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.
About 30% of people with depression have treatment-resistant depression (TRD). Ketamine can help, but how it works in the human brain was unclear. Using a PET tracer that shows AMPAR density, researchers found that AMPAR density was lower in patients with more severe TRD, and its distribution differed from healthy people. After ketamine, changes in AMPAR density in certain brain areas correlated with antidepressant effects, partially restoring normal AMPAR patterns. AMPAR dynamics underlie ketamine's antidepressant effect in TRD.
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.
A higher baseline ratio of glutamate+glutamine (Glx) to GABA in the dorsal anterior cingulate cortex predicted greater improvement in depressive symptoms after ketamine treatment in adults with treatment-resistant depression. In the ketamine group, a reduction in this Glx/GABA ratio correlated with symptom improvement, but no such association appeared in the placebo group. The findings suggest that the balance between excitatory and inhibitory neurotransmission in this brain region may serve as a biomarker for predicting antidepressant response to ketamine.