Obsesif-Kompulsif Bozuklukta Psikofarmakolojik Tedavi
Özet
Obsesif-Kompulsif Bozukluk (OKB), obsesyonlar ve tekrarlayıcı kompulsiyonlarla seyreden, yaşam boyu prevalansı %1 ila %3 olan kronik psikiyatrik bir bozukluktur. OKB’nin psikofarmakolojik tedavisinde basamaklı bir yaklaşım önerilmekte olup, birinci basamakta etkinlik ve tolerabilite açısından Seçici Serotonin Gerialım İnhibitörleri (SSGİ - sertralin, fluoksetin, fluvoksamin, paroksetin, sitalopram, essitalopram) ve klomipramin yer almaktadır. Etkin doz ve en az 8-12 haftalık yeterli süreye rağmen hastaların yaklaşık dörtte birinde tedaviye yanıtsızlık veya direnç gelişmektedir. En az üç farklı SSGİ ve altın standart kabul edilen klomipramin kullanımına rağmen iyileşme sağlanamaması durumunda, ikinci basamak tedavi stratejilerine geçilmektedir. Bu kapsamda en yaygın yaklaşım, birinci basamak tedaviye tipik (haloperidol) veya atipik antipsikotiklerin (risperidon, aripiprazol, ketiapin, olanzapin, paliperidon) eklenmesidir; yapılan çalışmalarda özellikle risperidon ve aripiprazolün plaseboya karşı belirgin üstünlüğü ve iyi tolerabilitesi gösterilmiştir. Antipsikotikler dışında, dirençli olgularda serotonin sistemini düzenleyen pindolol, duygudurum düzenleyici lamotrijin ve glutamaterjik sistemi etkileyen memantin gibi ajanların da tedaviye eklenmesinin klinik semptomları anlamlı ölçüde iyileştirdiği bildirilmektedir. Sonuç olarak OKB tedavisinde farmakolojik ajanların yanı sıra bilişsel-davranışçı terapiler ve elektrokonvülzif tedavi, derin beyin uyarımı gibi somatik yöntemler de güçlendirme amacıyla kullanılmaktadır.
Obsessive-Compulsive Disorder (OCD) is a chronic psychiatric disorder characterized by obsessions and repetitive compulsions, with a lifetime prevalence of 1% to 3%. A stepped approach is recommended in the psychopharmacological treatment of OCD, and Selective Serotonin Reuptake Inhibitors (SSRIs - sertraline, fluoxetine, fluvoxamine, paroxetine, citalopram, escitalopram) and clomipramine are included in the first line in terms of efficacy and tolerability. Despite effective doses and an adequate duration of at least 8-12 weeks, treatment non-response or resistance develops in approximately one-quarter of patients. When improvement cannot be achieved despite the use of at least three different SSRIs and clomipramine, which is considered the gold standard, second-line treatment strategies are initiated. In this context, the most common approach is the addition of typical (haloperidol) or atypical antipsychotics (risperidone, aripiprazole, quetiapine, olanzapine, paliperidone) to the first-line treatment; studies have shown the significant superiority and good tolerability of risperidone and aripiprazole compared to placebo. Apart from antipsychotics, it is reported that adding agents such as pindolol, which regulates the serotonin system, the mood stabilizer lamotrigine, and memantine, which affects the glutamatergic system, significantly improves clinical symptoms in resistant cases. Consequently, in addition to pharmacological agents, cognitive-behavioral therapies and somatic methods such as electroconvulsive therapy and deep brain stimulation are also utilized for augmentation in OCD treatment.
Referanslar
Amerikan Psikiyatri Birliği. Ruhsal Bozuklukların Tanısal ve Sayımsal El Kitabı, Beşinci Baskı, (DSM-5). (Ertuğrul Köroğlu, Çev. Ed.). Ankara: Hekimler Yayın Birliği; 2013.
Sadock BJ. Kaplan & Sadock Klinik Psikiyatri El Kitabı. (Lut Tamam, Çev. Ed). Ankara: Güneş Tıp Kitabevleri; 2020.
