Intravenous ketamine is a fast-acting treatment for treatment-resistant depression in both unipolar and bipolar forms. Its benefits last days, longer in unipolar depression, and it may reduce suicidality, though data are limited. Strategies to extend effects—multiple doses, maintenance, or additional medications—have shown mixed results. Alternative routes (intramuscular, intranasal, oral) show promise but lack sufficient data. Adverse effects are mainly mild, transient dissociative and sympathomimetic symptoms, indicating good tolerability. Ketamine's unique properties could shift depression treatment paradigms.
Ketamine reduced brain-wide low-frequency fluctuations and decreased prefrontal global brain connectivity in healthy adults, while also increasing pulse rate and electrodermal activity. A combination of neural and physiological metrics may predict subjective mystical experiences and reductions in depressive symptoms. The study used time-domain functional near-infrared spectroscopy to measure acute brain dynamics after intramuscular ketamine (0.75 mg/kg) or placebo in 15 participants within a clinical setting, demonstrating the feasibility of this neuroimaging method for larger clinical studies on psychedelics.