Abstract: Objective To investigate the efficacy and safety of agomelatine to treat insomnia in perimenopausal patients with anxiety and depression. Methods Eighty patients were randomly divided into two groups (n=40): a treatment group and a control group. Patients in the treatment group received agomelatinem, while those in the control group were treated with estazolam for six weeks. Then, before and after treatment, the Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), and Pittsburgh Sleep Quality Index (PSQI) were adopted to evaluate clinical efficacy, while the Asberg's Side Effects Rating Scale (SERS) was used to assess adverse reactions. Results Before treatment, no statistical difference was found as to the scores of PSQI, SAS and SDS between the two groups (P>0.05). After treatment, the treatment group presented remarkable decreases in the scores of PSQI, SAS and SDS compared with the control group, which was statistically different from those before treatment (P<0.05). The scores of SERS in the treatment group were significantly lower than those in the control group at Weeks 2 and 6 (P<0.05). Conclusions Agomelatine is more effective than estazolam to treat insomnia in perimenopausal patients with anxiety and depression, with fewer adverse reactions.