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

Assessing the relationship between symptomatic and functional changes in treatment-resistant depression (TRD) patients after repeated subcutaneous esketamine injections

Introdução: A resposta sintomatológica proporcionada pelo uso de escetamina em casos refratários de depressão já é conhecida. Contudo, em relação à recuperação funcional, pouco se sabe sobre o assunto. Neste estudo, foi investigada a correlação entre mudanças dos sintomas depressivos e a mudança funcional dos pacientes submetidos a múltiplas infusões de escetamina subcutânea em uma clínica universitária. Métodos: Os dados de setenta pacientes foram analisados. Para avaliar a evolução sintomatológica durante as infusões, usou-se a Montgomery-Asberg Depression Rating Scale (MADRS). Para a avaliação da funcionalidade, a Functioning Assesment Short Test (FAST) foi o instrumento escolhido. As escalas foram avaliadas em tempos determinados e então correlacionadas. Resultados: Correlações de Pearson significativas foram observadas no grupo de pacientes unipolares, mas não na amostra bipolar. Após imputação múltipla, reduções na magnitude das associações foram observadas para a amostra combinada. Mesmo quando a trajetória de MADRS e FAST foram consideradas, nenhuma significância estatística pode ser mostrada. Discussão: Neste estudo, apenas uma correlação discreta entre MADRS e FAST pode ser vista e em um grupo específico, os pacientes unipolares. O estudo da funcionalidade dos pacientes submetidos à administração de escetamina é de extrema importância para que não se limite o conceito de melhora à recuperação sintomática, mas sim, que se amplie e considere a funcionalidade, consequentemente, a recuperação da qualidade de vida. Possivelmente devido as limitações deste estudo como o curto período de coleta de dados, o número reduzido de indivíduos incluídos e a quantidade de dados ausentes, não foi possível demonstrar estatisticamente a relação entre mudança sintomática e funcional. Conclusão: Este é o primeiro estudo analisando a funcionalidade em pacientes submetidos ao tratamento com escetamina subcutânea. A utilização de uma escala mais abrangente para avaliar a funcionalidade é outro fator importante que também a individualiza. Ensaios clínicos randomizados e controlados precisam ser desenvolvidos para melhorar nosso conhecimento sobre o papel da funcionalidade tanto como desfecho como preditora na terapia com escetamina em pacientes com depressão resistente.Não recebi financiament

Impact of Repeated Doses of Subcutaneous Esketamine on Acute Dissociative Symptoms in Treatment-Resistant Depression

Background: Esketamine has been approved by the US Food and Drug Administration (FDA) as an adjunctive treatment for use in conjunction with an oral antidepressant for patients with treatment-resistant depression (TRD), but dissociative symptoms are common adverse effects. Methods: A retrospective analysis of 394 subcutaneous esketamine injections given to 70 patients with TRD that were administered once a week during a six-week trial in conjunction with oral antidepressant therapy. Doses between 0.5 to 1.0 mg/kg were administered according to the patient’s response. Dissociative symptoms were assessed using the Clinician-Administered Dissociative States Scale (CADSS) 30 and 60 min after every weekly treatment (day 1, 8, 15, 22, 29 and 36). Results: Seventy patients received a total of 394 subcutaneous esketamine injections over six weeks. Over time, the evolution of CADSS scores demonstrated a significant mean difference of CADSS at 60 min post-injection (p = 0.010) throughout the six infusions. The mean CADSS scores at 60 min on day 22, 29 and 36 were similar. There were no differences between mean CADSS scores 30 min after the injections, no clinical correlation between response and dissociative symptoms, no correlation between time and demographic and clinical characteristics and no interactions between time and combined medication. Conclusions: Our results suggest that repeated subcutaneous esketamine doses are safe and well-tolerated regarding their acute dissociative and psychotomimetic symptoms. Symptoms usually peak at 30 min and decrease at 60 min post-injection, returning to their pretreatment levels at 120 min. Dissociative symptoms do not correlate with antidepressant response

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