Effect of three days vs five days adjunctive accelerated intermittent theta burst stimulation (aiTBS) on outcomes in patients with depression a randomized Controlled Open Label Interventional Trial

India reportedly has the highest prevalence of suicide in Southeast Asia with a reported prevalence of 11.3 per 100,000 population in 2020, much higher than the global average (Menon et al, 2023). Emerging evidence suggests that iTBS exhibits superior clinical efficacy in managing major depressive disorder (MDD) when contrasted with traditional rTMS approaches (Di Lazzaro et al., 2011; Chung et al., 2015; Prasser et al., 2015). A notable advantage of TBS is its reduced administration duration relative to conventional rTMS procedures. The rTMS applied to bilateral right-sided cTBS and left-sided iTBS of the DLPFC in major unipolar depression is regarded as a probable, Level B recommendation whereas unilateral right-sided cTBS is possibly ineffective Level C. Research has explored the potential therapeutic benefits of modulating Brain-Derived Neurotrophic Factor (BDNF) levels through Repetitive Transcranial Magnetic Stimulation (rTMS) in the context of depression (Chen et al,2017, Numbero et al, 2021). HR variability is proposed as a novel cardiovascular biomarker. (Sheen et al, 2022). Previous studies have compared High-frequency rTMS vs Low-frequency rTMS for assessing neurocognitive decline, clinical improvement, and suicide risk. One study has evaluated the levels of BDNF in augmented repetitive transcranial magnetic stimulation using high-frequency rTMS (4).

However, as per our analysis, most reported studies have only followed antidepressant effects for 4 weeks (18). Ours will have an 8-week follow-up period and attempt to assess the response to an aITBS session. This will help identify response rates and frequency intervals for aiTBS sessions. There have been limited reported studies comparing the clinical efficacy of two different protocols of accelerated iTBS and a few ongoing trials that are using both - heart rate variability and serum BDNF levels in patients diagnosed with depression and their potential role as biomarkers in indication treatment response.