To date P2X7 selective antagonists have already been tested in Phase I/II clinical trials for the treatment of Crohn’s disease, rheumatoid arthritis, basal cell carcinoma with an overall good tolerability and variable efficacy [72] and a new trial is currently ongoing assessing the effects of JNJ-54175446, a potent, brain-penetrant, selective P2X7 antagonist [73] in patients with major depressive disorder (ClinicalTrials.gov Identifier: NCT04116606). This evidence concerns the gene P2RX7 and major depressive disorder.