and Anxiety in the Epileptic Patients: the Association With Demographic and Seizure-Related Variables Seon-Hee Heo, MD, Hyeon-Mi Park, MD a Graduate School of Medicine, Gachon University of Medicine and Science, Department of Neurology, Gachon University Gil Hospital a, Incheon, Korea Background: Depression and anxiety are common psychiatric symptoms in patients with epilepsy, exerting a profound negative effect on health-related quality of life. Several issues, however, pertaining to their association with psychosocial, seizure-related and medication factors, remain controversial. In the present study we have investigated the association of depression and anxiety with various demographic and seizure-related variables in patients with newly-diagnosed and chronic epilepsy. Methods: We investigated 80 patients with epilepsy (46.3% males, mean age 36.1±11.4 years, range 18~64; mean disease duration, 13.4±12.2 years). Depression and anxiety were assessed in the interictal state with the Beck Depression Inventory, 21-item version (BDI-21) and the state and trait subscales of the State-Trait Anxiety Inventory (STAI-S and STAI-T), respectively. The association of depression and anxiety with various variables was investigated using univariate analyses and multiple linear regression analyses. Results: Duration of epilepsy, the number of side effects and the number of GABAergic anti-epileptic drugs were correlated with depression, together accounting for 25.1% of the variation of the BDI-21. The STAI-S index was significantly associated with occupation status and the number of GABAergic anti-epileptic drugs accounting for 27.4% of the variation of the STAI-S. Finally, the number of side effects was correlated with trait anxiety. Conclusions: Our study shows that the duration of epilepsy, occupation status, GABAergic anti-epileptic drugs and the number of side effects are risk factors for the development of depression and/or anxiety. J Korean Neurol Assoc 27(4): , 2009 Key Words: Epilepsy, Depression, Anxiety 서론 간질환자치료의일차적인목표는발작의완전한조절이다. 1 최근적절한항경련제의사용으로환자의 80% 이상에서발작이 Received August 18, 2009 Revised October 14, 2009 Accepted October 14, 2009 *Hyeon-Mi Park, MD Department of Neurology, Gachon University Gil Hospital, 1198, Guwol-dong, Namdong-gu, Incheon, , Korea Tel: Fax: neurohm@gilhospital.com 잘조절되며그빈도와정도를충분히줄일수있게되었다. 2 하지만이런발작의조절에도불구하고간질환자에서는우울, 불안등의정신과적문제들이많이나타나고있으며, 3,4 간질환자의자살률이일반인구에비해 5배이상높은것으로보고되었다. 5 간질환자에서나타나는우울과불안은발작자체로인한증상들에비해간과되기쉬운데, 이는환자자신이정신과적증상을잘드러내지않고우울및불안의양상이일반인에서나타나는것과는다르며이런정신과적증상들을단순히질병을받아들이는과정의하나로보기때문인것으로생각된다. 6 하지만우울, 불안과같은정신과적문제는건강관련삶의질을낮추 J Korean Neurol Assoc Volume 27 No. 4,

