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Description: Depressive disorder is a highly prevalent psychiatric disorder that negatively affects the emotional well-being, and also causes a significant impact on health care costs and workplace productivity. Despite the wide range of antidepressants available, they are only marginally effective in patients. Therefore, there is a criticism related to the abundance of “positive results” contrasting with the partial success of antidepressant treatments in clinical trials or in therapeutics. Besides the lack of representativeness in animal models, many different reasons may contribute to the poor translation from preclinical to clinical studies in antidepressant research. Methodological factors such as poor experimental design and low power analysis as well as confirmation bias and publication bias may account for the low reproducibility and poor representation of animal models of depression. All these factors may contribute to the reduced translation of preclinical studies. In this regard, we aim to estimate the influence of methodological qualities on the outcomes of preclinical studies employing animal models and to determine the effect sizes for primary and secondary outcomes according to species, strains, sex, age, via of administration, natural compound class, treatment schedule and protocols of animal models of depression.