Psychedelics and ketamine/esketamine show promise for treating depressive disorders by inducing rapid and sustained antidepressant effects. The review examines their biological mechanisms, including modulation of glutamate and serotonin systems, promotion of neuroplasticity, and changes in brain connectivity and network function. Neuroimaging studies reveal alterations in default mode network, fronto-limbic connectivity, and thalamic activity. Clinical changes are associated with these brain alterations, though the precise relationships remain under investigation. The work synthesizes current evidence on how these compounds produce observable brain changes and symptom improvement, highlighting the need for further research to clarify mechanisms and optimize therapeutic applications.
A 56-year-old man with rapid cycling bipolar disorder, experiencing four or more mood episodes per year, received esketamine nasal spray during a depressive episode and was followed for 18 months. He showed substantial mood stabilization, with only a brief depressive episode when treatment was stopped for three months, which resolved after restarting esketamine. Mild dissociative symptoms occurred with initial doses, but no other serious side effects were reported. This case suggests esketamine nasal spray may have mood-stabilizing effects for rapid cycling bipolar disorder, a condition that often responds poorly to lithium and standard treatments.