vortioxetine and Cognitive-Dysfunction

Dementia and depression are increasingly common worldwide, and their effective control could ease the burden on economies, public health systems, and support networks. Vortioxetine is a new antidepressant with multipharmacologic actions that elevate the concentration of serotonin and modulate multiple neurotransmitter receptors in the brain. We conducted a meta-analysis to explore whether the cognitive function of patients with major depressive disorder (MDD) treated with vortioxetine would improve.. We systematically reviewed randomized controlled trials (RCTs) in the PubMed, Embase, and Cochrane databases to assess the treatment effects of vortioxetine on the cognitive function of patients with MDD. The outcome measures included the Digit Symbol Substitution Test (DSST), Perceived Deficits Questionnaire (PDQ), and Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Pooled results were calculated using a fixed-effects or random-effects model according to the heterogeneity of the included trials.. Six RCTs with a total of 1782 patients were included in the meta-analysis, which demonstrated that vortioxetine improved DSST, PDQ, and MADRS scores in patients with MDD. The results were consistent at the 10- and 20-mg doses. In the 20-mg group, the decrease in MADRS scores was more significant than that in the placebo group.. Both the 10- and 20-mg doses of vortioxetine can significantly increase DSST scores and decrease PDQ and MADRS scores in patients with MDD and cognitive dysfunction, but further studies with longer follow-up periods to assess mental function are required.

Topics: Cognitive Dysfunction; Depressive Disorder, Major; Double-Blind Method; Humans; Piperazines; Randomized Controlled Trials as Topic; Sulfides; Treatment Outcome; Vortioxetine

Vortioxetine is a novel multimodal antidepressant that acts as a serotonin (5-HT)3, 5-HT7, and 5-HT1D receptor antagonist; 5-HT1B receptor partial agonist; 5-HT1A receptor agonist; and 5-HT transporter inhibitor in vitro. In preclinical and clinical studies vortioxetine demonstrates positive effects on cognitive dysfunction. Vortioxetine's effect on cognitive function likely involves the modulation of several neurotransmitter systems. Acute and chronic administration of vortioxetine resulted in changes in histamine concentrations in microdialysates collected from the rat prefrontal cortex and ventral hippocampus. Based on these results and a literature review of the current understanding of the interaction between the histaminergic and serotonergic systems and the role of histamine on cognitive function, we hypothesize that vortioxetine through an activation of the orexinergic system stimulates the tuberomammilary nucleus and enhances histaminergic neurotransmission, which contributes to vortioxetine's positive effects on cognitive function.

Topics: Animals; Cognition; Cognitive Dysfunction; Histamine; Hypothalamic Area, Lateral; Orexins; Piperazines; Serotonin Agents; Sulfides; Synaptic Transmission; Vortioxetine

Vortioxetine (Brintellix

Topics: Animals; Anti-Anxiety Agents; Antidepressive Agents; Cognition; Cognitive Dysfunction; Depression; Depressive Disorder, Major; Humans; Piperazines; Sulfides; Vortioxetine

Cognitive dysfunction is frequent in major depressive disorder (MDD), and brain-derived neurotrophic factor (BDNF) is involved both in regulation of cognition and in therapeutic response in MDD.. The aim of this study was to determine if baseline plasma BDNF might predict change in cognitive function in MDD patients treated with vortioxetine or escitalopram, and whether the alterations in BDNF levels correlate with changes in cognitive performance during treatment.. Drug-naive or drug-free patients with MDD (N=121) were sampled and evaluated at baseline and 4 weeks after treatment initiation with vortioxetine or escitalopram. Cognitive function was evaluated using the F-A-S test, Digit Span test, and Digit Symbol Coding test. Plasma BDNF was determined using ELISA.. The results of the study indicate that both vortioxetine (V) and escitalopram (E) improved cognitive functions evaluated with F-A-S test (V: p<0.001; r=-0.427, E: p<0.001; r=-0.370), Digit Symbol Coding test (V: p<0.001; r=-0.706, E: p<0.001; r=-0.435), and Digit Span test-backward span (V: p=0.001; r=-0.311, E: p=0.042; r=-0.185), while only vortioxetine (p<0.001; r=-0.325) improved cognition evaluated with the Digit Span test-forward span. A moderate positive correlation between pretreatment plasma BDNF levels and improvement in cognitive performance was only detected in patients treated with vortioxetine (delta F-A-S test: p=0.011; r=0.325, delta Digit Span test-forward span: p=0.010, r=0.326).. These results suggest that higher baseline plasma BDNF levels might be associated with improvements in verbal fluency and working memory in vortioxetine, but not escitalopram treated patients. Vortioxetine treatment was superior in simple attention efficiency.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Brain-Derived Neurotrophic Factor; Citalopram; Cognition; Cognitive Dysfunction; Depressive Disorder, Major; Female; Humans; Male; Memory, Short-Term; Middle Aged; Vortioxetine; Young Adult