Demet MM. Obsesif-Kompulsif Bozuklukta İlaç Tedavisi. Yüksel N (Ed.), Temel Psikofarmakoloji içinde. Ankara: Türkiye Psikiyatri Derneği Yayınları; 2010. p.521-538.
Osser D. Psychopharmacology Algorithms: Clinical Guidance from the Psychopharmacology Algorithm Project at the Harvard South Shore Psychiatry Residency Program. (First Edition). Lippincott Williams & Wilkins; 2020.
Koran L, Simpson H. Guideline Watch: Practice Guideline for the Treatment of Patients with Obsessive–Compulsive Disorder. Arlington, VA: American Psychiatric Association; 2013.
Stein DJ, Koen N, Fineberg N, et al. A 2012 evidence-based algorithm for the pharmacotherapy for obsessive-compulsive disorder. Current Psychiatry Reports. 2012;14(3): 211-219. DOI:10.1007/s11920-012-0268-9
Fineberg NA, Reghunandanan S, Simpson HB, et al. Obsessive–compulsive disorder (OCD): practical strategies for pharmacological and somatic treatment in adults. Psychiatry Research. 2015;227(1): 114-125. DOI:10.1016/j.psychres.2014.12.003
Foa EB, Liebowitz MR, Kozak MJ, et al. Randomized, placebo-controlled trial of exposure and ritual prevention, clomipramine, and their combination in the treatment of obsessive-compulsive disorder. The American Journal of Psychiatry. 2005;162(1): 151-161. DOI:10.1176/appi.ajp.162.1.151
Arumugham SS, Reddy YJ. Commonly asked questions in the treatment of obsessive-compulsive disorder. Expert Review of Neurotherapeutics. 2014;14(2): 151-163. DOI:10.1586/14737175.2014.874287
Fineberg NA, Reghunandanan S, Brown A, et al. Pharmacotherapy of obsessive-compulsive disorder: evidence-based treatment and beyond. The Australian & New Zealand Journal of Psychiatry. 2013;47(2): 121-141. DOI:10.1177/0004867412461958
American Psychiatric Association. Practice guideline for the treatment of patients with obsessive-compulsive disorder. Arlington, VA: American Psychiatric Association; 2007.
Reddy YJ, Sundar AS, Narayanaswamy JC, et al. Clinical practice guidelines for obsessive-compulsive disorder. Indian Journal of Psychiatry. 2017;59(1): 74-90. DOI:10.4103/0019-5545.196976
Halaris A, Koran L, Liebowtiz M, et al. A 1 year double-blind placebo-controlled fixed dose study of sertraline in the treatment of obsessive-compulsive disorder. International Clinical Psychopharmacology. 1995;10: 57-65. DOI:10.1097/00004850-199506000-00001
Ninan PT, Koran LM, Kiev A, et al. High-dose sertraline strategy for nonresponders to acute treatment for obsessive-compulsive disorder: a multicenter double-blind trial. The Journal of Clinical Psychiatry. 2006;67(1): 15-22. DOI:10.4088/jcp.v67n0103
Koran LM, Hackett E, Rubin A, et al. Efficacy of sertraline in the long-term treatment of obsessive-compulsive disorder. The American Journal of Psychiatry. 2002;159(1): 88-95. DOI:10.1176/appi.ajp.159.1.88
Etain B, Bonnet-Perrin E. Intérêt de la fluoxétine dans les troubles obsessionnels et compulsifs de l'adulte: revue de la littérature. L'Encéphale. 2001;27(3): 280-289. DOI:ENC-7-2001-27-3-0013-7006-101019-ART11
