The international journal of neuropsychopharmacology
June 6, 2025
Naim Zaki, Li Nancy Chen, Rosanne Lane et al.
32 citations
In a long-term extension study (SUSTAIN-3) involving 1,148 adults with treatment-resistant depression, esketamine nasal spray combined with an oral antidepressant was evaluated for safety and efficacy over up to 79 months (median 45.8 months). Common adverse events included headache (36.9%), dizziness (33.9%), and nausea (33.6%). Nine participants died, with causes including COVID-19 and suicide. Depressive symptoms, measured by the MADRS, improved during the initial induction phase (average reduction of 12.8 points) and this improvement was maintained during the optimization/maintenance phase. At the end of maintenance, 49.6% of participants were in remission. No new safety concerns emerged, and depression improvement generally persisted for those continuing treatment.
European archives of psychiatry and clinical neuroscience
December 16, 2024
Gustavo C Leal, Isabel Lima-Araújo, David G Roiter et al.
7 citations
Arketamine, an enantiomer of ketamine, has been less studied than esketamine or racemic ketamine, but recent preclinical work suggests it may have prolonged antidepressant effects and a better safety profile. This scoping review of 20 studies involving 410 subjects found arketamine was primarily investigated for pain management and depression. Early evidence indicates it may reduce pain, though most studies were small and in non-clinical settings. In psychiatry, trials show potential antidepressant effects, but results are inconsistent and some studies unpublished. A consistent finding is arketamine's favorable safety profile, with fewer dissociative and psychotomimetic effects than esketamine or racemic ketamine. Larger, well-designed studies are needed to determine its therapeutic potential.
Schizophrenia research
September 1, 2024
Ana Teresa Caliman-Fontes, Flávia Vieira, Gustavo C Leal et al.
7 citations
Catatonia, a condition recognized since the 1800s, remains difficult to diagnose and treat. A systematic review of 20 studies involving 25 patients who received ketamine or esketamine for catatonia found that 80% of patients responded to treatment and 44% achieved remission, with no worsening of catatonic or psychotic symptoms. Only one patient stopped treatment due to intolerable dissociative effects. Most patients were female (61.9%), with an average age of 44.4 years, and had underlying mood disorders. The evidence suggests ketamine may be effective for catatonia, even in patients with psychotic disorders, where it has traditionally been considered contraindicated. The authors advocate reevaluating this contraindication, noting potentially greater benefits for those with mood disorders.
Journal of affective disorders
August 1, 2026
João Paulo Atidio, Rodrigo Simonini Delfino, Igor Saque Garios et al.
In patients with treatment-resistant depression receiving subcutaneous esketamine over six weeks, depressive symptoms improved significantly, with MADRS scores dropping by an average of 2.82 points per week. Those also taking benzodiazepines had higher depression scores throughout treatment, while lamotrigine and lithium showed no significant effect on outcomes. No medication altered the rate of improvement over time. The findings suggest benzodiazepine use may blunt the antidepressant response to esketamine, but further prospective research is needed.
Journal of psychiatric research
August 1, 2023
Igor D Bandeira, Gustavo C Leal, Fernanda S Correia-Melo et al.
In a pilot trial of six people with bipolar I or II disorder who had been depressed for at least four weeks, two intravenous infusions of arketamine (0.5 mg/kg followed one week later by 1 mg/kg) rapidly reduced depression severity. Depression scores on the Montgomery-Åsberg Depression Rating Scale fell from a baseline mean of 36.66 to 27.83 one day after the first infusion and from 32.0 to 17.66 one day after the second infusion. The drug was well tolerated with almost no dissociation and no manic symptoms. The findings suggest arketamine has rapid-acting antidepressant properties for bipolar depression, consistent with earlier animal research on major depression.
Journal of affective disorders
June 1, 2023
Gustavo C Leal, Breno Souza-Marques, Rodrigo P Mello et al.
In a small pilot trial, the antidepressant arketamine was compared with placebo for treatment-resistant depression. Ten participants received both arketamine (0.5 mg/kg) and saline one week apart in a randomized, double-blind, crossover design. Depression improved over time, but there was no significant difference between arketamine and placebo. Dissociation and other adverse events were minimal. The study was underpowered, and the authors conclude that arketamine was not superior to placebo but was extremely safe, recommending larger trials with different dosing strategies.