Obsessive-compulsive disorder (OCD) is a chronic and potentially disabling neuropsychiatric condition characterized by persistent obsessions, compulsions, or both, which can substantially interfere with social, occupational, and daily functioning [1]. Although pharmacotherapy with selective serotonin reuptake inhibitors and cognitive behavioral therapy with exposure and response prevention remain established first-line treatments, a clinically important proportion of patients experience incomplete response, residual symptoms, or treatment resistance [2]. These limitations have encouraged the development of neuromodulation approaches targeting neural circuits implicated in the pathophysiology of OCD [3]. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a non-invasive therapeutic option for patients with difficult-to-treat OCD [4]. Deep transcranial magnetic stimulation (dTMS), in particular, enables modulation of deeper cortical and interconnected neural regions involved in cortico-striato-thalamo-cortical circuitry [5]. The medial prefrontal cortex represents an important therapeutic target because of its involvement in cognitive control, emotional regulation, and obsessive-compulsive symptomatology. Theta-burst stimulation is a patterned form of TMS that delivers high-frequency bursts over relatively short treatment sessions [6]. Intermittent theta-burst stimulation (iTBS) may therefore offer practical advantages by reducing treatment duration while retaining the neuromodulatory effects of conventional stimulation protocols. Accelerated treatment schedules, in which multiple stimulation sessions are administered within a shorter period, have generated increasing interest as a strategy to achieve earlier clinical improvement. However, evidence regarding accelerated deep iTBS (d-iTBS) for OCD remains comparatively limited [6,7]. Importantly, assessment of treatment efficacy should extend beyond immediate post-treatment improvement because OCD follows a chronic course and early therapeutic gains may attenuate after treatment cessation. Characterizing the trajectory of symptom change during follow-up and identifying factors associated with sustained response may therefore improve patient selection, prognostication, and individualized treatment planning. Accordingly, the aim of this study was to evaluate the trajectory and durability of clinical response following accelerated d-iTBS targeting the medial prefrontal cortex in patients with OCD. The objectives were to assess longitudinal changes in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores from baseline through post-treatment and follow-up; determine treatment response and remission rates over time; evaluate the maintenance of therapeutic benefit; and identify demographic and clinical predictors of sustained response, including baseline symptom severity, age at OCD onset, depressive comorbidity, medication status, and early treatment response.

Study design and setting This single-center retrospective observational cohort study was conducted at Asha Hospitals, Hyderabad, India in March 2025 on electronic medical records of patients treated between January 2017 and February 2025, which were retrospectively reviewed. Prior to commencement of the study, approval was obtained from the Institutional Ethics Committee. Owing to the retrospective nature of the investigation, which involved analysis of anonymized existing clinical records without direct patient contact or modification of treatment, the requirement for individual informed consent was waived by the Ethics Committee. Patient confidentiality was maintained throughout the study by assigning unique identification numbers and removing all personally identifiable information before data extraction and statistical analysis. Study participants All consecutive patients aged ≥18 years with a physician-confirmed diagnosis of OCD according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) [8], who had received a complete course of accelerated d-iTBS targeting the medial prefrontal cortex (mPFC), were considered for inclusion. The detailed eligibility criteria has been mentioned in Table 1. Patients were required to have documented Y-BOCS scores [9] at baseline before treatment and at treatment completion, together with a documented Y-BOCS score at a minimum of one follow-up assessment at 2 weeks, 1 month, and/or 3 months after treatment. Complete demographic, clinical, and treatment-related records were additionally required. Concurrent psychotropic medication use at the initiation of d-iTBS was also extracted from the medical records, including selective serotonin reuptake inhibitor (SSRI)/serotonin–norepinephrine reuptake inhibitor (SNRI) therapy, antipsychotic augmentation, and benzodiazepine use. To minimize potential confounding from treatment modification, only patients whose psychotropic medication regimen remained unchanged throughout the treatment and follow-up period were included. Accelerated d-iTBS protocol The accelerated d-iTBS protocol consisted of five daily sessions administered over two consecutive weeks, resulting in a total of 50 d-iTBS sessions. Stimulation targeted the medial prefrontal cortex and was delivered using an H7 coil (BrainsWay Ltd., Jerusalem, Israel). Each session delivered intermittent theta-burst stimulation at 20 Hz, with a total of 600 pulses administered per session. The accelerated stimulation protocol was administered according to the treatment parameters documented in the clinical records. Only patients who completed the full prescribed treatment course were included in the study. Treatment-related information, including the number of sessions completed, stimulation target, and concurrent pharmacological treatment, was extracted from the respective clinical records. Assessment of clinical outcomes The primary outcome measure was the Y-BOCS total score, which was used to quantify changes in OCD symptom severity over time. Clinical outcomes were evaluated at five predefined assessment points: baseline (T0), within 7 days before initiation of treatment; treatment completion/post-treatment (T1), immediately following the final d-iTBS session on Day 10; early follow-up (T2), 2 weeks (±3 days) after treatment completion; short-term follow-up (T3), 1 month (±7 days) after treatment completion; and long-term follow-up (T4), 3 months (±14 days) after treatment completion. Secondary clinical outcomes included treatment response, remission, and durability of response. Treatment response was defined as a ≥35% reduction in the Y-BOCS total score from baseline, whereas remission was defined as a Y-BOCS total score ≤12. The trajectory of symptom improvement was assessed by comparing Y-BOCS scores across the predefined assessment periods. Predictor variables Baseline demographic and clinical characteristics were extracted to investigate potential predictors of treatment response and its durability. Demographic variables included age, sex, educational level, and occupation. Clinical characteristics comprised age at OCD onset, duration of illness, and OCD symptom subtype, including contamination, checking, symmetry, and hoarding symptoms. Baseline clinical severity was characterized using the Y-BOCS total score, Hamilton Depression Rating Scale (HAM-D) score, and Hamilton Anxiety Rating Scale (HAM-A) score [10,11]. The Y-BOCS is a clinician-administered 10-item scale assessing the severity of obsessive and compulsive symptoms, with total scores ranging from 0 to 40 and higher scores indicating greater OCD severity [9]. The HAM-D was used to assess depressive symptom severity, with higher scores indicating greater depressive symptom burden [10]. Similarly, the HAM-A was used to evaluate anxiety severity, with higher scores reflecting greater anxiety symptom burden [11]. Treatment-history variables included the number of previous pharmacological trials, history of psychotherapy, and previous exposure to TMS. Medication-related variables included concurrent SSRI/SNRI therapy, antipsychotic augmentation, and benzodiazepine use. The presence of comorbid depression, anxiety disorders, and tic disorders was also recorded. Data collection and reliability Demographic, clinical, treatment-related, and outcome variables were extracted from electronic medical records using a standardized electronic data collection form. Data extraction was independently performed by two trained investigators, comprising a psychiatrist and a clinical psychologist, to enhance accuracy and completeness. Any discrepancies identified during data extraction were resolved by re-evaluation of the original clinical records. All Y-BOCS assessments had been performed by trained and certified raters as part of routine clinical care. Inter-rater reliability for the Y-BOCS assessments was maintained through regular calibration exercises. The intraclass correlation coefficient (ICC) remained >0.90 throughout the study period, indicating excellent inter-rater reliability. Sample size estimation The sample size was determined a priori using G*Power software, version 3.1.9.7 (Heinrich Heine University Düsseldorf, Düsseldorf, Germany), to ensure adequate statistical power for detecting significant changes in Y-BOCS scores across time points using a linear mixed-effects model. Based on