Brain-derived neurotrophic factor serum levels following ketamine and esketamine intervention for treatment-resistant depression: secondary analysis from a randomized trial

Abstract 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, double-blind clinical trial comparing the efficacy of single-dose ketamine (0.5mg/kg, n = 27) and esketamine (0.25mg/kg, n = 26) in TRD. Depression severity was assessed before and 24 hours, 72 hours, and 7 days after the intervention, using the Montgomery-Åsberg Depression Rating Scale (MADRS). Blood samples were collected before infusion, 24 hours, and 7 days afterwards. Results There were no significant changes in BDNF levels at post-infusion evaluation points, and no difference in BDNF levels comparing ketamine and esketamine. Both drugs exhibited similar therapeutic effect. There was no association between BDNF levels and response to treatment or severity of depressive symptoms. Conclusion There was no significant treatment impact on BDNF serum levels - neither with ketamine nor esketamine - despite therapeutic response. These results suggest that ketamine or esketamine intervention for TRD has no impact on BDNF levels measured at 24 hours and 7 days after the infusion. This clinical trial is registered on the Japan Primary Registries Network: UMIN000032355.

Transtornos de humor e de ansiedade comórbidos em vítimas de violência com transtorno do estresse pós-traumático / Comorbid mood and anxiety disorders in victims of violence with posttraumatic stress disorder

OBJETIVO: Buscar estudos que avaliem a comorbidade entre transtorno de estresse pós-traumático e transtornos do humor, bem como entre transtorno de estresse pós-traumático e outros transtornos de ansiedade. MÉTODO: Revisamos a base de dados do Medline em busca de estudos publicados em inglês até abril de 2009, com as seguintes palavras-chave: "transtorno de estresse pós-traumático", "TEPT", "transtorno de humor", "transtorno depressivo maior", "depressão maior", "transtorno bipolar", "distimia", "transtorno de ansiedade", "transtorno de ansiedade generalizada", agorafobia", "transtorno obsessivo-compulsivo", "transtorno de pânico", "fobia social" e "comorbidade". RESULTADOS: Depressão maior é uma das condições comórbidas mais frequentes em indivíduos com transtorno de estresse pós-traumático, mas eles também apresentam transtorno bipolar e outros transtornos ansiosos. Essas comorbidades impõem um prejuízo clínico adicional e comprometem a qualidade de vida desses indivíduos. Comportamento suicida em pacientes com transtorno de estresse pós-traumático, com ou sem depressão maior comórbida, é também uma questão relevante, e sintomas depressivos mediam a gravidade da dor em sujeitos com transtorno de estresse pós-traumático e dor crônica. CONCLUSÃO: Os estudos disponíveis sugerem que pacientes com transtorno de estresse pós-traumático têm um risco maior de desenvolver transtornos afetivos e, por outro lado, transtornos afetivos pré-existentes aumentam a propensão ao transtorno de estresse pós-traumático após eventos traumáticos. Além disso, vulnerabilidades genéticas em comum podem ajudar a explicar esse padrão de comorbidades. No entanto, diante dos poucos estudos encontrados, mais trabalhos são necessários para avaliar adequadamente essas comorbidades e suas implicações clínicas e terapêuticas.

OBJECTIVE: To review studies that have evaluated the comorbidity between posttraumatic stress disorder and mood disorders, as well as between posttraumatic stress disorder and other anxiety disorders. METHOD: We searched Medline for studies, published in English through April, 2009, using the following keywords: "posttraumatic stress disorder", "PTSD", "mood disorder", "major depressive disorder", "major depression", "bipolar disorder", "dysthymia", "anxiety disorder", "generalized anxiety disorder", "agoraphobia", "obsessive-compulsive disorder", "panic disorder", "social phobia", and "comorbidity". RESULTS: Major depression is one of the most frequent comorbid conditions in posttraumatic stress disorder individuals, but individuals with posttraumatic stress disorder are also more likely to present with bipolar disorder, other anxiety disorders and suicidal behaviors. These comorbid conditions are associated with greater clinical severity, functional impairment, and impaired quality of life in already compromised individuals with posttraumatic stress disorder. Depression symptoms also mediate the association between posttraumatic stress disorder and severity of pain among patients with chronic pain. CONCLUSION: Available studies suggest that individuals with posttraumatic stress disorder are at increased risk of developing affective disorders compared with trauma-exposed individuals who do not develop posttraumatic stress disorder. Conversely, pre-existing affective disorders increase a person's vulnerability to the posttraumatic stress disorder--inducing effects of traumatic events. Also, common genetic vulnerabilities can help to explain these comorbidity patterns. However, because the studies addressing this issue are few in number, heterogeneous and based on a limited sample, more studies are needed in order to adequately evaluate these comorbidities, as well as their clinical and therapeutic implications.