Depressive disorders impose a heavy global public health burden, with a gap between how common they are and the availability of fast, effective treatments that lead to remission. Brexanolone and zuranolone, the first FDA-approved drugs for postpartum depression, mark a critical advance for a vulnerable patient group. Psilocybin shows promise for treatment-resistant depression and for people who have not found relief with existing options. This review discusses these transformative therapies as major steps forward for postpartum depression, major depressive disorder, and treatment-resistant depression.
Nasal esketamine, a rapid-acting antidepressant, alters brain network activity by reducing top-down control and shifting the excitation/inhibition balance toward excitation. In eight individuals with major depressive disorder, EEG recordings before and up to 90 minutes after esketamine administration showed decreased frontoparietal alpha power and central beta power, along with increased frontal midline delta and low gamma power. The aperiodic exponent decreased, indicating cortical disinhibition. These neural changes correlated with increased subjective ratings of highness and happiness and decreased tension, linking the drug's neurophysiological effects to the immediate subjective experience.