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Objectives:  Depressive disorders are severe mental disorders Here, we perform a meta-analysis of the effect of zinc vs. placebo as an adjunct to conventional antidepressants on the scores in the Hamilton Rating Scale for Depression after 6 and after 12 weeks. A systematic literature search found only three such trials (total  n  = 124 at baseline,  n  = 103 at 6 weeks (imputed sample size) and  n  = 103 at endpoint after 12 weeks). We performed random effects meta-analysis We computed a weighted effect size (Hedges’ g) for the difference of the absolute scores of the Hamilton Depression Rating Scale between the group given zinc and the group given placebo after 6 and after 12 weeks. We performed subgroup analysis according to whether not it was stated in the original studies that patients in a clinical trial or subgroup within a trial had not reached remission with previous treatment with a standard antidepressant during the same illness episode. After 6 weeks, we obtained the following effect sizes: Overall effect size: Hedges’  g  = −0.67,  p  = 0.03. Subgroup with documented non-remission: Hedges’  g  = − 0.97,  p  = 0.001. Group without documented non-remission −0.35,  p  = 0.24. After 12 weeks: Overall effect size: Hedges’  g  = −1.0,  p  = 0.03. Subgroup with documented non-remission: Hedges’  g  = − 1.46,  p  &lt; 0.001. Group without documented non-remission: Hedges’  g  = − 0.54,  p  = 0.07. We provide preliminary evidence for the efficacy of zinc vs. placebo as an adjunct to antidepressant medication.

Zinc as an adjunct to antidepressant medication: a meta-analysis with subgroup analysis for different levels of treatment response to antidepressants