Creatine and Depression in Rodents: A Meta-Analysis
Abstract
Traditional treatments for major depression are based on the monoamine deficiency hypothesis, and they fail to achieve remission in a substantial portion of patients. Newer evidence suggests the pathophysiology of depression is a more complex story, highlighting a need for research in alternative therapies. Mounting evidence shows a linkage between depression and the supplement creatine monohydrate (CRMH). Research in rodent models suggests that CRMH may both alleviate depressive symptoms and enhance the efficacy of standard antidepressants like SSRIs. The following study describes findings from a combined fixed- and random-effects meta-analysis based on four empirical studies investigating the effect of CRMH on depression symptoms in rats in a forced swim test paradigm (FST). The overall results were ambiguous, with a small effect size of CRMH on swim immobility (d = 0.303). However, CRMH had a moderate augmenting effect when combined with SSRI medication (d = 0.505). A sex-based effect was also seen, with a moderate effect size for female rats (d = 0.509), and little to no effect for males (d = 0.05). Limitations to this study included the generalizability of animal model findings to human populations, some heterogeneity, a low number of studies (n = 4), and potential variability in experimental protocols. The results from this meta-analysis underscore the need for further investigation into CRMH's therapeutic potential, particularly in conjunction with conventional antidepressants.