Tedaviye Dirençli Obsesif Kompulsif Bozuklukta Transkraniyal Manyetik Uyarim: Yeri ve Etkinliği
Özet
Obsesif kompulsif bozukluk (OKB), yaşam boyu yaklaşık %2–3 oranında görülen ve işlevselliği belirgin biçimde bozan kronik seyirli bir psikiyatrik bozukluktur. Birinci basamak tedavi serotonin geri alım inhibitörleri (SRI) ve maruz bırakma-yanıt önleme (EX/RP) temelli bilişsel davranışçı terapidir. Ancak bu yaklaşımlara rağmen hastaların %25’inden daha azında tam remisyon sağlanabilmektedir. Bu durum tedaviye dirençli OKB için alternatif tedavi yaklaşımlarına olan ilgiyi artırmıştır. Nörogörüntüleme çalışmaları, OKB patofizyolojisinde kortiko-striato-talamo-kortikal (KSTK) devre başta olmak üzere frontolimbik, frontoparietal ve serebellar ağlarda işlevsel düzensizlikler olduğunu göstermiştir. Bu ağların hedeflenmesi, nöromodülasyon yaklaşımlarına temel oluşturmuştur. Transkraniyal manyetik uyarım (TMS), kortikal uyarılabilirliği etkileyebilen invaziv olmayan bir nöromodülasyon yöntemidir. Meta-analizler, özellikle pre-suplementer motor alan (pre-SMA) ve sağ dorsolateral prefrontal korteks (DLPFC) hedefli rTMS uygulamalarının OKB semptomlarında klinik olarak anlamlı azalma sağlayabildiğini göstermektedir. Ayrıca medial prefrontal korteks (mPFC) ve anterior singulat korteksi (ACC) hedefleyen derin TMS protokollerinin tedaviye dirençli OKB için FDA onayı almış olması, yöntemin klinik değerini desteklemektedir. TMS güvenli ve iyi tolere edilen bir nöromodülasyon yaklaşımıdır; farmakolojik güçlendirme stratejileri ve invaziv tedavilere alternatif olarak değerlendirilmektedir.
Obsessive-compulsive disorder (OCD) is a chronic psychiatric disorder with a lifetime prevalence of approximately 2–3%, associated with significant functional impairment. First-line treatment includes serotonin reuptake inhibitors (SRIs) and cognitive behavioral therapy with exposure and response prevention (EX/RP). However, despite these approaches, full remission is achieved in fewer than 25% of patients. This has increased interest in alternative treatment strategies for treatment-resistant OCD. Neuroimaging studies have demonstrated functional abnormalities in several neural networks involved in OCD pathophysiology, particularly the cortico-striato-thalamo-cortical (CSTC) circuit, as well as frontolimbic, frontoparietal, and cerebellar networks. Targeting these networks has provided the theoretical basis for neuromodulation approaches. Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique that can modulate cortical excitability. Meta-analyses indicate that repetitive TMS (rTMS), particularly when targeting the pre-supplementary motor area (pre-SMA) and the right dorsolateral prefrontal cortex (DLPFC), can produce clinically meaningful reductions in OCD symptoms. In addition, deep TMS protocols targeting the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC) have received FDA approval for treatment-resistant OCD, supporting the clinical relevance of this approach. TMS is considered a safe and well-tolerated neuromodulation approach and may serve as an alternative to pharmacological augmentation strategies and invasive treatments.
Referanslar
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Referanslar
Ruscio AM, Stein DJ, Chiu WT, Kessler RC. The epidemiology of obsessive-compulsive disorder in the National Comorbidity Survey Replication. Mol Psychiatry. 2010;15:53–63. doi: 10.1038/mp.2008.94.
Gershkovich M, Wheaton MG, Simpson HB. Management of Treatment-Resistant Obsessive-Compulsive Disorder. Curr Treat Options Psych. 2017;4:357–370. doi: 10.1007/s40501-017-0127-8.
Sahoo P, Sethy RR, Ram D. Functional Impairment and Quality of Life in Patients with Obsessive Compulsive Disorder. Indian J Psychol Med. 2017;39:760–765. doi: 10.4103/IJPSYM.IJPSYM_53_17. Cited in PMID: 29284808.
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Goodman WK, Ward HE, Kablinger AS, Murphy TK. Biological Approaches to Treatment-Resistant Obsessive-Compulsive Disorder. Obsessive-Compulsive Disorder. Routledge; 1999.
Del Casale A, Kotzalidis GD, Rapinesi C, Serata D, Ambrosi E, Simonetti A, Pompili M, Ferracuti S, Tatarelli R, Girardi P. Functional neuroimaging in obsessive-compulsive disorder. Neuropsychobiology. 2011;64:61–85.
van den Heuvel OA, van Wingen G, Soriano-Mas C, Alonso P, Chamberlain SR, Nakamae T, Denys D, Goudriaan AE, Veltman DJ. Brain circuitry of compulsivity. European Neuropsychopharmacology. 2016;26:810–827. doi: 10.1016/j.euroneuro.2015.12.005.
Swierkosz-Lenart K, Dos Santos JFA, Elowe J, Clair A-H, Bally JF, Riquier F, Bloch J, Draganski B, Clerc M-T, Pozuelo Moyano B, et al. Therapies for obsessive-compulsive disorder: Current state of the art and perspectives for approaching treatment-resistant patients. Front Psychiatry. 2023;14:1065812. doi: 10.3389/fpsyt.2023.1065812. Cited in PMID: 36873207.
Rossi S, Antal A, Bestmann S, Bikson M, Brewer C, Brockmöller J, Carpenter LL, Cincotta M, Chen R, Daskalakis JD, et al. Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines. Clinical Neurophysiology. 2021;132:269–306. doi: 10.1016/j.clinph.2020.10.003.
Auvichayapat P, Auvichayapat N. Basic principle of transcranial magnetic stimulation. J Med Assoc Thai. 2009;92:1560–1566.
Ozer U, Yucens B, Tumkaya S. Efficacy of accelerated deep transcranial magnetic stimulation wi̇th double cone coi̇l in obsessive-compulsive disorder: A double-blind, placebo-controlled study. Journal of Psychiatric Research. 2024;171:325–331.
Hoogendam JM, Ramakers GMJ, Di Lazzaro V. Physiology of repetitive transcranial magnetic stimulation of the human brain. Brain Stimulation. 2010;3:95–118. doi: 10.1016/j.brs.2009.10.005.
Sookman D, Steketee G. Specialized cognitive behavior therapy for treatment resistant obsessive compulsive disorder. 2009;
Carmi L, Tendler A, Bystritsky A, Hollander E, Blumberger DM, Daskalakis J, Ward H, Lapidus K, Goodman W, Casuto L, et al. Efficacy and Safety of Deep Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder: A Prospective Multicenter Randomized Double-Blind Placebo-Controlled Trial. American Journal of Psychiatry [Internet]. 2019 [cited 2025 Dec 14]; doi: 10.1176/appi.ajp.2019.18101180.
Issari Y, Jakubovski E, Bartley CA, Pittenger C, Bloch MH. Early onset of response with selective serotonin reuptake inhibitors in obsessive-compulsive disorder: a meta-analysis. J Clin Psychiatry. 2016;77:e605-611. doi: 10.4088/JCP.14r09758. Cited in PMID: 27249090.
Foa EB, Yadin E, Lichner TK. Exposure and response (ritual) prevention for obsessive-compulsive disorder: Therapist guide, 2nd ed. New York, NY, US: Oxford University Press; 2012. p. x, 182.
Huey ED, Zahn R, Krueger F, Moll J, Kapogiannis D, Wassermann EM, Grafman J. A Psychological and Neuroanatomical Model of Obsessive-Compulsive Disorder. JNP. 2008;20:390–408. doi: 10.1176/jnp.2008.20.4.390.
Rotge J-Y, Guehl D, Dilharreguy B, Cuny E, Tignol J, Bioulac B, Allard M, Burbaud P, Aouizerate B. Provocation of obsessive–compulsive symptoms: a quantitative voxel-based meta-analysis of functional neuroimaging studies. J Psychiatry Neurosci. 2008;33:405–412. doi: 10.1139/jpn.0838.
Thorsen AL, Hagland P, Radua J, Mataix-Cols D, Kvale G, Hansen B, van den Heuvel OA. Emotional Processing in Obsessive-Compulsive Disorder: A Systematic Review and Meta-analysis of 25 Functional Neuroimaging Studies. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. 2018;3:563–571. doi: 10.1016/j.bpsc.2018.01.009.
Del Casale A, Rapinesi C, Kotzalidis GD, De Rossi P, Curto M, Janiri D, Criscuolo S, Alessi MC, Ferri VR, De Giorgi R, et al. Executive functions in obsessive–compulsive disorder: An activation likelihood estimate meta-analysis of fMRI studies. The World Journal of Biological Psychiatry. 2016;17:378–393. doi: 10.3109/15622975.2015.1102323. Cited in PMID: 26642972.
Eng GK, Sim K, Chen S-HA. Meta-analytic investigations of structural grey matter, executive domain-related functional activations, and white matter diffusivity in obsessive compulsive disorder: An integrative review. Neuroscience & Biobehavioral Reviews. 2015;52:233–257. doi: 10.1016/j.neubiorev.2015.03.002.
Gillan CM, Robbins TW, Sahakian BJ, van den Heuvel OA, van Wingen G. The role of habit in compulsivity. European Neuropsychopharmacology. 2016;26:828–840. doi: 10.1016/j.euroneuro.2015.12.033.
Rasgon A, Lee WH, Leibu E, Laird A, Glahn D, Goodman W, Frangou S. Neural correlates of affective and non-affective cognition in obsessive compulsive disorder: A meta-analysis of functional imaging studies. European Psychiatry. 2017;46:25–32. doi: 10.1016/j.eurpsy.2017.08.001.
Barker AT, Jalinous R, Freeston IL. Non-invasive magnetic stimulation of human motor cortex. The Lancet. 1985;325:1106–1107.
Lefaucheur J-P, André-Obadia N, Antal A, Ayache SS, Baeken C, Benninger DH, Cantello RM, Cincotta M, de Carvalho M, De Ridder D, et al. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clinical Neurophysiology. 2014;125:2150–2206. doi: 10.1016/j.clinph.2014.05.021.
Galletly C, Fitzgerald P, Clarke P, Gill S, Burton C, Turnbull C. A Practical Guide to Setting up a Repetitive Transcranial Magnetic Stimulation (rTMS) Service. Australas Psychiatry. 2010;18:314–317. doi: 10.3109/10398561003686771.
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