Journal of affective disorders
May 1, 2025
Alessandro Cuomo, Simone Pardossi, Giovanni Barillà et al.
7 citations
In patients with treatment-resistant bipolar disorder, intravenous ketamine (average dose 0.8 mg/kg) significantly reduced depressive symptoms, including inner tension, sleep reduction, and suicidal ideation, over four weeks without triggering manic switches. Fifty-nine patients were treated consecutively, and improvements in Montgomery-Åsberg Depression Rating Scale scores were observed from the second week onward. Adverse events were generally mild to moderate. The findings suggest ketamine can be a well-tolerated option for bipolar depression when carefully monitored, though caution is warranted due to the inherent risk of mood switching in bipolar disorder.
Journal of psychopharmacology (Oxford, England)
June 20, 2025
Mutahira Qureshi, Daniel Silman, Romayne Gadelrab et al.
3 citations
A single dose of immediate-release oral ketamine (40–240 mg) was safe and generally well-tolerated in healthy adults, with no unexpected safety signals or discontinuations due to side effects. Eighty mild or moderate treatment-emergent adverse events occurred after ketamine doses, most commonly dissociation, dizziness, and headache, while only five occurred after placebo. Dissociation events increased with higher doses. Ketamine and its metabolites showed dose-proportional pharmacokinetics. Transient mood and dissociation changes appeared one hour after dosing and resolved within about four hours. These results support further investigation of oral ketamine capsules for treatment-resistant depression.
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.