Feasibility of transcranial magnetic stimulation over multiple brain areas compared to a single brain area for obsessive-compulsive disorder in adults

INTERVENTION: Eligible participants will be randomly assigned after consent and baseline assessment to one of two active treatment groups using permuted block randomization with variable block sizes, stratified by baseline obsessive‐compulsive disorder (OCD) severity (Yale‐Brown Obsessive‐Compulsive Scale score 16‐23 versus 24 or above). The randomization sequence will be generated by a statistician not involved in participant recruitment, and allocation will remain concealed to the clinician operating TMS and patient until immediately before treatment begins. To minimize assessment bias, all clinical outcome assessments will be conducted by an independent rater blinded to treatment allocation throughout the study. Participants will be instructed not to disclose their treatment allocation at each assessment. Both groups will receive continuous theta‐burst stimulation (cTBS) for 6 weeks, with 5 treatment days per week (Monday to Friday), for a total of 30 treatment days. Each treatment day will consist of three sub‐sessions separated by approximately 30 minutes. Brain sites will be located using scalp‐based anatomical landmarks. Stimulation intensity will be set at 80% of each participant's resting motor threshold (RMT), assessed by observation of contralateral leg or toe twitches. Treatment will be delivered as an add‐on to stable ongoing psychiatric medication, with or without psychotherapy. Safety screening will be conducted at each visit throughout the treatment and follow‐up phases. Arm A (Experimental): Participants will receive sequential bilateral (right‐then‐left) multi‐target cTBS across three brain regions. Sub‐session 1 will target the orbitofrontal corte X(OFC), sub‐session 2 will target the dorsomedial prefrontal cortex/anterior cingulate corte X(DMPFC/ACC), and sub‐session 3 will target the supplementary motor area (SMA). Each brain region will receive 600 pulses per hemisphere, delivered sequentially over 40 seconds per hemisphere (80 seconds total per brain region), totaling 1,200 pulses per sub‐session. Overall, participants will receive 3,600 pulses per treatment day and 108,000 pulses over the 6‐week intervention period. Arm B (Active Control): Participants will receive unilateral cTBS targeting the right dorsolateral prefrontal corte X(DLPFC) during each of the three daily sub‐sessions. Each sub‐session will deliver 1,200 pulses over 80 seconds, totaling 3,600 pulses per treatment day and 108,000 pulses over the 6‐week intervention period. Clinical assessments will be conducted at baseline, Weeks 2 and 4 during treatment, and Week 6 post‐intervention. After the 6‐week intervention, assessments will continue every 3 weeks for 12 weeks, all performed by the independent blinded rater. TMS operators and participants cannot be blinded because treatment procedures are distinguishable. CONDITION: Obsessive‐compulsive disorder in adults who did not respond to at least one standard medication regimen ; Mental and Behavioural Disorders INCLUSION CRITERIA: 1. Age 18 to 65 years 2. Diagnosis of moderate‐to‐severe obsessive‐compulsive disorder according to DSM‐5‐TR criteria 3. Current Yale‐Brown Obsessive Compulsive Scale (Y‐BOCS) score of 16 or above (clinician‐administered) 4. Lack of sufficient response to standard pharmacological therapy for OCD at an optimal dose and duration 5. Stable medication for at least 4 weeks before baseline assessment, with or without psychotherapy 6. Right‐handedness 7. Capacity to understand the study materials and procedures and provide informed consent 8. Ability to attend daily treatment for 6 weeks PRIMARY OUTCOME: Feasibility ‐ adverse events measured using number and proportion of participants experiencing adverse or serious adverse events, summarized by treatment arm at each treatment day during weeks 1 to 6 and weeks 9, 12, 15, and 18 Feasibility ‐ protocol deliverability measured using number and type of protocol deviations, summarized by treatment arm at weeks 1 to 6 Feasibility ‐ recruitment measured using participants randomized per month (target: =1 per month) at throughout the recruitment period Feasibility ‐ study retention measured using randomized participants completing the Week 18 assessment (target: =75% of participants) at week 18 Feasibility ‐ treatment adherence measured using proportion of randomized participants completing at least 24 of 30 treatment days (target: =80% of participants) at weeks 1 to 6 Feasibility ‐ treatment tolerability (dose needs) measured using number of treatment days required to reach the target protocol‐specified intensity, summarized by treatment arm at weeks 1 to 6 SECONDARY OUTCOME: Change in anxiety symptoms measured using Hamilton Anxiety Rating Scale (HAM‐A) [clinician‐rated] at baseline; weeks 2 and 4 (during treatment); week 6 (post‐intervention); and weeks 9, 12, 15, and 18 (follow‐up) Change in depressive symptoms measured using Montgomery‐Asberg Depression Rating Scale (MADRS) [clinician‐rated] at baseline; weeks 2 and 4 (during treatment); week 6 (post‐intervention); and weeks 9, 12, 15, and 18 (follow‐up) Change in insight into obsessive beliefs measured using Brown Assessment of Beliefs Scale (BABS) [clinician‐rated] at baseline; weeks 2 and 4 (during treatment); week 6 (post‐intervention); and weeks 9, 12, 15, and 18 (follow‐up) Change in obsessive‐compulsive symptoms measured using Yale‐Brown Obsessive‐Compulsive Scale (Y‐BOCS) [clinician‐rated] at baseline; weeks 2 and 4 (during treatment); week 6 (post‐intervention); and weeks 9, 12, 15, and 18 (follow‐up) Change in tic severity measured using Yale Global Tic Severity Scale (YGTSS) total tic score among participants with tics at baseline [clinician‐rated] at baseline; weeks 2 and 4 (during treatment); week 6 (end of treatment); and weeks 9, 12, 15, and 18 (follow‐up) Clinical global impression of improvement measured using Clinical Global Impression‐Improvement Scale (CGI‐I) [clinician‐rated] at weeks 2 and 4 (during treatment); week 6 (post‐intervention); and weeks 9, 12, 15, and 18 (follow‐up). CGI‐I is not assessed at baseline because it is relative to previous assessment Clinical global impression of severity measured using Clinical Global Impression‐Severity Scale (CGI‐S) [clinician‐rated] at baseline; weeks 2 and 4 (during treatment); week 6 (post‐intervention); and weeks 9, 12, 15, and 18 (follow‐up)