Clinical depression is a serious mental disorder characterized by low mood, anhedonia, loss of interest in daily activities, and other symptoms, and is associated with severe consequences including suicide and increased risk of cardiovascular events. Depression affects nearly 15% of the population. Treatment for the last 50 years has focused on monoamine neurotransmitters, including such treatments as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) (which have serious side-effects including death, stroke, heart disease, suicidal ideation, homicidal ideation, aggression and heart failure). However, these treatments have significant limitations: they can take weeks before showing mood-altering effects, and only one to two out of ten patients shows clinical effects beyond those associated with placebo. A major paradigm shift in research into the treatment of depression is underway, based on promising results with the glutamatergic NMDA receptor antagonist ketamine (its hallucinogenic and dissociative effects limit its therapeutic use). Further research has demonstrated the significance of glutamatergic pathways in depression and the association of this system with the stress pathway and magnesium homeostasis. Treatment with NMDA receptor antagonists and magnesium have shown the ability to sprout new synaptic connections and reverse stress-induced neural changes.
Expert Commentary: Carolyn Dean MD, ND
Due to ketamine’s hallucinogenic and dissociative effects limiting its therapeutic use, can it be that magnesium homeostasis is the key to therapeutic benefits. Serotonin, the feel good brain chemical that is boosted artificially by some medications, depends on magnesium for its production and function. Magnesium is known as the anti-stress, anti-anxiety mineral for this reason.
Zarate C, Duman RS, Liu G, Sartori S, Quiroz J, Murck H. “New paradigms for treatment-resistant depression.” Ann N Y Acad Sci. 2013 Jul;1292(1):21-31. doi: 10.1111/nyas.12223.