findings from an observational study of accelerated intermittent theta-burst stimulation, which reported a small effect size (Cohen's d = 0.20) for the mean reduction in Y-BOCS scores, the required sample size was calculated [12]. Assuming a two-tailed alpha error of 0.05, statistical power of 0.95, and a small effect size (Cohen's d = 0.20) for the primary trajectory analysis, the minimum required sample size was estimated as 125 participants. Accounting for an anticipated 15% rate of incomplete records or loss to follow-up, the target sample was adjusted to 145 participants. Statistical analysis Statistical analyses were performed using IBM SPSS Statistics, version 28.0 (IBM Corp., Armonk, NY, USA). All statistical tests were two-tailed, and a p-value <0.05 was considered statistically significant. Data normality was assessed using the Shapiro-Wilk test. Continuous variables were summarized as mean ± standard deviation (SD) or median with interquartile range (IQR), as appropriate, whereas categorical variables were expressed as frequencies and percentages. Baseline demographic and clinical characteristics were compared between responders and non-responders using the independent-samples t-test or Mann-Whitney U test for continuous variables, according to their distribution. Categorical variables were compared using the chi-square test or Fisher's exact test, as appropriate. Longitudinal changes in Y-BOCS scores from baseline (T0) to post-treatment (T1), 2-week (T2), 1-month (T3), and 3-month (T4) follow-up were analyzed using a linear mixed-effects model with patient-specific random intercepts and an unstructured covariance matrix. Fixed effects included time, age, sex, age at OCD onset, baseline Y-BOCS score, medication status, and group-by-time interactions. Bonferroni-adjusted pairwise comparisons were performed for post-hoc analyses. Treatment response, defined as a ≥35% reduction in Y-BOCS score, and remission, defined as a Y-BOCS score ≤12, were compared across follow-up assessments using Cochran's Q test. Where appropriate, subsequent pairwise comparisons were performed using Bonferroni-adjusted McNemar's tests. Predictors of sustained response at the 3-month follow-up were identified using multivariable logistic regression with forward stepwise selection. The results were expressed as adjusted odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Model fit was evaluated using the Hosmer-Lemeshow goodness-of-fit test. Subgroup analyses were performed to examine differences in symptom trajectories according to age at OCD onset, presence of comorbid depression, concurrent SSRI use, and treatment response status. Interaction effects were assessed using group-by-time terms and reported using F-statistics, p-values, and partial eta-squared (ηp²) effect sizes. A two-sided p < 0.05 was considered indicative of statistical significance throughout the analyses

A total of 145 patients with OCD were included, of whom 90 (62.1%) were classified as responders and 55 (37.9%) as non-responders at treatment completion (T1). The mean age was 34.2 ± 9.8 years, and 53.8% of participants were male. Age, sex, age at OCD onset, and duration of illness did not differ significantly between responders and non-responders. However, responders had significantly lower baseline Y-BOCS (27.6 ± 4.2 vs. 29.8 ± 4.9; p=0.006), HAM-D (p=0.005), and HAM-A (p=0.020) scores. Medication use, previous TMS exposure, and comorbid depression were comparable between groups (Table 2). Longitudinal changes in OCD symptoms Y-BOCS scores decreased substantially following accelerated d-iTBS, from 28.4 ± 4.6 at baseline to 15.9 ± 5.2 immediately after treatment (mean change, −12.5; 95% CI, −13.4 to −11.6; p<0.001). The greatest improvement was observed at 2 weeks, with a mean Y-BOCS score of 14.7 ± 5.6 and a reduction of 13.7 points from baseline (p<0.001; Cohen's d=2.05). Improvement remained significant at 1 month and 3 months, although modest attenuation was observed by the 3-month assessment (16.8 ± 6.4; mean change, −11.6; p<0.001; Cohen's d=1.56) (Table 3). Response and remission At treatment completion, 62.1% of participants met the response criterion and 29.0% achieved remission. Response and remission peaked at the 2-week follow-up at 68.8% and 34.8%, respectively. At 3 months, 61.2% remained responders and 28.9% remained in remission, with a mean Y-BOCS reduction of 52.3%, indicating persistence of the therapeutic effect despite some attenuation over time (Table 4). Predictors of sustained response Multivariable logistic regression identified baseline Y-BOCS severity, comorbid depression, and early treatment response as