주요우울증에 대한 Milnacipran의 효과 및 안정성 : Fluoxetine과의 비교

이민수,함병주,기백석,김정범,연병길,오강섭,오병훈,이철,정한용,지익성,최병무,백인호 大韓神經精神醫學會 2004 신경정신의학 Vol.43 No.4

Objectives : This 6-week, open label randomized, multicenter study was conducted to evaluate the antidepressant effect and safety of milnacipran and fluoxetine in patients with major depression. Methods : The study was done in patients with major depression diagnosed by DSM-IV who score ≥17 in 17 items Hamilton Rating Scale for Depression (17-item HAM-D) and score ≥25 in Montgomery and Asberg Depression Rating Scale (MADRS). A total of 87 patients were randomized to milnacipran group and fluoxetine group. In cases of the patients taking other antidepressants, 6 weeks of each medication was administered after 7 days of drug excretion period. The evaluation was done using 17 item HAM-D, MADRS, Clinical Global Impression Scale (CGI), and COVI scale after baseline, 1 week, 2 weeks, 4 weeks, and 6 weeks. The side effects that had occurred during the period of our study were put in records by developed/disappeared time, severities, incidences, managements and results. Results : A total of 87 patients were enrolled. 70 (mitnacipran group 39 ; fluoxetine group 31) of them were included for the 6 weeks of research and 17 of them dropped out with in the first week, not due to adverse reactions or deficiency of effects. Total 17 item HAM-D scores, total points of MADRS, and CGI showed significant decrease after 1 week in each treatment group and continued decrease after 2 weeks and 4, 6 weeks. But there was no difference between milnacipran group and fluoxetine group in the antidepressant effect. There were no significant changes in vital sign, CBC, chemistry, and EKG in each treatment group. The commonly reported side elfects of minlacipran were nausea (25.0%), headache (10.7%), vomiting (7.1%),constipation (7.1%), dizziness (7.1%) and those of fluoxetne were GI trouble (11.1%), diarrhea (11.1%), insomnia (11.1%),agitation (5.6%), and dizziness (5.6%). Conclusion : Milnacipran was effective for the improvement of depressive symptoms and was well tolerated and safe in patients with depression.

Comparison of efficacy and safety of milnacipran and fluoxetine in Korean patients with major depression

Lee, Min-Soo,Ham, Byung Joo,Kee, Baik Seok,Kim, Jung‐,Bum,Yeon, Byeong Kil,Oh, Kang‐,Seob,Oh, Byoung Hoon,Lee, Chul,Jung, Han Yong,Chee, Ik‐,Seung,Choe, Byeong Moo,Paik, In Ho Informa UK (Librapharm) 2005 Current medical research and opinion Vol.21 No.9

<P>OBJECT: To compare efficacy and safety of milnacipran and fluoxetine in a population of Korean patients with major depression. RESEARCH DESIGN AND METHODS: The design was a multi-centre, randomised, comparative clinical study. Patients with major depression (DSM-IV diagnostic criteria) scoring over 17 points on the 17-item Hamilton Depression Scale (HAM-D) and over 21 points on the Montgomery-Asberg Depression Rating Scale (MADRS) were recruited and randomised to receive milnacipran (50 mg/day increasing after 1 week to 100 mg/day) or fluoxetine (20 mg/day) for 6 weeks. All previous medication was stopped at least 7 days before entry into the study. Patients were evaluated (HAM-D, MADRS and clinical global impression scale, CGI) at baseline and after 1, 2, 4 and 6 weeks of treatment. All adverse events which developed during the study period were recorded. RESULTS: 70 patients (milnacipran 39; fluoxetine 31) were included in the study. Total score on both HAM-D, MADRS and CGI decreased significantly in both groups after 1 week and continued to decrease throughout the study. There was no significant difference between the two groups for any measurement at any time point. Both antidepressants were well tolerated. In the milnacipran group, 13 patients reported 28 adverse reactions, and in the fluoxetine group 11 patients reported 18 adverse reactions. Two patients discontinued due to adverse events in the milnacipran group and three in the fluoxetine group. There were no clinically significant modifications in vital signs, routine blood laboratory tests, biochemistry or ECG throughout the study. Nausea and headache were the most frequently reported adverse events with milnacipran while digestive disturbances, diarrhoea and insomnia were more common with fluoxetine. CONCLUSION: Milnacipran, like fluoxetine, was found to be effective and well tolerated for the treatment of major depression in this population of depressed Korean patients. Principal limitations of the study were its open design, its small sample size and its relatively short duration.</P>

