1. 연구대상 연구대상및방법

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1 KISEP Original Articles 생물정신의학 Vol. 4, No. 2, December 1997 우울장애의치료에있어서 dothiepin-sertraline 병합과 dothiepin 단독요법의비교 차지현 * 정인과 * 이민수 * Comparison between Dothiepin-Sertraline Combination and Dothiepin Alone Therapy in the Treatment of Depressive Disorder Ji Hyun Cha, M.D.,* In-Kwa Jung, M.D.,* Min Soo Lee, M.D.* ABSTRACT T he dysfunction of either or both noradrenaline and serotonin system are important in the pathophysiology of depression. Previous reports have suggested that there may be an important interaction between these two systems. Recently, some investigators have suggested that the combination of tricyclic antidepressantstcas and selective serotonin reuptake inhibitorsssris would produce a rapid synergistic effect on down-regulation of either or both of these two systems and that this combination may produce a more rapid and absolute antidepressant effect. We compared the treatment efficacy, treatment associated side effects, treatment satisfaction, and the quality of life between the combination therapy of dothiepin-sertraline as well as the therapy of dothiepin alone in the treatment of major depressive disorder and dysthymic disorder. In our study, the combination therapy of dothiepin and sertraline produced a more rapid and absolute antidepressant effect than dothiepin alone. And the patients with combination therapy experienced relatively high treatment satisfaction than the patients with dothiepin therapy. The patients quality of life improved more rapidly in the combination therapy, especially, in the health perception, social behavior, and life satisfaction, than dothiepin alone. These results support the hypothesis that the combination of TCA and SSRI may produce a rapid synergistic effect on either or both norepinephrine and serotonin system, and more rapid antidepressant effect and high treatment satisfaction. KEY WORDSDepressive disorderscombination therapydothiepinsertraline. 서 Department of Neuropsychiatry, College of Medicine, Korea University, Seoul, Korea 론

2 1. 연구대상 연구대상및방법

3 2. 연구방법 1) 약물치료 2) 치료효능, 부작용, 삶의질의평가 3) 통계분석방법 1. 대상군의특성 결 과 Table 1. Demography and patient charateristics Charateristic Combination groupn20 Dothiepin groupn16 Ageyear SexMaleFemale Diagnosis Major depression 15 9 Dysthymic disorder 5 7 Duration of illnessyear Baseline HAM-D-17 total score

4 2. 두군간의치료효과비교 Table 2. Mean daily dosage of medication during the treatment Combination groupn20 Dothiepin groupn16 dothiepinmg sertralinemg dothiepinmg Baseline st week nd week th week th week 부작용및안전성 Table 3. Comparison between combination group and dothiepin group in HAM-D-17* total score and change during the treatment Combination groupn20 total score % change% Dothiepin groupn16 total score % change% Baseline st week nd week th week 11.1 a 49.7 b th week asignificantly lower than dothiepin group p.05 bsignificantly higher than dothiepin group p.05 *HAM-D-1717-item Hamilton depression rating scale Fig item Hamilton depression rating scaleham-d-17 change during the treatment. **Statistically different p.05 Fig item Hamilton depression rating scaleham-d-17 total score during the treatment. **Statistically different p.05 Fig. 3. The rate of responder* during the treatment. *responderimproved HAM-D-17 total score50 **Statistically differentp

5 Table 4. The Efficacy index ratio, Efficacy index therapeutic effect, and Efficacy index side effects during the treatment Combinationn20 Dothiepinn16 Baseline EIR** EITE** EISE** EIR** EITE** EISE** 1st week 2.11* 2.40* nd week 2.08* th week * th week *significantly higher than dothiepin group p.05 **EIREfficacy Index Ratio, EITEEfficacy Index Therapeutic Effect, EISEEfficacy Index Side Effects Table 5. The incidence of treatment associated side effects of combination therapy and dothiepin alone therapy Combination group n20 Dothiepin group n16 Dry mouth 70%14 81%13 Visual disturbance 45% 9 56% 9 Constipation 40% 8 38% 6 General fatigue 10% 2 38% 6 Anorexia 35% 7 0% 0 Dyspepsia 30% 6 19% 3 Headache 15% 3 25% 4 Nausea 20% 4 0% 0 Dizziness 20% 4 13% 2 Tremor 15% 3 19% 3 Increased sweat 15% 3 13% 2 Mictuition disturbance 15% 3 13% 2 Agitation 15% 3 0% 0 Palpitation 10% 2 13% 2 Amnesia 5% 1 13% 2 Diarrhea 5% 1 13% 2 Taste perversion 10% 2 6% 1 Sexual dysfunction 10% 2 0% 0 Insomnia 5% 1 0% 0 Vomiting 5% 1 0% 0 4. 치료만족도 5. 두군간의삶의질비교 고 찰 Table 6. Comparison of Health related quality of life battery between combination group and dothiepin group during the treatment Combination group(n20) Dothiepin group(n16) HP** COG** HM** SB** LS** HP** COG** HM** SB** LS** baseline nd week 4.53* * 27.0* 27.0* * th week 4.16* * 26.4* 4.17* * * 6th week 4.07* 3.21* 2.83* 26.4* 4.08* * 1.86* 24.2* 4.40* *significantly improved compared with the baseline scorep. 05 **HPhealth perception, COGcognitive fuction, HMhome management, SBsocial behavior, LSlife satisfaction

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8 sertraline:a double blind, placebo and amitriptyline controlled, multicenter study in outpatients with major depression. J Clin Psychiatry 51:18-27 Revicki DA, Brown TR, Martindale JJ(1992):Reliability and validity of health related quality of life battery for evaluating outpatient antidepressant treatment. Quality of Life Research 1: Seth R, Jennings AL, Bindman J(1992):Combination treatment with noradrenaline and serotonin reuptake inhibitors in resistant depression. Br J Psychiatry 161: Shopsin B, Gershon S, Goldstein M, Freidman F, Wilk S(1975): Use of synthesis inhibitors in defining a role for biogenic amines during imipramine treatment in depressive patients. Psychopharmacol Commun 1: Stochmeier CA, Martino AM, Kellar KJ(1985):A strong influence of serotonergic axons on betha adrenergic receptors in rat brain. Science 230: Sulser F, Vetulani J, Mobley PL(1978):Mode of action of antidepressant drugs. Biochemical Pharmacology 27: Vetulani J, Stawartz RJ, Dingell JV(1976):A possible common mechanism of action of antidepressant treatment. Arch Pharmacol 293: Weilberg JB, Rosenbaum JF, Biedermann J, Sachs GS, Pollack MH, Kelly K(1989):Fluoxetine added to non-maoi antidepressant converts nonresponder to responder. J Clin Psychiatry 50: Warrington SJ(1992):Clinical implication of the pharmacology of serotonin reuptake inhibitors. Int Clin Psyhopharmacol 7 Suppl. 2:13 Zajecka JM, Jefferiess H, Fawrett J(1995):The efficacy of fluoxetine combined with a heterocyclic antidepressant in treatmentresistant depression. J Clin Psychiatry 56: