Repetitive transcranial magnetic stimulation versus Fluvoxamine in the treatment of obsessive-compulsive disorder: A randomized open-label pilot study

Repetitive transcranial magnetic stimulation versus Fluvoxamine in the treatment of obsessive-compulsive disorder: A randomized open-label pilot study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Repetitive transcranial magnetic stimulation versus Fluvoxamine in the treatment of obsessive-compulsive disorder: A randomized open-label pilot study Yanhua Qin, Liqiang Cai, Lingling Cheng, Ludan Xiang MA, Xingyue Hu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6655404/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Obsessive-compulsive disorder (OCD) is a chronic, disabling mental disorder. While repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising neuromodulation intervention for psychiatric disorders, its efficacy in treatment-naïve OCD populations remains understudied. This randomized controlled trial investigates the comparative effectiveness of low-frequency rTMS versus first-line pharmacotherapy in treatment-naïve OCD patients. Methods: Treatment-naïve OCD patients (n = 41) were randomized to receive either standardized fluvoxamine therapy (150-200 mg/day) or daily low-frequency (1 Hz) rTMS targeting the supplementary motor area (SMA) for 2 weeks. Clinical outcomes were longitudinally assessed using validated instruments: Yale-Brown Obsessive-Compulsive Scale score reduction rate ≥ 25% as primary endpoint, supplemented by Beck Depression Inventory and Beck Anxiety Inventory for comorbid symptom evaluation. Safety profiles were monitored throughout the trial. Results: The experimental results showed that the difference of response rate at the end of intervention between two groups had no statistical significance ( χ 2 = 0.183, p = 0.669 ), with 41.7% (5/12) in rTMS group versus 60% (6/10) in fluvoxamine cohort. No severe adverse events were reported in either group, and no patients withdrew due to adverse events in the rTMS group. Conclusion: This trail found that low-frequency rTMS over SMA might have a similar therapeutic effect as that of fluvoxamine for treatment-naïve patients with OCD. These findings support rTMS as a potential treatment option for medication-averse OCD populations. Trial registration: The study was retrospectively registered in https://www.chictr.org.cn on June 30, 2023 (ChiCTR2300072654). Obsessive-compulsive disorder repetitive transcranial magnetic stimulation Treatment-naïve patients fluvoxamine Figures Figure 1 1. Introduction Obsessive-compulsive disorder (OCD) is a chronic, disabling mental disorder characterized by intrusive thoughts or images (obsessions) and repetitive behaviors (compulsions). It may be only obsessive or compulsive symptoms. The lifetime prevalence that fully meets OCD criteria of the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) is 2.4%, the 12-month prevalence is 1.6% in China (1), and the global prevalence is 1.3% (2). OCD patients and their caregivers have a poorer life quality and higher illness burden than that healthy controls (3). Selective serotonin-reuptake inhibitors (SSRIs), including fluvoxamine, sertraline, paroxetine and fluoxetine, are recommended as the first-line interventions (4), however, 40–60% of patients still exhibit no or less response to these traditional treatments (5). The side effects or low effective rate of medication may sometime influence the obedience to medical orders. Therefore, more alternative options are required. Deep brain stimulation and gamma knife radiosurgery, as alternative treatments for refractory cases, partially improve clinical obsessive and compulsive symptoms. However, both strategies are invasive treatments with side effects, such as brain edema and infection (6–8). Repetitive transcranial magnetic stimulation (rTMS), a non-invasive treatment with fewer side effects and less time spent, can change or restore neuron activity via magnetic fields (9). Greenberg first applied rTMS to treat OCD in 1997 (10); since then, numerous studies have emerged in this area. Low-frequency stimulation (≤ 1 Hz) decreases cortical excitability, while high-frequency stimulation (≥ 5 Hz) increases underlying cortical excitability (11). Cortical-striatal-thalamus-cortical (CSTC) pathways have been related to motor execution control, habit formation, and reward. The CSTC pathway activity is highly associated with OCD symptoms. The inhibitory threshold reduction activates the direct pathway in OCD patients, leading to over-activating the orbitofrontal cortico-subcutaneous nucleus pathway and making the patient overly concerned with stimuli, such as danger, hygiene, or injury. Patients use compulsive behavior to temporarily alleviate the anxiety and pain caused by the threat (12). According to previous studies, SMA has extensive connections with subcortical striatum areas involved in response control. Hyperactivity in the SMA may explain deficient inhibitory control over behavior in OCD patients (13). The rTMS modulates neural plasticity via long-time depression and potentiation (14). Meta-analysis implied that the beneficial curative effect of active rTMS are superior to the sham group in treating OCD (15), and low-frequency stimulation of the SMA yielded the greatest reductions in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores relative to other cortical targets (16). The participant heterogeneity in clinical trials, including resistant patients, untreated patients, or ones under treatment (17, 18), led to the inconsistency in research findings to some degree. Previous studies primarily focused on the rTMS efficacy in refractory OCD or combined therapy, making it difficult to rule out the possibility of synergism between rTMS and pharmacotherapy. On the basis of safety of rTMS from published articles, and no trial yet has been designed to compare rTMS treatment with pharmacotherapy on treatment-free patients directly, therefore, we performed treatment-naïve OCD patients to active rTMS or fluvoxamine and compared effectiveness. 2. Methods 2.1 Participants Eligible participants were male and female individuals recruited from the outpatient or inpatient between 10, September, 2020 and 22, February, 2023. All participants signed an informed consent form prior to inclusion in the study, and could comply with the rTMS therapy protocol and scale assessment. The study inclusion criteria were as follows: (1) met the Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria for OCD; (2) aged from 18 to 65 years; (3) were initially diagnosed without medication or other treatment. The exclusion criteria included: (1) refractory OCD; (2) any major physical diseases; (3) other severe mental illness illnesses, schizophrenia, current suicidal ideas or attempt (the third item of Hamilton Depression Rating Scale ≥ 3), bipolar disorder, substance, and alcohol dependence; (4) existed metallic or foreign implantation in the brain, severe or unstable physical conditions, history of epilepsy and brain organic diseases, and severe cardiac disorder; (5) patients who were pregnant, planning to become pregnant, or breastfeeding during the study period. All study procedures were reviewed and approved by Sir Run Run Shaw Hospital's human research ethics committee (No.20200908-9). 2.2 Procedures The participants were assigned to rTMS treatment and fluvoxamine pharmacotherapy groups, using a single random sequence number in a series of opaque and sealed envelopes. We used the CONSORT reporting guidelines during the entire process of the experiment. The demographic data and basic clinical characteristics, including sex, age, age of symptoms onset, and the duration of disease, were collected. The Y-BOCS is a 10-item scale assessing the severity of OCD symptoms over the past week (19). The Beck Depression Inventory (BDI-13) is a self-rating scale assessing depressive symptoms (20), and the Beck Anxiety Inventory (BAI) is a 21-item scale assessing anxiety symptoms over the past week (21). BAI and BDI were used to measure the accompanying depressive mood and anxiety, respectively. The clinical raters and rTMS administrators were blinded to the randomization procedure and were separate individuals. The assessment of patient symptoms was performed at the baseline and 2-week of treatment using Y-BOCS, BAI, and BDI. Y-BOCS score reduction rate = (baseline scores – scores at 2-week of treatment) / baseline score * 100%. The score reduction rate ≥ 25% was an effective response(22). The response rate = (number of effective responses/total number of participants in each group) * 100%. 2.3 Intervention The rTMS was administered using a 70-mm, eight-shaped coil Magstim Rapid2 stimulator (Magstim Company, Whitland, Wales, United Kingdom) and presented at 100% of resting motor threshold with 1,200 pulses per day for 20 minutes. Participants received 10 treatment sessions, five days a week for either 1 Hz rTMS applied to the SMA. Resting motor threshold was defined as the minimum TMS intensity to elicit a motor-evoked potential of the right abductor pollicis brevis muscle in 5/10 trials using single-pulse TMS administered to the left primary motor cortex. The TMS coil was held tangential to the scalp of the stimulation location. The stimulus site was 15% of the distance anterior to vertex (Cz), on the line of inion and nasion, corresponding to the bilateral SMA according to the 10–20 International EEG localization system (23). Fluvoxamine was started with 50 mg daily and increased slowly in one week to the target dose (150–200 mg daily) with tolerable adverse reactions, then maintained this dose for one week. 2.4 Statistical analyses All statistical analyses were performed using R version 4.1.2 software. Finally, 22 were collected for the statistics. One patient in the rTMS group received seven sessions, but the data were still included in our statistics. Age, illness duration, onset age, and Y-BOCS were described using mean ± standard deviation; the difference between the two groups was analyzed by independent sample t-test. Chi-square ( χ 2 ) test or Fischer’s exact test was used for comparing categorical variables (gender and response rate). The effects of time (baseline and after treatment) and grouping (fluvoxamine and rTMS) variables on secondary outcomes (BDI and BAI) were analyzed using ANCOVA. The alpha level of significance was set at 0.05. 3. Results 3.1 Demographic and Clinical Characteristics at Baseline A total of 45 eligible participants were males and females recruited from the outpatient and inpatient between September 2020 and February 2023. Prior to randomization, 1 patient was excluded from study due to suicidal attempt, 3 withdrew due to personal reasons. The study enrolled 41 patients, with 21 and 20 randomized to the fluvoxamine and rTMS groups, respectively. Among them, 8 patients couldn’t follow up as planed because of isolation and locking down for COVID-19 in each group, and 3 patients withdrew from the study due to drug side effects. Consequently, data were collected from 22 patients (Fig. 1 .), comprising 10 participants in the drug intervention group and 12 in the rTMS therapy group. The demographic and clinical characteristics of the study participants were summarized in Table 1 . The overall sample consisted of 13 males (59.1%) and 9 females (40.9%). The mean age was 29.08 ± 10.47 years in the rTMS group and 32.4 ± 16.81 years in the fluvoxamine group. The illness duration was 72 ± 90.51 months in the rTMS group and 54 ± 55.16 months in the fluvoxamine group. Baseline Y-BOCS scores were 20 ± 5.13 and 17 ± 5.58 in the rTMS and fluvoxamine groups, respectively. No significant differences were observed between the two groups in terms of gender distribution, illness duration, or baseline morbidity ( p>0.05 ). Similarly, there were no significant differences in baseline scores for the Y-BOCS, BDI, or BAI ( p>0.05 ). Table 1 Baseline demographic and clinical characteristics of the participants. Fluvoxamine (n = 10) rTMS (n = 12) t/χ 2 P Gender (M/F) 5/5 8/4 0.666 Age (years), Mean ± SD 32.4 ± 16.81 29.08 ± 10.47 0.542 0.596 Illness duration (months), Mean ± SD 54 ± 55.16 72 ± 90.5 -0.573 0.574 Onset age (years), Mean ± SD 26.25 ± 12.28 23.08 ± 7.97 0.702 0.494 Y-BOCS score, Mean ± SD 17 ± 5.58 20 ± 5.13 -1.302 0.209 BDI score, Mean ± SD 9.6 ± 7.5 9 ± 5.91 0.205 0.840 BAI score, Mean ± SD 46.4 ± 13.87 41.58 ± 11.52 0.875 0.393 Response Condition at two-week of Treatment At the two-week follow-up, 11 out of 22 patients (50%) demonstrated a positive response to treatment. Specifically, the response rate for rTMS was 41.7% (5/12), while fluvoxamine treatment showed a response rate of 60% (6/10). Although the rTMS group had a lower response rate than the fluvoxamine group, the difference between the two groups has no statistical significance (Table 2 . χ 2 = 0.183, p = 0.669 ). However, neither depression nor anxiety symptoms improved significantly between the two groups. The repeated measures ANCOVA showed no significant group effect ( p>0.05 ) and time effect ( p>0.05 ) on BDI/BAI scores before and aftertreatment (Table 3 .). Table 2 The response rate in rTMS and fluvoxamine treatment groups. Total (n = 22) Fluvoxamine (n = 10) rTMS (n = 12) χ 2 P Response rate 11 (50) 6 (60) 5 (41.7) 0.183 0.669 Nonresponse rate 11 (50) 4 (40) 7 (58.3) Table 3 BDI and BAI scores at the beginning and 2 weeks of treatment. Baseline ( n = 22 ) 2 weeks of treatment ( n = 22 ) Group Time Fluvoxamine (n = 10) rTMS (n = 12) Fluvoxamine (n = 10) rTMS (n = 12) F (p) F (p) BDI score (Mean ± SD) 9.6 ± 7.5 9 ± 5.9 7.3 ± 7.4 5.9 ± 5.4 0.257 (0.615) 1.958 (0.169) BAI score (Mean ± SD) 46.4 ± 13.9 41.6 ± 11.5 37.5 ± 13.6 38.8 ± 13.2 0.207 (0.652) 2.050 (0.160) 3.2 Adverse events Among patients receiving rTMS, two of twelve reported transient headaches following the initial stimulation session, though the pain intensity remained within tolerable limits. Importantly, no subjects withdrew from the rTMS cohort due to adverse events, in contrast, three participants in the fluvoxamine group (3/13, 23.1%) withdrew from the study owing to severe nausea and dizziness that necessitated discontinuation. 4. Discussion 4.1 Interpretation To our knowledge, this represents the first investigation of repetitive transcranial magnetic stimulation (rTMS) in treatment-naïve patients with OCD. At 2-weeks of treatment, the results revealed that the response rate was 41.7% (5/12) in the rTMS group and 60% (6/10) in the fluvoxamine group. The therapeutic effect did not differ significantly between the two groups ( χ 2 = 0.183, p > 0.05 ), both groups exhibited similar efficacy. It should be noted that this pilot study was not powered for equivalence or noninferiority analysis, therefore, we cannot definitively conclude that rTMS is noninferior to fluvoxamine. Multi-site studies and double-blind trials demonstrated that modulating SMA via rTMS could relieve symptoms in resistant OCD. Sarah et al. discovered that after two weeks of low-frequency rTMS delivered to SMA in refractory OCD patients, the response rate was 44% (4/9) in the active group and 11% (1/9) in the sham group (24). Our results were consistent with these studies, confirming that inhibiting the SMA overactivity could improve OCD symptoms. While prior studies observed delayed therapeutic onset (6 weeks) with sustained effects post-treatment (23), our cohort, comprising predominantly treatment-naïve and non-refractory patients, exhibited earlier responsiveness, suggesting differential neuroplasticity in early-stage disease, where these patients might be more responsive to treatment, however, this hypothesis needs to be tested with functional magnetic resonance imaging in the future. While multiple randomized trials have established its efficacy as an augmentation strategy in refractory OCD(18, 23, 25, 26), our findings highlight its viability as a primary intervention in early-stage disease. The therapeutic potential of rTMS extends beyond its monotherapy applications as an adjunctive therapy. No significant between-group differences emerged in BAI or BDI scores post-intervention. This null finding may reflect limited statistical power due to the modest sample size ( n = 22) and low baseline prevalence of comorbid anxiety/depression in our cohort. 4.2 Limitations This study has several limitations. First, the design did not include a placebo condition. Given that first-line recommended medications for OCD are widely available, establishing a placebo control group would not align with the best interests of patients. Second, this was an open-label exploratory study with a small sample size. While preliminary positive outcomes were observed, larger multicenter trials with double-blind protocols and extended follow-up periods are required to validate and further investigate the efficacy of rTMS. Third, the SMA exhibits anatomical variability across individuals. Conventional localization methods based on standardized neuroanatomical landmarks may lead to inaccuracies in targeting stimulation sites. Incorporating individualized Magnetic Resonance Imaging (MRI)-guided navigation could enhance precision in future studies. Forth, the open-label nature of the trial introduced potential response bias, as participants were aware of their assigned intervention. Finally, the generalizability of our findings is limited to the specific SSRI (fluvoxamine) and rTMS protocol (1 Hz over SMA) used in this trial. Results may not extend to other SSRIs, alternative rTMS parameters (e.g., frequency, duration), or different cortical targets. Despite these limitations, our findings provide a meaningful foundation for future research. A randomized, double-blind, sham-controlled trial with longer follow-up is warranted to confirm these results. 4.3 Conclusion This trail found that low-frequency rTMS over supplementary motor area (SMA) might have a similar therapeutic effect as that of fluvoxamine for treatment-naïve patients with OCD. These findings support rTMS as a potential treatment option for treatment-naïve patients with OCD or medication-averse OCD populations. Abbreviations Obsessive-compulsive disorder, OCD; repetitive transcranial magnetic stimulation, rTMS; supplementary motor area, SMA; Yale-Brown Obsessive-Compulsive Scale, Y-BOCS; Beck Depression Inventory, BDI; Beck Anxiety Inventory, BAI; Selective serotonin-reuptake inhibitors, SSRIs; Cortical-striatal-thalamus-cortical, CSTC. Declarations Acknowledgments We would like to express our gratitude to participants in this study. Ethics approval All study procedures were reviewed and approved by Sir Run Run Shaw Hospital's human research ethics committee (20200908-9). Consent for publication Not applicable. Data availability Data sets generated during the current study are available from this published article and raw data is accessible in the supplementary information files. Conflict of Interests The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Author Contributions Xingyue Hu contributed to the conception and design of the study, reviewed and revised the manuscript prior to submission. Yanhua Qin and Liqiang Cai contributed to collecting data, conducted analyses and drafted the initial manuscript. Lingling Cheng and Ludan Xiang contributed to Scale evaluation. All authors read and approved the final manuscript. Funding This work was supported by Medical and Health Science and Technology Project of Hangzhou (OO20190215) and Medical Science and Technology Project of Zhejiang province (2023KY796). References Huang Y, Wang Y, Wang H, Liu Z, Yu X, Yan J, et al. Prevalence of mental disorders in China: a cross-sectional epidemiological study. Lancet Psychiatry. 2019;6(3):211-24. Fawcett EJ, Power H, Fawcett JM. 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Repetitive transcranial magnetic stimulation of the supplementary motor area in treatment-resistant obsessive-compulsive disorder: An open-label pilot study. J Clin Neurosci. 2017;44:264-8. Huang Y, Yang H, Zhu C, Jiang X, Zhu W, Liang Y, et al. An Exploratory Study of a Novel Combined Therapeutic Modality for Obsessive-Compulsive Disorder. Brain Sci. 2022;12(10). Additional Declarations No competing interests reported. Supplementary Files CONSORT2010Checklist2.pdf MicrosoftExcel.xlsx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6655404","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":485620723,"identity":"a766fde7-e3d4-41ab-9891-3bf567123944","order_by":0,"name":"Yanhua Qin","email":"","orcid":"","institution":"Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yanhua","middleName":"","lastName":"Qin","suffix":""},{"id":485620724,"identity":"4bae91fe-2fb9-4c71-b499-fbc62710dad4","order_by":1,"name":"Liqiang Cai","email":"","orcid":"","institution":"Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Liqiang","middleName":"","lastName":"Cai","suffix":""},{"id":485620725,"identity":"ac1a0b98-f6e4-459e-8ffd-494b788cfa22","order_by":2,"name":"Lingling Cheng","email":"","orcid":"","institution":"Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Lingling","middleName":"","lastName":"Cheng","suffix":""},{"id":485620726,"identity":"c2f151e2-f2fe-47f7-8864-bf42bfc3dfdd","order_by":3,"name":"Ludan Xiang MA","email":"","orcid":"","institution":"Tongde Hospital of Zhejiang Province","correspondingAuthor":false,"prefix":"","firstName":"Ludan","middleName":"Xiang","lastName":"MA","suffix":""},{"id":485620727,"identity":"6d88cc71-c4ce-49da-8b57-7b2d35f20aa7","order_by":4,"name":"Xingyue Hu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCklEQVRIiWNgGAWjYBACAyA+AGaxNzYc/FDBwAxiSxCnhefwwccSZ4jUAgESackGvG1QNj4t5hI5hocLfh1O7GfIMZOQnFfHbnCA+eBtHga7PFxaLGekJRye2Xc4cWbDGTOJwm1szAYH2JKteRiSi3E67EbygcO8PYcTNxzsAdqyjQeohcdMmofhQGIDTi2JDWAt+w/zmEnwzpEAauH/RkAL0BaeH0Bb2NiA3m8wANnChl/LmWcJh3kb0o1nnGEGBvKxBGbJw2zGlnMMknFrOZ5j/Jnnj7Vs//yHwKisqUvmO9788MabCjucWsCAsa0Zzk6GRKYBTsVQ8KcOzrQjpHYUjIJRMApGHgAAJOZc3csdzaQAAAAASUVORK5CYII=","orcid":"","institution":"Zhejiang University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Xingyue","middleName":"","lastName":"Hu","suffix":""}],"badges":[],"createdAt":"2025-05-13 12:23:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6655404/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6655404/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":87266325,"identity":"fc341df7-0cc3-4f40-94d3-9920dba65f73","added_by":"auto","created_at":"2025-07-22 08:00:52","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":132301,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCONSORT diagram of patients with OCD in a randomized open-label clinic study.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6655404/v1/2d618a31ac8aec1bc0a098f9.png"},{"id":98945461,"identity":"76cc8f75-9b21-4ac1-a0d7-997795b6ef93","added_by":"auto","created_at":"2025-12-24 12:10:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":740065,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6655404/v1/ba7841a7-572f-4dfd-b156-c397fb342f93.pdf"},{"id":87268371,"identity":"0e0be475-3c32-48ce-982c-a8d7ea8a93a5","added_by":"auto","created_at":"2025-07-22 08:08:52","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":190514,"visible":true,"origin":"","legend":"","description":"","filename":"CONSORT2010Checklist2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6655404/v1/e6622b7b2a7c41cf1a01f693.pdf"},{"id":87266328,"identity":"93131ce6-5559-4152-a11b-f612faa160d9","added_by":"auto","created_at":"2025-07-22 08:00:52","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":9892,"visible":true,"origin":"","legend":"","description":"","filename":"MicrosoftExcel.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-6655404/v1/bebd4575376f5c22d57078ab.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Repetitive transcranial magnetic stimulation versus Fluvoxamine in the treatment of obsessive-compulsive disorder: A randomized open-label pilot study","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eObsessive-compulsive disorder (OCD) is a chronic, disabling mental disorder characterized by intrusive thoughts or images (obsessions) and repetitive behaviors (compulsions). It may be only obsessive or compulsive symptoms. The lifetime prevalence that fully meets OCD criteria of the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) is 2.4%, the 12-month prevalence is 1.6% in China (1), and the global prevalence is 1.3% (2). OCD patients and their caregivers have a poorer life quality and higher illness burden than that healthy controls (3). Selective serotonin-reuptake inhibitors (SSRIs), including fluvoxamine, sertraline, paroxetine and fluoxetine, are recommended as the first-line interventions (4), however, 40\u0026ndash;60% of patients still exhibit no or less response to these traditional treatments (5). The side effects or low effective rate of medication may sometime influence the obedience to medical orders. Therefore, more alternative options are required. Deep brain stimulation and gamma knife radiosurgery, as alternative treatments for refractory cases, partially improve clinical obsessive and compulsive symptoms. However, both strategies are invasive treatments with side effects, such as brain edema and infection (6\u0026ndash;8).\u003c/p\u003e\u003cp\u003eRepetitive transcranial magnetic stimulation (rTMS), a non-invasive treatment with fewer side effects and less time spent, can change or restore neuron activity via magnetic fields (9). Greenberg first applied rTMS to treat OCD in 1997 (10); since then, numerous studies have emerged in this area. Low-frequency stimulation (\u0026le;\u0026thinsp;1 Hz) decreases cortical excitability, while high-frequency stimulation (\u0026ge;\u0026thinsp;5 Hz) increases underlying cortical excitability (11). Cortical-striatal-thalamus-cortical (CSTC) pathways have been related to motor execution control, habit formation, and reward. The CSTC pathway activity is highly associated with OCD symptoms. The inhibitory threshold reduction activates the direct pathway in OCD patients, leading to over-activating the orbitofrontal cortico-subcutaneous nucleus pathway and making the patient overly concerned with stimuli, such as danger, hygiene, or injury. Patients use compulsive behavior to temporarily alleviate the anxiety and pain caused by the threat (12). According to previous studies, SMA has extensive connections with subcortical striatum areas involved in response control. Hyperactivity in the SMA may explain deficient inhibitory control over behavior in OCD patients (13). The rTMS modulates neural plasticity via long-time depression and potentiation (14). Meta-analysis implied that the beneficial curative effect of active rTMS are superior to the sham group in treating OCD (15), and low-frequency stimulation of the SMA yielded the greatest reductions in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores relative to other cortical targets (16). The participant heterogeneity in clinical trials, including resistant patients, untreated patients, or ones under treatment (17, 18), led to the inconsistency in research findings to some degree. Previous studies primarily focused on the rTMS efficacy in refractory OCD or combined therapy, making it difficult to rule out the possibility of synergism between rTMS and pharmacotherapy. On the basis of safety of rTMS from published articles, and no trial yet has been designed to compare rTMS treatment with pharmacotherapy on treatment-free patients directly, therefore, we performed treatment-na\u0026iuml;ve OCD patients to active rTMS or fluvoxamine and compared effectiveness.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1 Participants\u003c/h2\u003e\u003cp\u003eEligible participants were male and female individuals recruited from the outpatient or inpatient between 10, September, 2020 and 22, February, 2023. All participants signed an informed consent form prior to inclusion in the study, and could comply with the rTMS therapy protocol and scale assessment.\u003c/p\u003e\u003cp\u003eThe study inclusion criteria were as follows: (1) met the Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria for OCD; (2) aged from 18 to 65 years; (3) were initially diagnosed without medication or other treatment. The exclusion criteria included: (1) refractory OCD; (2) any major physical diseases; (3) other severe mental illness illnesses, schizophrenia, current suicidal ideas or attempt (the third item of Hamilton Depression Rating Scale\u0026thinsp;\u0026ge;\u0026thinsp;3), bipolar disorder, substance, and alcohol dependence; (4) existed metallic or foreign implantation in the brain, severe or unstable physical conditions, history of epilepsy and brain organic diseases, and severe cardiac disorder; (5) patients who were pregnant, planning to become pregnant, or breastfeeding during the study period.\u003c/p\u003e\u003cp\u003e All study procedures were reviewed and approved by Sir Run Run Shaw Hospital's human research ethics committee (No.20200908-9).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2 Procedures\u003c/h2\u003e\u003cp\u003eThe participants were assigned to rTMS treatment and fluvoxamine pharmacotherapy groups, using a single random sequence number in a series of opaque and sealed envelopes. We used the CONSORT reporting guidelines during the entire process of the experiment. The demographic data and basic clinical characteristics, including sex, age, age of symptoms onset, and the duration of disease, were collected. The Y-BOCS is a 10-item scale assessing the severity of OCD symptoms over the past week (19). The Beck Depression Inventory (BDI-13) is a self-rating scale assessing depressive symptoms (20), and the Beck Anxiety Inventory (BAI) is a 21-item scale assessing anxiety symptoms over the past week (21). BAI and BDI were used to measure the accompanying depressive mood and anxiety, respectively. The clinical raters and rTMS administrators were blinded to the randomization procedure and were separate individuals. The assessment of patient symptoms was performed at the baseline and 2-week of treatment using Y-BOCS, BAI, and BDI. Y-BOCS score reduction rate = (baseline scores \u0026ndash; scores at 2-week of treatment) / baseline score * 100%. The score reduction rate\u0026thinsp;\u0026ge;\u0026thinsp;25% was an effective response(22). The response rate = (number of effective responses/total number of participants in each group) * 100%.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3 Intervention\u003c/h2\u003e\u003cp\u003eThe rTMS was administered using a 70-mm, eight-shaped coil Magstim Rapid2 stimulator (Magstim Company, Whitland, Wales, United Kingdom) and presented at 100% of resting motor threshold with 1,200 pulses per day for 20 minutes. Participants received 10 treatment sessions, five days a week for either 1 Hz rTMS applied to the SMA. Resting motor threshold was defined as the minimum TMS intensity to elicit a motor-evoked potential of the right abductor pollicis brevis muscle in 5/10 trials using single-pulse TMS administered to the left primary motor cortex. The TMS coil was held tangential to the scalp of the stimulation location. The stimulus site was 15% of the distance anterior to vertex (Cz), on the line of inion and nasion, corresponding to the bilateral SMA according to the 10\u0026ndash;20 International EEG localization system (23).\u003c/p\u003e\u003cp\u003eFluvoxamine was started with 50 mg daily and increased slowly in one week to the target dose (150\u0026ndash;200 mg daily) with tolerable adverse reactions, then maintained this dose for one week.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.4 Statistical analyses\u003c/h2\u003e\u003cp\u003eAll statistical analyses were performed using R version 4.1.2 software. Finally, 22 were collected for the statistics. One patient in the rTMS group received seven sessions, but the data were still included in our statistics. Age, illness duration, onset age, and Y-BOCS were described using mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation; the difference between the two groups was analyzed by independent sample t-test. Chi-square (\u003cem\u003eχ\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e) test or Fischer\u0026rsquo;s exact test was used for comparing categorical variables (gender and response rate). The effects of time (baseline and after treatment) and grouping (fluvoxamine and rTMS) variables on secondary outcomes (BDI and BAI) were analyzed using ANCOVA. The alpha level of significance was set at 0.05.\u003c/p\u003e\u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e3.1 Demographic and Clinical Characteristics at Baseline\u003c/h2\u003e\u003cp\u003eA total of 45 eligible participants were males and females recruited from the outpatient and inpatient between September 2020 and February 2023. Prior to randomization, 1 patient was excluded from study due to suicidal attempt, 3 withdrew due to personal reasons. The study enrolled 41 patients, with 21 and 20 randomized to the fluvoxamine and rTMS groups, respectively. Among them, 8 patients couldn\u0026rsquo;t follow up as planed because of isolation and locking down for COVID-19 in each group, and 3 patients withdrew from the study due to drug side effects. Consequently, data were collected from 22 patients (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.), comprising 10 participants in the drug intervention group and 12 in the rTMS therapy group.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe demographic and clinical characteristics of the study participants were summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The overall sample consisted of 13 males (59.1%) and 9 females (40.9%). The mean age was 29.08\u0026thinsp;\u0026plusmn;\u0026thinsp;10.47 years in the rTMS group and 32.4\u0026thinsp;\u0026plusmn;\u0026thinsp;16.81 years in the fluvoxamine group. The illness duration was 72\u0026thinsp;\u0026plusmn;\u0026thinsp;90.51 months in the rTMS group and 54\u0026thinsp;\u0026plusmn;\u0026thinsp;55.16 months in the fluvoxamine group. Baseline Y-BOCS scores were 20\u0026thinsp;\u0026plusmn;\u0026thinsp;5.13 and 17\u0026thinsp;\u0026plusmn;\u0026thinsp;5.58 in the rTMS and fluvoxamine groups, respectively. No significant differences were observed between the two groups in terms of gender distribution, illness duration, or baseline morbidity (\u003cem\u003ep\u0026gt;0.05\u003c/em\u003e). Similarly, there were no significant differences in baseline scores for the Y-BOCS, BDI, or BAI (\u003cem\u003ep\u0026gt;0.05\u003c/em\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline demographic and clinical characteristics of the participants.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFluvoxamine\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;10)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003erTMS\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;12)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003et/χ\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender (M/F)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5/5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8/4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.666\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (years), Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e32.4\u0026thinsp;\u0026plusmn;\u0026thinsp;16.81\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e29.08\u0026thinsp;\u0026plusmn;\u0026thinsp;10.