A novel oral prolonged-release formulation of racemic ketamine (KET01) was tested as an add-on therapy for treatment-resistant depression. Patients received 160 mg/day, 240 mg/day, or placebo for 14 days. The 240 mg/day group showed a numerically larger but statistically non-significant improvement in depression scores compared to placebo. The trial was terminated early due to poor recruitment during the COVID-19 pandemic, with only 27 patients completing the protocol. Adverse event rates were similar across groups, and no increased risk of suicidality, dissociation, or blood pressure changes was observed. Baseline leukocyte count correlated with response to KET01 in exploratory analysis.
Mindful self-awareness, a core component of mindfulness meditation, is linked to reduced activity in brain regions involved in self-referential thinking (cortical midline structures) and emotion (amygdala), alongside increased activity in somatosensory areas. Using fMRI, experienced meditators (average 4,652 practice hours) and meditation-naïve participants engaged in short periods of mindful self-awareness and self-referential thinking. Both groups showed somatosensory activation and decreased cortical midline activity during mindful awareness, but experienced meditators exhibited significantly stronger decreases in prefrontal midline regions and reduced activity in language-related areas. Higher amygdala and midline activity during mindful awareness correlated with depressiveness. Meditation training may reduce self-reference and verbalization during mindful awareness, supporting its role in healthy self-related neural functions.
Mid-to-long-term mindfulness meditators show distinct brain activity and emotional responses to self-criticism and self-praise compared to meditation-naïve individuals. In an fMRI study with 22 meditators and 22 matched controls, meditators had greater activation in the dorsomedial prefrontal cortex during both self-criticism and self-praise, which correlated with higher scores on non-reactivity to inner experience. Meditators also showed reduced functional connectivity between this region and posterior midline and parietal areas, suggesting less self-focus. Behaviorally, meditators reported smaller differences in emotional response between self-criticism and self-praise than controls, indicating more mindful regulation of self-related emotions.