independent predictors of sustained response at 3 months. Higher baseline Y-BOCS scores were associated with lower odds of sustained response (adjusted OR=0.93; 95% CI, 0.87–0.99; p=0.022), as was comorbid depression (adjusted OR=0.48; 95% CI, 0.24–0.96; p=0.037). In contrast, response at treatment completion was the strongest positive predictor of sustained benefit (adjusted OR=4.12; 95% CI, 1.89–8.98; p<0.001). Age, age at OCD onset, and concurrent SSRI/SNRI therapy were not significant predictors (Table 5). Subgroup analysis Symptom trajectories differed significantly according to age at OCD onset and comorbid depression. Patients with late-onset OCD demonstrated greater sustained reductions in Y-BOCS scores than those with early-onset OCD (group × time, p=0.038). Similarly, patients without comorbid depression showed greater improvement than those with depression (p=0.014). Concurrent SSRI/SNRI use was not associated with a significant difference in symptom trajectory (p=0.412) (Table 6). Table 1. The inclusion and exclusion criteria for the study. Inclusion criteria Exclusion criteria 1. Age ≥ 18 years 1. Age < 18 years 2. Physician-confirmed diagnosis of OCD according to DSM-5 criteria 2. No confirmed diagnosis of OCD or diagnosis other than OCD 3. Completed a full course of accelerated d-iTBS targeting the medial prefrontal cortex (mPFC) 3. Received fewer than the prescribed number of d-iTBS sessions (incomplete treatment course) 4. Documented Y-BOCS scores at baseline (pre-treatment) 4. Missing baseline Y-BOCS scores 5. Documented Y-BOCS scores at treatment completion (post-treatment) 5. Missing post-treatment Y-BOCS scores 6. Documented Y-BOCS scores at a minimum of one follow-up time point (2 weeks, 1 month, and/or 3 months post-treatment) 6. No follow-up Y-BOCS scores available at any of the designated time points 7. Complete demographic records available 7. Incomplete demographic records 8. Complete clinical records available 8. Incomplete clinical records 9. Complete treatment-related records available 9. Incomplete treatment-related records 10. No change in psychotropic medication during the treatment or follow-up period 10. Any change in psychotropic medication during the treatment or follow-up period that could confound outcome assessment 11. No history of seizures or other TMS contraindications 11. History of seizures or other TMS contraindications 12. Available electronic medical records for data extraction 12. Incomplete medical records or missing outcome records DSM-5: Diagnostic and Statistical Manual of Mental Disorders, d-iTBS: deep intermittent theta-burst stimulation, mPFC: medial prefrontal cortex, OCD: obsessive-compulsive disorder, TMS: transcranial magnetic stimulation, Y-BOCS: Yale-Brown Obsessive Compulsive Scale. Table 2: Baseline demographic and clinical characteristics of the study participants. Variable Overall (N = 145) Responders at T1 (n = 90) Non-responders at T1 (n = 55) Test statistic p-value Age (years), Mean ± SD 34.2 ± 9.8 33.5 ± 9.4 35.6 ± 10.3 t = 1.25 0.212 Sex, n (%), Male 78 (53.8%) 49 (54.4%) 29 (52.7%) χ² = 0.04 0.847 Female 67 (46.2%) 41 (45.6%) 26 (47.3%) — — Age at OCD onset (years), Mean ± SD 21.4 ± 7.2 20.8 ± 6.9 22.5 ± 7.6 t = 1.31 0.192 Duration of illness (years), Mean ± SD 12.6 ± 7.9 11.8 ± 7.2 13.9 ± 8.9 t = 1.52 0.131 Baseline Y-BOCS Total, Mean ± SD 28.4 ± 4.6 27.6 ± 4.2 29.8 ± 4.9 t = 2.78 0.006* Baseline HAM-D, Mean ± SD 14.2 ± 6.1 13.1 ± 5.6 16.1 ± 6.6 t = 2.85 0.005* Concurrent SSRI/SNRI, n (%) 118 (81.4%) 76 (84.4%) 42 (76.4%) χ² = 1.51 0.219 Antipsychotic augmentation, n (%) 32 (22.1%) 17 (18.9%) 15 (27.3%) χ² = 1.42 0.233 Prior TMS exposure, n (%) 21 (14.5%) 11 (12.2%) 10 (18.2%) χ² = 1.02 0.312 Comorbid depression, n (%) 58 (40.0%) 31 (34.4%) 27 (49.1%) χ² = 3.06 0.080 Data are presented as mean ± standard deviation (SD) for continuous variables and number (percentage) for categorical variables, continuous variables were compared using the independent-samples t-test, and categorical variables were compared using the chi-square (χ²) test, as appropriate, *p < 0.05 was considered statistically significant, HAM-A: Hamilton Anxiety Rating Scale, HAM-D: Hamilton Depression Rating Scale, OCD: obsessive-compulsive disorder, SNRI: serotonin–norepinephrine reuptake inhibitor, SSRI: selective serotonin reuptake inhibitor, T1: treatment completion, TMS: transcranial magnetic stimulation, Y-BOCS: Yale-Brown Obsessive Compulsive Scale. Table 3: Longitudinal changes in Y-BOCS scores across follow-up time points. Time point Mean Y-BOCS ± SD Mean change from baseline (95% CI) Test value p-value (vs. Baseline) Cohen's d Baseline (T0) (n = 145) 28.4 ± 4.6 Reference — — — Post-treatment (T1) (n = 145) 15.9 ± 5.2 −12.5 (−13.4 to −11.6) t = 27.4 < 0.001* 1.87 2-week follow-up (T2) (n = 138) 14.7 ± 5.6 −13.7 (−14.6 to −12.8) t = 29.8 < 0.001* 2.05 1-month follow-up (T3) (n = 132) 15.3 ± 5.9 −13.1 (−14.1 to −12.1) t = 26.3 < 0.001* 1.89 3-month follow-up (T4) (n = 121) 16.8 ± 6.4 −11.6 (−12.7 to −10.5) t = 20.9 < 0.001* 1.56 Data are presented as mean ± standard deviation (SD) and mean change from baseline with 95% confidence intervals (CIs), longitudinal changes in Y-BOCS scores were evaluated using a linear mixed-effects model with patient-specific random intercepts and an unstructured covariance matrix, post-hoc pairwise comparisons were Bonferroni-adjusted, Cohen's d represents the standardized effect size, *p < 0.05 was considered statistically significant, T0: baseline, T1: post-treatment, T2: 2-week follow-up, T3: 1-month follow-up, T4: 3-month follow-up, Y-BOCS: Yale-Brown Obsessive Compulsive Scale. Table 4: Treatment response and remission rates across follow-up time points. Time point Responders n (%) * Remitters n (%) Mean % Y-BOCS Reduction (95% CI) Post-treatment (T1) (n = 145) 90 (62.1%) 42 (29.0%) 55.8% (52.6–59.0%) 2-week follow-up (T2) (n = 138) 95 (68.8%) 48 (34.8%) 59.4% (56.1–62.7%) 1-month follow-up (T3) (n = 132) 88 (66.7%) 44 (33.3%) 57.1% (53.6–60.6%) 3-month follow-up (T4) (n = 121) 74 (61.2%) 35 (28.9%) 52.3% (48.4–56.2%) Data are presented as number (percentage) or mean percentage reduction with 95% confidence intervals (CIs), as appropriate, Treatment response was defined as a ≥35% reduction in Y-BOCS total score from baseline, whereas remission was defined as a Y-BOCS total score ≤12, Changes in response and remission rates across follow-up assessments were evaluated using Cochran's Q test, followed by Bonferroni-adjusted McNemar's tests for pairwise comparisons, as appropriate, *p < 0.05 was considered statistically significant, T0: baseline, T1: post-treatment, T2: 2-week follow-up, T3: 1-month follow-up, T4: 3-month follow-up, Y-BOCS: Yale-Brown Obsessive Compulsive Scale. Table 5: Predictors of sustained treatment response at the 3-month follow-up. Predictor Unadjusted OR (95% CI) Adjusted OR (95% CI) β SE Wald χ² p-value Age (per year) 0.98 (0.95–1.01) 0.99 (0.96–1.03) −0.012 0.018 0.44 0.507 Age at OCD onset (per year) 0.96 (0.92–1.00) 0.97 (0.93–1.02) −0.031 0.024 1.67 0.196 Baseline Y-BOCS (per point) 0.91 (0.86–0.97) 0.93 (0.87–0.99) −0.073 0.032 5.21 0.022* Concurrent SSRI/SNRI (Yes) 1.85 (0.92–3.72) 1.62 (0.77–3.41) 0.482 0.379 1.62 0.203 Comorbid depression (Yes) 0.52 (0.27–0.98) 0.48 (0.24–0.96) −0.734 0.352 4.35 0.037* Response at T1 (Yes) 4.86 (2.31–10.22) 4.12 (1.89–8.98) 1.416 0.398 12.65 < 0.001* Data are presented as unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals (CIs), Predictors of sustained response were evaluated using multivariable logistic regression with forward stepwise selection, Model fit was assessed using the Hosmer–Lemeshow goodness-of-fit test, *p < 0.05 was considered statistically significant, β: regression coefficient, OCD: obsessive-compulsive disorder, SE: standard error, SNRI: serotonin–norepinephrine reuptake inhibitor, SSRI: selective serotonin reuptake inhibitor, T1: treatment completion, Y-BOCS: Yale-Brown Obsessive Compulsive Scale, χ²: chi-square statistic. Table 6: Trajectory of Y-BOCS scores according to baseline clinical characteristics. Parameter Subgroup n Mean Y-BOCS change from baseline to 1 Month (95% CI) Mean Y-BOCS change from baseline to 3 Months (95% CI) Test statistic (Group × Time) p-value Effect size (Partial η²) Age at OCD onset Early-onset (≤18 years) 54 −12.1 (−13.8 to −10.4) −10.4 (−12.2 to −8.6) F (4, 472) =2.86 0.038* 0.024 Late-onset (>18 years) 91 −13.7 (−14.8 to −12.6) −12.3 (−13.5 to −11.1) Comorbid depression Present 58 −11.5 (−13.2 to −9.8) −10.1 (−12.0 to −8.2) F (4, 472) =3.47 0.014* 0.032 Absent 87 −14.2 (−15.3 to −13.1) −12.6 (−13.8 to −11.4) Concurrent SSRI/SNRI Yes 118 −13.2 (−14.2 to −12.2) −11.7 (−12.8 to −10.6) F (4, 472) =0.99 0.412 0.008 No 27 −12.8 (−15.1 to −10.5) −11.2 (−13.8 to −8.6) Data are presented as mean changes in Y-BOCS scores from baseline with 95% confidence intervals (CIs), Subgroup differences in longitudinal symptom trajectories were evaluated using group × time interaction terms within the longitudinal model, Effect sizes are reported as partial eta-squared (η²), , *p < 0.05 was considered statistically significant, OCD: obsessive-compulsive disorder, SNRI: serotonin–norepinephrine reuptake inhibitor, SSRI: selective serotonin reuptake inhibitor, Y-BOCS: Yale-Brown Obsessive Compulsive Scale.

The present study demonstrated a substantial and sustained reduction in obsessive-compulsive symptoms following accelerated d-iTBS targeting the mPFC. Y-BOCS scores decreased markedly immediately after treatment, with the greatest improvement observed at the 2-week follow-up, followed by modest attenuation at 1 and 3 months. Nevertheless, more than 60% of patients continued to meet the response criterion at 3 months. Higher baseline OCD severity and comorbid depression were associated with reduced durability of response, whereas an early response at treatment completion strongly predicted sustained clinical benefit. The observed improvement in OCD symptoms is consistent with growing evidence supporting TMS as an effective neuromodulatory strategy for OCD [4]. Carmi et al. [13] demonstrated the efficacy of high-frequency dTMS targeting the mPFC and anterior cingulate cortex (ACC) in a multicenter randomized sham-controlled trial, providing important evidence for modulation of this circuitry in OCD. Reddy et al. [14] reported a significantly greater reduction in Y-BOCS scores with active H7-coil dTMS targeting the dorsal ACC and mPFC compared with sham stimulation [2]. The evidence also indicates that active TMS produces significant reductions in obsessive-compulsive symptoms, with the ACC/mPFC among the neural targets associated with therapeutic benefit [15,16]. These findings provide biological and clinical support for the stimulation target employed in the present study. The rapid reduction in symptom severity observed with the accelerated protocol is particularly noteworthy. Jiang et al. [17] evaluated accelerated high-dose theta-burst stimulation in OCD and demonstrated significant reductions in Y-BOCS scores following an intensive 5-day treatment schedule, with short-term efficacy comparable to conventional 1-Hz rTMS. Although the stimulation parameters and treatment schedule differed from those of the present study, both findings suggest that concentrating stimulation sessions within a shorter period may produce clinically meaningful improvement. Accelerated schedules may facilitate cumulative neuroplastic changes through repeated modulation of dysfunctional cortico-striato-thalamo-cortical circuits, potentially allowing therapeutic effects to emerge over a compressed timeframe. An interesting observation was that the greatest symptom improvement occurred at 2 weeks rather than immediately after treatment. This delayed peak may indicate that the neurobiological effects of d-iTBS continue to develop following completion of active stimulation. Repeated stimulation of the mPFC and interconnected ACC-striatal networks may induce longer-lasting changes in cortical excitability, synaptic plasticity, and network connectivity. The importance of these regions is supported by systematic evidence demonstrating significant effects of stimulation over the ACC/mPFC in OCD [16]. However, theta-burst findings remain heterogeneous, and recent evidence indicates that therapeutic efficacy may depend considerably on stimulation target, pulse dose, treatment duration, and protocol characteristics [18,19]. Our findings are strongly supported by Akyol et al. [7], who evaluated a comparable accelerated d-iTBS protocol targeting the mPFC and reported that its therapeutic effects may become more apparent after treatment completion. Notably, the greater improvement observed during the post-treatment period supports our finding of a delayed therapeutic trajectory, with maximal symptom reduction occurring at the 2-week follow-up. Despite modest attenuation after the 2-week peak, clinical improvement remained evident at 3 months. This is consistent with evidence that TMS-related benefits can persist beyond active treatment. In a large real-world study across 22 clinical sites, Roth et al. [20] reported initial and sustained response rates of 72.6% and 52.4%, respectively, following H7-coil dTMS for OCD. A meta-analysis of randomized controlled trials similarly demonstrated superiority of active dTMS over sham treatment both immediately after treatment and at 1-month follow-up [5]. Together, these observations support the possibility of durable neuromodulatory effects, although the modest attenuation observed in our cohort suggests that maintenance or booster stimulation deserves further investigation. In contrast, Liu et al. [21] found no significant improvement in Y-BOCS scores following 2 weeks of continuous theta-burst stimulation targeting the right orbitofrontal cortex in patients with treatment-resistant OCD. Ni et al. [22] reported that the therapeutic effects of accelerated cTBS were more pronounced in patients with moderate OCD, whereas significant Y-BOCS improvement was not observed among those with severe symptoms. Although their stimulation paradigm and target differed from those used in the present study, their findings support our observation that greater baseline OCD severity was associated with a lower likelihood of sustained treatment response, suggesting that pretreatment symptom burden may influence the effectiveness and durability of theta-burst stimulation. Baseline OCD severity was an independent negative predictor of sustained response in the present study. This finding agrees closely with Singh et al. [23], who reported that higher pretreatment Y-BOCS scores were associated with a lower likelihood of response to rTMS. Li et al. [24] similarly emphasized the importance of pretreatment predictors of response to cTBS in OCD. Following cTBS of