Baseline Cognition Is Not Associated With Depression Outcomes in Vortioxetine for Major Depressive Disorder: Findings From Placebo-Controlled Trials.

Objective: Major depressive disorder (MDD) is a common psychiatric disorder for which pharmacologic standard-of-care treatments have limited efficacy, particularly among individuals with cognitive dysfunction. Cognitive dysfunction is observed in approximately 25%-50% of those with MDD, wherein response to standard-of-care medications is reduced. Vortioxetine is an approved antidepressant that has shown evidence of procognitive effects in patients. It is not known if it has greater clinical efficacy in MDD patients with cognitive dysfunction, a more difficult to treat population, than other antidepressants.Methods: This study was a reanalysis of 1,812 subjects with MDD across 4 placebo controlled trials. Baseline cognition was measured by the Digit Symbol Substitution Test (DSST), the primary measure used to demonstrate vortioxetine's procognitive effects in clinical studies. Analyses examined whether baseline cognitive function was associated with differences in treatment outcomes.Results: Baseline DSST did not predict placebo-adjusted treatment effects of vortioxetine on depressive symptoms (pooled Cohen d = -0.02, 95% CI = -0.12 to 0.07). Analyses of additional cognitive measures similarly did not predict placebo-adjusted treatment effects on depression (all 95% CI contained zero). Finally, analyses of trials with selective serotonin reuptake inhibitors (SSRIs)/serotonin and norepinephrine reuptake inhibitors (SNRIs) as active comparators also revealed no prediction of SSRI/SNRI adjusted treatment effects of vortioxetine on depression.Conclusions: These findings, taken together, suggest that cognitive function does not moderate depression outcomes in vortioxetine, with results comparable to other antidepressants.

Proteomic profiles of cytokines and chemokines in moderate to severe depression: Implications for comorbidities and biomarker discovery.

Objective: This study assessed the proteomic profiles of cytokines and chemokines in individuals with moderate to severe depression, with or without comorbid medical disorders, compared to healthy controls. Two proteomic multiplex platforms were employed for this purpose. Metods: An immunofluorescent multiplex platform and an aptamer-based method were used to evaluate 32 protein analytes from 153 individuals with moderate to severe major depressive disorder (MDD) and healthy controls (HCs). The study focused on determining the level of agreement between the two platforms and evaluating the ability of individual analytes and principal components (PCs) to differentiate between the MDD and HC groups. Additionally, the study investigated the relationship between PCs consisting of chemokines and cytokines and comorbid inflammatory and cardiometabolic diseases. Findings: Analysis revealed a small or moderate correlation between 47% of the analytes measured by the two platforms. Two proteomic profiles were identified that differentiated individuals with moderate to severe MDD from HCs. High eotaxin, age, BMI, IP-10, or IL-10 characterized profile 1. This profile was associated with several cardiometabolic risk factors, including hypertension, hyperlipidemia, and type 2 diabetes. Profile 2 is characterized by higher age, BMI, interleukins, and a strong negative loading for eotaxin. This profile was associated with inflammation but not cardiometabolic risk factors. Conclusion: This study provides further evidence that proteomic profiles can be used to identify potential biomarkers and pathways associated with MDD and comorbidities. Our findings suggest that MDD is associated with distinct profiles of proteins that are also associated with cardiometabolic risk factors, inflammation, and obesity. In particular, the chemokines eotaxin and IP-10 appear to play a role in the relationship between MDD and cardiometabolic risk factors. These findings suggest that a focus on the interplay between MDD and comorbidities may be useful in identifying potential targets for intervention and improving overall health outcomes.