Study of rTMS in Maintenance in Treatment Resistant Depression

Treatment‐resistant depression (TRD) is a major cause of disability and is associatedwith persistent symptoms, reduced quality of life, increased healthcare utilization, anda high risk of relapse despite evidence‐based treatment. Although repetitive transcranialmagnetic stimulation (rTMS) is an established treatment for TRD, many patients experiencerecurrence of depressive symptoms after completion of the acute treatment course. Atpresent, there is no universally accepted maintenance strategy following successful acuterTMS.Maintenance rTMS has shown promise in reducing relapse; however, existing randomizedstudies have primarily compared maintenance rTMS with sham stimulation, antidepressants,or lithium. No randomized controlled trial has directly compared maintenance acceleratedintermittent theta burst stimulation (aiTBS) with quetiapine augmentation, despitequetiapine having Level 1 evidence as an augmentation strategy for TRD in the CanadianNetwork for Mood and Anxiety Treatments (CANMAT) guidelines. This represents an importantgap in evidence for long‐term management following acute neuromodulation.The present study is a hospital‐based, investigator‐initiated, randomized, open‐label,rater‐blinded, parallel‐group clinical trial conducted at the Department of Psychiatry,AIIMS Bhubaneswar. All participants will receive an acute course of acceleratedintermittent theta burst stimulation while continuing treatment as usual (TAU). Followingcompletion of the acute phase, participants will be randomly allocated to receive eithermaintenance aiTBS or quetiapine augmentation in addition to TAU. This design allowsdirect comparison of two evidence‐based maintenance approaches after a common acuteneuromodulation intervention.The study will evaluate whether maintenance aiTBS provides sustained clinical benefitcomparable or superior to quetiapine augmentation while maintaining an acceptable safetyprofile. In addition to clinical assessments, the study will examine changes in serumbrain‐derived neurotrophic factor (BDNF), a biomarker associated with neuroplasticity, toexplore its relationship with treatment response during the maintenance phase.The findings from this trial are expected to provide evidence regarding the comparativeeffectiveness and safety of maintenance neuromodulation versus pharmacologicalaugmentation after acute rTMS in treatment‐resistant depression. The results may helpinform future maintenance treatment strategies and improve long‐term outcomes forindividuals with TRD.