In a phase 3 trial across seven mood disorders centers in Australia and New Zealand, subcutaneous racemic ketamine was tested against midazolam for treatment-resistant depression. With flexible dosing (0.5–0.9 mg/kg), ketamine led to a 19.6% remission rate compared to 2.0% for midazolam, a significant difference. Fixed dosing (0.5 mg/kg) showed no difference. Acute side effects, such as psychotomimetic effects and blood pressure increases, resolved within two hours. The subcutaneous route proved practical and feasible.
A single injection of ketamine produces opposite behavioral effects in stressed versus unstressed male mice. In mice subjected to chronic mild stress and unpredictable chronic stress, ketamine (10 or 30 mg/kg) decreased immobility and increased swimming in the forced swim test 24 hours later, indicating antidepressant-like effects. In unstressed mice, however, ketamine increased immobility and reduced swimming, opposite to its effects in stressed animals. These results suggest that chronic psychological stress interacts with ketamine to modulate its effects, reinforcing the relevance of the forced swim test and this mouse strain for studying stress-induced depression.