2 허선희박현미 는주요요인으로서 7 환자의원활한사회생활에도부정적인요소로작용하기때문에그병인을이해하고조기에발견하여치료하는것이매우중요하다. 한편, 간질환자에서는당뇨병이나천식등의다른만성질환군보다우울이더빈번히나타나고그양상도다른데 8 이는간질환자의정신과적문제가사회심리학적장애요인뿐아니라간질자체에의한요인도관련되어있음을나타내며이를규명하기위해최근간질유발병터 (epileptogenic foci) 의대뇌측위 (cerebral laterality), 항경련제의복용과그로인한부작용과의연관성등이연구되고있다. 8 따라서본연구는항경련제를투여중인간질환자들을대상으로우울과불안을객관적인방법으로평가하고인구학적요인및항경련제를포함한간질관련요인과의연관성에대해알아보고자하였다. 항경련제복용과관련하여발생할수있는부작용의항목들을설문지에제시하여환자가해당항목에표시하도록하였고, 환자가표시하지않은항목중병원기록상에존재하는부작용과환자자신이답하기어려운혈액검사이상등은병원기록을이용하여조사하였다. 관련부작용에는우울과불안을제외한용량의존성부작용과피부발진, 빈혈, 혈소판감소증등의특이체질성부작용이포함된다. 모든연구대상자는국제간질기구 (international league against epilepsy, ILAE, 1981) 의분류를기준으로환자가갖고있는주되고반복적인임상발작양상에따라단순부분발작, 복합부분발작, 부분발작에서 2차전신발작, 그리고전신발작으로나누었고, 뇌파, 뇌영상결과등을토대로원인은특발성 (idiopathic), 증후성 (symptomatic), 잠재성 (cryptogenic) 세가지로나누어분류하였다. 대상과방법 1. 대상 대상은총 80명으로 2008 년 1월 14일부터 2008 년 7월 1일까지신경과외래에내원한 18세부터 65세사이의환자를대상으로하였으며다음의기준을모두만족시킨환자로하였다. (1) 스스로설문지를읽고작성할수있을것 (2) 신경과전문의가임상증상과뇌파검사로간질로확진하였을것 (3) 조사당시간질발작에따른증상이없을것 (4) 간질이주증상이며다른진행되는뇌질환이없을것 (5) 간질발병전에정신장애에대한진단병력이없을것 2. 방법우울및불안평가를위한설문지는연구목적과취지설명에동의한환자들로하여금외래에서작성케하였고, 필요한경우연구자가도움을주었다. 설문지와병원기록을통하여교육수준, 직업상태, 결혼상태, 종교, 손잡이 (sinistrality), 간질이외의만성질환유무, 흡연과음주, 정신과적가족력과같은인구사회학적특징과발병연령, 이완기간, 발작횟수, 전조증상, 항경련제투여기간과관련부작용수, 투여중인항경련제의수와종류와같은간질관련특성에대한자료를얻었다. 항경련제관련부작용수란전체치료기간중환자가한번이상경험한모든부작용의수를말한다. 부작용에대한조사는 3. 도구우울의평가는 Beck 우울척도 (Beck Depression Inventory; BDI) 를사용하였고, 9,10 불안의평가는상태 -특성불안척도 (The State-Trait Anxiety Inventory; STAI) 를사용하였다. 11,12 BDI 는 21 개문항에대해각각 0~3 점의점수범위가있어, 전체점수범위는 0~63 점이되며우울증진단의절단점 (cut-off score) 은 21점으로하였다. STAI 는상태불안 (state subscales of the State-Trait Anxiety Inventory, STAI-S) 과특성불안 (trait subscales of the State-Trait Anxiety Inventory, STAI-T) 을측정하는총 40문항으로구성되는데상태불안은환자가일과성으로느끼는주관적긴장과걱정을, 특성불안은위협적인것으로지각한상황에반응하는비교적변화하지않는개인차를측정한다. 4. 자료처리통계프로그램은 SPSS version 12.0 을이용하였고, 통계적유의수준은 α=0.05 를기준으로하였으며연구대상자의특성은빈도와백분율, 평균과표준편차를이용하여제시하였다. 인구학적요인, 간질관련요인에따른우울및불안을비교하기위하여 t-검정, 분산분석, Pearson 상관분석을이용하였으며최종적으로단순분석에서유의한관련성을보인변수들을이용하여단계적다중회귀분석 (stepwise multiple linear regression) 을실시하였다. 376 대한신경과학회지제 27 권제 4 호, 2009

