A Clinical Rationale for Assessing the Impact of Childhood Sexual Abuse on Adjunctive Subcutaneous Esketamine for Treatment-Resistant Depression

Background: A history of child sexual abuse (CSA) is related to higher suicide rates and poor treatment outcomes in depressed adult patients. Twenty years after the first study investigating the effects of ketamine/esketamine on depression and suicide, there is a lack of data on the CSA effects on this emerging treatment. Here, we assess the impact of CSA on adjunctive subcutaneous (SC) esketamine for treatment-resistant depression (TRD). Methods: A directed acyclic graphic (DAG) was designed to identify clinical confounders between CSA and esketamine predictors of response. The confounders were applied in a statistical model to predict depression symptom trajectory in a sample of 67 TRD outpatients. Results: The patient sample had a relatively high prevalence rate of CSA (35.82%). Positive family history of first-degree relatives with alcohol use disorder and sex were clinical mediators of the effects of esketamine in a CSA adult population. Overall, the presence of at least one CSA event was unrelated to esketamine symptom reduction. Conclusions: Unlike responses to conventional antidepressants and psychotherapy, CSA does not appear to predict poor response to esketamine.publishedVersio

Comparação da eficácia de doses repetidas de escetamina subcutânea no tratamento da suicidalidade na depressão unipolar e bipolar

Background: Major depressive and bipolar disorders account for most cases of suicide. The pharmacological arsenal to treat suicidality is limited and available agents take too long to take effect. There is a growing body of evidence showing the optimal results of ketamine for treating depression, but the evidence concerning suicidality has not been fully described. Herein, we report the first real-world study with severely depressed patients presenting with suicide ideation that were treated with repeated infusions of subcutaneous esketamine. Methods: Data from 70 acutely depressed subjects diagnosed with unipolar or bipolar major depressive episode who had failed to respond to ≥ 2 treatments were analyzed. Subjects were administered subcutaneous esketamine once a week for 6 weeks. The primary efficacy endpoint, change from baseline to 24h post-infusion 6 in item 10 MADRS score, was analyzed using a mixed-effects repeated measures model. Results: We found significant effects for time on item 10 MADRS scores (F=5.657; p<0.0001) but not for time x diagnosis interaction (F=1.48; p=0.164) from baseline to end of study. Efficacy of esketamine did not differ between groups (MDD vs bipolar depression) at any time point. Statistical significance in both groups was observed since 24h after the first infusion (t=5.811; p<0.001), and further reduction on suicidality scores were observed with repeated infusions. Conclusions: Repeated SC esketamine infusions had significant antisuicidality effects in both unipolar and bipolar groups, with a rapid onset of action. Limitations: Large randomized controlled trials are warranted to confirm these preliminary findings.Introdução: Os transtornos de humor respondem pela maior parte dos casos de suicídio. O arsenal farmacológico para tratar suicidalidade é limitado e os agentes disponíveis para tratamento da depressão resistente ao tratamento tem um longo início de ação. Existe um corpo de evidências crescente mostrando bons resultados da escetamina no tratamento da depressão, mas faltam estudos avaliando adequadamente sua ação na suicidalidade. Nós apresentamos os resultados do primeiro estudo de mundo real realizado com pacientes gravemente deprimidos com ideação suicida tratados com infusões repetidas de escetamina subcutânea. Métodos: Dados de 70 pacientes gravemente deprimidos diagnosticados com depressão unipolar ou bipolar que não responderam a pelo menos 2 tratamentos prévios foram analisados. Os participantes receberam aplicações subcutâneas de escetamina 1 vez por semana durante 6 semanas. O desfecho primário, mudança de pontuação da baseline para 24 horas após a sexta infusão no item 10 da MADRS, foi analisado utilizando o modelo misto (análise de medidas repetidas). Resultados: Foram encontrados efeitos significantes para o tempo na pontuação do item 10 da MADRS (F=5.657; p<0.0001) mas não para a interação tempo x diagnóstico (F=1.48; P=0.164) do baseline ao fim do estudo. A eficácia da escetamina não diferiu entre os grupos (TDM [transtorno depressivo maior] vs depressão bipolar) em nenhum ponto de avaliação. Foi observada significância estatística em ambos os grupos desde 24h após a primeira infusão (t=5.811; P<0.001), e maiores reduções da suicidalidade foram observadas com infusões repetidas. Conclusões: Infusões repetidas de escetamina subcutânea tiveram significante efeito anti-suicidalidade nos 2 grupos, com rápido início de ação. Limitações: Ensaios clínicos controlados com amostras maiores são necessários para confirmar estes resultados preliminares.Dados abertos - Sucupira - Teses e dissertações (2021

A Clinical Rationale for Assessing the Impact of Childhood Sexual Abuse on Adjunctive Subcutaneous Esketamine for Treatment-Resistant Depression

Background: A history of child sexual abuse (CSA) is related to higher suicide rates and poor treatment outcomes in depressed adult patients. Twenty years after the first study investigating the effects of ketamine/esketamine on depression and suicide, there is a lack of data on the CSA effects on this emerging treatment. Here, we assess the impact of CSA on adjunctive subcutaneous (SC) esketamine for treatment-resistant depression (TRD). Methods: A directed acyclic graphic (DAG) was designed to identify clinical confounders between CSA and esketamine predictors of response. The confounders were applied in a statistical model to predict depression symptom trajectory in a sample of 67 TRD outpatients. Results: The patient sample had a relatively high prevalence rate of CSA (35.82%). Positive family history of first-degree relatives with alcohol use disorder and sex were clinical mediators of the effects of esketamine in a CSA adult population. Overall, the presence of at least one CSA event was unrelated to esketamine symptom reduction. Conclusions: Unlike responses to conventional antidepressants and psychotherapy, CSA does not appear to predict poor response to esketamine