Results of the phase 2 OLIVE trial testing the vasopressin 1b antagonist nelivaptan (BH-200) in major depressive disorder

Major depressive disorder is clinically and biologically heterogeneous, which may dilute treatment effects in trials of mechanism-based antidepressants. This challenge is particularly relevant for psychiatric genetics, where treatment-relevant biology is unlikely to be captured by single variants and their discovery is constrained by the limited sample sizes of clinical trials. The OLIVE Phase 2 study evaluated nelivaptan/BH-200, a selective vasopressin V1b receptor antagonist, and explored whether a physiology-anchored genetic classifier could identify patients with differential treatment response. The presentation will introduce the biological rationale for targeting vasopressin V1b signalling in depression, focusing on HPA-axis dysregulation as a plausible treatment-relevant pathway. It will then describe the translational logic from the dexamethasone/CRH challenge test to the V1b polygenic score, before summarising the OLIVE trial design and key results.