The Interactive Effects of Ketamine and Magnesium Upon Depressive-like Pathology

Approximately one third of patients with major depressive disorders (MDD) are resistant to current treatment. This has resulted in novel treatments being adopted, including sub-anaesthetic doses of ketamine, which affects aberrant neuroplastic circuits; glutamatergic signaling and the production of brain derived neurotrophic factor (BDNF). Ketamine rapidly relieves depressive symptoms in treatment resistant MDD patients with effects that last for up to two weeks. However, it is also a drug with abusive potential and can have marked side effects. Hence, we conducted studies aimed at enhancing the anti-depressant-like effects of ketamine (allowing for lower dosing regimens) by co-administering magnesium hydroaspartate (Mg2+ normally affects the same receptors as ketamine). To this end, we found that ketamine alone induced rapid anti-depressant-like effects in the forced swim test and influence brain levels of BDNF. However contrary to our hypothesis, magnesium had no effect on these outcomes nor did it enhance the effects of ketamine.