In 100 mechanically ventilated adults with septic shock but without acute brain injury, a low-dose continuous ketamine infusion (0.3 μg/kg/hr) was added to standard sedation. Only one of three noninvasive intracranial pressure (ICP) measures—ICP derived from diastolic flow velocity—showed a statistically significant but very small increase over 24 hours. Cerebral perfusion pressure and vital signs (heart rate, blood pressure, respiratory rate) remained stable. Doses of midazolam, fentanyl, and norepinephrine decreased substantially, especially in the first 12 hours. The findings suggest low-dose ketamine can be used adjunctively without raising ICP or destabilizing hemodynamics, while reducing overall medication burden.
Psychedelics show significant potential for treatment-resistant depression (TRD) by promoting neuroplasticity, corticolimbic function, and epigenetic changes beyond serotonergic agonism. Psilocybin-assisted therapy induces short-term symptom improvement lasting weeks to months. Ketamine, in intravenous, subcutaneous, and oral forms, produces rapid and robust reductions in depressive symptoms and relapses without impairing cognitive function. Esketamine yields early, clinically meaningful improvements in function and productivity. Ayahuasca demonstrates fast and sustained effects with higher remission rates and good safety. Despite encouraging findings, large, well-designed studies are needed before psychedelics become standard recommendations for TRD.