Study of rTMS in Maintenance in Treatment Resistant Depression

Overview

The goal of this clinical trial is to learn which treatment works better to help people with treatment-resistant depression stay well after they improve with repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation treatment. It will also learn about the safety of maintenance rTMS and maintenance quetiapine. The main questions it aims to answer are: Does maintenance rTMS help prevent depression from returning better than maintenance quetiapine? Do participants receiving maintenance rTMS have greater improvement in depression symptoms over time than those receiving maintenance quetiapine? What side effects or medical problems occur with each treatment? Researchers will compare maintenance rTMS with maintenance quetiapine after all participants have completed the initial course of rTMS. Participants will: Receive an initial course of rTMS. Be randomly assigned to receive either maintenance rTMS or maintenance quetiapine. Attend regular follow ups to assess depression symptoms with MADRS , assess overall improvement by CGI , and any side effects. Provide blood samples at selected visits to measure brain-derived neurotrophic factor (BDNF), a protein that may be be linked to recovery from depression. Be followed for several months to monitor whether their depression returns and how well they continue to improve.

Treatment-resistant depression (TRD) is a major cause of disability and is associated with persistent symptoms, reduced quality of life, increased healthcare utilization, and a high risk of relapse despite evidence-based treatment. Although repetitive transcranial magnetic stimulation (rTMS) is an established treatment for TRD, many patients experience recurrence of depressive symptoms after completion of the acute treatment course. At present, there is no universally accepted maintenance strategy following successful acute rTMS. Maintenance rTMS has shown promise in reducing relapse; however, existing randomized studies have primarily compared maintenance rTMS with sham stimulation, antidepressants, or lithium. No randomized controlled trial has directly compared maintenance accelerated intermittent theta burst stimulation (aiTBS) with quetiapine augmentation, despite quetiapine having Level 1 evidence as an augmentation strategy for TRD in the Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines. This represents an important gap 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 accelerated intermittent theta burst stimulation while continuing treatment as usual (TAU). Following completion of the acute phase, participants will be randomly allocated to receive either maintenance aiTBS or quetiapine augmentation in addition to TAU. This design allows direct comparison of two evidence-based maintenance approaches after a common acute neuromodulation intervention. The study will evaluate whether maintenance aiTBS provides sustained clinical benefit comparable or superior to quetiapine augmentation while maintaining an acceptable safety profile. In addition to clinical assessments, the study will examine changes in serum brain-derived neurotrophic factor (BDNF), a biomarker associated with neuroplasticity, to explore its relationship with treatment response during the maintenance phase. The findings from this trial are expected to provide evidence regarding the comparative effectiveness and safety of maintenance neuromodulation versus pharmacological augmentation after acute rTMS in treatment-resistant depression. The results may help inform future maintenance treatment strategies and improve long-term outcomes for individuals with TRD.