3 결과 1. 연구대상자의우울및불안정도 우울정도를평가하기위한 BDI 는평균 15.9±10.7 로한홍무등 (1986) 의연구에서보고한정상집단의평균 13.01±7.8 보다높았으며 21점을절단점으로하여 9 우울증여부를판별하였을때전체대상자의 22명 (27.5%) 이포함되었다. 불안에대한평가결과상태불안 (STAI-S) 은평균 43.0±12.4 이며, 특성불안 (STAI-T) 은평균 46.8±11.2 였다. 2. 인구학적요인과우울및불안과의관련성성별과연령에따른우울, 상태불안, 특성불안은유의한차이가없었다. 교육수준에따라서우울은유의한차이를보였으며 (p=0.009) 상태불안, 특성불안은유의한차이가없었다. 직업이없는경우가직업이있는경우보다우울 (p=0.024), 상태불안 (p<0.001), 특성불안 (p=0.006) 이유의하게높았으며결혼상태에따른우울, 상태불안, 특성불안간의유의한차이는없었다. 종교를가지지않은경우종교를가진경우보다상태불안에서유의하게높았으며 (p=0.021) 손잡이와간질이외의만성질환유무에따른우울과상태불안, 특성불안은모두유의 Table 1. Univariate analyses of demographic variables associated with BDI, STAI-S and STAI-T Variable Total (n=80) BDI STAI-S STAI-T mean±sd p value mean±sd p value mean±sd p value Sex Men 37 (46.3) 16.5± ± ± Women 43 (53.8) 15.4± ± ±10.5 Age(yr) 36.1± ± ± ± Education Elementary school 4 (5.0) 12.3± ± ± Middle school 6 (7.5) 26.0± ± ±4.3 High school 46 (57.5) 17.3± ± ±10.3 College 24 (30.0) 11.3± ± ±14.4 Occupation Employed 34 (42.5) 12.8± ±10.0 < ± Unemployed 46 (57.5) 18.2± ± ±11.2 Marital status Unmarried 32 (40.0) 14.2± ± ± Married 34 (42.5) 15.3± ± ±9.5 Others a 11 (13.8) 21.2± ± ±10.1 Religion Yes 51 (63.8) 14.4± ± ± No 29 (31.3) 18.7± ± ±10.7 Sinistrality Left-handed 11 (13.8) 18.5± ± ± Right-handed 69 (86.3) 15.5± ± ±11.2 Other chronic illness b Present 23 (28.8) 16.3± ± ± Absent 57 (71.3) 15.8± ± ±11.4 Current smoking status Yes 21 (26.3) 11.9± ± ± No 48 (60.0) 16.4± ± ±10.6 Alcohol drinking Yes 41 (51.3) 16.4± ± ± No 30 (37.5) 14.3± ± ±11.1 Family history of psychiatric disorder c Present 7 (8.8) 20.9± ± ± Absent 73 (91.3) 15.4± ± ±11.1 a divorced, separated, widowed, cohabitating, b current disease including hypertension, diabetes, cancer, heart disease, thyroid disease, liver disease, rheumatoid arthritis, pulmonary disease, renal disease, c including depression, suicide, alcohol abuse, dementia, BDI; Beck Depression Inventory, STAI-S; state subscales of the State-Trait Anxiety Inventory, STAI-T; trait subscales of the State-Trait Anxiety Inventory, SD; standard deviation J Korean Neurol Assoc Volume 27 No. 4,

4 허선희박현미 한차이가없었다. 흡연을하는경우가흡연을하지않는경우보다특성불안에대해유의하게높은점수를보였고 (p= 0.030), 음주나정신과적가족력유무에따른차이는없었다 (Table 1). 3. 간질관련요인과우울및불안과의관련성발병연령에따른우울, 상태불안, 특성불안은유의한차이가없었으며, 이완기간에따라서는우울에서유의한차이를보였다 (p=0.012). 지난한달간발작횟수와지난일년간발작횟수에따른우울, 상태불안, 특성불안은유의한차이가없었 Table 2. Univariate analyses of seizure-related variables associated with BDI, STAI-S and STAI-T Variable Total (n=80) BDI STAI S STAI T mean±sd p value mean±sd p value mean±sd p value Age at onset (yr) 22.1± ± ± ± Duration of epilepsy (yr) 13.4± ± ± ± Seizure frequency in past month None 58 (72.5) 15.5± ± ± ~2 13 (16.3) 16.6± ± ± (6.3) 12.0± ± ±11.5 Seizure frequency in past year 0~1 44 (55.0) 14.9± ± ± ~5 15 (18.8) 15.6± ± ±12.9 6~10 5 (6.3) 18.4± ± ± (3.8) 9.3± ± ±14.6 Aura Present 33 (41.3) 18.1± ± ± Absent 47 (58.8) 12.8± ± ±11.8 Type of epileptic seizures Simple partial 4 (5.0) 13.8± ± ± Complex partial 7 (8.8) 13.1± ± ±11.7 Partial seizure evolving secondarily generalized 42 (52.5) 17.5± ± ±10.8 Generalized 27 (33.8) 14.5± ± ±10.8 Type of epilepsies and syndromes FLE 29 (36.3) 14.0± ± ± TLE 29 (36.3) 18.6± ± ±10.6 OLE 2 (2.5) 20.0± ± ±1.4 Generalized 20 (25.0) 14.3± ± ±11.2 Etiology Idiopathic 21 (26.3) 14.1± ± ± Symptomatic 31 (38.8) 16.5± ± ±9.0 Cryptogenic 28 (35.0) 16.5± ± ±13.5 Duration of treatment (yr) 9.3± ± ± ± Number of side effects a 2.9± ± ± ± Number of anti epileptics 1.8± ± ± ± Number of GABAergic anti epileptic agents b None 38 (47.5) 12.1± ± ± (30.0) 17.5± ± ± (18.8) 20.9± ± ± (3.8) 26.3± ± ±7.6 Use of Lamotrigine Not use 50 (62.5) 16.9± ± ± Monotherapy 14 (17.5) 11.1± ± ±11.1 Multitherapy with other drug 16 (20.0) 17.1± ± ±10.5 a including dose-related side effects and idiosyncratic side effects excepting mood disorders such as depression and anxiety, b including Phenobarbital, Valproate, Topiramate, Vigabarin, benzodiazepine, BDI; Beck Depression Inventory, STAI-S; state subscales of the State-Trait Anxiety Inventory, STAI-T; trait subscales of the State-Trait Anxiety Inventory, SD; standard deviation, GABA; gamma-amino butyric acid 378 대한신경과학회지제 27 권제 4 호, 2009

5 으며, 전조증상이있는경우전조증상이없는경우보다우울에서높은점수를보였다 (p=0.027). 간질발작분류와간질증후군의분류에서우울, 상태불안, 특성불안은유의한차이가없었고, 원인에따른분류에서도유의한차이는없었다. 항경련제투여기간에따른우울은유의한차이를보였으며 (p= 0.023), 부작용수가많을수록우울 (p=0.001), 상태불안 (p= 0.002), 특성불안 (p=0.002) 은높은점수를보였다. 사용하는항경련제의수가많을수록우울에서높은점수를보였으며 (p= 0.012), 특히 GABAergic 항경련제를많이사용할수록우울 (p= 0.007), 상태불안 (p=0.008) 에서높은점수를보였다. 또한통계학적으로유의한결과를보이지는않았으나 lamotrigine 만을사용한환자에서우울및불안이낮은평균값을보였다 (Table 2). 4. 우울및불안에미치는요인 ( 단계적다중회귀분석 ) 간질환자의우울및불안에미치는요인을알아보기위하여 단순분석에서유의한관련성을보인변수들을이용하여단계적다중회귀분석 (stepwise multiple linear regression) 을하였다. 우울에대해서는성별, 연령과함께교육수준, 직업상태, 이완기간, 전조증상, 치료기간, 부작용의수와 GABAergic 항경련제의수를사용하였는데, 이중부작용의수와 GABAergic 항경련제의수, 이완기간이관련요인으로분석되었다. 각요인의영향력을살펴보면부작용의수만사용한경우 (Model 1) 의설명력은 14.2% 이며, 부작용의수와 GABAergic 항경련제의수를사용한경우 (Model 2) 의설명력은 20.5% 로 6.3% 가증가하였고, 부작용의수, GABAergic 항경련제의수, 이완기간을사용한경우 (Model 3) 의설명력은 25.1% 로 4.6% 가증가하였다. Model 3에서우울에대한세요인을살펴보면부작용의수 (t=2.283, p=0.025), GABAergic 항경련제의수 (t=2.282, p= 0.025), 이완기간 (t=2.116, 0.038) 중부작용의수가가장큰영향을미치는것으로나타났다 (Table 3). 