The depressive disorders remain one of the global problems of modern society. Many issues related to this topic remain open for discussion. It is reliably known that tropical fish Danio rerio (zebrafish) are the most studied and practical model methods of preclinical studies. They have several advantages over other laboratory animals. Danio Rerio is great for modeling stress and depression in order to identify the manifestations of medication to identify the manifestations of this condition. Methods. Danio Rerio when exposed to non-selective antidepressants and related serotonin reuptake inhibitors. Danio Rerio is under stress and depression due to acute exposure to caffeine and the subsequent use of antidepressants with timely recording and processing of the results. Results. The effect of sertraline on the Danio rerio group in order to identify the state of stress and depression was more effective in comparison with the results obtained using amitriptyline as an antidepressant. Conclusions. Sertraline in therapeutic concentration has a greater rate of elimination from anxiety and depression, which in turn allows us to argue about its greater effectiveness. In medical practice, it is better to prescribe drugs of the group of selective serotonin reuptake inhibitors in order to achieve a faster effect.