외적 환경을 고려한 최적의 항우울제 치료

함병주,한창환 大韓神經精神醫學會 2008 신경정신의학 Vol.47 No.1

Depressive illness is a major public health problem with important medical, social and economic implications. The effcacy of various antidepressants in treating depression has been demonstrated in randomized controlled trials (RCTs). However, these studies do not adequately address the complexities of clinical practice. Although most of RCTs assumed there was no difference in effcacy between the tncyclic antidepressants (TCAs) and serotonin specific reuptake inhibitors (SSRIs), natumlistic studies show that patients who take TCAs often receive subtherapeutic doses for inadequate duration than those with SSRIs. Because the benefits of the implementation of current guidelines are limited, the optimal choice of medication must be guided by detailed history and careful consideration ofthe real-world efficacy of antidepressants and long-term health care costs.

하지불편 증후군과 주기성 사지운동장애의 진단과 치료

함병주 大韓睡眠-精神生理學會 2003 수면·정신생리 Vol.10 No.1

만성 불면증 환자의 성격특성

함병주,서광윤,김인 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.2

연구배경 :임상 실제에서 만성 불면증을 진단. 치료하는데 있어 환자의 성격적 특성을 이해한다는 것은 매우 중요하다. 이에 본 저자들은 만성 불면증환자의 성격적 특성을 파악하여 불면증의 취약성에 관여하는 성격적 요인을 보다 명확히 하고자 본 연구를 시행하였다. 연구방법 :만성 불면증의 진단에는 ICSD진단기준을 적용하였고 평가척도로는 환자의 성격 성향을 평가할 수 있는 성격요인검사 및 대처방식척도를 이용하였다. 1995년 11월부터 1996년 12월까지 불면증을 주소로 고려대학교 병원 수면장애 크리닉에 내원하여 정신생리성 불면중, 부적절한 수면위생 그리고 수면제 의존성 불면증으로 진단된 만성 불면증환자는 21명이었다. 이들과 성별, 연령. 학력을 고려하여 정상인 26명을 무작위로 추출하였고 이를 정상대조군으로 하였다. 연구결과: 만성 불면증환자들은 성격요인검사상 대조군보다 자아강도(C 요인 : 4.57±1.89 vs 7.35±1.83), 지능도요인(B 요인 : 3.76±2.23 vs 6.54±1.96). 동기왜곡척도(MD 요인 : 5.05±1.72 vs6.62±1.53)에서 유의하게 낮은 점수를 나타내었으며 , 죄책감 요인(0 요인 ; 6.67±2.11 vs 3.81±1.65). 불안감 요인(0,요인 ; 7.57±2.29 vs 3.46±1.88)에서 유의하게 높은 점수를 나타내었다(p<.05).대처척도상에서는 만성불면증 환자들이 대조군보다 감정집중적 대처척도(30.30±9.53 vs 24.52±5.71) 상 유의하게 높은 점수를 나타내었다. 대처양식을 적극적, 소극적 대처로 분류하였을 경우 환자군이 소극적 대처(50.75±13.76 vs 43.26±8.73)에서 통계적으로 유의하게 보다 높은 점수를 보였다. 결 론 : 만성불면증 환자들은 낮은 자아강도, 놓은 불안감과 죄책감 때문에 스트레스 상황에서 일반인들보다 더욱 쉽게 우울해지거나 불안상태에 빠지기 쉽게 되고 따라서 보다 높은 각성과 조건화가 유발될 것이라는 것이 시사되었다. 또한 만성불면증 환자들은 소극적이고 감정집중적 대처양식을 사용함으로써 스트레스 상황시 외적으로 반응하지 뭇하고 내향화하기 쉬우며. 결과적으로 생긴 고조된 감정적 각성과 생리적 활성 상태의 유발이 불면증을 일으키고 만성화시킨다고 추정할 수 있었다. Objectives: It is very important to understand the personality characteristics of chronicinsomniacs for diagnosis and treatment in clinical practice. The authors investigated the personality factors and the ways of coping to define the personality characteristics which underly the development of insomnia. Methods :The authors used the diagnostic criteria of International Classification of Sleep Disorders to diagnose chronic insomnia, and performed 16 Personality Factors(PF) test and the Ways of Coping Checklist to both chronic insomniacs and normal controls. The diagnosis of chronic insomnia included psychophysiologic insomnia, poor sleep hygiene, and hypnotics dependent insomnia. The subjects were 21 chronic insomniacs and 26 normal controls: Results: The chronic insomniacs showed significantly lower stableness(C factor ; 4.57±1.89VS 7.38± 1.83), intelligence(B factor : 3.76±2.23 VS 6.54±1.96), motivation distorsion(B factor ; 3.76±2.23 VS 6.54±1.96) factor scores, and higher guilt-proneness(0 factor ,6.67± 2.11 VS 3.81 ±1.65), tension and anxiety(0₄ factor .7.57±2.29 VS 3.46±1.88) factor scores than controls in 16 PF. The chronic insomniacs had significantly higher emotional-focused coping(30.30±9.53 VS 24.52± 5.71) and passive coping pattern scores(50.75 ± 13.76 VS 43.26±8.73) than controls in the Ways of Coping Checklist. Conclusion : The authors suggest that chronic insomniacs are characterized by depressive mood and anxiety-proneness from low ego strength, high levels of anxiety and guilty feelings, and passive and emotion-concentrated coping pattern. This traits are supposed to be factors contributing the state of emotional arousal and resultant physiological activation that has developed and maitained the insomnia.