the bilateral supplementary motor area, 37.9% of patients responded to treatment, while baseline functional connectivity between specific cerebellar and frontal regions predicted therapeutic response with an AUC of 0.85. These findings complement our identification of clinical predictors and suggest that integrating baseline clinical characteristics with neuroimaging biomarkers may improve patient selection and individualized prediction of response to theta-burst stimulation. Comorbid depression was another significant negative predictor of sustained response. Singh et al. [23] similarly identified comorbid depression as a predictor of poorer rTMS response in patients with OCD. This observation is clinically plausible because depression may increase overall disease burden and involve overlapping abnormalities within prefrontal-limbic networks, potentially influencing the responsiveness of OCD-related circuitry to neuromodulation. The subgroup findings in the present study further reinforce this association, as patients without comorbid depression demonstrated greater sustained reductions in Y-BOCS scores than those with depression. In contrast, early response at treatment completion was the strongest positive predictor of sustained benefit, increasing the odds of response at 3 months by more than fourfold. This finding has important practical implications. Early Y-BOCS improvement may represent an accessible clinical marker for identifying patients likely to maintain benefit. Real-world observations by Roth et al. [20] also indicate that response to dTMS can emerge relatively early during the treatment course and that extending treatment may provide additional benefit in some patients. Consequently, repeated symptom assessment during and immediately after treatment could potentially guide decisions regarding continuation, extension, or subsequent maintenance treatment. Concurrent SSRI/SNRI therapy was not significantly associated with sustained response or symptom trajectory in the present cohort. This should not be interpreted as indicating that pharmacotherapy is unnecessary. Rather, it suggests that medication status alone did not explain the observed variation in d-iTBS response. Because medication use was not randomized and patients differed in previous treatment histories and illness characteristics, the independent and potentially synergistic contributions of pharmacotherapy and neuromodulation cannot be determined from this observational study. Clinical implications The findings of this study have several clinically relevant implications. Accelerated d-iTBS targeting the medial prefrontal cortex was associated with rapid improvement in OCD symptoms, with a substantial proportion of patients maintaining clinical response at 3 months. The accelerated schedule may therefore represent a practical, time-efficient neuromodulatory approach, particularly for patients with persistent symptoms despite conventional treatment. Importantly, early response at treatment completion was the strongest predictor of sustained benefit, suggesting that serial Y-BOCS assessment during and immediately after treatment may help identify patients likely to maintain improvement. Conversely, patients with greater baseline symptom severity or comorbid depression may require closer monitoring, adjunctive treatment, or consideration of individualized maintenance strategies. These clinical characteristics could therefore contribute to treatment stratification and more personalized follow-up after accelerated d-iTBS. Limitations Several limitations should be considered when interpreting these findings. First, the retrospective observational design precludes causal inference and introduces the possibility of selection bias and residual confounding. Second, the absence of a sham or active comparator group limits the ability to distinguish treatment-specific effects from nonspecific clinical improvement or concurrent treatment effects. Third, reliance on routinely collected medical records may have resulted in variability in the completeness of clinical information. Although medication changes during treatment and follow-up were an exclusion criterion, the potential influence of concurrent pharmacotherapy, psychotherapy, previous treatment exposure, and other unmeasured clinical factors cannot be completely excluded. In addition, the number of patients with available assessments progressively decreased across follow-up, which may have introduced attrition bias despite the use of longitudinal mixed-effects modeling. Finally, follow-up was limited to 3 months; therefore, the persistence of therapeutic benefit beyond this period and the potential role of maintenance or booster d-iTBS sessions could not be determined. Prospective multicenter controlled studies with standardized protocols and longer follow-up are warranted to confirm these findings.

Accelerated deep intermittent theta-burst stimulation targeting the mPFC was associated with substantial improvement in obsessive-compulsive symptoms, with clinical benefits persisting for up to 3 months. Early treatment response was the strongest predictor of sustained benefit, whereas greater baseline symptom severity and comorbid depression were associated with reduced response durability. These findings support accelerated d-iTBS as a promising therapeutic approach for OCD and highlight the importance of early response monitoring and individualized follow-up strategies to optimize longer-term clinical outcomes.