This study investigated the effects of vortioxetine on cognitive function in adults with mild cognitive impairment (MCI). This single-arm, open-label, phase II study enrolled 111 adults with MCI without depressive symptoms to receive 5-10 mg/day vortioxetine for 6 months. Main outcomes assessed: cognitive function [Montreal Cognitive Assessment (MoCA); Digit Symbol Substitution Test (DSST)], disease severity [Clinical Dementia Rating (CDR)], clinician-assessed improvement and safety. Mean MoCA score increased from 24.2 points (baseline) to 29.7 points (month 6), placing most subjects within the cognitively normal range (≥26 points). Compared with baseline, MoCA and DSST scores were significantly improved at months 1, 3 and 6 (P < 0.001 for all). Global CDR scores significantly improved from baseline to month 6 (mean change -0.37 points; P < 0.001), representing an improvement from very mild impairment (0.50 points) to cognitively normal status (0.13 points), mainly in CDR memory scores. At month 6, 89.6% of subjects had improved disease severity. Adverse events and adverse drug reactions were reported in 9.9% (n = 11) and 2.7% (n = 3) of subjects, respectively. Vortioxetine treatment was associated with significant improvement in cognitive function and a favorable safety profile in community-dwelling older adults with MCI. Given the lack of evidence for efficacious pharmacologic interventions for MCI, our results are encouraging and warrant further investigation.

Topics: Adult; Cognitive Dysfunction; Humans; Treatment Outcome; Vortioxetine

Antidepressant pharmacotherapy dominates current treatment in psychiatry, including treatment for major depressive disorder (MDD). However, the current trial-and-error process of medication selection contributes to treatment failure and unnecessarily exposes patients to lengthy and insufficient treatment trials. Notably, improvements in measures of cognition have been demonstrated to occur early during treatment and prior to improvements in clinical state. Cognitions have been categorized based on emotional valence (i.e., cold versus hot cognitions). Cold cognitions describe cognitive operations that are relevant to the processing of non-emotional information. The current analysis investigates whether early changes in cold cognition can predict response after 8 weeks of vortioxetine treatment in adults with MDD. This was secondary analysis of an 8-week, open-label study. Cognition was assessed at week 0 and week 2 to measure early cognitive change. Depressive symptom severity was assessed at week 0 and week 8 to measure treatment response. Eighty-one subjects were analyzed using binomial logistic regression models. Early change in cognition was a non-significant predictor of response (p = 0.845, SE = 0.599, OR = 1.124), which may have resulted from high data variability. The overall predictive accuracy of the model was low (sensitivity = 37.5%, specificity = 89.8%, PPV = 70.6%, NPV = 68.8%). Future studies should include larger samples and stratify patients based on potentially moderating variables, such as baseline cognitive impairment and occupation. Stratification would likely produce more homogenous samples, reducing the amount of variability observed for early cognitive change.

Topics: Adult; Antidepressive Agents; Cognition; Cognitive Dysfunction; Depressive Disorder, Major; Female; Humans; Male; Middle Aged; Ontario; Predictive Value of Tests; Treatment Outcome; Vortioxetine

Age-related cognitive decline, the deterioration in functions such as memory and executive function, is faced by most older adults and affects function and quality of life. No approved treatments exist for age-related cognitive decline. Computerized cognitive training has been shown to provide consistent albeit modest improvements in cognitive function as measured by neuropsychological testing. Vortioxetine, an antidepressant medication, has putative procognitive and proneuroplastic properties and therefore may be able to augment cognitive training. In this placebo-controlled study, the authors tested the cognitive benefits of vortioxetine added to cognitive training for adults age 65 or older with age-related cognitive decline.. After a 2-week lead-in period of cognitive training, 100 participants were randomly assigned to receive either vortioxetine or placebo in addition to cognitive training for 26 weeks. The primary outcome measure was global cognitive performance, assessed by the NIH Toolbox Cognition Battery Fluid Cognition Composite. The secondary outcome measure was functional cognition, assessed by the UCSD Performance-Based Skills Assessment. All participants received motivational messaging and support from study staff to maximize adherence to the training.. Participants who received vortioxetine with cognitive training showed a greater increase in global cognitive performance compared with those who received placebo with cognitive training. This separation was significant at week 12 but not at other assessment time points. Both groups showed improvement in the secondary outcome measure of functional cognition, with no significant difference between groups.. Vortioxetine may be beneficial for age-related cognitive decline when combined with cognitive training. These findings provide new treatment directions for combating cognitive decline in older adults.

