KISEP Overview 강박장애의약물치료전략 김세주 1 권준수 2 김찬형 1 ABSTRACT Pharmacotherapeutic Strategy for Obsessive-Compulsive Disorder Se Joo Kim, MD, 1 Jun S

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1 KISEP Overview 강박장애의약물치료전략 김세주 1 권준수 2 김찬형 1 ABSTRACT Pharmacotherapeutic Strategy for Obsessive-Compulsive Disorder Se Joo Kim, MD, 1 Jun Soo Kwon, MD 2 and Chan-Hyung Kim, MD 1 1 Department of Psychiatry, Yonsei University College of Medicine, Seoul, 2 Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea Obsessive-compulsive disorder OCD has a lifetime prevalence of approximately 23%. Until relatively recently, effective treatments for OCD were lacking. Fortunately, over the past decades, the availability of serotonin reuptake inhibitors SRIs and behavioral treatments using exposure-response prevention techniques has altered the outlook for patients suffering from OCD. But, treating OCD with medication still requires a blend of science and art. SRIs provide clinically significant relief to most patients, but they are not effective in all patients. Because significant number of patient with OCD do not respond to adequate trials of SRIs, other treatment options such as augmentation, switching, combination, or neurosurgical and device-based approaches may be needed. In this paper, the first-line treatment options and several alternative treatment options for OCD were reviewed. Finally, we reviewed several treatment guidelines and algorithm for OCD introduced previously by other researchers. We have a plan to develop Korean treatment algorithm for OCD based on expert s opinions. Also, we hope to use this algorithm for OCD in the clinical setting in near future. (Korean J Psychopharmacol 2005;16(3): ) KEY WORDSObsessive-compulsive disorder Treatment guideline Algorithm. 서 교신저자 론 197

2 본 론 1. 강박장애치료에있어서일반적인고려사항들 1) 일차약제로어떤약물을선택할것인가? ) 어떤용량을어느기간동안사용하면효과가나타날것인가? 198 Korean J Psychopharmacol 2005;163:

3 - 3) 유지치료는얼마동안어떻게해야하는가? 2. 1차선택약물이외에다른치료적접근 1) 병용요법전략 (Combination drug treatment strategies) - 199

4 Korean J Psychopharmacol 2005;163:

5 - 2) Clomipramine 또는 citalopram 정주투여 (Intravenous clomipramine or citalopram administration) 3) 인지행동치료 (Cognitive-behavioral therapy) 4) 신경외과적수술및기구를이용한치료법들 (neurosurgical and device-based approaches)

6 치료-저항성강박장애 (Treatment-resistant OCD) 4. 강박장애치료지침및알고리듬 (Treatment guideline and algorithm of OCD) Korean J Psychopharmacol 2005;163:

7 - DSM-IV diagnosis of OCD CMI SSRI #1 No Partial Alternate OCD drug If comorbid tics spectrum disorder add SSRI #1 CMI NL Clonazpm Buspirone CMI or SSRI Lithium No Partial No OCD drug OCD drug SSRI #2 No Partial No OCD drug SSRI #3 No Partial No OCD drug OCD drug MAOI Clonazepam Figure 1. Algorithm for the treatment of obsessive-compulsive disorder. 70) CMIclomipramine, NLneuroleptic, OCD obsessive-compulsive disorder, SSRIselective serotoinin reuptake inhibitor, enter augmentation section at nonredundant level, enter alternate OCD drug at non-redundant level. 203

8 Table 1. Flow sheet of treatment option for obsessive-compulsive disorder 23) 01. Selective serotonin reuptake inhibitor trials for 12 weeks at full dosage or highest tolerated Fluoxetine trial-40 to 80 mg daily Clomipramine trial-to 250 mg daily Sertraline trial-to 200 mg daily Paroxetine trial-40 to 60 mg daily Fluvoxamine trial-to 300 mg daily 02. Try augmenting fluoxetine or clomipramine or sertraline or paroxetine or fluvoxamine 03. Try the other selective serotonin reuptake inhibitors each drug for at least 12 weeks with augmentation of each drug 04. Try venlafaxine to 375 mg for 3 months 05. Stop fluoxetine for 5 weeks or sertraline, fluvoxamine, clomipramine, venlafaxine, or paroxetine for 2 weeks 06. Monoamine oxidase inhibitor trial 07. Try augmenting monoamine oxidase inhibitors for 1 month not buspirone 08. Trials of experimental agents when available 09. Other medication trials e.g., trazodone, imipramine, etc 10. If severe personality disorder present, consider halfway house or day treatment program 11. If patient is severely disabled, despite adequate treatment, consider psychosurgery 12. If poor compliance is a persistent problem, or patient prefers symptoms to being rid of them, or if patient also has obsessive-compulsive personality disorder or had early-onset OCD, consider concomitant psychodynamic psychotherapy As soon as patient has at least a partial response to medicationif patient has rituals, begin behavior therapy of exposure and response prevention. Drug trials should be continued for at least 12 weeks before they are considered failures 204 Korean J Psychopharmacol 2005;163:

9 Treatment start 1st phase 2nd phase 3rd phase 0 week 결 SRI 론 48 week Behavioral therapy 12 week ation or other drug Intensive CBT TMS or psychosurgery Figure 2. Flow chart of obsessive-compulsive disorder treatment. 72) SRIselective serotonin reuptake inhibitor, CBTcognitive behavioral therapy, TMStranscranial magnetic stimulation. 중심단어 참고문헌 1) Karno M, Golding JM, Sorenson SB, Burnam MA. The epidemiology of obsessive-compulsive disorder in five U.S. communities. Arch Gen Psychiatry 1988;45: ) McDougle CJ, Goodman WK, Leckman JF, Price LH. The psychopharmacology of obsessive compulsive disorder. Psychitr Clin North Am 1993;16: ) Denys D, Van Megen H, Westenberg H. The adequacy of pharmacotherapy in outpatients with obsessive-compulsive disorder. Int Clin Psychopharmacol 2002;17: ) Ellingrod VL. Pharmacotherapy of primary obsessive-compulsive disorder: review of the literature. Pharmacotherapy 1998;18: ) Dougherty DD, Rauch SL, Jenike MA. Pharmacotherapy for obsessive-compulsive disorder. J Clin Psychol 2004;60: ) Piccinelli M, Pini S, Bellantuono C, Wilkinson G. of drug treatment in obsessive-compulsive disorder. A meta-analytic review Br J Psychiatry 1995;166: ) Bisserbe JC, Lane RM, Flament MF. A double-blind comparison of sertraline and clomipramine in outpatients with obsessive compulsive disorder. Eur Psychiatry 1997;153: ) Pigott TA, Pato MT, Bernstein SE, Grover GN, Hill JL, Tolliver TJ, et al. Controlled comparisons of clomipramine and fluoxetine in the treatment of obsessive-compulsive disorder. Behavioral Biological Results Arch Gen Psychiatry 1990;47: ) Freeman CP, Trimble MR, Deakin JF, Stokes TM, Ashford JJ. Fluvoxamine versus clomipramine in the treatment of obsessive compulsive disorder: a multicenter, randomized, double-blind, parallel group comparison. J Clin Psychiatry 1994;55: ) Mundo E, Bareggi SR, Pirola R, Bellodi L, Smeraldi E. Long-term pharmacotherapy of obsessive-compulsive disorder: a doubleblind controlled study. J Clin Psychopharmacol 1997;17: ) Mundo E, Bianchi L, Bellodi L. of fluvoxamine, paroxetine, and citalopram in the treatment of obsessive-compulsive disorder: a single-blind study. J Clin Psychopharmacol 1997;17: ) Ereshefsky L, Riesenman C, Lam YW. Serotonin selective reuptake inhibitor drug interactions and the cytochrome P450 system. J Clin Psychiatry 1996;57 Suppl 8:17-24;discussion ) Harvey AT, Preskorn SH. Cytochrome P450 enzymes: interpretation of their interactions with selective serotonin reuptake inhibitors. Part II. J Clin Psychopharmacol 1996;16: ) Harvey AT, Preskorn SH. Cytochrome P450 enzymes: interpretation of their interactions with selective serotonin reuptake inhibitors. Part I. J Clin Psychopharmacol 1996;16: ) Gregor KJ, Way K, Young CH, James SP. Concomitant use of selective serotonin reuptake inhibitors with other cytochrome P450 2D6 or 3A4 metabolized medications: how often does it really happen? J Affect Disord 1997;46: ) Gury C, Cousin F. Pharmacokinetics of SSRI antidepressants: 205

10 206 half-life and clinical applicability. Encephale 1999;25: ) Mundo E, Rouillon F, Figuera ML, Stigler M. Fluvoxamine in obsessive-compulsive disorder: similar but superior tolerability in comparison with clomipramine. Hum Psychopharmacol 2001;16: ) Rasmussen S, Hackett E, DuBoff E, Greist J, Halaris A, Koran LM, et al. A 2-year study of sertraline in the treatment of obsessive-compulsive disorder. Int Clin Psychopharmacol 1997; 12: ) Koran LM, Hackett E, Rubin A, Wolkow R, Robinson D. of sertraline in the long-term treatment of obsessive-compulsive disorder. Am J Psychiatry 2002;159: ) Romano S, Goodman W, Tamura R, Gonzales J. Long-term treatment of obsessive-compulsive disorder after an acute response: a comparison of fluoxetine versus placebo. J Clin Psychopharmacol 2001;21: ) Hollander E, Allen A, Steiner M, Wheadon DE, Oakes R, Burnham DB. Acute and long-term treatment and prevention of relapse of obsessive-compulsive disorder with paroxetine. 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Psychopharmacol Bull 1990;26: ) Pallanti S, Quercioli L, Paiva RS, Koran LM. Citalopram for treatment-resistant obsessive-compulsive disorder. Eur Psychiatry 1999;14: ) Browne M, Horn E, Jones TT. The benefits of clomipraminefluoxetine combination in obsessive-compulsive disorder. Can J Psychiatry 1993;38: ) Hollander E, Bienstock CA, Koran LM, Pallanti S, Marazziti D, Rasmussen SA, et al. Refractory obsessive-compulsive disorder: state-of-the-art treatment. J Clin Psychiatry 2002;63 Suppl 6: ) McDougle CJ, Walsh KH. Treatment of refractor OCD. In: Fineberg N, Marazziti D, Stein DJ editors. Obsessive compuslvie disorder: a practical guide. London: Martin Dunitz;2001. p ) De Montigny C. Enhancement of the 5-HT neurotransmission by antidepressant treatments. J Physiol 1981;77: ) Golden RN, Morris JE, Sack DA. Combined lithium-tricyclic treatment of obsessive-compulsive disorder. Biol Psychiatry 1988; 23: ) Rasmussen SA. Lithium and tryptophan augmentation in clomipramine-resistant obsessive-compulsive disorder. Am J Psychiatry 1984;141: ) Blier P, de Montigny C. Lack of of lithium augmentation in obsessive-compulsive disorder: the perspective of different regional effects of lithium on serotonin release in the central nervous system. J Clin Psychopharmacol 1992;12: ) McDougle CJ, Price LH, Goodman WK, Charney DS, Heninger GR. A controlled trial of lithium augmentation in fluvoxaminerefractory obsessive-compulsive disorder: lack of. J Clin Psychopharmacol 1991;11: ) Markovitz PJ, Stagno SJ, Calabrese JR. Buspirone augmentation of fluoxetine in obsessive-compulsive disorder. Am J Psychiatry 1990;147: ) Pigott TA, L Heureux F, Hill JL, Bihari K, Bernstein SE, Murphy DL. A double-blind study of adjuvant buspirone hydrochloride in clomipramine-treated patients with obsessive-compulsive disorder. J Clin Psychopharmacol 1992;12: ) Grady TA, Pigott TA, L Heureux F, Hill JL, Bernstein SE, Murphy DL. Double-blind study of adjuvant buspirone for fluoxetinetreated patients with obsessive-compulsive disorder. Am J Psychiatry 1993;150: ) McDougle CJ, Goodman WK, Leckman JF, Holzer JC, Barr LC, McCance-Katz E, et al. Limited therapeutic effect of addition of buspirone in fluvoxamine-refractory obsessive-compulsive disorder. Am J Psychiatry 1993;150: ) Judd FK, Chua P, Lynch C, Norman T. Fenfluramine augmentation of clomipramine treatment of obsessive compulsive disorder. Aust NZJ Psychiatry 1991;25: ) Koran LM, Mueller K, Maloney A. Will pindolol augment the response to a serotonin reuptake inhibitor in obsessive-compulsive disorder? J Clin Psychopharmacol 1996;16: ) Dannon PN, Sasson Y, Hirschmann S, Iancu I, Grunhaus LJ, Zohar J. Pindolol augmentation in treatment-resistant obsessive compulsive disorder: a double-blind placebo controlled trial. Eur Neuropsychopharmacol 2000;10: ) McDougle CJ, Goodman WK, Price LH, Delgado PL, Krystal JH, Charney DS, et al. Neuroleptic addition in fluvoxamine-refractory obsessive-compulsive disorder. Am J Psychiatry 1990;147: ) McDougle CJ, Goodman WK, Leckman JF, Lee NC, Heninger GR, Price LH. Haloperidol addition in fluvoxamine-refractory obsessive-compulsive disorder. A double-blind, placebo-controlled study in patients with and without tics. Arch Gen Psychiatry 1994;51: ) Erzegovesi S, Guglielmo E, Siliprandi F, Bellodi L. Low-dose risperidone augmentation of fluvoxamine treatment in obsessivecompulsive disorder: a double-blind, placebo-controlled study. Eur Neuropsychopharmacol 2005;15: ) Hollander E, Baldini Rossi N, Sood E, Pallanti S. Risperidone augmentation in treatment-resistant obsessive-compulsive disorder: a double-blind, placebo-controlled study. Int J Neuropsychopharmacol 2003;6: ) Pfanner C, Marazziti D, Dell Osso L, Presta S, Gemignani A, Milanfranchi A, et al. Risperidone augmentation in refractory obsessive-compulsive disorder: an open-label study. 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11 54) Pallanti S, Quercioli L, Koran LM. Citalopram intravenous infusion in resistant obsessive-compulsive disorder: an open trial. J Clin Psychiatry 2002;63: ) 윤화영 정승희 신민섭 김중술 김명선 권준수. 강박증의집단인지행동치료의효과. 정신병리학 2001;9: ) Jenike MA. Neurosurgical treatment of obsessive-compulsive disorder. Br J Psychiatry Suppl 1998: ) Dougherty DD, Baer L, Cosgrove GR, Cassem EH, Price BH, Nierenberg AA, et al. Prospective long-term follow-up of 44 patients who received cingulotomy for treatment-refractory obsessivecompulsive disorder. Am J Psychiatry 2002;159: ) Jenike MA, Baer L, Ballantine T, Martuza RL, Tynes S, Giriunas I, et al. Cingulotomy for refractory obsessive-compulsive disorder. A long-term follow-up of 33 patients. Arch Gen Psychiatry 1991; 48: ) Greenberg BD, Price LH, Rauch SL, Friehs G, Noren G, Malone D, et al. Neurosurgery for intractable obsessive-compulsive disorder and depression: critical issues. Neurosurg Clin N Am 2003;14: ) Kim CH, Chang JW, Koo MS, Kim JW, Suh HS, Park IH, et al. Anterior cingulotomy for refractory obsessive-compulsive disorder. Acta Psychiatr Scand 2003;107: ) Lippitz BE, Mindus P, Meyerson BA, Kihlstrom L, Lindquist C. Lesion topography and outcome after thermocapsulotomy or gamma knife capsulotomy for obsessive-compulsive disorder: relevance of the right hemisphere. Neurosurgery 1999;44: ; discussion ) Khanna S, Gangadhar BN, Sinha V, Rajendra PN, Channabasavanna SM. Electroconvulsive therapy in obsessive-compulsive disorder. Convuls Ther 1988;4: ) Strassnig M, Riedel M, Muller N. Electroconvulsive therapy in a patient with Tourette s syndrome and co-morbid obsessive compulsive disorder. World J Biol Psychiatry 2004;5: ) Sachdev PS, McBride R, Loo CK, Mitchell PB, Malhi GS, Croker VM. Right versus left prefrontal transcranial magnetic stimulation for obsessive-compulsive disorder: a preliminary investigation. J Clin Psychiatry 2001;62: ) Greenberg BD, George MS, Martin JD, Benjamin J, Schlaepfer TE, Altemus M, et al. Effect of prefrontal repetitive transcranial magnetic stimulation in obsessive-compulsive disorder: a preliminary study. Am J Psychiatry 1997;154: ) Cosyns P, Gabriels L, Nuttin B. Deep brain stimulation in treatment refractory obsessive compulsive disorder. Verh K Acad Geneeskd Belg 2003;65: ;discussion ) Gabriels L, Cosyns P, Nuttin B, Demeulemeester H, Gybels J. Deep brain stimulation for treatment-refractory obsessive-compulsive disorder: psychopathological and neuropsychological outcome in three cases. Acta Psychiatr Scand 2003;107: ) Aouizerate B, Cuny E, Martin-Guehl C, Guehl D, Amieva H, Benazzouz A, et al. Deep brain stimulation of the ventral caudate nucleus in the treatment of obsessive-compulsive disorder and major depression. Case report. J Neurosurg 2004;101: ) March JS, Frances A, Carpenter D, Kahn DAE. Treatment of obsessive-compulsive disorder. The expert consensus panel for obsessive-compulsive disorder. J Clin Psychiatry 1997;58 Suppl 4: ) Jefferson JW, Altemus M, Jenike MA, Pigott TA, Stein DJ. Algorithm for the treatment of obsessive-compulsive disorder (OCD). Psychopharmacol Bull 1995;31: ) Bouvard MA, Milliery M, Cottraux J. Management of obsessive compulsive disorder. Psychother Psychosom 2004;73: ) 권준수 하태현. 치료저항성강박장애의약물학적치료및통합적치료모형의제안. 신경정신의학 2003;42:

KISEP Review Article J Korean Neuropsychiatr Assoc Vol 42, No 3 치료저항성강박장애의약물학적치료및통합적치료모형의제안 서울대학교의과대학정신과학교실 권준수 하태현 Pharmacotherapy and the Proposal o

KISEP Review Article J Korean Neuropsychiatr Assoc Vol 42, No 3 치료저항성강박장애의약물학적치료및통합적치료모형의제안 서울대학교의과대학정신과학교실 권준수 하태현 Pharmacotherapy and the Proposal of the Integrative Therapy Model for Treatment Resistant