상태불안에대해서는성별, 연령과함께직업상태, 종교, Table 3. Significant predictors of depression (measured as Beck Depression Inventory score) in stepwise multiple linear regression analysis a Model (BDI) Unstandardized coefficient Standardized B SE coefficient T p value F R 2 Change R 2 1 (Constant) Number of side effects (Constant) Number of side effects b Number of GABAergic anti epileptic agents c (Constant) Number of side effects b Number of GABAergic anti epileptic agents c Duration of epilepsy (yr) a Regression analysis controlling for sex, age, education, occupation, duration of epilepsy, aura, duration of treatment, number of side effects and number of GABAergic anti-epileptic agents, b including dose-related side effects and idiosyncratic side effects excepting mood disorders such as depression and anxiety, c including Phenobarbital, Valproate, Topiramate, Vigabarin, benzodiazepine, BDI; Beck Depression Inventory, SE; standard error, GABA; gamma-amino butyric acid Table 4. Significant predictors of anxiety (measured as state subscales of the State-Trait Anxiety Inventory score) in stepwise multiple linear regression analysis a Model (STAI S) Unstandardized coefficient Standardized B SE coefficient T p value F R 2 Change R 2 1 (Constant) Occupation (Constant) Occupation Number of GABAergic anti epileptic agents b a Regression analysis controlling for sex, age, occupation, religion, number of side effects and number of GABAergic anti-epileptic agents, b including Phenobarbital, Valproate, Topiramate, Vigabarin, benzodiazepine, STAI-S; state subscales of the State-Trait Anxiety Inventory, SE; standard error, GABA; gamma-amino butyric acid J Korean Neurol Assoc Volume 27 No. 4,

6 허선희박현미 부작용의수, GABAergic 항경련제의수를사용하였는데, 이중직업상태와 GABAergic 항경련제의수가관련요인으로분석되었다. 각요인의영향력을살펴보면직업상태만을사용한경우 (Model 1) 의설명력은 16.8% 이고, 직업상태와 GABAergic 항경련제의수를사용한경우 (Model 2) 의설명력은 27.4% 로 10.6% 가증가하였다. Model 2에서상태불안에대한두요인을살펴보면직업상태 (t=-3.932, p=0.000), GABAergic 항경련제의수 (t=3.357, p=0.001) 중직업상태가더큰영향을미치는것으로나타났다 (Table 4). 특성불안에서대해서는성별, 연령과함께직업상태, 흡연, 부작용의수를사용하였는데, 이중부작용의수 (t=3.035, p=0.003) 만관련요인으로나타났고, 설명력은 12.1% 였다 (Table 5). 고찰 본연구에서는간질환자에서나타나는가장흔한정신과적합병증인우울과불안에관여하는인구학적요인과간질관련요인에대하여알아보았다. 우울에대해서는부작용의수, GABAergic 항경련제의수, 이완기간이관련이있으며, 이중부작용의수가가장큰영향을미치는것으로나타났다. 상태불안에대해서는직업상태와 GABAergic 항경련제의수가관련요인으로분석되었으며특성불안에대해서는부작용의수가관련요인으로나타났다. 1. 인구학적요인우울증은일반적으로여성에많은것으로알려져있으나, 간질환자에서는남성에서우울증과정신병의빈도가더높고, 13 간질을가진남성의자살시도율이여성에비해 2배정도높은것으로보고되었다. 14 성별에따른불안정도의차이는논란의여지가있지만 15 Jacoby 등 (1996) 의연구에서는여성이남성에비해높은불안정도를나타내는것으로나타났다. 16 하지만 Robertson 등 (1994) 은우울증지표들과성별, 연령, 간질및우 울증의가족력사이에는유의한상관관계가없다고하였고 17 본연구에도성별, 연령, 정신과적가족력에따른우울및불안에서유의한차이를보이지않았다. 본연구대상자의교육수준은고등학교가 57.5% 로가장많은수를차지하였고비록단계적다중회기분석에서유의한결과를보이지않았지만단순분석에서는우울에서평균 BDI 점수가중학교 26.0±10.2, 고등학교 17.3±11.4, 초등학교 12.3 ±5.6, 대학교 11.3±7.6 으로통계적으로유의한차이를보였다 (p=0.009). 