Efficacy of adjunctive intermittent theta-burst stimulation on depressive and insomnia symptoms in elderly patients with depression and comorbid insomnia: A randomized, sham-controlled trial

BACKGROUND: Intermittent theta-burst stimulation (iTBS) may hold potential for treating late-life depression (LLD) accompanied by comorbid insomnia; however, its underlying neural mechanisms remain incompletely understood. This study aimed to explore the therapeutic effects of iTBS on depressive and insomnia symptoms in this population and to explore related alterations in brain neural function using resting-state functional magnetic resonance imaging (fMRI). METHODS: In this study, 36 elderly patients with LLD and insomnia were assigned to receive either sham or active iTBS over the left dorsolateral prefrontal cortex (DLPFC) for 3 weeks (15 sessions). Primary outcomes were assessed using the Pittsburgh Sleep Quality Index (PSQI) and Hamilton Depression Rating Scale (HAMD-17) at baseline, as well as at Weeks 1, 2, 3, and 6. Resting-state fMRI data were obtained at baseline and after the 3-week treatment to quantify the amplitude of low-frequency fluctuations (ALFF) and functional connectivity. RESULTS: Active iTBS significantly improved depressive and insomnia symptoms compared with sham stimulation (p < 0.05). Reductions in ALFF were observed in limbic-temporal regions (e.g., parahippocampal gyrus, temporal poles) and correlated with sleep improvement. The connectivity between the visual cortex and the left DLPFC also decreased, with trend-level association to better sleep. LIMITATIONS: Larger multi-center trials with prolonged follow-up are needed to confirm findings and elucidate mechanisms. CONCLUSION: iTBS over the left DLPFC may reduce depression and insomnia in LLD patients, possibly by modulating limbic-temporal activity and prefrontal-sensory connectivity. This small, exploratory, single-center study suggests that iTBS could be a promising adjunctive treatment for this population.