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.