Magnesium in major depression

Magnes Res. 2009 Sep;22(3):163S-166S.


There are contradictory data regarding the levels of magnesium in patients with major depression (MD) and how antidepressants influence their concentration. Our results show erythrocyte magnesium in patients with MD (44.39 +/- 2.7 mg/L vs. 59.1 +/- 3.2 mg/L in control group, p < 0.05) and only in patients with severe MD (Hamilton score > 23) was a moderate decrease in plasmatic magnesium observed (17.7 +/- 1.5 mg/L vs. 22.9 +/- 3.3 mg/L in control group). Therapy with antidepressants from different groups and with different mechanisms of action, such as amytriptiline (25 mg x 3/day per os, 4 weeks) and sertraline (50 mg x 3/day per os, 4 weeks) leads to a significant increase of magnesium concentration in erythrocytes (57.6 +/- 4.5 mg/L after amytriptiline, respectively 56.9 +/- 3.2 mg/L after sertraline, p < 0.05 vs. before therapy). At the same time, in patients with MD, plasmatic levels of zinc were significantly decreased before therapy and increased after treatment with amytriptiline and sertraline (0.68 +/- 0.09 mg/L before treatment vs. 0.9 +/- 0.07 after amytriptiline). There is a positive correlation between concentrations of magnesium in erythrocytes and the clinical evolution of patients with MD. We consider that increasing intracellular concentration is a component of the antidepressant mechanism of sertraline and amytriptiline and maybe of other antidepressants. Anhedonia and autolytic tendencies are important elements of MD symptomatology. We tested the influence of MgCl2 0.2 mM/kg/day on a reward system using conditioned place preference (Panlab) in rats. Our data show a moderate stimulation of the reward system by magnesium (290.6 +/- 27 s time spent in a conditioned compartment before magnesium treatment and 363.3 +/- 16 s after magnesium treatment) that reflects a stimulation of the reward system (RS). We consider that a magnesium-induced stimulation of the RS is an important issue for treating anhedonia in patients with MD. An increase of intracellular magnesium may be part of the mechanism of action of antidepressants.

Publication types

  • Review

MeSH terms

  • Animals
  • Antidepressive Agents / therapeutic use*
  • Depressive Disorder, Major / drug therapy*
  • Erythrocytes / chemistry
  • Humans
  • Magnesium / blood*
  • Magnesium / therapeutic use*


  • Antidepressive Agents
  • Magnesium