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1 KISEP Original Articles 우울증의치료초기에 Nefazodone과 Benzodiazepine의병용투여 ABSTRACT 신일선 윤진상 정현준 이정길 이형영 Coadministration of Nefazodone and Benzodiazepine in the Early Phase of Treatment of Depression Il-Seon Shin, MD, Jin-Sang Yoon, MD, Hyeon-Joon Jeong, MD, Jeong-Gil Lee, MD and Hyung-Yung Lee, MD Department of Neuropsychiatry & Research Institute of Medical Science, Chonnam National University Medical School, Kwangju, Korea ObjectiveThe purpose of this study was to examine the efficacy and safety of coadministration of nefazodone NEF and benzodiazepine BZD in the clinical setting, particularly during the initial period of treatment. MethodsThis study was based on data collected in an open, multi-center, 8-week, clinical trial of NEF in depressed patients and focused on the first 2 weeks of treatment and the concurrent use of two BZDs alprazolam ALP, metabolized largely by the same cytochrome P450-3A4 isoform that metabolizes NEF and lorazepam LOR, eliminated by conjugation with glucuronic acid and less likely to interact with NEF. Patients receiving NEF alone NEF-mono group, n82 and those receiving adjunctive BZD therapy BZD-combi group, n29 were selected and their data were reviewed for demographic and clinical characteristics at baseline and various outcome measures at weeks 1 and 2. The BZD-combi group consisted of patients receiving alprazolam ALP-combi subgroup, n15 and those receiving lorazepam LOR-combi subgroup, n14. Efficacy was analysed according to the individual groups and subgroups. In addition, the efficacy at each time point was compared between NEF-mono and BZD-combi groups as well as between ALP-combi and LOR-combi subgroups. Safety and tolerability were judged by reported adverse effects and were compared. Results In NEFmono and BZD-combi groups, the mean daily dose for NEF was less than 200 mg/day range, mg/day and did not differ between groups and subgroups. The mean daily doses for BZDs were 0.61 mg/day range, mg/day for ALP and 1.49 mg/day range, mg/day for LOR. Sleep, anxiety and depression in both NEF-mono and BZD-combi groups were, in general, significantly improved compared to baseline. Furthermore, BZD-combi group showed greater improvement in anxiety and sleep but not in depression compared to NEF-mono group. Within the BZD-combi group, there was no significant difference in clinical effects between ALP-combi and LOR-combi subgroups. In terms of safety and tolerability, there was no evidence to suggest that BZD combination caused daytime sedation or any other particular adverse events more severely than NEF alone. Also, there was no significant difference in the side effect profiles of ALP-combi and LOR-combi subgroups. ConclusionThese results suggest that combining low doses of ALP or LOR with NEF is beneficial 222

2 for the control of insomnia and anxiety without substantial adverse effects, at least during the early period of treatment of depression when therapeutic dosages of NEF are not yet reached. Korean J Psychopharmacol 2001;123: KEY WORDSNefazodone Benzodiazepine Coadministration Depression. 서론 223

3 연구방법 1. 연구대상 2. 약물투여 3. 평가내용및도구 1) 인구사회학적및임상적특성 2) 우울및불안의평가 3) 야간의수면및주간의상태평가 224 Korean J Psychopharmacol 2001;123:

4 4) 전반적인임상적인상 5) 약물의부작용및안전성평가 4. 자료분석 결과 1. 기준시점에서인구사회학적및임상적특성 225

5 2. 약물의용량및 BZD 의사용목적 Table 1. Demographic and clinical characteristics of patients at baseline Parameters NEF only n82 NEFALP n15 NEFBZD NEFLOR n14 Total n29 NEF only vs. NEFBZD t-test or x 2 test NEFALP vs. NEFLOR t or x 2 p t or x 2 p Gender, M/F, N 27/55 5/10 3/11 8/ n.s n.s. Mean SD age, years Marriage, N 4.265* n.s * n.s. Single/married/others 19/62/1 1/12/2 2/12/0 3/24/2 Hospital setting, N n.s * n.s. Inpatient Outpatient Inpatient and outpatient Previous anti-depressant, N n.s n.s. Yes/no 36/46 7/8 9/5 16/13 Concomitant medication, N n.s * n.s. Yes/no 16/66 4/11 2/12 6/23 Concurrent disease, N n.s * n.s. Yes anxiety/others /no 19 13/6/63 2 1/1/13 4 4/0/10 6 5/1/23 Diagnosis, N n.s * n.s. Major depression, single Major depression, recurrent Dysthymia Mean scores SD on assessment scales HAM-D Total n.s n.s. Insomnia items n.s n.s. BDI Total n.s n.s. Insomnia item n.s n.s. Fatigue item n.s n.s. STAI-SA n.s WSQ Night sleep n.s. Daytime status n.s n.s. CGI-SI n.s n.s. *Fisher s exact test NEFNefazodone, BZDBenzodiazepine, ALPAlprazolam, LORLorazepam, HAM-DHamilton Rating Scale for Depression, BDIBeck Depression Inventory, STAI-SAState-Trait Anxiety Inventory-State Anxiety, WSQWeekly Sleep Questionnaire, CGI-SIClinical Global Impression for Severity of Illness 226 Korean J Psychopharmacol 2001;123:

6 Table 2. Doses of NEF during 1st week and 2nd week Week 1 Week NEF only n82 NEFALP n15 NEFBZD NEFLOR n14 Total n29 NEF only vs. NEFBZD t-test NEFALP vs. NEFLOR t p t p Mean SD, mg/day n.s n.s. Range, mg/day Week 2 Mean SD, mg/day n.s n.s. Range, mg/day NEFNefazodone, BZDBenzodiazepine, ALPAlprazolam, LORLorazepam Table 3. Mean SD scores on assessment scales at week 1 Parameters NEF only n82 NEFALP n15 NEFBZD NEFLOR n14 Total n29 t-test or ANCOVA NEF only vs. NEFBZD NEFALP vs. NEFLOR t p t p STAI-SA c c c n.s * n.s. WSQ Night sleep a c b c 6.783* n.s. Daytime status c b b n.s n.s. abcsignificant difference from baseline score at p.05, p.01, p.001 by paired t-test, respectively *ANCOVA with baseline as a covariate NEFNefazodone, BZDBenzodiazepine, ANCOVAanalysis of covariance, ALPAlprazolam, LORLorazepam, STAI-SAState-Trait Anxiety Inventory-State Anxiety, WSQWeekly Sleep Questionnaire 3. 치료 1주말의효과와군간의비교 4. 치료 2주말의효과와군간의비교 5. 부작용과안전성 227

7 Table 4. Mean SD scores on assessment scales at week 2 HAM-D Parameters NEF only n82 NEFALP n15 NEFBZD NEFLOR n14 Total n29 NEF only vs. NEFBZD t-test or ANCOVA NEFALP vs. NEFLOR t or F p t or F p Total c c c c n.s n.s. Insomnia items c c b c n.s n.s. BDI Total c c c c n.s n.s. Insomnia item c c c n.s n.s. Fatigue item c c a c n.s n.s. STAI-SA c c c c * n.s. WSQ Night sleep c c b c.941* n.s. Daytime status c b c n.s n.s. CGI-SI c c c n.s n.s. CGI-GI n.s n.s. abcsignificant difference from baseline score at p.05, p.01, p.001 by paired t-test, respectively *ANCOVA with baseline as covariate NEFNefazodone, BZDBenzodiazepine, ANCOVAanalysis of covariance, ALPAlprazolam, LORLorazepam, HAM-DHamilton Rating Scale for Depression, BDIBeck Depression Inventory, STAI-SAState-Trait Anxiety Inventory-State Anxiety, WSQWeekly Sleep Questionnaire, CGI-SIClinical Global Impression for Severity of Illness, CGI-GIClinical Global Impression for Global Improvement 고찰 228 Korean J Psychopharmacol 2001;123:

8 Table 5. Adverse effects over the 2 weeks b Adverse effectsa NEF only n82 NEFALP n15 NEFBZD NEFLOR n14 Total n29 Dizziness Dry mouth Nausea Headache Constipation Insomnia Absent mindedness Slurred speech Sedation Daytime sleepiness Hand tremor Weight gain Blurred vision Total a A patient may report more than one side effect b There was no statistically significant difference between NEF only and the combined NEFBZD Total or within NEFBZD subgroups NEFALP, NEFLOR. Due to the development of adverse events, NEF dosage was reduced in 4 cases in the NEF only group and in 1 case in the NEFALP subgroup after recording the adverse events 229

9 요약 연구목적 : 방법 : 결과 : 230 결론 : 중심단어 감사의글 Korean J Psychopharmacol 2001;123:

10 참고문헌 1) Thase ME, Kupfer DJ. Current status of EEG sleep in the assessment and treatment of depression. In: Burrow GD and Werry JS, Greenwich, editors. Advances in Human Psychopharmacology, Vol 4. Conn: JAI Press Inc;1987. p ) American Psychiatric Association. Diagnostic and Statistical Manual of Mental disorders. 2nd ed. Washington DC: American Psychiatric Association;1994. p324. 3) Reynolds CF 3rd, Kupfer DJ. Sleep research in affective illness: state of art circa Sleep 1987;10(3): ) Rodin J, McAvay G, Timko C. A longitudinal study of depressed mood and sleep disturbances in elderly adults. J Gerontol 1988;43(2): ) Beekman AT, de Beurs E, van Balkom AJ, Deeg DJ, van Dyck R, van Tilburg W. Anxiety and depression in later life: Co-occurrence and communality of risk factors. Am J Psychiatry 2000;157(1): ) Lenze EJ, Mulsant BH, Shear MK, Schulberg HC, Dew MA, Begley AE, et al. Comorbid anxiety disorders in depressed elderly patients. Am J Psychiatry 2000;157(5): ) Kent JM. SNaRIs, NaSSAs, and NaRIs. new agents for the treatment of depression. Lancet 2000;355(9207): ) Eison AS, Eison MS, Torrente JR, Wright RN, Yocca FD. Nefozodone: preclinical pharmacology of a new antidepressant. Psychopharmacol Bull 1990;26(3): ) Bolden-Watson C, Richelson E. Blockade by newly developed antidepressant of biogenic amine uptake into rat brain synaptosomes. Life Sci 1993;52(12): ) Fontaine R, Ontiveros E, Elie R, Kensler TT, Roberts DL, Kaplita S, et al. A double-blind comparison of nefazodone, imipramine, and placebo in major depression. J Clin Psychiatry 1994;55(6): ) Feigner JP, Pambakian R, Fowler RC, Bayer WF, D Amico MF. A comparison of nefazodone, imipramine, and placebo in patients with moderate to severe depression. Psychopharmacol Bull 1989;25(2): ) Baldwin DS, Hawley CJ, Abed RT, Maragakis BP, Cox J, Buckingham SA, et al. A multicenter double-blind comparison of nefazodone and paroxetine in the treatment of outpatients with modrate-to-severe depression. J Clin Psychiatry 1996;57(suppl 2): ) Feiger A, Kiev A, Shrivastava RK, Wisselink PG, Wilcox CS. Nefazodone versus sertraline in outpatients with major depression: focus on efficacy, tolerability, and effects on sexual function and satisfaction. J Clin Psychiatry 1996;57(suppl 2): ) Gillin JC, Rapaport M, Erman MK, Winokur A, Albala BJ. A comparison of nefazodone and fluoxetine on mood and on objective, subjective, and clinician-rated measures of sleep in depressed patients: a double-blind, 8-week clinical trial. J Clin Psychiatry 1997;58(5): ) Feiger AD, Bielski RJ, Bremner J, Heiser JF, Trivedi M, Wilcox CS, et al. Double-blind, placebo-substitution study of nefazodone in the prevention of release during continuation treatment of outpatients with major depression. Int Clin Psychopharmacol 1997;14(1): ) 민성길 강병조 정인과 조맹제 윤진상 김동기등. 우울증환자에서 Nefazodone 의항우울효과, 항불안효과및수면 성기능 삶의질등에미치는영향에관한다기관연구. 대한정신약물학회지 2001;12(3): ) Richelson E. Pharmacokinetic drug interactions of new antidepressants: a review of the effects on the metabolism of other drugs. Mayo Clin Proc 1997;72(9): ) Owen JR, Nemeroff CB. New antidepressants and the cytochrome P450 system: focus on venlafaxine, nefazodone and mirtazapine. Depress Anxiety 1998;7(suppl 1): ) Barbhaiya RH, Shukla UA, Kroboth, PD, Greene DS. Coadministration of nefazodone and benzodiazepines: II. A pharmacokinetic interaction study with triazolam. J Clin Psychopharmacol 1995;15(5): ) Greene DS, Salazar DE, Dockens RC, Kroboth P, Barbhaiya RH. Coadministration of nefazodone and benzodiazepines: III. A pharmacokinetic interaction study with alprazolam. J Clin Psychopharmacol 1995;15(6): ) Kroboth PD, Folan MM, Lush RM, Chaikin PC, Shukla UA, Barbhaiya RH, et al. Coadministration of nefazodone and benzodiazepines: I. Pharmacodynamic assessment. J Clin Psychopharmacol 1995;15(5): ) Greene DS, Salazar DE, Dockens RC, Kroboth P, Barbhaiya RH. Coadministration of nefazodone and benzodiazepines: IV. A pharmacokinetic interaction study with lorazepam. J Clin Psychopharmacol 1995;15(6): ) Rickels K, Schweizer E, Case WG, DeMartinis N, Greenblatt DJ, Mandos LA, et al. Nefazodone in major depression: adjunctive benzodiazepine therapy and tolerability. J Clin Psychopharmacol 1998;18(2): ) Hamilton M. A rating scale for deprssion. J Neurol Neurosurg Psychiatry 1960;23: ) Hamilton M. Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 1967;6(4): ) 김광일. 우울증의증후학적연구. 제 1 편 : Hamilton 우울증측정표의적응을위한연구. 신경정신의학 1977;16(1): ) Beck AT, Ward CH, Mendelson M, Mock JE, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry 1961;4: ) 신민섭 김중술 박광배. 한국판 BECK 우울척도의분할점과분류오류. 한국심리학회지 1993; 임상 12: ) 한홍무 염태호 신영우 김교헌 윤도준 정근재. Beck Depression Inventory 의한국판표준화연구 정상집단을중심으로 (1). 신경정신의학 1986;25(3): ) Spielberger CD, Gorsuch RL, Lushene RE. Manual for the State-Trait Anxiety Inventory. Palo Alto, California: Consulting Psychologists Press; ) 김정택. 특성불안과사회성과의관계 -Spielberger 의 STAI 를중심으로 ( 석사학위 ). 서울 : 고려대학교대학원 ; ) Davis R, Whittington R, Bryson HM. Nefazodone. A review of its pharmacology and clinical efficacy in the management of major depression. Drugs 1997;53(4): ) Marangel LB, Yudofsky SC, Silver JM. Psychopharmacology and Electiveconvulsive therapy. In: Hales RE, Yudofsky SC, Talbot JA. editors, Textbook of psychiatry. 3rd ed. Washington DC: American Psychiatric Press;1999. p ) Ray WA, Griffin MR, Malcolm E. Cyclic antidepressants and the risk of hip fracture. Arch Intern Med 1991;151(4):

