Repeated subcutaneous esketamine for treatment-resistant depression: Impact of the degree of treatment resistance and anxiety comorbidity.

BACKGROUND: A large number of studies indicate that subanesthetic doses of ketamine induce a fast antidepressant effect. Limited studies have investigated the subcutaneous (SC) route, and it remains unclear for whom this treatment is most suitable. AIMS: The aim of this study was to examine the effect on depressive symptoms of repeated subanesthetic doses of SC esketamine in unipolar and bipolar treatment-resistant depression (TRD) and clinical predictors of response. METHODS: A retrospective analysis of 70 patients who received six SC esketamine doses weekly as an adjunctive treatment was carried out. Doses started at 0.5 mg/kg and it could be titrated up to 1 mg/kg, according to response. The primary outcome was reduction in depressive symptoms. Statistical analysis to investigate clinical predictors of effectiveness included logistic regression analysis using a dependent variable of a 50% reduction in rating scale scores at the end of treatment. Comparisons between groups were made through analysis of variance and treatment effects. RESULTS: At baseline, our sample presented with severe treatment resistance in 65.7%, as assessed by the Maudsley Staging Method (MSM), and 47.1% had anxiety disorder comorbidity. The response rate was 50%. A better outcome was predicted by mild and moderate MSM scores (OR = 3.162, p = 0.041) and anxiety disorder comorbidity (OR = 3.149, p = 0.028). CONCLUSIONS: Our results suggest that higher levels of treatment resistance may be associated with a poor response to SC esketamine. Unlike traditional pharmacotherapies, it might benefit those with poor prognosis such as patients with depression and comorbid anxiety. Therefore, future research could investigate whether esketamine should receive a more prominent place in the treatment algorithm for TRD.

Efficacy and safety of adjunctive therapy using esketamine or racemic ketamine for adult treatment-resistant depression: A randomized, double-blind, non-inferiority study.

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 randomized, double-blind, active-controlled, bicentre, non-inferiority clinical trial, with two parallel groups. Participants were randomly assigned to a 40-min single intravenous infusion of ketamine 0.5 mg/kg or esketamine 0.25 mg/kg. The primary outcome was the difference in remission rates for depression 24 h following intervention using the Montgomery-Åsberg Depression Rating Scale (MADRS), with a non-inferiority margin of 20%. RESULTS: 63 subjects were included and randomly assigned (29 to receive ketamine and 34 to receive esketamine). At 24 h, 24.1% of participants in the ketamine group and 29.4% of participants in the esketamine group showed remission, with a difference of 5.3% (95% CILB -13.6%), confirming non-inferiority. MADRS scores improved from 33 (SD 9.3) to 16.2 (SD 10.7) in the ketamine group and from 33 (SD 5.3) to 17.5 (SD 12.2) in the esketamine one, with a difference of -5.27% (95% CILB, -13.6). Both groups presented similar mild side effects. CONCLUSIONS: Esketamine was non-inferior to ketamine for TRD 24 h following infusion. Both treatments were effective, safe, and well tolerated. TRIAL REGISTRATION: Registered in Japan Primary Registries Network: UMIN000032355.

Comparative study of esketamine and racemic ketamine in treatment-resistant depression: Protocol for a non-inferiority clinical trial.

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 tolerability. However, no study so far has directly compared esketamine with racemic ketamine. Here we propose a protocol of a clinical trial to evaluate esketamine as a noninferior medication when compared to ketamine in the treatment of patients with treatment-resistant depression. METHODS/DESIGN: This study protocol is for a randomized, controlled, double-blind noninferiority clinical trial. Subjects will be 18 years or older, with major depression characterized as treatment-resistant. Participants will receive a single infusion of either esketamine (0.25 mg/kg) or ketamine (0.5 mg/kg) over 40 minutes. The primary outcome will be the difference in remission rates between the 2 treatment arms at 24 and 72 hours after drug infusion. Secondary outcomes will include other timepoints, measurements of cognition, dissociation, and blood biomarkers. DISCUSSION: A head-to-head study is the best way to evaluate whether the esketamine is in fact comparable to the racemic ketamine in terms of both efficacy and safety, and, if positive, it would be an initial step to increase the access to that type of treatment worldwide. ETHICS AND DISSEMINATION: The study was approved by the local Institutional Review Board (University Hospital Professor Edgard Santos-Federal University of Bahia-Number: 46657415.0.0000.0049). Subjects will only participate after voluntarily agreeing and signing the Informed Consent Form. The study findings will be published in peer-reviewed journals and presented at national and international conferences. TRIAL REGISTRATION: This trial has been registered in the Japan Primary Registries Network (JPRN): UMIN000032355, which is affiliated with the World Health Organization.

