Ketamine's mechanism of action with an emphasis on neuroimmune regulation: can the complement system complement ketamine's antidepressant effects?
Molecular Psychiatry September 1, 2024 Brandi Quintanilla, Carlos A. Zarate, Anilkumar Pillai 17 citations
Over 300 million people worldwide have major depressive disorder (MDD), but only 30-40% achieve remission with standard antidepressants. Ketamine offers rapid relief within hours, unlike weeks for conventional drugs. While many studies focus on ketamine's effects on glutamate, this review highlights its anti-inflammatory actions, especially through the complement system—a part of innate immunity involved in synaptic plasticity. The complement system is linked to depression, with increased complement component 3 (C3) expression found in the prefrontal cortex of suicidal individuals with depression. Given ketamine's anti-inflammatory properties and the complement system's role in glutamate modulation, the review suggests a common link between the complement system and ketamine's mechanism of action.