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.