Depression is a leading cause of disability, and many adults with major depression do not achieve remission with first-line treatments. Magnesium influences several neurotransmitter systems involved in emotional processes, including serotonergic, noradrenergic, dopaminergic, GABAergic, and glutamatergic systems. The mechanism of antidepressants' action involves the glutamatergic system, and magnesium ions may play a role in major depressive disorder pathophysiology by blocking the N-methyl-D-aspartate receptor (NMDAR). Ketamine, an NMDAR antagonist, has fast-acting antidepressant and antisuicidal effects. The evidence discussed suggests a possible synergistic interaction between magnesium and ketamine's pharmacodynamic activity in mood disorders.
Impulsive behaviors are common in major depressive disorder and bipolar disorder, raising suicide risk and mood instability. Ketamine, an NMDA receptor antagonist, can produce rapid antidepressant and antisuicidal effects, and magnesium given with low-dose NMDA antagonists reduces anxiety- and depression-like behaviors in animals. This observational study of 49 inpatients with treatment-resistant mood disorders measured impulsivity with the Barratt Impulsiveness Scale (BIS-11) and magnesium levels before and during a four-week course of eight ketamine infusions. Magnesium ion concentration during treatment was not associated with changes in BIS-11 scores. The findings provide no evidence for a relationship between magnesium levels and impulsivity during ketamine therapy.