Long‑acting injectable (LAI) formulations have transformed adherence in several psychiatric conditions, yet no depot antidepressant currently exists. People with major depressive disorder (MDD) remain at risk of accidental overdose from prescribed oral medications, particularly during periods of cognitive impairment or crisis. Artificial intelligence (AI)–driven molecular modelling now enables the design of antidepressant compounds optimised for slow‑release, water‑based depot systems that avoid the fibromas and granulomatous reactions associated with oil‑based injectables. This study outlines an AI‑enabled workflow for generating a novel antidepressant molecule with favourable receptor‑binding properties, low toxicity, and compatibility with biodegradable, aqueous depot carriers. The resulting formulation has the potential to reduce overdose risk, improve adherence, and decrease the burden of frequent GP prescribing.