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.542\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.596\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIllness duration (months),\u003c/p\u003e\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e54\u0026thinsp;\u0026plusmn;\u0026thinsp;55.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e72\u0026thinsp;\u0026plusmn;\u0026thinsp;90.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-0.573\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.574\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOnset age (years), Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26.25\u0026thinsp;\u0026plusmn;\u0026thinsp;12.28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23.08\u0026thinsp;\u0026plusmn;\u0026thinsp;7.97\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.702\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.494\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eY-BOCS score, Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17\u0026thinsp;\u0026plusmn;\u0026thinsp;5.58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20\u0026thinsp;\u0026plusmn;\u0026thinsp;5.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-1.302\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.209\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBDI score, Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.6\u0026thinsp;\u0026plusmn;\u0026thinsp;7.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.91\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.205\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.840\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBAI score, Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e46.4\u0026thinsp;\u0026plusmn;\u0026thinsp;13.87\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e41.58\u0026thinsp;\u0026plusmn;\u0026thinsp;11.52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.875\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.393\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eResponse Condition at two-week of Treatment\u003c/p\u003e\u003cp\u003eAt the two-week follow-up, 11 out of 22 patients (50%) demonstrated a positive response to treatment. Specifically, the response rate for rTMS was 41.7% (5/12), while fluvoxamine treatment showed a response rate of 60% (6/10). Although the rTMS group had a lower response rate than the fluvoxamine group, the difference between the two groups has no statistical significance (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. \u003cb\u003eχ\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u0026thinsp;\u003cem\u003e=\u0026thinsp;0.183, p\u0026thinsp;=\u0026thinsp;0.669\u003c/em\u003e). However, neither depression nor anxiety symptoms improved significantly between the two groups. The repeated measures ANCOVA showed no significant group effect (\u003cem\u003ep\u0026gt;0.05\u003c/em\u003e) and time effect (\u003cem\u003ep\u0026gt;0.05\u003c/em\u003e) on BDI/BAI scores before and aftertreatment (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eThe response rate in rTMS and fluvoxamine treatment groups.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFluvoxamine\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;10)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003erTMS\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;12)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eχ\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eResponse rate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5 (41.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.183\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.669\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNonresponse rate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e7 (58.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBDI and BAI scores at the beginning and 2 weeks of treatment.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"10\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eBaseline (\u003cem\u003en\u0026thinsp;=\u0026thinsp;22\u003c/em\u003e)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e2 weeks of treatment (\u003cem\u003en\u0026thinsp;=\u0026thinsp;22\u003c/em\u003e)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTime\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFluvoxamine\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003erTMS\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eFluvoxamine\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003erTMS\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eF (p)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eF (p)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBDI score\u003c/p\u003e\u003cp\u003e(Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.6\u0026thinsp;\u0026plusmn;\u0026thinsp;7.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7.3\u0026thinsp;\u0026plusmn;\u0026thinsp;7.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e5.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.257 (0.615)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e1.958 (0.169)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBAI score\u003c/p\u003e\u003cp\u003e(Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e46.4\u0026thinsp;\u0026plusmn;\u0026thinsp;13.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e41.6\u0026thinsp;\u0026plusmn;\u0026thinsp;11.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e37.5\u0026thinsp;\u0026plusmn;\u0026thinsp;13.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e38.8\u0026thinsp;\u0026plusmn;\u0026thinsp;13.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.207 (0.652)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e2.050 (0.160)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003e3.2 Adverse events\u003c/h2\u003e\u003cp\u003eAmong patients receiving rTMS, two of twelve reported transient headaches following the initial stimulation session, though the pain intensity remained within tolerable limits. Importantly, no subjects withdrew from the rTMS cohort due to adverse events, in contrast, three participants in the fluvoxamine group (3/13, 23.1%) withdrew from the study owing to severe nausea and dizziness that necessitated discontinuation.\u003c/p\u003e\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003e4.1 Interpretation\u003c/h2\u003e\u003cp\u003eTo our knowledge, this represents the first investigation of repetitive transcranial magnetic stimulation (rTMS) in treatment-na\u0026iuml;ve patients with OCD. At 2-weeks of treatment, the results revealed that the response rate was 41.7% (5/12) in the rTMS group and 60% (6/10) in the fluvoxamine group. The therapeutic effect did not differ significantly between the two groups (\u003cb\u003eχ\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u0026thinsp;\u003cem\u003e=\u0026thinsp;0.183, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05\u003c/em\u003e), both groups exhibited similar efficacy. It should be noted that this pilot study was not powered for equivalence or noninferiority analysis, therefore, we cannot definitively conclude that rTMS is noninferior to fluvoxamine.