Expanding access to MDMA-assisted psychotherapy (MDMA-AT) for US patients with chronic and severe PTSD would likely provide substantial health and financial benefits. A decision-analytic model compared three coverage targets (25%, 50%, and 75% of eligible patients) against standard care. All three targets were cost-saving and projected to avert 43,618 to 106,932 deaths and gain 3.3 to 8.2 million quality-adjusted life years over 10 years. Sensitivity analyses confirmed that MDMA-AT remained dominant under various assumptions, though the precise magnitude of benefits depends on the number of eligible patients and other inputs.
Ketamine provides rapid antidepressant effects for treatment-resistant depression by blocking NMDA receptors, which triggers glutamatergic signaling that promotes synaptic plasticity and neurogenesis. This review synthesizes preclinical and clinical evidence on how these neuroplastic changes unfold over hours to days, linking molecular mechanisms like BDNF signaling and mTOR pathway activation to improvements in mood, motivation, cognition, and functional outcomes. It emphasizes the temporal trajectory of ketamine's effects and offers a plasticity-centered model to integrate neuroscience with clinical psychiatry, while identifying gaps in translational research for optimizing fast-acting antidepressants.