Topics: Aged; Cognition; Cognitive Aging; Cognitive Dysfunction; Cognitive Remediation; Combined Modality Therapy; Female; Humans; Male; Mental Status and Dementia Tests; Serotonin 5-HT3 Receptor Antagonists; Therapy, Computer-Assisted; Treatment Outcome; Vortioxetine

To evaluate the effect of vortioxetine combined with cognitive behaviour intervention on the level of brain-derived neurotrophic factor (BDNF) in the serum of patients with depression and its therapeutic effect.. A total of 82 depressive patients treated at the School of Basic Medicine, Heilongjiang University of Chinese Medicine from January 2017 to June 2017 were randomised into a control group (n = 41) and intervention group (n = 41) according to a random number table. Both groups were given vortioxetine treatment, while the intervention group adopted an additional cognitive-behavioural therapy at the same time. The therapeutic effect was evaluated using the Hamilton Depression Scale (HAMD). The cognitive function was evaluated using continuous performance test (CPT) and Wisconsin card sorting test (WCST). The changes of BDNF level were detected with the use of enzyme-linked immunosorbent assay.. The HAMD score of the intervention group was obviously lower than that of the control group after treatment (P < 0.001). WCST test showed that the number of trials, perseverative errors and non-perseverative errors in the intervention group were significantly lower than those in the control group, while the correct matching number and the number of categories achieved were significantly higher than those in the control group (all P < 0.001). Results of CPT showed that the correct number of responses to stimulus, the verbal fluency and the fluency of classification in the intervention group were significantly higher than those in the control group (all P < 0.05). Moreover, after treatment, the serum BDNF level of the intervention group was significantly higher than that in the control group (P < 0.001).. Vortioxetine combined with cognitive behavioural therapy has a good clinical effect and can largely improve the cognitive function of depressive patients.

Topics: Adult; Brain-Derived Neurotrophic Factor; Cognitive Behavioral Therapy; Cognitive Dysfunction; Combined Modality Therapy; Depressive Disorder; Female; Humans; Male; Outcome Assessment, Health Care; Selective Serotonin Reuptake Inhibitors; Vortioxetine

Major depressive disorder (MDD) is one of the most prevalent mental illnesses associated with impairments in different spheres of functioning. Cognitive deficits are currently investigated as a possible factor of functional decline. We aimed: 1) to assess the influence of cognitive domains among other MDD symptoms on functional impairment; 2) to compare effects of eight weeks` vortioxetine versus escitalopram treatments on cognitions and consequent influence on various domains of functioning.. At baseline, 119 MDD (according to DSM-5, MADRS ≥ 7) patients and 71 healthy controls completed neurocognitive tests (RAVLT, TMT-B, DSST) and Sheehan Disability Scale. After 8 weeks of vortioxetine/escitalopram treatment, 56 patients had repeated clinical and neuropsychological evaluations. Linear regression analyses were performed to find significant predictors of impairment (at baseline) and improvement (after treatment) of functioning. Differences between groups after treatment were analyzed using mixed models for repeated measurements.. Cognitive impairments predominantly affected social functioning and were crucial for working productivity and total functioning along with anhedonia, hypothymia. Working memory disturbances impaired all aspects of functioning. Executive dysfunction made an additional contribution to workplace performance disturbances. At week 8, vortioxetine compared with escitalopram greater improved all impaired cognitive parameters and aspects of functioning and had higher remission rates. Cognitive improvement was the most significant factor for total functioning recovery and among crucial contributors to workplace performance recovery.. No placebo group.. Cognitions play a key role in social, working, overall functioning in Ukrainian MDD patients. Compared to escitalopram, vortioxetine treatment greater improves all cognitive and functioning domains, which leads to higher remission rates.

