In a double-blind randomized placebo-controlled trial with 34 Japanese patients suffering from treatment-resistant depression, intravenous ketamine (0.5 mg/kg) given twice a week for two weeks did not show a statistically significant advantage over placebo in reducing depression scores when all participants were analyzed together. However, among those who completed the full treatment protocol, ketamine led to a significantly greater reduction in depressive symptoms than placebo. Higher baseline depression severity and body mass index were linked to greater symptom improvement with ketamine. Adverse events were more common with ketamine but no serious events occurred. These results suggest ketamine may be effective for treatment-resistant depression across diverse ethnic groups.
About 30% of people with treatment-resistant depression respond to ketamine, but reliable predictors of response have been lacking. This study examined whether the ratio of glutamate+glutamine (Glx) to GABA in the dorsal anterior cingulate cortex (dACC) could predict ketamine's effectiveness. In a double-blind randomized trial with an open-label extension involving 30 participants, a higher baseline Glx/GABA ratio in the dACC correlated with greater improvement in depression scores (measured by the HDRS-17). After ketamine treatment, a reduction in this ratio also correlated with symptom improvement. The findings suggest that an excitatory-inhibitory imbalance in the dACC may help predict which patients will benefit from ketamine therapy.
In patients with treatment-resistant depression, higher baseline levels of magnetic substances in the right nucleus accumbens and the left amygdala, measured by brain imaging, predicted a greater reduction in specific depressive symptoms after repeated ketamine infusions. The study included 17 Japanese patients and used a double-blind, randomized placebo-controlled design followed by an open-label phase. Baseline magnetic susceptibility in the right nucleus accumbens correlated with improvement in retardation symptoms, while baseline R2* in the left amygdala correlated with improvement in vegetative symptoms. These brain markers may help predict which patients will benefit from ketamine treatment.