Journal of Child and Adolescent Psychopharmacology
October 9, 2026
Inês Vasconcelos Sousa Magalhães, Daniel N. Lopes, Isabel de Andrade Amato et al.
OBJECTIVE: To describe the feasibility, acute tolerability, and short-term symptom trajectories of adjunctive subcutaneous esketamine in adolescents with severe depressive episodes treated in specialized outpatient care. METHODS: This observational case series included five adolescents aged 15-17 years with severe depressive symptoms, suicidal ideation and/or behavior, and insufficient response...
Journal of Affective Disorders
August 1, 2026
João Paulo Atidio, Rodrigo Simonini Delfino, Igor Saque Garios et al.
Ketamine and esketamine have been increasingly used as adjunctive treatments for treatment-resistant depression (TRD), yet evidence on pharmacological interactions with commonly prescribed psychotropic medications remains limited. This study evaluated the association between concomitant lamotrigine, lithium, and benzodiazepine use and antidepressant outcomes during subcutaneous esketamine...
The International Journal of Neuropsychopharmacology
June 6, 2025
Naim Zaki, Li Nancy Chen, Rosanne Lane et al.
32 citations
The rates of relapse and suicide risk are higher in treatment-resistant depression (TRD) vs non-treatment-resistant major depressive disorder. Even among patients with TRD who initially respond, the majority (70%) relapse within 6 months. To evaluate the long-term safety and efficacy of esketamine nasal spray, combined with an oral antidepressant, in patients with TRD. Phase 3, open-label,...
Trends in Psychiatry and Psychotherapy
May 27, 2025
Mariana V F Echegaray, Rodrigo P Mello, Guilherme M. Magnavita et al.
11 citations
Abstract Objective Ketamine and esketamine have both shown significant antidepressant effects in treatment-resistant depression (TRD) and conflicting evidence suggests that dissociation induced by these drugs could be a clinical predictor of esketamine/ketamine's efficacy. Methods This study is a secondary analysis of data from a two-center, randomized, controlled trial. Participants were...
International Review of Psychiatry
2025
Iury P A Magalhães, Daniel N. Lopes, Isabel Amato et al.
Major depressive disorder (MDD) significantly impairs adolescents' development, with increasing rates of treatment resistance and suicide risk. Ketamine has emerged as a promising, rapid-acting antidepressant in adults, but its efficacy and safety in adolescents remain unclear. This systematic review and meta-analysis aimed to evaluate short-term outcomes of ketamine administration in youth...
European Archives of Psychiatry and Clinical Neuroscience
December 16, 2024
Gustavo C. Leal, Isabel Lima-Araújo, David G Roiter et al.
7 citations
Arketamine (R-ketamine), an enantiomer of ketamine, has historically been less studied than esketamine (S-ketamine) and the racemic mixture. Recent preclinical studies suggest that arketamine may offer prolonged antidepressant effects and a superior safety profile. This scoping review aims to assess and synthesise existing literature on the clinical use of arketamine in humans. This review...
Schizophrenia Research
September 1, 2024
Ana Teresa Caliman-Fontes, Flávia Vieira, Gustavo C. Leal et al.
7 citations
Catatonia, documented since the 19th century, remains a significant challenge in terms of recognition and treatment. Over the last two decades, ketamine has brought new perspectives to psychiatry, sparking widespread interest. Concurrently, catatonia has attracted heightened scientific attention. Preliminary evidence suggests the therapeutic potential of ketamine for catatonia. We...
Journal of Psychiatric Research
August 1, 2023
Igor D. Bandeira, Gustavo C. Leal, Fernanda S. Correia-Melo et al.
There are significantly fewer options for the treatment of bipolar depression than major depressive disorder, with an urgent need for alternative therapies. In this pilot study, we treated six subjects with bipolar disorder types I and II (according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria) who had been in a current depressive episode for at...
Journal of Affective Disorders
June 1, 2023
Gustavo C. Leal, Breno Souza-Marques, Rodrigo P Mello et al.
Racemic ketamine is a mixture of (R)-ketamine (arketamine) and (S)-ketamine (esketamine), with the latter regarded as the main isomer for antidepressant effects. However, preclinical data and one open-label human trial suggest arketamine might exert a more potent and longer-lasting antidepressant effect with fewer side effects. We aimed to explore the feasibility of a randomized controlled...
Trends in Psychiatry and Psychotherapy
March 7, 2023
Ana Teresa Caliman-Fontes, Gustavo C. Leal, Fernanda S. Correia-Melo et al.
Objectives: Evidence suggests that ketamine's influence on brain-derived neurotrophic factor (BDNF) might be involved in its mechanism of rapid antidepressant action. We aimed to evaluate the differential impact of ketamine and esketamine on serum BDNF levels and its association with response patterns in treatment-resistant depression (TRD). Methods: Participants (n = 53) are from a randomized,...