Safiloo S, Mehrabi Y, Asadi S, et al. Response to Fluvoxamine in the Obsessive-Compulsive Disorder Patients: Bayesian Ordinal Quantile Regression. Clinical Practice and Epidemiology in Mental Health: CP & EMH. 2021;17: 146. DOI:10.2174/1745017902117010151
Marks DM, Park MH, Ham BJ, et al. Paroxetine: safety and tolerability issues. Expert Opinion on Drug Safety. 2008;7(6): 783-794. DOI:10.1517/14740330802423168
Fava M, Judge R, Hoog SL, et al. Fluoxetine versus sertraline and paroxetine in major depressive disorder: changes in weight with long-term treatment. The Journal of Clinical Psychiatry. 2000;61(11): 863-867. DOI:10.4088/jcp.v61n1109
Stein DJ, Wreford Andersen E, Tonnoir B, et al. Escitalopram in obsessive–compulsive disorder: a randomized, placebo-controlled, paroxetine-referenced, fixed-dose, 24-week study. Current Medical Research and Opinion. 2007;23(4): 701-711. DOI:10.1185/030079907x178838
Montgomery S, Kasper S, Stein D, et al. Citalopram 20 mg, 40 mg and 60 mg are all effective and well tolerated compared with placebo in obsessive-compulsive disorder. International Clinical Psychopharmacology. 2001;16(2): 75-86. DOI:10.1097/00004850-200103000-00002
Bird ST, Crentsil V, Temple R, et al. Cardiac safety concerns remain for citalopram at dosages above 40 mg/day. The American Journal of Psychiatry. 2014;171(1): 17-19. DOI: 10.1176/appi.ajp.2013.13070905
Beach SR, Celano CM, Noseworthy PA, et al. QTc prolongation, torsades de pointes, and psychotropic medications. Psychosomatics. 2013;54(1): 1-13. DOI:10.1016/j.psym.2012.11.001
The U.S. Food and Drug Administration. FDA Drug Safety Communication: Revised recommendations for Celexa (citalopram hydrobromide) related to a potential risk of abnormal heart rhythms with high doses. (Content current as of: 12/15/2017, https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-revised-recommendations-celexa-citalopram-hydrobromide-related).
Thorén P, Åsberg M, Cronholm B, et al. Clomipramine treatment of obsessive-compulsive disorder: I. A controlled clinical trial. Archives of General Psychiatry. 1980;37(11): 1281-1285. DOI:10.1001/archpsyc.1980.01780240079009
Fallon BA, Liebowitz MR, Campeas R, et al. Intravenous clomipramine for obsessive-compulsive disorder refractory to oral clomipramine: a placebo-controlled study. Archives of General Psychiatry. 1998;55(10): 918-924. DOI:10.1001/archpsyc.55.10.918
Mataix-Cols D. Fernández de la Cruz L, Nordsletten AE,et al. Towards an international expert consensus for defining treatment response, remission, recovery and relapse in obsessive-compulsive disorder. World Psychiatry: Official Journal of the World Psychiatric Association (WPA). 2016;15(1): 80-81. DOI:10.1002/wps.20299
Pallanti S, Hollander E, Bienstock C, et al. Treatment non-response in OCD: methodological issues and operational definitions. The International Journal of Neuropsychopharmacology. 2002;5(2): 181-191. DOI:10.1017/S1461145702002900
Jenike MA, Rauch SL. Managing the patient with treatment-resistant obsessive compulsive disorder: current strategies. The Journal of Clinical Psychiatry. 1994;(55): 11-17.
