Bipolar Disorders
January 13, 2023
Giovanni Martinotti, Bernardo Dell’osso, Giorgio Di Lorenzo et al.
72 citations
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.
Psychiatry Research
July 29, 2023
Mauro Pettorruso, Roberto Guidotti, Giacomo D’andrea et al.
56 citations
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.
Current neuropharmacology
January 1, 2025
Gianluca Rosso, Giacomo d'Andrea, Stefano Barlati et al.
23 citations
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.
Journal of Personalized Medicine
April 1, 2025
Marco Di, M. Pepe, G. D’andrea et al.
18 citations
Most patients with treatment-resistant depression reported positive experiences with esketamine nasal spray. In a survey of 236 outpatients, 88.4% reported enhanced quality of life. Satisfaction levels varied: 10.2% were unsatisfied, 19.1% partially satisfied, 44.4% satisfied, and 26.3% very satisfied. The most satisfied patients noted early improvements in depressed mood, suicidal thoughts, and restlessness, and reported functional gains across all domains. Artificial intelligence analysis of open-ended responses identified themes of personal growth and a desire for tailored treatment settings. Integrating patient-reported experiences may help personalize care and improve adherence.
Psychiatry Research
July 26, 2025
G. D’andrea, C. Cavallotto, M. Pettorruso et al.
16 citations
Anhedonia, the reduced ability to experience pleasure, is a core symptom of both unipolar and bipolar depression that often responds poorly to standard antidepressants. In a real-world observational study of 253 treatment-resistant patients (199 with unipolar depression, 54 with bipolar depression), repeated doses of esketamine nasal spray added to ongoing medication significantly reduced anhedonia over three months. The effect was distinct from overall mood improvement. At three months, 51.92% of bipolar and 38% of unipolar patients showed at least a 50% reduction in anhedonia scores. Dropout rates were low (around 13–14%), and manic switches were rare. The findings suggest esketamine has a targeted, transdiagnostic anti-anhedonic effect.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
July 17, 2026
Allan H Young, Bernhard T Baune, Beatrice Benatti et al.
A panel of 30 European psychiatrists with expertise in treatment-resistant depression (TRD) reached consensus on strategies for using esketamine nasal spray across treatment phases. During the acute phase (4-12 weeks), even modest reductions in core symptoms support continuing esketamine, especially for patients with long disease course or resistance to multiple therapies. Dose and frequency maximization (84 mg weekly) was recommended to improve acute outcomes. In the continuation phase (6-9 months), monitoring should focus on residual symptoms, functional recovery, and comorbidities. Prolonging maintenance treatment (≥12 months) depends on the degree of worsening when tapering, relapse risk, and recurrence history. Across all phases, integrating psychotherapy, optimizing antidepressants, managing comorbidities, and strengthening support networks were recommended.