Purpose: Depression combined with insomnia is a complex bidirectional relationship that is more difficult to treat versus a single disorder, and there is a lack of effective treatments available. In this study, we carried out a novel way to simultaneously intervene in depression combined with insomnia and examined functional magnetic resonance imaging (fMRI) to help further elucidate the mechanisms. Patients and methods: A total of 105 patients with depression and insomnia were included in this observational and prospective study. 17-item Hamilton Depression Scale (HAMD-17), Pittsburgh Sleep Quality Index (PSQI) were collected from medical records at baseline (T0), 24 hours (T1), 7 days (T2), 14 days (T3), 21 days (T4), one month (T5), two months (T6), three months (T7) follow-up. fMRI scans were performed at baseline and two hours after treatment. Results: Compared with baseline, the symptoms of depression in T1-T7 were significantly reduced. At two hours after treatment, the left amygdala, the left hippocampus, the left superior temporal gyrus, the left anterior cingulate gyrus, and the left paracingulate gyrus showed a consistent reduction in spontaneous neural functional activity. In contrast, the right dorsolateral superior frontal gyrus, middle frontal gyrus, infraorbital frontal gyrus, middle orbital frontal gyrus and right caudate nucleus showed increased consistency of spontaneous neural function. No unanticipated safety issues were detected, and the rate of side effects was equivalent to those reported in RCTs. Conclusion: Our findings support the efficacy and safety of esketamine combined with dexmedetomidine (Dex) in patients with depression and insomnia, which provides a new approach to clinical improvement of depression combined with insomnia.

The authors have declared no competing interest.

ChiCTR2300070756

This work was supported by the program of the National Natural Science Foundation of China (82072086).

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The clinical trial has been approved by the Institutional Review Board (IRB) of the Shandong Second Medical University (wyfy-2023-ky-057)

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The data that support the findings of this study are available from the corresponding author upon reasonable request.