Treatment Resistant Depression (TRD)Phase 3NCT07760168
Study of rTMS in Maintenance in Treatment Resistant Depression
A Phase 3 study testing Transcranial Magnetic Stimulation and quetiapine in people with Treatment Resistant Depression (TRD), run by All India Institute of Medical Sciences, Bhubaneswar.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Treatment Resistant Depression (TRD)
- What is being tested?
- Transcranial Magnetic Stimulation and quetiapine
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- No sites listed yet
- Study dates
- 30 Aug 2026to 30 Aug 2028
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Patients of both genders, between the ages 18- 60 years
- Clinically diagnosed as depression according to ICD-11.
- Diagnosis of treatment resistance depression according to US-FDA.
- On stable dosing of antidepressant venlafaxine 150 mg per day.
- Right-handed.
Who cannot join
- Pregnant or lactating women.
- Any kind of psychiatric emergency (E.g., Suicide risk, Catatonia, aggression or excitement)
- Any co-morbid neurological disease
- History of seizure/ epilepsy.
- History of migraine.
- History of head trauma/ organic brain condition.
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- Any contraindications to rTMS procedure:
- Metallic or electronic implants in the brain or heart, or any cochlear implants
- Injury or local lesion in the scalp/head.
About this study
Official title: Efficacy and Safety of Acute Followed by Maintenance rTMS in Treatment Resistant Depression: A Randomized Controlled Trial
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:
Read more
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.
Read the detailed description
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.
- Conditions
- Treatment Resistant Depression (TRD)
- Being tested
- Transcranial Magnetic Stimulation, quetiapine
- Medical subject headings
- Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Magnetic StimulationDevice
Treatment Schedule: After completion of acute treatment with rTMS, Patients will receive 5 days of treatment (as per previously mentioned schedule) per week for one week only in a month for maintenance sessions, for a total patient treatment duration of 3 months.
quetiapineDrug
After completion of acute course of rTMS, Patients will receive Quetiapine as a pharmacological augmentation to their standard TAU, dosed and titrated as per standard clinical guidelines for Treatment-Resistant Depression.
| Study group | Role | What they receive |
|---|---|---|
| Acute iTBS + Maintenance iTBS + Treatment as Usual (TAU) | Active comparator | Arm 1 (aiTBS + TAU) Accelerated iTBS will be provided with a 100X transcranial magnetic stimulator with a 70 mm active cooled figure of eight coil. The parameters to be given are 3 pulses, frequency- 50 Hz bursts, 2 seconds on and 10 seconds off for 3 minutes and a total of 600 pulses per session. Each patient will receive 5 sessions per week for 4 weeks with a total of 20 sessions. Considering the high frequency of stimulation a round of three iTBS per treatment will be given separated by 15minutes, a total of 1800 pulses per day. The sessions will be given after calculating a resting motor threshold. Stimulation target will be dorsolateral prefrontal cortex. Receives: Device: Transcranial Magnetic Stimulation |
| Acute iTBS + Quetiapine + Treatment as Usual (TAU) | Active comparator | The active intervention consists of Quetiapine Extended-Release (XR) administered once daily. Treatment will be individually tailored to patient requirements, with the daily maintenance dose adjusted between 100 mg and 200 mg based on clinical efficacy and side-effect tolerability. Receives: Drug: quetiapine |
What is being measured
The primary outcome is the main question the study is designed to answer.
To compare the efficacy of maintenance accelerated intermittent theta burst stimulation vs Quetiapine on symptomatology in terms of change in MADRS score in patients with treatment resistance depression
Measured: Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 12
Secondary outcomes (3)
To compare the efficacy of maintenance accelerated intermittent theta burst stimulation vs Quetiapine on biomarker in terms of change in BDNF levels in patients with treatment resistance depression.
Measured: Change From Baseline in Serum Brain-Derived Neurotrophic Factor (BDNF) Levels at 12 Weeks.
To compare the efficacy of maintenance accelerated intermittent theta burst stimulation vs Quetiapine on severity of illness in terms of change in CGI score in patients with treatment resistance depression.
Measured: Change From Baseline in Clinical Global Impression-Improvement (CGI-I) and Clinical Global Impression- Severity (CGI-S) Score at 12 Weeks
To compare treatment-emergent adverse events (TEAEs) between the study groups.
Measured: Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) during the 12-Week Study Period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2026
- Study start30 Aug 2026 (estimated)
- Primary completion30 Aug 2028 (estimated)
- Study completion30 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Treatment Resistant Depression (TRD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 68 participants (estimated)
Sponsor and investigators
- Lead sponsor
- All India Institute of Medical Sciences, Bhubaneswar
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Debadatta Mohapatra, All India Institute of Medical Sciences, Bhubaneswar
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07760168
- Sponsor's protocol ID
- AIIMSBBSR/PG Thesis/2026-27/82
- Status last verified
- Aug 2026
- First submitted
- 7 Aug 2026
- Last updated
- 12 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Noda Y, Wada M, Mimura Y, Taniguchi K, Tarumi R, Moriyama S, Arai N, Tsugawa S, Thorpe KE, Daskalakis ZJ, Uchida H, Mimura M, Blumberger DM, Nakajima S. Repetitive Transcranial Magnetic Stimulation as Maintenance Treatment of Depression: The MAINT-R Randomized Clinical Trial. JAMA Netw Open. 2025 Jun 2;8(6):e2515881. doi: 10.1001/jamanetworkopen.2025.15881.
PubMed 40522661Arns M, Bervoets C, van Eijndhoven P, Baeken C, van den Heuvel OA, Aleman A, Schutter DJLG, van der Werf Y, van Belkum S, Sommer IE, van Ruth R, Haarman B, Spijker J, Sack AT. [Consensus statement on the application of rTMS in depression in the Netherlands and Belgium]. Tijdschr Psychiatr. 2019;61(6):411-420. Dutch.
PubMed 31243751