Hirschtritt ME, Bloch MH, Mathews CA. Obsessive-compulsive disorder: advances in diagnosis and treatment. JAMA. 2017;317(13): 1358-1367. DOI:10.1001/jama.2017.2200
Bloch M, Landeros-Weisenberger A, Kelmendi B, et al. A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder. Molecular Psychiatry. 2006;11(7): 622-632. DOI:10.1038/sj.mp.4001823
Dold M, Aigner M, Lanzenberger R, et al. Antipsychotic augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder: an update meta-analysis of double-blind, randomized, placebo-controlled trials. The International Journal of Neuropsychopharmacology. 2015;18(9): 1-11. DOI:10.1093/ijnp/pyv047
Mc Dougle CJ, Goodman WK, Price LH, et al. Neuroleptic addition in fluvoxamine-refractory obsessive-compulsive disorder. The American Journal of Psychiatry. 1990;147(5): 652-654. DOI:10.1176/ajp.147.5.652
Mc Dougle CJ, Goodman WK, Leckman JF, et al. Haloperidol addition in fluvoxamine-refractory obsessive-compulsive disorder: a double-blind, placebo-controlled study in patients with and without tics. Archives of General Psychiatry. 1994;51(4): 302-308. DOI:10.1001/archpsyc.1994.03950040046006
Li X, May RS, Tolbert LC, et al. Risperidone and haloperidol augmentation of serotonin reuptake inhibitors in refractory obsessive-compulsive disorder: a crossover study. The Journal of Clinical Psychiatry. 2005;66(6):736-743. DOI:10.4088/jcp.v66n0610
Albert U, Marazziti D, Di Salvo G, et al. A systematic review of evidence-based treatment strategies for obsessive-compulsive disorder resistant to first-line pharmacotherapy. Current Medicinal Chemistry. 2018;25(41): 5647-5661. DOI:10.2174/0929867325666171222163645
Mc Dougle CJ, Epperson CN, Pelton GH, et al. A double-blind, placebo-controlled study of risperidone addition in serotonin reuptake inhibitor–refractory obsessive-compulsive disorder. Archives of General Psychiatry. 2000;57(8): 794-801. DOI:10.1001/archpsyc.57.8.794
Erzegovesi S, Guglielmo E, Siliprandi F, et al. Low-dose risperidone augmentation of fluvoxamine treatment in obsessive-compulsive disorder: a double-blind, placebo-controlled study. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology. 2005;15(1): 69-74. DOI:10.1016/j.euroneuro.2004.04.004
Muscatello MRA, Bruno A, Pandolfo G, et al. Effect of aripiprazole augmentation of serotonin reuptake inhibitors or clomipramine in treatment-resistant obsessive-compulsive disorder: a double-blind, placebo-controlled study. Journal of Clinical Psychopharmacology. 2011;31(2): 174-179. DOI:10.1097/JCP.0b013e31820e3db6
Sayyah M, Sayyah M, Boostani H, et al. Effects of aripiprazole augmentation in treatment‐resistant obsessive‐compulsive disorder (a double blind clinical trial). Depression and Anxiety. 2012;29(10): 850-854. DOI:10.1002/da.21996
Atmaca M, Kuloglu M, Tezcan E, et al. Quetiapine augmentation in patients with treatment resistant obsessive–compulsive disorder: a single-blind, placebo-controlled study. International Clinical Psychopharmacology. 2002;17(3): 115-119. DOI:10.1097/00004850-200205000-00004
Diniz JB, Shavitt RG, Fossaluza V, et al. A double-blind, randomized, controlled trial of fluoxetine plus quetiapine or clomipramine versus fluoxetine plus placebo for obsessive-compulsive disorder. Journal of Clinical Psychopharmacology. 2011;31(6): 763-768. DOI:10.1097/JCP.0b013e3182367aee
Carey PD, Vythilingum B, Seedat S, et al. Quetiapine augmentation of SRIs in treatment refractory obsessive-compulsive disorder: a double-blind, randomised, placebo-controlled study. BMC Psychiatry. 2005;5(1): 1-8. DOI:10.1186/1471-244X-5-5
Fineberg NA, Sivakumaran T, Roberts A, et al. Adding quetiapine to SRI in treatment-resistant obsessive–compulsive disorder: a randomized controlled treatment study. International Clinical Psychopharmacology. 2005;20(4): 223-226. DOI:10.1097/00004850-200507000-00005
Kordon A, Wahl K, Koch N, et al. Quetiapine addition to serotonin reuptake inhibitors in patients with severe obsessive-compulsive disorder: a double-blind, randomized, placebo-controlled study. Journal of Clinical Psychopharmacology. 2008;28(5): 550-554. DOI.10.1097/JCP.0b013e318185e735
Bystritsky A, Ackerman DL, Rosen RM, Vapnik T, et al. Augmentation of serotonin reuptake inhibitors in refractory obsessive-compulsive disorder using adjunctive olanzapine: a placebo-controlled trial. The Journal of Clinical Psychiatry. 2004;65(4): 565-568. DOI:10.4088/jcp.v65n0418
Shapira NA, Ward HE, Mandoki M, et al. A double-blind, placebo-controlled trial of olanzapine addition in fluoxetine-refractory obsessive-compulsive disorder. Biological Psychiatry. 2004;55(5): 553-555. DOI:10.1016/j.biopsych.2003.11.010
Storch EA, Goddard AW, Grant JE, et al. Double-blind, placebo-controlled, pilot trial of paliperidone augmentation in serotonin reuptake inhibitor-resistant obsessive-compulsive disorder. The Journal of Clinical Psychiatry. 2013;74(6): 527-532. DOI:10.4088/JCP.12m08278
Angelucci F, Ricci V, Martinotti G, et al. Paliperidone for treatment of obsessive compulsive resistant symptoms in schizophrenia: a case report. Progress in Neuro-psychopharmacology & Biological Psychiatry. 2009;33(7): 1277-1278. DOI:10.1016/j.pnpbp.2009.06.014
Mc Dougle CJ, Price LH, Goodman WK, et al. A controlled trial of lithium augmentation in fluvoxamine-refractory obsessive-compulsive disorder: lack of efficacy. Journal of Clinical Psychopharmacology. 1991;11(3): 175-184.
