1. 체중증가 본 1) 선택적세로토닌억제제 (SSRI) 와체중증가 론 17

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1 KISEP Special Article 장기유지치료에서새로운항우울제의내약성 : Bupropion SR(Wellbutrin SR ) 을중심으로 ABSTRACT 박원명 김 원 가톨릭대학교의과대학정신과학교실 Long-Term Tolerability of New Antidepressants: Focusing on Bupropion SR(Wellbutrin SR ) Won-Myong Bahk, MD and Won Kim, MD Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Korea Depressive disorders often develop into chronic course and relapse of symptoms is prevalent. Long-term treatment with antidepressants consolidates the improvement of residual symptoms and prevents relapses and recurrences. In the long-term treatment, the long-term tolerability of antidepressant is a major factor which impact on the compliance and the success of treatment. Although new antidepressants have better side effect profiles than TCA and MAOI, the safety issues of the former are also a concern during continuation and maintenance phases of treatment. Nowadays, weight gain and sexual dysfunction are at a center of concern in this field. SSRI, venlafaxine and mirtazapine can cause weight gain in some patients. Many studies report that weight gain and sexual dysfunction cause significant sufferings and act as major reasons of non-compliance. Bupropion SR is a new antidepressants that has a unique pharmacological property. It produce neither substantial weight gain nor sexual side effect. It was also shown to be effective and well-tolerated in decreasing the risk for relapse of depression. So, Bupropion SR can be used preferentially as a first-line antidepressant or augmentation on other agents in the long-term treatment without significant weight gain and sexual side effects. (Korean J Psychopharmacol 2005;16(1):16-24) KEY WORDS:Long-term treatment Tolerability Side effect Antidepressants Bupropion SR. 서 교신저자 론 16

2 1. 체중증가 본 1) 선택적세로토닌억제제 (SSRI) 와체중증가 론 17

3 - 18 2) Mirtazapine, Venlafaxine과체중증가 3) Bupropion과체중증가 Korean J Psychopharmacol 2005;16(1):16-24

4 성기능부작용 1) 선택적세로토닌억제제 (SSRI) 와성기능부작용 19

5 ) Mirtazapine, Venlafaxine 과성기능부작용 - 3) Bupropion과성기능부작용 Korean J Psychopharmacol 2005;16(1):16-24

6 - 3. 장기유지치료의새로운대안, Bupropion SR 21

7 결론 중심단어 참고문헌 1) Menting JE, Honing A, Verhey FR, Hartmans M, Rozendaal N, de Vet HC, et al. Selective serotonin reuptake inhibitors (SSRI) in the treatment of elderly depressed patients. A qualitative analysis of the literature on their efficacy and side-effects. Int Clin Psychopharmachol 1996;11: ) Steffens DC, Krishnan KR, Helms MJ. Are SSRIs better than TCAs? Comparison of SSRIs and TCAs. A meta-analysis. Depress Anxiety 1997;6: ) Masand PS, Gupta S. Selective serotonin-reuptake inhibitors. An update. Harvard Rev Psychiatry 1999;7: ) Weissman MM BM, Lear PJ, Florio LP. The Epidemiologic Catchment Area Study. Affective Disorders. In Robins LN and Regier DA des. Psychiatric disorders in America. New York. The Free Press;1991. p ) Goldney RD, Fisher LJ, Wilson DH, Cheok F. Major depression and its associated morbidity and qualify of life in a random, representative Australian community sample. Aust NZJ Psychiatry 2000;34: ) Hirschfeld RM. Clinical importance of long-term antidepressant treatment. Br J Psychiatry 2001;42Supple:s4-8. 7) Fava M, Kaji J. Continuation and maintenance treatments of major depressive disorder. Psychiatry Ann 1994;24: ) Kupfer DJ, Frank E, Perel JM, Cornes C, Mallinger AG, Thase ME, et al. Five-year outcome for maintenance therapies in recurrent depression. Arch Gen Psychiatry 1992;49: ) Zajecka J, Amsterdam JD, Quitkin FM, Reimherr FW, Rosenbaum JF, Tamura RN, et al. Changes in adverse event reported by patient during 6months of fluoxetine therapy. J Clin Psychiatry 1999;60: ) Katon W, von Korff M, Lin E, Bush T, Ormel J. Adequacy and duration of antidepressant treatment in primary care. Med Care 1992;30: ) Lin EH, von Korff M, Katon W, Bush T, Simon GE, Walker E, et al. The role of the primary care physician in patients adherence to antidepressant therapy. Med Care 1995;33: ) Lin EH, Silmon GE, Katon WJ Russo JE, Von Korff M, Bush TM, et al. Can enhanced acute-phase treatment of depression improve long term outcomes? A report of randomized trials in primary care. Am J Psychiatry 1999;156: ) Masand PS. Weight gain associated with psychotropic drugs. Exp Opin Pharmacother 2000;1: ) Kawachi I. Physical and psychological consequences of weight gain. J Clin Psychiatry 1999;60: ) de Jonghe F, Ravelli DP, Tuynman-Qua H. A randomized, doubleblind study of fluoxetine and maprotiline in the treatment of major depression. Pharmacopsychiatry 1991;24: ) Michelson D, Amsterdam JD, Quitkin FM, Reimherr FW, Rosenbaum JF, Zajecka J, et al. Changes in weight during a 1-year trial of fluoxetine. Am J Psychiatry 1999;156: ) Croft H, Settle E Jr, Houser T, Batey SR, Donahue RM, Ascher JA. A placebo-controlled comparison of the antidepressant efficacy and effects on sexual functioning of sustained release bupropion and sertraline. Clin Ther 1999;21: ) Moon CA, Jesinger DK. The effects of psychomotor performance 22 Korean J Psychopharmacol 2005;16(1):16-24

