〔Abstract〕 Objective To observe the efficacy of low dose Olanzapine combined with Agomelatine in the treatment of senile insomnia with anxiety and depression. Methods 100 elderly insomnia patients with anxiety and depression admitted to the Ninth People's Hospital of Zhengzhou from September 2021 to September 2022 were selected as the research subjects. According to different nursing intervention methods, they were divided into a control group and an observation group, with 50 cases in each group. The control group was treated with routine dose of Olanzapine, and the observation group was treated with low dose of Olanzapine combined with Agomelatine. Compare the clinical efficacy of two groups of patients. Results The clinical treatment efficiency of the observation group was higher than that of the control group, and the difference was statistically significant (P < 0.05). The scores of rapid rating scale, side effect scale and 90 symptom scale in the observation group were lower than those in the control group, and the differences were statistically significant (P < 0.05). The negative scale score and the social function scale score of the observation group was higher than those of the control group, the differences were statistically significant (P < 0.05). The incidence of adverse reactions in the observation group was lower than that in the control group, and the difference was statistically significant (P < 0.05). Conclusion In the treatment of senile insomnia with anxiety and depression, low-dose Olanzapine combined with Agomelatine has better clinical efficacy and can improve the prognosis of patients.