Pigott TA, Pato MT, L'Heureux F, et al. A controlled comparison of adjuvant lithium carbonate or thyroid hormone in clomipramine-treated patients with obsessive-compulsive disorder. Journal of Clinical Psychopharmacology. 1991;11(4): 242-248.
Pigott TA, L'Heureux F, Hill JL, et al. A double-blind study of adjuvant buspirone hydrochloride in clomipramine-treated patients with obsessive-compulsive disorder. Journal of Clinical Psychopharmacology. 1992;12(1): 11-18. DOI:10.1097/00001573-199202000-00003
Mc Dougle CJ, Goodman WK, Leckman JF, et al. Limited therapeutic effect of addition of buspirone in fluvoxamine-refractory obsessive-compulsive disorder. The American Journal of Psychiatry. 1993;150(4): 647-649. DOI:10.1176/ajp.150.4.647
Grady TA, Pigott TA, L'Heureux F, et al. Double-blind study of adjuvant buspirone for fluoxetine-treated patients with obsessive-compulsive disorder. The American Journal of Psychiatry. 1993;150(5): 819-821. DOI:10.1176/ajp.150.5.819
Barr LC, Goodman WK, Anand A, et al. Addition of desipramine to serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder. The American Journal of Psychiatry. 1997;154(9): 1293-1295. DOI:10.1176/ajp.154.9.1293
Fux M, Benjamin J, Belmaker R. Inositol versus placebo augmentation of serotonin reuptake inhibitors in the treatment of obsessive–compulsive disorder: a double-blind cross-over study. The International Journal of Neuropsychopharmacology. 1999;2(3): 193-195. DOI:10.1017/S1461145799001546
Dannon PN, Sasson Y, Hirschmann S, et al. Pindolol augmentation in treatment-resistant obsessive compulsive disorder: a double-blind placebo controlled trial. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology. 2000;10(3): 165-169. DOI:10.1016/s0924-977x(00)00065-1
Corá-Locatelli G, Greenberg BD, Murphy DL. Gabapentin augmentation for fluoxetine-treated patients with obsessive-compulsive disorder. The Journal of Clinical Psychiatry. 1998;59(9): 480-481. DOI:10.4088/jcp.v59n0907d
Crockett BA, Churchill E, Davidson JR. A double-blind combination study of clonazepam with sertraline in obsessive-compulsive disorder. Annals of Clinical Psychiatry: Official Journal of the American Academy of Clinical Psychiatrists. 2004;16(3): 127-132. DOI:10.1080/10401230490486972
Amiaz R, Fostick L, Gershon A, et al. Naltrexone augmentation in OCD: a double-blind placebo-controlled cross-over study. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology. 2008;18(6): 455-461. DOI:10.1016/j.euroneuro.2008.01.006
Mowla A, Khajeian AM, Sahraian A, et al. Topiramate augmentation in resistant OCD: a double-blind placebo-controlled clinical trial. CNS Spectrums. 2010;15(11): 613-617. DOI:10.1017/S1092852912000065
Berlin HA, Koran LM, Jenike MA, et al. Double-blind, placebo-controlled trial of topiramate augmentation in treatment-resistant obsessive-compulsive disorder. The Journal of Clinical Psychiatry. 2011;72(5): 716-721. DOI:10.4088/JCP.09m05266gre
Afshar H, Akuchekian S, Mahaky B, et al. Topiramate augmentation in refractory obsessive-compulsive disorder: A randomized, double-blind, placebo-controlled trial. Journal of Research in Medical Sciences: The Official Journal of Isfahan University of Medical Sciences. 2014;19(10): 976–981.
