Objective: To investigate agomelatine effects on first-episode senile depression patients. Methods: One hundred and sixteen elderly patients with first-episode senile depression were randomly and evenly divided into an observation group and a control group. The observation subjects were treated with agomelatine. The control subjects were treated with sertraline. The treatment effects, sleep improvement, and adverse reactions were compared. Results: After one week of treatment observation group The Hamilton Depression Rating Scale (HAMD) and Pittsburgh Sleep Quality Index (PSQI) scores after one week of treatment decreased significantly. After two weeks of treatment control group scores also decreased significantly (p < 0.01). Observation group HAMD scores were significantly lower than control group scores after weeks 1, 2, 4, and 8 (p < 0.05). Observation group PSQI scores were significantly lower than control group at the end of weeks 4 and 8 (p < 0.05). Observation group adverse incidence rate during administration was significantly lower than the control group (p < 0.05). Conclusion: Both agomelatine and sertraline are effective in treating first-episode depression elderly patients. Agomelatine has an earlier response, fewer adverse reactions and superior insomnia improvement.