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

Avaliação da efetividade da escetamina subcutânea para o tratamento da anedonia em pacientes com episódio depressivo resistente ao tratamento

Anhedonia is a symptom associated with poorer outcomes in depression treatment, including resistance to treatment, greater functional impact and suicidality. Few treatments have proven efficacious to treat anhedonia in both unipolar and bipolar depression. The NMDA antagonist ketamine has been demonstrated to be effective in rapidly ameliorating anhedonia in acute depressive episodes. The main aim of present study is to evaluate the anti-anhedonic effect of esketamine, the S-enantiomer of ketamine recently approved for treatment-resistant depression, in acute depressive episodes in both unipolar and bipolar resistant-depression. Methods: In an open, real-world study, 70 acutely depressed subjects with unipolar or bipolar depression were treated with 6 weekly subcutaneous esketamine infusions (0.5-1mg/kg). Severity of anhedonia was assessed through MADRS item 8 before and 24h after each infusion. Results: A significant reduction in anhedonia severity was observed (p<0.0001) after 6 infusions. The effect was statistically significant since the first posttreatment evaluation, 24h after the first infusion (p<0.001), in both unipolar and bipolar groups and remained clinically and statistically significant throughout the entire series of subcutaneous infusions. Anti-anhedonic effect of esketamine did not differ between groups. Limitations: This is an open-label, real-world study. Lack of blinding and of a control group limits the interpretation and generalization of findings. Conclusion: Although preliminary, present findings suggest that repeated subcutaneous esketamine infusions are effective for the treatment of anhedonia in both unipolar and bipolar depressed patients. Present results should be confirmed large randomized, controlled trials.A anedonia é um sintoma associado a piores desfechos no tratamento da depressão, incluindo maior resistência ao tratamento, maior impacto funcional e taxas maiores de suicidalidade. Poucas intervenções se têm mostrado eficazes para o tratamento da anedonia, tanto na depressão unipolar quanto na depressão bipolar. A cetamina, um antagonista NMDA, teve sua eficácia demonstrada na melhora rápida da anedonia em episódios depressivos agudos. O principal objetivo do presente estudo é avaliar o efeito antianedônico da escetamina, o enantiômero S da cetamina – recentemente aprovada para depressão resistente ao tratamento – em episódios depressivos agudos em indivíduos com depressão maior ou depressão bipolar resistentes ao tratamento. Métodos: Em um estudo de mundo real, aberto 70 pacientes com episódio depressivo agudo (unipolar ou bipolar) foram tratados com 6 infusões semanais de escetamina subcutânea (0,5-1mg/kg). A anedonia foi medida por meio do item 8 da escala MADRS antes e 24h após cada infusão. Resultados: Foi observada redução significativa da gravidade da anedonia (p <0,0001) após 6 infusões de escetamina. O efeito já se mostrou estatisticamente significativo 24h após a primeira infusão (p <0,001) em ambos os grupos unipolar e bipolar e se manteve clinicamente e estatisticamente significativo ao longo de toda a série de infusões subcutâneas. O efeito antianedônico da escetamina não diferiu entre os grupos. A escetamina apresentou um bom perfil de tolerabilidade e segurança, com efeitos adversos transitórios de intensidade baixa a moderada. Não foi registrado evento adverso sério durante o estudo. Limitações: Este é um estudo aberto, de mundo real. A falta de cegamento e de grupo controle limita a interpretação e generalização dos resultados. Conclusão: Embora preliminares, os presentes achados sugerem que infusões repetidas de escetamina subcutânea são efetivas para o tratamento da anedonia em pacientes com depressão unipolar e bipolar. Esses resultados precisam ser confirmados por meio de replicação em ensaios clínicos duplocegos, randomizados e controlados.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