8 of fluvoxamine versus mianserin in depressed patients in general practice. Br J Clin Practice 1991;45: ) Mackle M, Kocsis J. Effects on body weight of the SSRI citalopram. Presented at the 37th annual meeting of the American College of Neuropsychopharmacology: Dec 14-18, Las Croabas, Puerto Rico; ) Fava M, Rosenbaum JF. Treatment-emergent side effects of the newer antidepressant. In: The Psychiatric Clinics of North America: Annual of Drug Therapy, vol 3. Philadelphia, Pa: WB Saunders Co;1996. p ) Sussman N, Ginsberg D. Rethinking side effects of the selective serotonin reuptake inhibitors: sexual dysfunction and weight gain. Psychatr Ann 1998;28: ) Benazzi F. Weight gain in depression remitted with antidepressants: pharmacological or recovery effect? Psychother Psychosom 1998;67: ) Fava M, Judge R, Hoog SL, Nilsson ME, Koke SC. Fluoxetine versus sertraline and paroxetine in major depressive disorder: changes in weight with long-term treatment. 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Prim Psychiatry 1998;3: ) Silverstone PH, Ravindran A. Once-daily venlafaxine extended release (XR) compared with fluoxetine in outpatients with depression and anxiety. Venlafaxine XR 360 Study Group. J Clin Psychiatry 1999;60: ) Harto-Traux N, Stren WC, Miller LL, Sato TL, Cato AE. Effects of bupropion on body weight. J Clin Psychiatry 1983;44: ) Weisler RH, Johnson JA, Lineberry CG, Samara B, Branconnier RJ, Billow AA. Comparison of bupropion and trazodone for the treatment of major depression. J Clin Psychopharmacol 1994; 14: ) Settle EC, Stahl SM, Batey SR, Johnston JA, Ascher JA. Safety profile of sustained-release bupropion in depression: results of three clinical trials. Clin Ther 1999;21: ) Weihs K, Houser T, Batey S, Ascher JA, Bolden-Watson C, Donahue RM, et al. Continuation phase treatment with bupropion SR effectively decreases the risk for relapse of depression. Biol Psychiatry 2002;51: ) Chouinrd G. Bupropion and amitriptyline in the treatment of depressed patients. J Clin Psychiatry 1983;44: ) Feighner J, Hendrickson G, Miller L, Stern W. Double-blind comparison of doxepin versus bupropion in outpatients with a major depressive disorder. J Clin Psychopharmacol 1986;6: ) Rosen RC, Lane RM, Menza M. Effect of SSRIs on sexual function: A critical review. J Clin Psychopharmacol 1999;19: ) Laumann EO, Paik A, Rosen RC. Sexual dysfunction in the Unite States: Prevalence and predictors. JAMA 1999;281: ) Finer WW, Lund M, Slagle MA. Medication that contribute to sexual disorders: A guide to assessment and treatment in family practice. J Fam Pract 1997;44: ) Mathew RJ, Weinman ML. Sexual dysfunctions in depression. Arch Sex Behav. 1982;11: ) Angst J. Sexual problems in healthy and depressed persons. Int Clin Psychopharmacol 1998;13:S1-S4. 43) Roose SP. Compliance: the impact of adverse events and tolerability on the physician s treatment decisions. Eur Neuropsychopharmacol 2003;13 Suppl 3:S ) Montejo-González AL, Llorca G, Izquierdo JA, Ledesma A, Bousono M, Calcedo A, et al. SSRI induced sexual dysfunction: Fluoxetine, paroxetine, sertraline and fluvoxamine in a prospective, multicenter, and descriptive clinical study of 344 patients. J Sex Marital Ther 1997;23: ) Stark P, Hardison CD. A review of multicenter controlled studies of fluoxetine vs imipramine and placebo in outpatients with major depressive disorder. J Clin Psychiatry 1985;46: ) Herman JB, Brotman AW, Pollack MH, Falk WE, Biederman J, Rosenbaum JF. Fluoxetine-induced sexual dysfunction. J Clin Psychiatry 1990;51: ) Zajecka J, Fawcett J, Schaff M, Jeffriess H, Guy C. The role of serotonin in sexual dysfunction: fluoxetine-associated orgasm dysfunction. J Clin Psychiatry 1991;52: ) Jacobsen FM. Fluoxetine-induced sexual dysfunction and an open trial of yohimbine. J Clin Psychiatry 1992;53: ) Balon R, Yeragani VK, Pohl R, Ramesh C. Sexual dysfunction during antidepressant treatment. J Clin Psychiatry 1993;54: ) Pattersin WM. Fluoxetine-induced sexual dysfunction [letter]. J Clin Psychiatry 1993;54:71. 51) Fisher S, Byant SG, Kent TA. Post-marketing surveillance by patient self-monitoring: trazodone versus fluoxetine. J Clin Psychopharmacol 1993;12: ) Medical economics data. In: Physicians desk reference. 51st ed. Montavale, NJ: Medical Economics Data Production Co; ) Montejo AL, Llorca G, Izquierdo JA, Rico-Villademoros F. Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients. Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction. J Clin Psychiatry 2001;62 Suppl 3: ) Rothschild AJ. Sexual Side Effects of Antidepressants. J Clin Psychiatry 2001;61: ) Ashton AK, Hamer R, Rosen RC. Serotonin reuptake inhibitorinduced sexual dysfunction and its treatment: a large-scale retrospective study of 596 psychiatric outpatients. J Sex Marital Ther 1997;23: ) Nemeroff CB, Ninan PT, Ballenger J, Lydiard RB, Feighner J, Patterson WM, et al. Double-blind multicenter comparison of fluvoxamine versus sertraline in the treatment of depressed outpatients. Depression 1995;3: ) Waldinger MD, Hengeveld MW, Zwinderman AH, Olivier B. Effect of SSRI antidepressants on ejaculation: a double-blind, randomized, placebo-controlled study with fluoxetine, fluvoxamine, paroxetine, and sertraline. J Clin Psychopharmacol 1998;18: ) Kiev A, Feiger A. A double-blind comparison of fluvoxamine and paroxetine in the treatment of depressed outpatients. J Clin Psychiatry 1997;58: ) Modell JG, Katholi CR, Modell JD, DePalma RL. Comparative sexual side effects of bupropion, fluoxetine, paroxetine, and sertraline. Clin Pharmacol Ther 1997;61: ) Montgomery SA. Safety of mirtazapine: a reivew. Int Clin Psychopharmacol 1995;10: ) Labbate LA, Croft HA, Oleshansky MA. 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9 64 Suppl 10: ) Hirschfeld RM. Management of sexual side effects of antidepressant therapy. J Clin Psychiatry 1999;60: ) Gelenberg AJ, McGahuey C, Laukes C, Okayli G, Moreno F, Zentner L, et al. Mirtazapine substitution in SSRI-induced sexual dysfunction. J Clin Psychiatry 2000;61: ) Segraves RT, Kavoussi R, Hughes AR, Batey SR, Johnston JA, Donahue R, et al. Evaluation of sexual functioning in depressed outpatient: A double-blind comparison of sustained-release bupropion and sertraline treatment. J Clin Psychopharmacol 2000; 20: ) Berigan TR, Harazin JS. Sexual dysfunction associated with mirtazapine: a case report. J Clin Psychiatry 1998;59: ) Clayton AH, Pradko JF, Croft HA, Montano CB, Leadbetter RA. Bolden-Watson C, et al. Prevalence of sexual dysfunction among newer antidepressants. J Clin Psychiatry 2002;63: ) Croft H, Settle Jr H, Houser T, Batey SR, Donahue RM, Ascher JA. A placebo-controlled comparison of the antidepressant efficacy and effects on sexual functioning of sustained-release bupropion and sertraline. Clin Ther 1999;21: ) Preskorn SH. Comparison of the tolerability of bupropion, fluoxetine, imipramine, nefazodone, paroxetine, sertraline, and venlafaxine. J Clin Psychiatry 1995;56: ) Settle EC. Bupropion sustained release: side effect profile. J Clin Psychiatry 1998;9: ) Cassano P, Fava M. Tolerability issues during long-term treatment with antidepressants. Annal Clin Psychiatry 2004;16: ) Masand PS, Gupta S. Long-Term side Effects of Newer-Generation Antidepressants: SSRIS, Venlafaxine, Nefazodone, Bupropion, and Mirtazapine. Annal Clin Psychiatry 2002;14: ) Jain AK, Kaplan RA, Gadde KM, Wadden TA, Allison DB, Brewer ER, et al. Bupropion SR vs. placebo for weight loss in obese patients with depressive symptoms. Obes Res 2002;10: ) Anderson JW, Greenway FL, Fujioka K, Gadde KM, McKenney J, O Neil PM. Bupropion SR enhances weight loss: a 48-week double-blind, placebo-controlled trial. Obes Res 2002;10: ) Zajecka JM. Clinical issues in long-term treatment with antidepressants. J Clin Psychiatry 2000;61 Suppl 2: ) Walker PW, Cole JO, Gardner EA, Hughes AR, Johnston JA, Batey SR, et al. Improvement in fluoxetine-associated sexual dysfunction in patients switched to bupropion. J Clin Psychiatry 1993;54: ) Ashton AK, Rosen RC. Bupropion as an antidote for serotonin reuptake inhibitor-induced sexual dysfunction. J Clin Psychiatry 1998;59: ) Van Putten T, Shaffer I. Delirium associated with bupropion [letter]. J Clin Psychopharmacol 1990;10: ) Preskorn SH. Should bupropion dosage be adjusted based on therapeutic drug monitoring? Psychopharmacol Bull 1991;27: ) Zubieta JK, Demitrack MA. Possible bupropion precipitation of mania and a mixd affective state. J Clin Psychopharmacol 1991; 11: ) Gerner RH, Kaufman KR, Rosen R. Seizures associatied with burpropion and SSRI co-therapy [abstract]. Biol Psychiatry 1998;43:99S. 81) Segraves RT, Clayton A, Croft A, Wolf A, Wornock J. Bupropion sustained release for the treatment of hypoactive sexual desire disorder in premenopausal women. J Clinical Psychopharmaco 2004;24: ) Weihs KL, Houser TL, Batey SR, Ascher JA, Bolden-Watson C, Donahue RMJ, Metz A. Continuation Phase Treatment with Bupropion SR Effectively Decreases the Risk for Relapse of Depression. Biol Psychiatry 2002;51: Korean J Psychopharmacol 2005;16(1):16-24

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