Medicine
September 1, 2018
Fernanda S. Correia-Melo, Gustavo C. Leal, Michelle S. Carvalho et al.
61 citations
A protocol describes a planned randomized, controlled, double-blind noninferiority trial comparing a single infusion of esketamine (0.25 mg/kg) with racemic ketamine (0.5 mg/kg) for treatment-resistant depression. The primary outcome is remission rates at 24 and 72 hours after infusion. Secondary outcomes include cognition, dissociation, and blood biomarkers. The authors state that no study has directly compared these two forms, and a head-to-head test is needed to see if esketamine is comparable in efficacy and safety.
Harvard Review of Psychiatry
March 1, 2022
Igor D. Bandeira, Daniel H Lins-Silva, Vitor Breseghello Cavenaghi et al.
35 citations
Ketamine shows potential for fast onset of action and good tolerability in treating obsessive-compulsive disorder (OCD), but results have been erratic. The systematic review included nine articles: three randomized controlled trials, three case reports, two open-label trials, and one retrospective chart review. Most studies used only single-session racemic ketamine administered intravenously. No evidence demonstrates whether racemic ketamine, S-ketamine, or R-ketamine has the best efficacy, and only sparse evidence suggests combining ketamine with psychotherapy could benefit patients. Future randomized, double-blind, placebo-controlled trials with larger samples, multiple sessions, and appropriate washout periods are needed.
Trends in Psychiatry and Psychotherapy
May 27, 2025
Mariana V F Echegaray, Rodrigo P Mello, Guilherme M. Magnavita et al.
11 citations
Among people with treatment-resistant depression, the intensity of dissociation caused by a single infusion of ketamine or esketamine is linked to greater antidepressant effect one day later, but only when dissociative symptoms are mild to moderate. For every one-point increase on a dissociation scale up to 15 points, depression scores improved by an average of 0.5 points after 24 hours. This relationship was not observed at 72 hours or 7 days after infusion. The study was not originally designed to test this relationship, so confounding factors were not controlled, and the finding should be considered suggestive rather than definitive.
The American journal of psychiatry
June 1, 2026
Jason M Tucciarone, Igor D. Bandeira, Christine Blasey et al.
5 citations
Ketamine rapidly reduces suicidal thoughts in major depressive disorder, but the effect is short-lived. In this trial, adults with major depression and active suicidal ideation received a single ketamine infusion, then were randomly assigned to take either low-dose buprenorphine or a placebo daily for four weeks. Suicidal thoughts dropped significantly more in the buprenorphine group (average decrease of 11.6 points on the Scale for Suicide Ideation) than in the placebo group (average decrease of 6.3 points). Depression scores did not differ between groups. No serious side effects occurred. Buprenorphine appears to sustain and boost ketamine's antisuicidal effects, offering a potentially safe, scalable option for suicide prevention.
iScience
February 21, 2026
Andrew Geoly, John P. Coetzee, Derrick Matthew Buchanan et al.
In a small study of 22 military veterans with traumatic brain injury, a single treatment with magnesium-ibogaine was associated with changes in brain structure one month later. Brain scans showed an average reduction in predicted brain age of 1.3 years, increased thickness in 11 cortical regions, and volume expansion in 8 subcortical regions. While the authors note that the imaging technique can also reflect nonstructural changes, the overall pattern of results is consistent with neuroplastic change.
Bipolar Disorder
January 1, 2025
Breno Souza-Marques, Ana Teresa Caliman-Fontes, Gustavo C. Leal et al.
Some people with bipolar disorder continue to have symptoms despite available treatments, leading researchers to explore repurposing drugs of abuse—such as stimulants, ketamine, and psychedelics—as novel therapies. While clinical trials show promising efficacy for some of these drugs, concerns about their risks have emerged. This chapter examines the potential benefits and, especially, the associated risks, including addiction, worsening of psychiatric symptoms, and adverse physical and cognitive effects. It offers a balanced risk–benefit analysis that weighs these factors against the severity of bipolar disorder, alternative treatments, and the possibility of individualized risk stratification, aiming to inform clinical decisions and guide future research.
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.