1. Singh A, Anjankar VP, Sapkale B: Obsessive-compulsive disorder (OCD): A comprehensive review of diagnosis, comorbidities, and treatment approaches. Cureus. 2023, 15:e48960. 10.7759/cureus.48960. 2. Arumugham SS, Narayanaswamy JC, Balachander S, et al.: Clinical practice guidelines for obsessive-compulsive disorder: 2025 update. Indian J Psychiatry. 2026, 68:44-67. 10.4103/indianjpsychiatry_1259_25. 3. Kammen A, Cavaleri J, Lam J, et al.: Neuromodulation of OCD: A review of invasive and non-invasive methods. Front Neurol. 2022, 13:909264. 10.3389/fneur.2022.909264. 4. Lusicic A, Schruers KR, Pallanti S, Castle DJ: Transcranial magnetic stimulation in the treatment of obsessive-compulsive disorder: current perspectives. Neuropsychiatr Dis Treat. 2018, 14:1721-36. 10.2147/NDT.S121140. 5. Li K, Qian L, Zhang C, Li R, Zeng J, Xue C, Deng W: Deep transcranial magnetic stimulation for treatment-resistant obsessive-compulsive disorder: A meta-analysis of randomized-controlled trials. J Psychiatr Res. 2024, 180:96-102. 10.1016/j.jpsychires.2024.09.043. 6. Kujovic M, Benz D, Riesbeck M, et al.: Theta burst stimulation add on to dialectical behavioral therapy in borderline-personality-disorder: methods and design of a randomized, single-blind, placebo-controlled pilot trial. Eur Arch Psychiatry Clin Neurosci. 2024, 274:87-96. 10.1007/s00406-023-01692-w. 7. Akyol GK, Yucens B, Tumkaya S: Accelerated deep intermittent theta-burst stimulation for obsessive-compulsive disorder: A double-blind, randomized, controlled study. J Psychiatr Res. 2025, 189:365-72. 10.1016/j.jpsychires.2025.06.034. 8. Vahia VN: Diagnostic and statistical manual of mental disorders 5: A quick glance. Indian J Psychiatry. 2013, 55:220-3. 10.4103/0019-5545.117131. 9. Goodman WK, Price LH, Rasmussen SA, et al.: The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability: I. Development, use, and reliability. Arch Gen Psychiatry. 1989, 46:1006-11. 10.1001/archpsyc.1989.01810110048007. 10. Hamilton M: A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960, 23:56-62. 10.1136/jnnp.23.1.56. 11. Hamilton M: The assessment of anxiety states by rating. Br J Med Psychol. 1959, 32:50-5. 10.1111/j.2044-8341.1959.tb00467.x. 12. Dragon K, Janthur C, Hebel T, Abdelnaim MA, Reißmann A, Langguth B, Schecklmann M: Four weeks standard vs. one week accelerated intermittent Theta Burst Stimulation for the treatment of depression - A retrospective analysis. Behav Brain Res. 2025, 479:115361. 10.1016/j.bbr.2024.115361. 13. Carmi L, Tendler A, Bystritsky A, et al.: Efficacy and safety of deep transcranial magnetic stimulation for obsessive-compulsive disorder: A prospective multicenter randomized double-blind placebo-controlled trial. Am J Psychiatry. 2019, 176:931-8. 10.1176/appi.ajp.2019.18101180. 14. Reddy S, Shreekantiah U, Goyal N, Roy C: Brain activation alterations with adjunctive deep transcranial magnetic stimulation in obsessive-compulsive disorder: an fMRI study. CNS Spectr. 2023, 28:361-6. 10.1017/S1092852922000803. 15. Reddy SM, Rains CB, Ng VC, Kugley SA, Ovelman CM, Gaynes BN, Kahwati LC: A systematic review of transcranial magnetic stimulation for generalized anxiety disorder, obsessive-compulsive disorder, and posttraumatic stress disorder. BMC Psychiatry. 2026, 26:. 10.1186/s12888-026-07930-4. 16. Grassi G, Moradei C, Cecchelli C: Will transcranial magnetic stimulation improve the treatment of obsessive-compulsive disorder? A systematic review and meta-analysis of current targets and clinical evidence. Life (Basel). 2023, 13:1494. 10.3390/life13071494. 17. Jiang J, Wan K, Liu Y, et al.: A controlled clinical study of accelerated high-dose theta burst stimulation in patients with obsessive-compulsive disorder. Neural Plast. 2023, 2023:2741287. 10.1155/2023/2741287. 18. Steuber ER, McGuire JF: A meta-analysis of transcranial magnetic stimulation in obsessive-compulsive disorder. Biol Psychiatry Cogn Neurosci Neuroimaging. 2023, 8:1145-55. 10.1016/j.bpsc.2023.06.003. 19. Khosravi M, Khosravi R, Tavassoli AR, Jahanian-Najafabadi A: Optimizing non-invasive brain stimulation for obsessive-compulsive disorder: a systematic review of protocol heterogeneity, personalized targets, and adjunctive efficacy. BMC Psychiatry. 2026, 26:101. 10.1186/s12888-025-07723-1. 20. Roth Y, Tendler A, Arikan MK, et al.: Real-world efficacy of deep TMS for obsessive-compulsive disorder: Post-marketing data collected from twenty-two clinical sites. J Psychiatr Res. 2021, 137:667-72. 10.1016/j.jpsychires.2020.11.009. 21. Liu W, Shao H, Liao J, Yang D, Ma M, Yang J: Continuous theta-burst stimulation over the right orbitofrontal cortex in treatment-resistant obsessive-compulsive disorder treatment: A randomized sham-controlled trial. Int J Gen Med. 2021, 14:3109-18. 10.2147/IJGM.S318069. 22. Ni R, Liu Y, Jiang J, et al.: Continuous theta burst stimulation to relieve symptoms in patients with moderate obsessive-compulsive disorder: a preliminary study with an external validation. Transl Psychiatry. 2024, 14:321. 10.1038/s41398-024-03041-4 23. Singh S, Kumar S, Gupta A, Verma R, Kumar N: Effectiveness and predictors of response to 1-Hz repetitive transcranial magnetic stimulation in patients with obsessive-compulsive disorder. J ECT. 2019, 35:61-6. 10.1097/YCT.0000000000000530. 24. Li P, Cheng J, Fan Q, et al.: The functional connectivity predictor of therapeutic effect of continuous theta burst stimulation on obsessive-compulsive disorder: A preliminary study. J Affect Disord. 2022, 311:231-8. 10.1016/j.jad.2022.05.110.