A medication-driven magnesium deficiency score is associated with increased depressive symptoms prevalence independent of renal function: Evidence from NHANES 1999-2018.

BACKGROUND

Magnesium deficit is considered to be a risk factor for depression. This study aimed to determine the relationship between Magnesium Depletion Score (MgDS) and depressive symptoms.

METHODS

A total of 20,893 participants were included from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2018. Depressive symptoms was defined using a 9-item Patient Health Questionnaire (PHQ-9) (categorized as ≥5 [mild], ≥10 [clinical], and ≥ 15 [moderate-to-severe]). Weighted linear regression examined MgDS association with continuous PHQ-9 scores (range 0-27), while weighted logistic regression analyzed categorical depressive symptoms. Restricted cubic splines (RCS) assessed nonlinear relationships in both models. Sensitivity analyses included severity-stratified and subgroup analyses.

RESULTS

For each one-point increase in MgDS, the PHQ-9 score increased by 0.23 points (95 % CI: 0.13-0.32) in the continuous analysis. Similarly, the odds of clinical depressive symptom were increased by 12 % (OR = 1.12, 95 % CI: 1.04-1.21). Use of diuretics and PPIs was independently associated with increased likelihood of having depressive symptoms (OR = 1.24, 95 % CI: 1.04-1.46; OR = 1.95, 95 % CI: 1.64-2.32). In sensitivity analyses, per-unit MgDS increases corresponded to 11 % (mild; OR = 1.11, 1.04-1.17) and 17 % (moderate-to-severe; OR = 1.17, 1.05-1.31) higher odds of depressive symptoms. RCS analysis showed that there was a linear dose-response relationship across the MgDS. The association remained significant in stratified analyses by age, sex, magnesium intake, and comorbidity status.

CONCLUSION

MgDS was independently associated with depressive symptoms in a dose-response manner. The use of diuretics and PPIs may contribute to this association through magnesium imbalance, necessitating mechanistic studies and clinical monitoring in high-risk patients.