톨루엔 폭로근로자의 요중 마뇨산과 자각증상에 관한 연구

김주자,함정오,안규동,이병국,남택승,백남원 大韓産業醫學會 1989 대한직업환경의학회지 Vol.1 No.2

To study the relationship between the urinary hippuric acid and subjective symptoms in toluene exposed workers, urinary hippuric acid was measured and subjective symptoms questionnarire was surveyed in 93 toluene exposed male workers and 96 non-exposed office male workers. The results are as follows: 1. Mean concentration of urinary hippuric acid, which is significantly higher in exposed group than in non-exposed group, was 1.3 g/1, 1.2(GM, GSD respectively) in exposed group and 0.6 g/1, 1.2(GM, GSD respectively) in non-exposed group. 2. Mean concentration of toluene in the air in the workplace, which is significantly higher in the department of coater than in the department of mexing, was 23.4 ppm, 6.2(GM, GSD respectively) in the department of mixing and 59.8 ppm, 3.4(GM, GSD respectively) in the department of coater. 3. Complained rates of subjective symptoms were significantly higher in exposed group than in non-exposed group in all items. 4. In exposed group, complained rate of CNS related symptoms was higher than that of irritation ralated symptoms in the first part but there was no significant difference and complained rate of irritation related symptoms in the second part was significantly higher than that of CNS related symptoms. 5. In exposed group, complained rates of subjective symptoms were not compatible with dose-response relationship by the concentration of urinary hippuric acid, duration of work, department of work, and age group retrospectively.

주요우울증이 근로자의 생산성에 미치는 영향 : WHO-HPQ(Health and Work Performance Questionnaire)를 이용한 예비연구

김원,황태연,함병주,이준석,최병휘,김세주,서용진,강은호,우종민 大韓神經精神醫學會 2007 신경정신의학 Vol.46 No.6

Objectives : Major depressive disorder (MDD) causes patients' distress and makes socioeconomic burden, both directly and indirectly. We used the concept of lost productive time (LPT) to estimate the indirect costs and calculated both absenteeism and presenteeism among workers with MDD. Mcthods : Depression group was recruited from workers visiting psychiatric outpatient clinic who had MDD without major physical or mental disorders (N= 106). Age and sex matched healthy control group was also recruited through advertisement (M=100). All participants completed a interview using WHO Health and Work Performance Questionnaire (HPQ), Job Stress Measurement Scale for Korean Employees, and Hamilton Rating Scale for Depression. Statistical analysis was performed with independent t-test or χ² test as characteristics of values (p=0.05). Results : The number of absence (0.94-day/month vs. 0.10-day/month, P=0.015) andthe numberofearly leaving (2.56-day/month vs. 0.24-day/month, P<0.001) were significantly higher in the depression group. Depression group evaluated their Perfor-mance level much lower than controls with significant value (5.16 vs. 7.62, P<0.001). In addition, depression group estimated their performance level during the last 4 weeks lower compared to the level of past 1-year (5.16 vs 6.63, P<0.001). The estimated costs of absenteeism in depression group were higher than controls by 2,520,000 Korean Won per year, and those of presenteeism were also higher by 4,880,000 Korean Won per year. The total costs of LPT in depression group were higher than controls by 7,400,000 Korean Won, which corresponds to 26% ofmean annual salary. In addition, the level of occupational stress, such as high demand and interpersonal conflict, was higher in the depression group. Conclusion : Major depressive disorder costs substantial productivity loss to workers and their company. Presenteeism imposes more time cost than absenteeism. Effectiveness trials are needed to devise cost-effective programs for the early detection and treatment of depression at the workplace.

