Therapeutic advances in psychopharmacology
January 1, 2026
Alessandro Cuomo, Roger Mcintyre, Despoina Koukouna et al.
1 citation
Among 45 patients with treatment-resistant depression treated with intranasal esketamine alongside oral antidepressants in a routine clinic, depression severity scores dropped from an average of 40.0 to 22.9 at four weeks and to 9.70 at 52 weeks, with scores remaining near 9-10 at later follow-ups. Eight patients stopped treatment, mostly due to lack of efficacy or side effects. No manic symptoms emerged, and side-effect ratings were low. The findings suggest sustained symptom improvement and a favorable long-term safety profile for those who continued treatment, though the observational design, concurrent treatments, and survivor bias limit the conclusions.
Psychiatry research
August 1, 2026
Pietro Carmellini, Andrea Fagiolini, Mario Pinzi et al.
In a real-world clinic, intravenous ketamine reduced depressive symptoms in patients with treatment-resistant unipolar and bipolar depression. Both groups improved significantly, but those with bipolar depression showed faster and greater improvement starting at two weeks and lasting through three months. Dissociative side effects were mild and did not increase over time; women with unipolar depression reported higher dissociative symptoms at three months. No sex differences in antidepressant efficacy were found. The findings suggest ketamine is effective for treatment-resistant depression, with stronger benefits for bipolar depression.
Pharmaceuticals (Basel, Switzerland)
April 24, 2026
Pietro Carmellini, Alessandro Cuomo, Maria Beatrice Rescalli et al.
Depression likely arises from a mix of two interacting biological problems: imbalances in monoamine neurotransmitters (like serotonin) and disruptions in glutamate signaling that impair the brain's ability to adapt and form new connections. These two systems can combine in different ways across individuals, helping explain why some people respond to standard antidepressants while others do not. Rapid-acting treatments such as ketamine work by directly targeting the glutamate system to boost synaptic plasticity, offering faster relief, especially for treatment-resistant depression. A framework called the 'monoamine-glutamate continuum' may guide future precision psychiatry by matching treatments to each person's specific neurobiological profile.
Expert opinion on pharmacotherapy
February 1, 2026
Alessandro Cuomo, Mario Pinzi, Andrea Fagiolini
Major depressive disorder remains a leading cause of disability globally. Many patients do not respond adequately to traditional antidepressants. This review examines phase 3 clinical trial evidence for newer agents, including brexanolone, intranasal esketamine, dextromethorphan-bupropion, vortioxetine, and glucagon-like peptide-1 receptor agonists. These treatments offer rapid symptom relief and potential cognitive or metabolic benefits for conditions like postpartum depression, acute suicidal ideation, and treatment-resistant depression. However, limited integration into clinical guidelines, insufficient long-term data, and implementation barriers restrict their use. The authors call for clearer treatment sequencing strategies and harmonized recommendations to support more individualized depression management.