\u003c/p\u003e\u003cp\u003eMulti-site studies and double-blind trials demonstrated that modulating SMA via rTMS could relieve symptoms in resistant OCD. Sarah et al. discovered that after two weeks of low-frequency rTMS delivered to SMA in refractory OCD patients, the response rate was 44% (4/9) in the active group and 11% (1/9) in the sham group (24). Our results were consistent with these studies, confirming that inhibiting the SMA overactivity could improve OCD symptoms. While prior studies observed delayed therapeutic onset (6 weeks) with sustained effects post-treatment (23), our cohort, comprising predominantly treatment-na\u0026iuml;ve and non-refractory patients, exhibited earlier responsiveness, suggesting differential neuroplasticity in early-stage disease, where these patients might be more responsive to treatment, however, this hypothesis needs to be tested with functional magnetic resonance imaging in the future. While multiple randomized trials have established its efficacy as an augmentation strategy in refractory OCD(18, 23, 25, 26), our findings highlight its viability as a primary intervention in early-stage disease. The therapeutic potential of rTMS extends beyond its monotherapy applications as an adjunctive therapy.\u003c/p\u003e\u003cp\u003eNo significant between-group differences emerged in BAI or BDI scores post-intervention. This null finding may reflect limited statistical power due to the modest sample size (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;22) and low baseline prevalence of comorbid anxiety/depression in our cohort.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003e4.2 Limitations\u003c/h2\u003e\u003cp\u003eThis study has several limitations. First, the design did not include a placebo condition. Given that first-line recommended medications for OCD are widely available, establishing a placebo control group would not align with the best interests of patients. Second, this was an open-label exploratory study with a small sample size. While preliminary positive outcomes were observed, larger multicenter trials with double-blind protocols and extended follow-up periods are required to validate and further investigate the efficacy of rTMS. Third, the SMA exhibits anatomical variability across individuals. Conventional localization methods based on standardized neuroanatomical landmarks may lead to inaccuracies in targeting stimulation sites. Incorporating individualized Magnetic Resonance Imaging (MRI)-guided navigation could enhance precision in future studies. Forth, the open-label nature of the trial introduced potential response bias, as participants were aware of their assigned intervention. Finally, the generalizability of our findings is limited to the specific SSRI (fluvoxamine) and rTMS protocol (1 Hz over SMA) used in this trial. Results may not extend to other SSRIs, alternative rTMS parameters (e.g., frequency, duration), or different cortical targets. Despite these limitations, our findings provide a meaningful foundation for future research. A randomized, double-blind, sham-controlled trial with longer follow-up is warranted to confirm these results.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003e4.3 Conclusion\u003c/h2\u003e\u003cp\u003eThis trail found that low-frequency rTMS over supplementary motor area (SMA) might have a similar therapeutic effect as that of fluvoxamine for treatment-na\u0026iuml;ve patients with OCD. These findings support rTMS as a potential treatment option for treatment-na\u0026iuml;ve patients with OCD or medication-averse OCD populations.\u003c/p\u003e\u003c/div\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eObsessive-compulsive disorder, OCD; repetitive transcranial magnetic stimulation, rTMS; supplementary motor area, SMA; Yale-Brown Obsessive-Compulsive Scale, Y-BOCS; Beck Depression Inventory, BDI; Beck Anxiety Inventory, BAI; Selective serotonin-reuptake inhibitors, SSRIs; Cortical-striatal-thalamus-cortical, CSTC.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to express our gratitude to participants in this study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll study procedures were reviewed and approved by Sir Run Run Shaw Hospital\u0026apos;s human research ethics committee (20200908-9).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData sets generated during the current study are available from this published article and raw data is accessible in the supplementary information files.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eXingyue Hu contributed to the conception and design of the study, reviewed and revised the manuscript prior to submission. Yanhua Qin and Liqiang Cai contributed to collecting data, conducted analyses and drafted the initial manuscript. Lingling Cheng and Ludan Xiang contributed to Scale evaluation. All authors read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by Medical and Health Science and Technology Project of Hangzhou (OO20190215) and Medical Science and Technology Project of Zhejiang province (2023KY796).\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHuang Y, Wang Y, Wang H, Liu Z, Yu X, Yan J, et al. Prevalence of mental disorders in China: a cross-sectional epidemiological study. Lancet Psychiatry. 2019;6(3):211-24.\u003c/li\u003e\n\u003cli\u003eFawcett EJ, Power H, Fawcett JM. Women Are at Greater Risk of OCD Than Men: A Meta-Analytic Review of OCD Prevalence Worldwide. J Clin Psychiatry. 2020;81(4).\u003c/li\u003e\n\u003cli\u003eCicek E, Cicek IE, Kayhan F, Uguz F, Kaya N. Quality of life, family burden and associated factors in relatives with obsessive-compulsive disorder. Gen Hosp Psychiatry. 2013;35(3):253-8.\u003c/li\u003e\n\u003cli\u003eStein DJ, Koen N, Fineberg N, Fontenelle LF, Matsunaga H, Osser D, et al. A 2012 evidence-based algorithm for the pharmacotherapy for obsessive-compulsive disorder. Curr Psychiatry Rep. 2012;14(3):211-9.\u003c/li\u003e\n\u003cli\u003ePallanti S, Hollander E, Bienstock C, Koran L, Leckman J, Marazziti D, et al. Treatment non-response in OCD: methodological issues and operational definitions. Int J Neuropsychopharmacol. 2002;5(2):181-91.\u003c/li\u003e\n\u003cli\u003eBrown LT, Mikell CB, Youngerman BE, Zhang Y, McKhann GM, 2nd, Sheth SA. Dorsal anterior cingulotomy and anterior capsulotomy for severe, refractory obsessive-compulsive disorder: a systematic review of observational studies. J Neurosurg. 2016;124(1):77-89.\u003c/li\u003e\n\u003cli\u003eGoodman WK, Storch EA, Cohn JF, Sheth SA. Deep Brain Stimulation for Intractable Obsessive-Compulsive Disorder: Progress and Opportunities. Am J Psychiatry. 2020;177(3):200-3.\u003c/li\u003e\n\u003cli\u003eMiguel EC, Lopes AC, McLaughlin NCR, Noren G, Gentil AF, Hamani C, et al. Evolution of gamma knife capsulotomy for intractable obsessive-compulsive disorder. Mol Psychiatry. 2019;24(2):218-40.\u003c/li\u003e\n\u003cli\u003eDi Ponzio M, Makris N, Tenerini C, Grassi E, Ragone S, Pallanti S. rTMS investigation of resistant Obsessive-Compulsive Related Disorders: Efficacy of targeting the reward system. Front Psychiatry. 