Aim: This study aimed to evaluate the relationship between a human GRIK4 gene polymorphism (rs1954787) and responsiveness to antidepressant treatment in depressed patients. Methods: A meta-analysis was carried out on five studies. Pooled odds ratios (ORs), 95% CIs and a χ² test measuring heterogeneity were calculated. A test of publication bias was also conducted. Results: Alleles and genotypes from a total of 2169 depressed patients were analyzed. The results showed that the C allele appeared more frequently than the T allele in responders to treatment (OR: 1.22; 95% CI: 1.035–1.445; z = 2.36; p = 0.018). Similarly, CC homozygotes were more likely than TT homozygotes to respond to treatment (OR: 1.45; 95% CI: 1.107–1.913; z = 2.69; p = 0.007). No evidence of publication bias was detected. Conclusion: Subjects possessing the C allele or CC genotype of the GRIK4 polymorphism rs1954787 are more likely to respond to antidepressant treatment relative to subjects harboring the T allele and TT genotype. Additional replication of this result is required before this association can be considered definitive, after which it may become possible to employ this marker in conjunction with other known predictors in order to anticipate the outcomes of treatment with antidepressant medications. Original submitted 25 April 2014; Revision submitted 6 June 2014