Table 2.

Immunometabolic modulators with potential applicability to MDD.

Drug	Molecular target	Clinical indication	Effect on cellular metabolism & function, or behavior; Advantages	Brain penetrance
Dimethyl Fumarate	Nrf2	Multiple sclerosis, psoriasis	•Specifically targets glycolytically active immune cells •Limits leukocyte entry to the brain	Derivative (MMF)-yes
Rapamycin	Inhibition of mTORC1	Prevention of organ rejection, cancer	•Reduces monocyte glycolysis and adhesion •Prolongs ketamine's antidepressant effects	Low
2-DG	Hexokinase	N/A. Pre-clinical applications	•Potent inhibitor of glycolysis •Reduces monocyte transmigration, adhesion •Some clinical evidence of safety & efficacy	Yes
Itaconate	Succinate dehydrogenase, Nrf2	N/A. Pre-clinical applications	•Specifically targets activated macrophages/monocytes •Endogenous, low toxicity	Derivatives-likely

Abbreviations: Nrf2, Nuclear factor erythroid 2-related factor 2; mTORC1, mechanistic target of rapamycin complex 1; 2-DG, 2-deoxy-D-glucose; MMF, monomethyl fumarate (active metabolite of dimethyl fumarate).