Feasibility of rTMS combined with dexmedetomidine in chronic insomnia disorder

To explore the efficacy and mechanism of repetitive transcranial magnetic stimulation (rTMS) combined with dexmedetomidine (DEX) in treating chronic insomnia disorder. 42 participants were divided into two groups: DEX (N = 23) and rTMS + DEX (N = 19). rTMS was processed with a frequency of 1 Hz, at an intensity of 100% resting motor threshold (RMT), with 1000 stimulation administered to the left dorsolateral prefrontal cortex (DLPFC), occurring 4 times a week for 4 weeks. DEX was administered nightly with an automatic intravenous infusion device for 4 weeks. The Pittsburgh Sleep Quality Index (PSQI), Hamilton Anxiety Rating Scale (HAMA), Hamilton Depression Rating Scale (HAMD), actigraphy, and the dosage of sedative and hypnotic drugs were recorded at baseline, therapy termination, and follow-up at 1, 3 and 6 month. Concentrations of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in plasma were measured at baseline and therapy termination using enzyme-linked immunosorbent assay (ELISA). The PSQI, HAMA and HAMD scores at therapy termination and follow-up period showed a significant decrease compared to baseline (P < 0.01). Light sleep duration and awakening times at therapy termination and follow-up period demonstrated a decrease compared to baseline, along with an increase in deep sleep and rapid eye movement (REM) sleep (P < 0.01). The concentrations of IL-6 and TNF-α in the rTMS + DEX group were lower than those in the DEX group, whereas the GSH-Px and SOD were higher (P < 0.05). The treatment-related adverse reactions primarily included dry mouth, thirst, bradycardia and hypertension. rTMS combined with DEX could improve the structure and quality of sleep with chronic insomnia disorder, and also alleviate anxiety and depression, with the efficacy persisting for 6 months. The improvement in sleep with rTMS might be associated with an increase in concentrations of GSH-Px and SOD, and a decrease in IL-6 and TNF-α. This trial was registered with the Chinese Clinical Trial Registry (Number: ChiCTR2100050114) on 16/08/2021.