This article proposes a clinical-neurobiological model for the strategic use of haloperidol in severe refractory depressions, focusing on hyperactive borderline patients, adolescentes with natural hormonal lability or patients with psychotic catatonias. Based on extensive hospital experience, an illustrative clinical case, and a literatur review, the direct, rapid , and safe antidepressant effect of haloperifol is discussed. Physiopathological hypothesis involving D2, D3, 5HT2A , sigma-1, receptors, the HPA axis, prolactin and calcium channels are integrated and discussed. The rational use of haloperidol is advocated as na accessible alternative in resource-limited contexts (no ECT, no ketamine, etc).