교육수준은직업상태와함께간질환자의사회적예후 (social prognosis) 를결정하는중요한요인이며 18 사회적고립, 정보의부족, 사회기술결여, 가족의지지부족등과함께간질환자의높은비고용률을설명하는중요한요인이다. 19 본연구에서는직업상태와상태불안간에가장큰연관관계를나타냈고, 단순분석에서는우울, 상태불안, 특성불안모두직업이없는경우가높은점수를나타내직업상태가간질환자의우울및불안에많은영향을미치는것으로나타났다. 간질환자의경우공공부분의운전이나위험한작업장에서의근무와같은특수한경우를제외한작업은충분히가능함에도불구하고직업을구하는것에어려움을겪고있는것이사실이다. 미국간질재단 (The Epilepsy Foundation of America) 이보고한자료에의하면, 20,21 간질환자중 13~25% 가직업이없는상태이고, 단지 48% 의환자만이안정적인직업을가지고있다고하며, 22 본연구에서도 42.5% 가직업이없는경우로답하였다. 또한간질을가지고있음으로인해생기는어려움은 22% 가취업에관련된것이고, 24% 는우울, 불안과같은심리적문제라고하여간질을가진사람들의직업재활문제에보다많은주의를기울일필요가있음을알수있다. 22 우리나라의경우간질을가진사람들의직업실태는이보다더낮은수준일것으로예상되므로직업재활문제는더욱시급하다고할수있다. 좌측측두엽간질환자에서손잡이와우울과의관계를보면오른손잡이보다왼손잡이에서높은우울을나타냈다는보고가있으나 23 본연구에서는손잡이와우울및불안에서유의한차이가나타나지않았는데이는전체대상자중왼손잡이가 11명에불과한것에기인하는것으로생각된다. Table 5. Significant predictor of anxiety (measured as trait subscales of the State-Trait Anxiety Inventory score) in stepwise multiple linear regression analysis a Unstandardized coefficient Standardized Model (STAI-T) T p value F R 2 Change R 2 B SE coefficient 1 (Constant) Number of side effects b a Regression analysis controlling for sex, age, occupation, current smoking and number of side effects, b including dose-related side effects and idiosyncratic side effects excepting mood disorders such as depression and anxiety, STAI-T; trait subscales of the State-Trait Anxiety Inventory, SE; standard error 380 대한신경과학회지제 27 권제 4 호, 2009

7 2. 간질관련특성 Indaco (1992) 는발병연령과이완기간및발작횟수와우울증발병은연관관계를찾지못하였다고하였으나, 24 Dodrill 및 Batzel (1986) 25 과 Jacoby 등 (1996) 26 은발병연령이늦을수록, 이완기간이길수록, 발작횟수가증가할수록우울증발병이증가한다고보고하였다. 본연구에서는발병연령, 발작횟수와우울및불안은관련이없는것으로나타났으며이완기간이길수록우울이높은점수로나타났다. 일부연구에서는부분발작, 특히측두엽기원 (temporal lobe origin) 의복합부분발작 (complex partial seizure) 의경우우울증의발병의위험인자라고하였으나 13,23,27-30 본연구에서는간질발작분류와간질증후군의분류에따른우울및불안이통계적으로유의한차이를보이지않았다. 또부분발작에서의높은우울증발병률과연관되어정신성전조증상 (psychiatric aura) 을겪는간질환자에서전조증상이없거나다른전조증상을갖는간질환자에비해더높은우울증을보이는것으로보고되었으며, 31 이는본연구결과와일치한다. 병인에따른분류와우울및불안과의관계에대해서는아직논란의여지가있으며일부에서는증후성간질 (symptomatic epilepsy) 이특발성간질 (idiopathic epilepsy) 이나잠복성간질 (cryptogenic epilepsy) 에비해연관이된다고하였으나 32,33 일부에는관련이없다는주장도있었는데 13,34 본연구에서는관련성이나타나지않았다. 최근항경련제가중요한정신과적합병증의원인이된다는연구들이발표되었는데 Kanner 등 (2000) 의우울증치료를받고있는간질환자 100 명을대상으로한연구에서 30% 에해당하는환자가항경련제에의해우울증이발병한것으로생각되었다. 31 항경련제는이온채널의영향유무, 억제성신경전달물질의증가또는흥분성신경전달물질의조절유무에따라분류되는데 voltage-dependent sodium channel 의억제작용, γ-aminobutyric acid (GABA) 매개신경억제작용의증강, glutamate 의수용체길항작용등이알려져있다. 