Decreased serum magnesium levels in depression: a systematic review and meta-analysis

Magnesium (Mg²⁺), an endogenous N-methyl-D-aspartate receptor antagonist, has received increased attention recently because of its role in the pathophysiology of and treatment response in depression. However, whether Mg²⁺ level is decreased in depression is not firmly established. We aimed to conduct a systematic review and meta-analysis to help making consensus for the association between Mg²⁺ levels and depression.

A systematic search was conducted in the electronic database resources PubMed and Embase. After a careful selection of relevant studies, a meta-analysis using the random effects model was conducted in each measuring source, such as serum, plasma, and cerebrospinal fluid (CSF).

A total of 18 studies were included in this study. Among 11 studies that measured Mg²⁺ in the serum, Mg²⁺ level was lower in patients with depression than in controls (weighted mean difference  = -.088, 95% confidence interval  = -.164 to -.012). In the sensitivity analysis by removing studies one by one, 2 out of the 11 studies obliterated such significant differences. There were no significant differences in the Mg²⁺ levels in the studies for plasma and CSF.

Despite some evidence supporting an association between decreased Mg²⁺ levels and depression from studies with serum, the results of our meta-analysis urge to use caution when associating Mg²⁺ levels and depression. Future studies are needed to establish a consensus for the role of low Mg²⁺ levels in depression.