Melancholia in Latin American studies: a distinct mood disorder for the ICD-11.

OBJECTIVE: Melancholic depression is a lifetime diagnosis, typically with recurrent episodes. Melancholia, a syndrome with a long history and distinctive psychopathological features, is differentiated from major depression by the DSM-IV specifiers and partly described in the International Classification of Diseases - 10th edition. Within the present classification, it is frequently seen in severely ill patients with major depression and bipolar disorder. Nevertheless, it has a distinctive psychopathology and biological homogeneity in clinical experience and laboratory test markers, and it is differentially responsive to specific treatment interventions according to international studies. The objective of this study is to review the literature published by Latin American authors about Melancholia. METHOD: We conducted a systematic search to identify scientific literature published by Latin American authors gathering information relevant to the revision of the classification of mental and behavioral disorders in patients with melancholic depression of the International Classification of Diseases - 10th edition. The review was specifically focused on literature from Brazil and Latin America in order to examine the specific Latin American contribution for the study of melancholia as a distinct entity. RESULTS AND CONCLUSION: Melancholia can be identified as a separate mood disorder with unique psychopathology and psychoneuroendocrinology, worthy of separate attention in the classification systems. We therefore suggest that melancholia be positioned as a distinct, identifiable mood disorder that requires specific treatment.

Estudos latino-americanos sobre melancolia: um transtorno do humor melhor definido para o CID-11 / Melancholia in Latin American studies: a distinct mood disorder for the ICD-11

OBJETIVO: A depressão melancólica é um diagnóstico psiquiátrico de história de vida, geralmente com episódios recorrentes. Melancolia é uma síndrome com longa duração e características específicas de psicopatologia, insuficientemente diferenciada de depressão maior por um especificador no DSM-IV e parcialmente descrito nos critérios da Classificação Internacional de Doenças-10ª Edição. Dentro da classificação atual, é frequentemente vista em pacientes gravemente doentes com depressão e transtorno bipolar. No entanto, a melancolia possui uma homogeneidade psicopatológica e biológica distinta na experiência clínica e nos marcadores de testes laboratoriais, e é diferencialmente sensível às intervenções terapêuticas específicas. O objetivo deste estudo é revisar a literatura de artigos publicados por autores latino-americanos sobre a melancolia. MÉTODO: Realizou-se busca de artigos latino-americanos de informações relevantes para a revisão da Classificação Internacional de Doenças-10ª Edição de transtornos mentais e comportamentais em pacientes com depressão melancólica. Foi avaliada a qualidade do design de todos os estudos e realizada uma revisão abrangente sobre o assunto, com o objetivo de considerar a contribuição latino-americana para inclusão da melancolia como uma entidade distinta na futura Classificação Internacional de Doenças-11ª Edição. RESULTADOS E CONCLUSÃO: Os estudos latino-americanos fundamentam o diagnóstico da melancolia com uma psicopatologia e psiconeuroendocrinologia própria que fundamentam ser reconhecida como um transtorno de humor identificável e merecedor de uma atenção específica nos sistemas de classificação, como um transtorno de humor distinto, identificável e especificamente tratável.

OBJECTIVE: Melancholic depression is a lifetime diagnosis, typically with recurrent episodes. Melancholia, a syndrome with a long history and distinctive psychopathological features, is differentiated from major depression by the DSM-IV specifiers and partly described in the International Classification of Diseases - 10th edition. Within the present classification, it is frequently seen in severely ill patients with major depression and bipolar disorder. Nevertheless, it has a distinctive psychopathology and biological homogeneity in clinical experience and laboratory test markers, and it is differentially responsive to specific treatment interventions according to international studies. The objective of this study is to review the literature published by Latin American authors about Melancholia. METHOD: We conducted a systematic search to identify scientific literature published by Latin American authors gathering information relevant to the revision of the classification of mental and behavioral disorders in patients with melancholic depression of the International Classification of Diseases - 10th edition. The review was specifically focused on literature from Brazil and Latin America in order to examine the specific Latin American contribution for the study of melancholia as a distinct entity. RESULTS AND CONCLUSION: Melancholia can be identified as a separate mood disorder with unique psychopathology and psychoneuroendocrinology, worthy of separate attention in the classification systems. We therefore suggest that melancholia be positioned as a distinct, identifiable mood disorder that requires specific treatment.