Human Psychopharmacology: Clinical and Experimental
February 18, 2022
A. P. Jesus-Nunes, Gustavo C. Leal, Fernanda S. Correia-Melo et al.
39 citations
Major depressive disorder (MDD) is a leading cause of disability worldwide and most people do not achieve symptom remission. Treatment‐resistant depression (TRD) is characterized by the failure of at least one adequate trial of a major class of antidepressant, with adequate time and dosage. We aimed to identify clinical predictors of depressive symptom remission and response 24 h and 7 days...
Frontiers in Psychiatry
May 28, 2021
V. B. Cavenaghi, Leandro Paulino da Costa, Acioly L T Lacerda et al.
41 citations
Background: Ketamine has been shown to produce a rapid and robust antidepressant effect. Though numerous routes of administration have been studied, subcutaneous (SC) has proven to be a convenient and cost-effective route making its use particularly relevant in developing countries. Here we provide a systematic review covering the use of SC racemic ketamine and esketamine in depression,...
Journal of Psychiatric Research
May 8, 2021
Rodrigo P Mello, Mariana V F Echegaray, A. P. Jesus-Nunes et al.
22 citations
Dissociative symptoms are common, possibly severe, side effects associated with the use of ketamine and esketamine in depression. We investigated the relationship between trait dissociation and dissociation induced by ketamine and esketamine used as augmentation therapy in treatment-resistant depression (TRD). Adults with TRD were randomly assigned to receive a single intravenous infusion, with...
European Archives of Psychiatry and Clinical Neuroscience
February 20, 2020
Gustavo C. Leal, Igor D. Bandeira, Fernanda S. Correia-Melo et al.
257 citations
We aimed to analyze the efficacy and safety of arketamine, the R (−)-enantiomer of ketamine, for treatment-resistant depression (TRD) in humans. Open-label pilot trial, seven subjects with TRD received a single intravenous infusion of arketamine (0.5 mg/kg); primary outcome was change in Montgomery–Åsberg Depression Rating Scale (MADRS) 24 h after. Mean MADRS dropped from 30.7 before infusion...
Journal of Affective Disorders
November 14, 2019
Fernanda S. Correia-Melo, Gustavo C. Leal, Flávia Vieira et al.
188 citations
BACKGROUND Ketamine and its enantiomers have recently been highlighted as one of the most effective therapeutic options in refractory depression. However, racemic ketamine and esketamine have not been directly compared. The aim of this study is to assess the efficacy and safety of esketamine compared to ketamine in patients with treatment-resistant depression (TRD). METHODS This is a...
Medicine
September 1, 2018
Fernanda S. Correia-Melo, Gustavo C. Leal, Michelle S. Carvalho et al.
61 citations
INTRODUCTION: The use of ketamine as an option in the treatment of depressive disorder is growing rapidly, supported by numerous clinical trials attesting its efficacy and safety. Esketamine, the S (+) enantiomer of ketamine, is the most widely used form in the anesthetic environment in some countries, and new studies have shown that it may also be effective in depression and with better...
December 1, 2017
Tatiana M N Rezende, J. P. Maia-De-Oliveira, Ludmyla Kandratavicius et al.
Background: Recent evidence has shown improvements in schizophrenia symptoms after the infusion of sodium nitroprusside (SNP), a nitric oxide (NO) donor. In the rat model of schizophrenia using ketamine injection, pretreatment with SNP seems to prevent behavioral changes associated with positive symptoms for up to one week. Objective: We investigated whether SNP would have preventative effects...
Neuropsychiatric Disease and Treatment
June 1, 2017
Fernanda S. Correia-Melo, Felipe Coelho Argôlo, Lucas Araújo-de-freitas et al.
44 citations
BACKGROUND: This study evaluated efficacy and safety of intravenous subanesthetic doses of esketamine using an administration time of 10 minutes in patients with treatment-resistant depression and bipolar depression. METHODS: , Fourth Edition, Text Revision criteria, and these patients received rapid infusion of esketamine between June 2012 and December 2015. The Montgomery-Åsberg Depression...
The British Journal of Psychiatry
May 31, 2011
Maria Alice Fontes, Karen I Bolla, Paulo Jannuzzi Cunha et al.
300 citations
BACKGROUND: Many studies have suggested that adolescence is a period of particular vulnerability to neurocognitive effects associated with substance misuse. However, few large studies have measured differences in cognitive performance between chronic cannabis users who started in early adolescence (before age 15) with those who started later. AIMS: To examine the executive functioning of...
Brazilian Journal of Psychiatry
March 1, 2008
Priscila Previato Almeida, Maria Alice Fontes Pinto Novaes, Rodrigo A. Bressan et al.
24 citations
OBJECTIVE: Cannabis is the most used illicit drug worldwide, however only a few studies have examined cognitive deficits related to its use. Clinical manifestations associated with those deficits include a motivational syndrome, impairment in cognitive flexibility, inattention, deficits in abstract reasoning and concept formation, aspects intimately related to the executive functions, which...