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To investigate the effect of escitalopram combined with zolpidem on sleep quality, anxiety and depression state and serum neurotransmitter in patients with primary insomnia. 100 cases of primary insomnia admitted to our hospital from January 2018 to December 2020 were selected as the study object. The above patients were divided into control group (treated with zolpidem, n=50) and study group (treated with escitalopram on the basis of the control group, n=50,) according to the random number table method. The sleep quality, anxiety and depression state, serum neurotransmitter and adverse reactions of the two groups were compared. 4 weeks after treatment, the sleep efficiency of the study group were higher than those of the control group, the total sleep time were longer than those of the control group, while the wake-up time and sleep time of the study group were shorter than those of the control group (P<0.05). 4 weeks after treatment, the pittsburgh sleep quality index (PSQI), hamilton Depression Rating Scale (HAMD) and hamilton Anxiety Rating Scale (HAMA) of the study group were lower than those of the control group (P<0.05). 4 weeks after treatment, the levels of 5-hydroxytryptamine (5-HT), r-aminobutyric acid (GABA) in the study group were higher than those in the control group, and the levels of norepinephrine(NE) in the study group were lower than those in the control group (P<0.05). There was no difference in adverse reactions between the two groups (P>0.05). Esmcitalopram combined with zolpidem can effectively improve the sleep quality, anxiety and depression of patients with primary insomnia, and improve the serum 5-HT, NE, CRH, with good safety. [ABSTRACT FROM AUTHOR]