11 35) Ray WA, Fought RL, Decker MD. Psychoactive drugs and the risk of injurious motor vehicle crashes in elderly drivers. Am J Epidemiol 1992;136(7): ) Rush AJ, Armitage R, Gillin JC, Yonkers KA, Winokur A, Moldofsky H, et al. Comparative effects of nefazodone and fluoxetine on sleep in outpatients with major depressive disorder. Biol Psychiatry 1998;44(1): ) Armitage R, Yonkers K, Cole D, Rush AJ. A multicenter, double-blind comparison of the effects of nefazodone and fluoxetine on sleep architecture and quality of sleep in depressed outpatients. J Cln Psychopharmacol 1997;17(3): ) Armitage R. Effects of antidepressant treatment on sleep EEG in depression. J Psychopharmacol 1996;10(suppl 1): ) Armitage R, Rush AJ, Trivedi M, Cain J, Roffwarg HP. The effects of nefazodone on sleep architecture in depression. Neuropsychopharmacology 1994;10(2): ) Sharpley AL, Willamson DJ, Attenburrow MEJ, Pearson G, Sargent P, Cowen PJ. The effect of paroxtine and nefazodone on sleep: a placebo controlled trial. Psychopharmacology 1996;126(1): ) van Laar MW, van Willigenburg AP, Volkerts ER. Acute and subchronic effects of nefazodone and imipramine on highway driving, cognitive functions, and daytime sleepiness in healthy adult and elderly subjects. J Clin Psychopharmacol 1995;15 (1): ) Fawcett J, Scheftner WA, Fogg L, Clark DC, Young MA, Hedeker D, et al. Time-related predictors of suicide in major affective disorder. Am J Psychiatry 1990;147(9): ) Nutt DJ. Care of depressed patients with anxiety symptoms. J Clin Psychiatry 1999;60(Suppl 17): Korean J Psychopharmacol 2001;123:

5 Department of Psychiatry, Chonnam University Medical School, Kwangju, 6 Department of Biostatistics, Yonsei University, College of Medicine, Seoul,

5 Department of Psychiatry, Chonnam University Medical School, Kwangju, 6 Department of Biostatistics, Yonsei University, College of Medicine, Seoul, KISEP Original Articles 12 3 2001 우울장애환자에서 Nefazodone의항우울효과, 항불안효과및수면 성기능 삶의질등에미치는영향에관한다기관연구 민성길 1 강병조 2 정인과 3 조맹제 4 윤진상 5 김동기 6 강민희 7 김도관 8 김명정 9 김석현 10 김용구 11 김정기 12 박민철 13 방계원 14 손봉기 15 신지용 16 오강섭 17