Plasma magnesium levels and treatment outcome in depressed patients

Nutr Neurosci. 2012 Mar;15(2):78-84. doi: 10.1179/1476830512Y.0000000002.


Objectives: High, normal, or low plasma magnesium (Mg) levels have been observed in depressed patients. The aim of our study was to investigate the relationship of Mg levels with depression severity, specific psychopathological dimensions, and treatment outcome.

Methods: A total of 123 outpatients during a major depressive episode were recruited. All patients showed at least two major depressive episodes and did not achieve remission in the former treatment trial. A blood sample was collected to determine total plasma Mg levels. The psychopathological status was assessed using Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Depression Retardation Rating Scale for psychomotor retardation, and Snaith-Hamilton Pleasure Scale for anhedonia. Hamilton Depression Rating Scale was repeated at 3 months after treatment.

Results: All patients showed Mg levels mostly within the normal range. No association between Mg levels and psychopathological severity was reported. Patients who responded to antidepressant treatment showed higher Mg levels and higher retardation scores at basal evaluation in comparison with non-responders.

Discussion: Although further studies investigating the relationship between hypomagnesaemia, depression, and treatment outcome are certainly necessary, we have hypothesized that hypomagnesaemia could be an epiphenomenic biochemical trait in less drug-responsive depressed patients. It is also plausible that lower Mg levels and hyperactive traits identify a biological subtype of patients with increased catecholaminergic functioning and a poorer response to aminergic drugs. Moreover, Mg depletion could partly account for the correlation between low Mg levels and poor outcome and this raises the question of Mg's possible therapeutic role in depression.

MeSH terms

  • Adult
  • Anhedonia / drug effects
  • Antidepressive Agents / therapeutic use
  • Depression / complications
  • Depression / drug therapy
  • Depression / psychology*
  • Depressive Disorder, Major / complications
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / psychology*
  • Female
  • Humans
  • Magnesium / blood*
  • Magnesium Deficiency / complications
  • Magnesium Deficiency / drug therapy*
  • Magnesium Deficiency / physiopathology
  • Male
  • Middle Aged
  • Outpatients
  • Treatment Outcome


  • Antidepressive Agents
  • Magnesium