한국인 주요우울장애 환자에서 혈중 ACTH, Cortisol 농도와 해밀턴 우울 평가 척도의 신체증상 항목과의 상관관계

여혜빈,김린,함병주,심세훈,권영준,정희연,정한용,한상우,이민수,이화영 대한생물치료정신의학회 2011 생물치료정신의학 Vol.17 No.2

Objectives:Hypothalamic-Pituitary-Adrenocortical(HPA) system dysregulation plays an important role in the pathophysiology of major depressive disorder. Medically unexplained somatic symptoms comprised the predominant complaints of korean patients with major depressive disorder. It might be related to dysregulation of HPA system and somatic symptoms. The aim of this study was to investigate the association between Hamilton Depression Rating Scale severity and the Plasma Adrenocorticotropic Hormone(ACTH) & Serum Cortisol level in Korean patients with major depressive disorder. Methods:Our study design was prospective. A total 111 hospitalized patients with major depressive disorder (DSM-IV) at Anam Hospital, Korea University Medical Center between Jan 2009 and May 2011 were selected. Hamilton Depression Rating Scale was measured by psychiatrist. Plasma ACTH, Serum Cortisol levels were analyzed at the time of admission. Results:There are significant correlations(p<0.05) between Hamilton Depression Rating Scale of somatic component(HAM-D 11-15 item) and Plasma ACTH and Serum Cortisol level. However, other HAM-D sub items were not significantly correlated with Plasma ACTH and Serum Cortisol level except somatic component. Conclusion:Our Study results suggest that hyperactivity of HPA axis might be correlation with somatic symptoms in korean patients with major depressive disorder.

한국의 노인우울증 환자에서 조발성 우울증과 만발성 우울증의 임상증상의 비교

박기홍,이화영,함병주,이민수,Park, Ki-Hong,Lee, Hwa-Young,Ham, Byung-Joo,Lee, Min-Soo 대한생물정신의학회 2010 생물정신의학 Vol.17 No.3

Objectives : Clinical differences between elderly patients with early and late onset depression have been described although these have been inconsistent. We aimed to compare differences of clinical symptoms using the 17 items Hamilton Rating Scale for Depression(HAM-D-17) between two groups. Methods : Data of 175 elderly patients with a diagnosis of major depressive disorder according to DSM-IV from January 2005 to November 2009 were collected. Seventy five patients were early onset depression and one hundred patients were late onset depression. Depressive symptoms were assessed by the 17-item Hamilton Rating Scale for depression. Results : There were some differences in HAM-D-17 scores between early and late onset depression. Early onset depression patients scored significantly higher in retardation(t = 2.41, p = 0.017) and somatic symptoms( general)(t = 2.37, p = 0.019) than late onset depression patients. Conclusion : We concluded that early onset depression patients have more severe psychomotor retardation and general somatic symptoms than late onset depression patients in Korea. Because of some limitations of this study, further investigations will be needed to validate this study results.

Association between the Catechol O-Methyltransferase Val108/158Met Polymorphism and Alexithymia

Ham, Byung-Joo,Lee, Min-Soo,Lee, Young-Mee,Kim, Meyoung-Kon,Choi, Myoung-Jin,Oh, Kang-Seob,Jung, Han Yong,Lyoo, In Kyoon,Choi, Ihn-Geun S. Karger AG 2005 Neuropsychobiology Vol.52 No.3

<P>It has been suggested that the characteristics of alexithymia result from deficits in frontal lobe functioning, and the prefrontal cortex is particularly dependent on the catechol O-methyltransferase (COMT) pathway. We investigated the relationship between COMT Val108/158Met, serotonin transporter coding sequence (5-HT transporter gene-linked polymorphic region; 5-HTTLPR) polymorphisms, and alexithymia.The study sample comprised 109 students at the Korea University. All participants were tested using the 20-item Toronto Alexithymia Scale (TAS-20). They were genotyped for COMT Val108/158Met and 5-HTTLPR polymorphisms. Genotyping was analyzed using polymerase chain reaction. Subjects with Val/Val genotype had significantly higher TAS-20 scores than those with Met/Met or Met/Val genotypes. However, there was no significant relationship between the 5-HTTLPR genotype and TAS-20 scores. This indicates a possible association between the COMT Val108/158Met gene polymorphism and alexithymia.</P><P>Copyright © 2005 S. Karger AG, Basel</P>