Esketamine nasal spray reduced depressive symptoms in people with treatment-resistant bipolar depression as effectively as in those with unipolar treatment-resistant depression, with no significant differences in response or remission rates after one and three months. The treatment also showed greater anxiety-reducing effects in the bipolar group. No treatment-emergent affective switch occurred, supporting the safety and tolerability of esketamine for bipolar treatment-resistant depression.
Machine learning models predicted which patients with treatment-resistant depression would respond to esketamine nasal spray. In a retrospective study of 149 patients, three random forest classifiers achieved 68.53% accuracy for response at one month and 66.26% at three months, and 68.60% accuracy for remission at three months. Features such as severe anhedonia, anxious distress, mixed symptoms, and bipolarity positively predicted response and remission, while benzodiazepine use and depression severity were linked to delayed responses. The findings suggest machine learning may aid personalized treatment decisions for treatment-resistant depression.
Among patients with treatment-resistant depression who continued esketamine nasal spray for at least six months, 76.2% responded or achieved remission. Of those who had not responded by six months, a subset improved by twelve months. Side effects occurred in 71.8% of patients at six months, decreasing to 42% at twelve months; the most common were sedation and dissociation. Only two patients stopped treatment due to tolerability issues. The findings suggest esketamine is effective and safe for mid- to long-term treatment, with a novel observation of late clinical response in some patients. Results require confirmation in larger samples and longer observation periods.
Treatment-resistant depression (TRD) affects about 20-30% of people with major depressive disorder. Esketamine nasal spray was approved for TRD in 2019, but its mechanisms of action remain unclear. This protocol describes the ReDREAM project, an observational, prospective study that will use metabolomics to identify metabolic biosignatures associated with response to esketamine. Sixty people with TRD from three Italian clinical sites will receive esketamine nasal spray twice weekly for four weeks (induction phase), then once weekly for four more weeks (maintenance phase). The study will test correlations between baseline metabolic profile and depressive symptom improvement at weeks 4 and 8, and explore metabolic differences between responders and non-responders. Hypothesized involvement includes energy metabolism, amino acid metabolism, urea cycle, and nitric oxide synthesis.