Bruno A, Micò U, Pandolfo G, et al. Lamotrigine augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive–compulsive disorder: a double-blind, placebo-controlled study. Journal of Psychopharmacology. 2012;26(11): 1456-1462. DOI:10.1177/0269881111431751
Haghighi M, Jahangard L, Mohammad-Beigi H, et al. In a double-blind, randomized and placebo-controlled trial, adjuvant memantine improved symptoms in inpatients suffering from refractory obsessive-compulsive disorders (OCD). Psychopharmacology. 2013;228(4): 633-640. DOI:10.1007/s00213-013-3067-z
Grant PJ, Joseph LA, Farmer CA, et al. 12-week, placebo-controlled trial of add-on riluzole in the treatment of childhood-onset obsessive–compulsive disorder. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology. 2014;39(6): 1453-1459. DOI:10.1038/npp.2013.343
Pittenger C, Bloch MH, Wasylink S, et al. Riluzole augmentation in treatment-refractory obsessive-compulsive disorder: a pilot randomized placebo-controlled trial. The Journal of Clinical Psychiatry. 2015;76(8): 1075-1084. DOI:10.4088/JCP.14m09123
Vulink NC, Denys D, Fluitman SB, et al. Quetiapine augments the effect of citalopram in non-refractory obsessive-compulsive disorder: a randomized, double-blind, placebo-controlled study of 76 patients. The Journal of Clinical Psychiatry. 2009;70(7): 1001-1008. DOI:10.4088/JCP.08m04269
Askari N, Moin M, Sanati M, et al. Granisetron Adjunct to Fluvoxamine for Moderate to Severe Obsessive-Compulsive Disorder. CNS Drugs. 2012;26(10): 883-892. DOI:10.2165/11635850-000000000-00000
Heidari M, Zarei M, Hosseini SM, et al. Ondansetron or placebo in the augmentation of fluvoxamine response over 8 weeks in obsessive–compulsive disorder. International Clinical Psychopharmacology. 2014;29(6): 344-350. DOI:10.1097/YIC.0000000000000043
Shalbafan M, Mohammadinejad P, Shariat SV, et al. Celecoxib as an adjuvant to fluvoxamine in moderate to severe obsessive-compulsive disorder: a double-blind, placebo-controlled, randomized trial. Pharmacopsychiatry. 2015;48(04/05): 136-140. DOI:10.1055/s-0035-1549929
Ghaleiha A, Entezari N, Modabbernia A, et al. Memantine add-on in moderate to severe obsessive-compulsive disorder: randomized double-blind placebo-controlled study. Journal of Psychiatric Research. 2013;47(2): 175-180. DOI:10.1016/j.jpsychires.2012.09.015
Emamzadehfard S, Kamaloo A, Paydary K, et al. Riluzole in augmentation of fluvoxamine for moderate to severe obsessive–compulsive disorder: R andomized, double‐blind, placebo‐controlled study. Psychiatry and Clinical Neurosciences. 2016;70(8): 332-341. DOI:10.1111/pcn.12394
Paydary K, Akamaloo A, Ahmadipour A, Pishgar F, et al. N‐acetylcysteine augmentation therapy for moderate‐to‐severe obsessive–compulsive disorder: Randomized, double‐blind, placebo‐controlled trial. Journal of Clinical Pharmacy and Therapeutics. 2016;41(2): 214-219. DOI:10.1111/jcpt.12370
Rodriguez CI, Kegeles LS, Levinson A, et al. Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder: proof-of-concept. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology. 2013;38(12): 2475-2483. DOI:10.1038/npp.2013.150