2022;13:1035469.\u003c/li\u003e\n\u003cli\u003eGreenberg 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(6):867-9.\u003c/li\u003e\n\u003cli\u003eSpeer AM, Benson BE, Kimbrell TK, Wassermann EM, Willis MW, Herscovitch P, et al. Opposite effects of high and low frequency rTMS on mood in depressed patients: relationship to baseline cerebral activity on PET. J Affect Disord. 2009;115(3):386-94.\u003c/li\u003e\n\u003cli\u003eLapidus KA, Stern ER, Berlin HA, Goodman WK. Neuromodulation for obsessive-compulsive disorder. Neurotherapeutics. 2014;11(3):485-95.\u003c/li\u003e\n\u003cli\u003eYucel M, Harrison BJ, Wood SJ, Fornito A, Wellard RM, Pujol J, et al. Functional and biochemical alterations of the medial frontal cortex in obsessive-compulsive disorder. Arch Gen Psychiatry. 2007;64(8):946-55.\u003c/li\u003e\n\u003cli\u003eHoogendam JM, Ramakers GM, Di Lazzaro V. Physiology of repetitive transcranial magnetic stimulation of the human brain. Brain Stimul. 2010;3(2):95-118.\u003c/li\u003e\n\u003cli\u003ePerera MPN, Mallawaarachchi S, Miljevic A, Bailey NW, Herring SE, Fitzgerald PB. Repetitive Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder: A Meta-analysis of Randomized, Sham-Controlled Trials. Biol Psychiatry Cogn Neurosci Neuroimaging. 2021;6(10):947-60.\u003c/li\u003e\n\u003cli\u003eRehn S, Eslick GD, Brakoulias V. A Meta-Analysis of the Effectiveness of Different Cortical Targets Used in Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Obsessive-Compulsive Disorder (OCD). Psychiatr Q. 2018;89(3):645-65.\u003c/li\u003e\n\u003cli\u003ePallanti S, Marras A, Salerno L, Makris N, Hollander E. Better than treated as usual: Transcranial magnetic stimulation augmentation in selective serotonin reuptake inhibitor-refractory obsessive-compulsive disorder, mini-review and pilot open-label trial. J Psychopharmacol. 2016;30(6):568-78.\u003c/li\u003e\n\u003cli\u003ePelissolo A, Harika-Germaneau G, Rachid F, Gaudeau-Bosma C, Tanguy ML, BenAdhira R, et al. Repetitive Transcranial Magnetic Stimulation to Supplementary Motor Area in Refractory Obsessive-Compulsive Disorder Treatment: a Sham-Controlled Trial. Int J Neuropsychopharmacol. 2016;19(8).\u003c/li\u003e\n\u003cli\u003eGoodman WK, Price LH, Rasmussen SA, Mazure C, Fleischmann RL, Hill CL, et al. The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability. Arch Gen Psychiatry. 1989;46(11):1006-11.\u003c/li\u003e\n\u003cli\u003eBeck AT, Beamesderfer A. Assessment of depression: the depression inventory. Mod Probl Pharmacopsychiatry. 1974;7(0):151-69.\u003c/li\u003e\n\u003cli\u003eBeck AT, Epstein N, Brown G, Steer RA. An inventory for measuring clinical anxiety: psychometric properties. J Consult Clin Psychol. 1988;56(6):893-7.\u003c/li\u003e\n\u003cli\u003eSimpson HB, Huppert JD, Petkova E, Foa EB, Liebowitz MR. Response versus remission in obsessive-compulsive disorder. J Clin Psychiatry. 2006;67(2):269-76.\u003c/li\u003e\n\u003cli\u003eHawken ER, Dilkov D, Kaludiev E, Simek S, Zhang F, Milev R. Transcranial Magnetic Stimulation of the Supplementary Motor Area in the Treatment of Obsessive-Compulsive Disorder: A Multi-Site Study. Int J Mol Sci. 2016;17(3):420.\u003c/li\u003e\n\u003cli\u003eMantovani A, Simpson HB, Fallon BA, Rossi S, Lisanby SH. Randomized sham-controlled trial of repetitive transcranial magnetic stimulation in treatment-resistant obsessive-compulsive disorder. Int J Neuropsychopharmacol. 2010;13(2):217-27.\u003c/li\u003e\n\u003cli\u003eLee YJ, Koo BH, Seo WS, Kim HG, Kim JY, Cheon EJ. Repetitive transcranial magnetic stimulation of the supplementary motor area in treatment-resistant obsessive-compulsive disorder: An open-label pilot study. J Clin Neurosci. 2017;44:264-8.\u003c/li\u003e\n\u003cli\u003eHuang Y, Yang H, Zhu C, Jiang X, Zhu W, Liang Y, et al. An Exploratory Study of a Novel Combined Therapeutic Modality for Obsessive-Compulsive Disorder. Brain Sci. 2022;12(10).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Obsessive-compulsive disorder, repetitive transcranial magnetic stimulation, Treatment-naïve patients, fluvoxamine","lastPublishedDoi":"10.21203/rs.3.rs-6655404/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6655404/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eObsessive-compulsive disorder (OCD) is a chronic, disabling mental disorder. While repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising neuromodulation intervention for psychiatric disorders, its efficacy in treatment-naïve OCD populations remains understudied. This randomized controlled trial investigates the comparative effectiveness of low-frequency rTMS versus first-line pharmacotherapy in treatment-naïve OCD patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eTreatment-naïve OCD patients (n = 41) were randomized to receive either standardized fluvoxamine therapy (150-200 mg/day) or daily low-frequency (1 Hz) rTMS targeting the supplementary motor area (SMA) for 2 weeks. Clinical outcomes were longitudinally assessed using validated instruments: Yale-Brown Obsessive-Compulsive Scale score reduction rate ≥ 25% as primary endpoint, supplemented by Beck Depression Inventory and Beck Anxiety Inventory for comorbid symptom evaluation. Safety profiles were monitored throughout the trial.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThe experimental results showed that the difference of response rate at the end of intervention between two groups had no statistical significance (\u003cem\u003e\u003cstrong\u003eχ\u003c/strong\u003e\u003c/em\u003e\u003csup\u003e\u003cem\u003e\u003cstrong\u003e2 \u003c/strong\u003e\u003c/em\u003e\u003c/sup\u003e\u003cem\u003e= 0.183, p = 0.669\u003c/em\u003e), with 41.7% (5/12) in rTMS group versus 60% (6/10) in fluvoxamine cohort. No severe adverse events were reported in either group, and no patients withdrew due to adverse events in the rTMS group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eThis trail found that low-frequency rTMS over SMA might have a similar therapeutic effect as that of fluvoxamine for treatment-naïve patients with OCD. These findings support rTMS as a potential treatment option for medication-averse OCD populations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration:\u003c/strong\u003e The study was retrospectively registered in https://www.chictr.org.cn on June 30, 2023 (ChiCTR2300072654).\u003c/p\u003e","manuscriptTitle":"Repetitive transcranial magnetic stimulation versus Fluvoxamine in the treatment of obsessive-compulsive disorder: A randomized open-label pilot study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-22 08:00:47","doi":"10.21203/rs.3.rs-6655404/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"91d96780-a8c4-4ee2-aeae-bda175796b5a","owner":[],"postedDate":"July 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-24T12:09:51+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-22 08:00:47","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6655404","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6655404","identity":"rs-6655404","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}