Divergent Mechanisms of Antidepressant Efficacy: A Unified Computational Comparison of Synaptogenesis, Stabilization, and Tonic Inhibition in a Model of Depression

These simulations demonstrate that antidepressants operate through mechanistically distinct routes-structural rebuilding (ketamine), gradual optimization of existing connectivity (SSRIs), or reversible dynamic stabilization (neurosteroids)-yielding trade-offs in onset speed, durability, and stress resilience. The findings support a multifaceted plasticity framework for depression and provide computational rationale for mechanism-based treatment selection and combination strategies.