35 Trimble (1998) 의연구에의하면 GABAergic 수용체관련물질, 즉 vigabatrin, tiagabine, topiramate, phenobarbital 이우울증을유발시킬수있는것으로보고되었고 36 이는본연구결과와도일치한다. Lamotrigine 의경우 Smith 등 (1993) 의연구에서인지기능저하등의부작용이거의없고 placebo 를사용한군보다주관적인행복감에서유의한증가가있었다고밝혔으며, 37 Meador 등 (2001) 의연구에서는 lamotrigine 을사용한환자에서주의집중력, 기억, 정동증상, 여러삶의질측정에서더나은결과를보였다. 38 본연구에서는통계학적으로유의한 결과를보이지는않았으나 lamotrigine 만을사용한환자에서 lamotrigine 을사용하지않거나다른약물과병용하여사용한경우보다우울및불안이낮은평균값을보였다. 정신과적부작용을제외한항경련제관련부작용과우울및불안과의연관성에대해보고한연구결과는없었으나, 일부연구에서항경련제관련부작용이건강관련삶의질에부정적인영향을미친다고하였고, 39 또다른연구에서는부작용프로파일 (adverse event profile) 과우울이주관적인건강상태 (subjective health state) 와상관관계가있음을보고하였다. 40,41 본연구에서는경험한부작용의수가많을수록우울및불안이모두높은정도로나타나발작의조절뿐아니라발생가능한부작용의가능성을최소화할수있는약물선택의중요성을다시확인할수있었다. 하지만본연구는전체치료기간동안나타난부작용수를조사한것이기때문에항경련제관련부작용과의연관성에대해보다정확히알기위해서는부작용의발생빈도와증상의심각성에대한조사가필요할것으로보인다. 3. 한계점본연구에서는정상대조군과의비교연구가이루어지지않아일반인과의우울및불안의유병률을비교할수없었다. 또한항경련제와의관련성에대하여보다명확한관계를밝히기위해항경련제의혈중농도측정을포함하는보다정교한연구가필요할것으로생각되며, 항경련제관련부작용의발생빈도와심각성, 항경련제용량과의관련성에대한조사가필요할것으로보인다. 또보다많은대상인원을선정하여간질분류를세분화하고 MRI, 뇌파결과를바탕으로뇌의기질적병변과의관련성을체계적으로고려해야할것이다. 결론 우울은간질환자의중요한정신과적인합병증이며, 42 이는발작횟수및정도, 직업상태등과함께환자의건강관련삶의질을떨어뜨리는데큰영향을미치는요인으로알려져있다. 7 또간질환자들은 66% 가량이불안을경험하는데, 13 이는사회화와직업상태생활을방해하여많은환자들이어려움을겪는다. 25 따라서간질환자에서나타나는우울과불안에대한병인을이해하고조기발견하여치료하는것은환자의건강관련삶의질을향상시키고사회생활을잘영위해나가는데매우중요한문제라하겠다. 본연구에서는환자의다양한인구학적특성과간질관련특 J Korean Neurol Assoc Volume 27 No. 4,

8 허선희박현미 성을조사하여우울및불안에영향을미칠수있는요인들을가능한한통제하였다. 연구결과항경련제사용과관련된부작용의수가간질환자에서나타나는우울및불안과가장큰관련이있으며 phenobarbital, vigabatrin, topiramate 등의 GABAergic 항경련제의사용도연관이있음이밝혀졌다. 또한이완기간이길수록우울이증가하였고직업상태가환자의불안정도와관련이있는것으로나타났다. 따라서간질환자를치료함에있어환자개개인의정신과적합병증의위험요인에대한측정과이를고려한적절한약물선택으로순응도를높이고항경련제로인한기능적손상과부작용을최소화하여야할것이다. 또한발작으로인한사회적편견및활동의제한등사회적인식을바꾸기위한노력과함께보다구체적인직업상태재활훈련프로그램을제공하기위한노력을계속하여야할것이다. REFERENCES 1. Allan HR, Martin AS. Adams and victor s principles of neurology. 9th ed. The United states of America: the McGraw-Hill Companies, 2009; Rimmer EM, Richens A. Clinical pharmacology and medical treatment. In: Laidlaw J, Richens A, Oxley J, editors. A textbook of epilepsy. 3rd ed. Edinburgh: Churchill Livingstone, 1988; Pond DA, Bidwell BH. A survey of epilepsy in Fourteen General Practice II: Social and Psychological Aspects. Epilepsia 1960;1: Currie S, Heathfield KW, Henson RA, Scott DF. Clinical course and prognosis of temporal lobe epilepsy: A Survey of 666 patients. Brain 1971;94: Mattews WS, Barabas G. 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A 617 Special Issue Diabetic Retinopathy Won Ki Lee, M.D. Department of Ophthalmology The Catholic University of Korea College of Medicine Kangnam St. Mary s Hospital E mail : wklee@catholic.ac.kr Abstract R