Topics: Adult; Anhedonia; Antidepressive Agents; Citalopram; Cognition; Cognitive Dysfunction; Depressive Disorder, Major; Efficiency; Female; Humans; Male; Mental Status and Dementia Tests; Middle Aged; Neuropsychological Tests; Treatment Outcome; Ukraine; Vortioxetine; Young Adult

Cognitive dysfunction is common in depression during both acute episodes and remission. Vortioxetine is a novel multimodal antidepressant that has improved cognitive function including executive function in depressed patients in randomised placebo-controlled clinical trials. However, it is unclear whether vortioxetine is able to target directly the neural circuitry implicated in the cognitive deficits in depression. Remitted depressed (n=48) and healthy volunteers (n=48) were randomised to receive 14 days treatment with 20 mg vortioxetine or placebo in a double-blind design. The effects of treatment on functional magnetic resonance imaging responses during an N-back working memory task were assessed at baseline and at the end of treatment. Neuropsychological measures of executive function, speed and information processing, attention and learning and memory were examined with the Trail Making Test (TMT), Rey Auditory Learning Test and Digit Symbol Substitution Test before and after treatment; subjective cognitive function was assessed using the Perceived Deficits Questionnaire (PDQ). Compared with placebo, vortioxetine reduced activation in the right dorsolateral prefrontal cortex and left hippocampus during the N-back task compared with placebo. Vortioxetine also increased TMT-A performance and self-reported cognitive function on the PDQ. These effects were seen across both subject groups. Vortioxetine modulates neural responses across a circuit subserving working memory in a direction opposite to the changes described in depression, when performance is maintained. This study provides evidence that vortioxetine has direct effects on the neural circuitry supporting cognitive function that can be dissociated from its effects on the mood symptoms of depression.

Topics: Adult; Affect; Antidepressive Agents; Cognition; Cognition Disorders; Cognitive Dysfunction; Depression; Depressive Disorder, Major; Double-Blind Method; Female; Humans; Magnetic Resonance Imaging; Male; Memory, Short-Term; Middle Aged; Neuroimaging; Neuropsychological Tests; Treatment Outcome; Vortioxetine

We evaluated vortioxetine's effects on functional capacity in demographic and clinical subgroups of patients with major depressive disorder.. This was an exploratory analysis of the CONNECT study (NCT01564862) that evaluated changes in functional capacity using University of California San Diego Performance-based Skills Assessment data, categorized by sex, age, education, employment status, and baseline disease severity (Montgomery-Åsberg Depression Rating Scale, Clinical Global Impressions-Severity of Illness).. Greater changes in University of California San Diego Performance-based Skills Assessment composite scores were observed with vortioxetine vs placebo in specific subgroups: males (∆+3.2), females (∆+2.9), 45-54 or ≥55 years (∆+5.6, ∆+3.4), working (∆+2.8), high school or greater education (∆+2.7, ∆+2.8), disease severity (Montgomery-Åsberg Depression Rating Scale, <30, ∆+3.5; ≥30, ∆+2.5; Clinical Global Impressions-Severity of Illness ≤4, ∆+2.8; >4, ∆+3.0), major depressive episodes (≤2, >2 [∆+2.7,+3.3]), and episode duration (≤22, >22 weeks [∆+3.7,+2.4]).. Our findings support the need for additional studies to assess whether vortioxetine improves functional capacity within specific patient subgroups.. clinicaltrials.gov: NCT01564862.

Topics: Adult; Antidepressive Agents; Cognitive Dysfunction; Depressive Disorder, Major; Diagnostic Self Evaluation; Double-Blind Method; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Outcome Assessment, Health Care; Vortioxetine

Major Depressive Disorder (MDD) is a heterogeneous disease characterized by emotional, physical and cognitive symptoms. This study explored the effects of vortioxetine versus escitalopram on outcomes of cognition, functioning and mood symptoms in depressed patients with inadequate response to current antidepressant treatment.. In this parallel-group, active-comparator study, adult patients (18-65 years, N = 101) with MDD, with inadequate response to current antidepressant monotherapy, were randomized 1:1 to 8 weeks' double-blind treatment with flexible doses (10-20mg/day) of either vortioxetine or escitalopram. Primary and key secondary efficacy measures were the Digit Symbol Substitution Test (DSST), analyzed using a mixed model for repeated measurements, and the University of San Diego Performance-based Skills Assessment - Brief (UPSA-B), analyzed using analysis of covariance (last observation carried forward method).. At week 8, DSST and UPSA-B performance had improved in both treatment groups, with no statistically significant treatment differences. Numerical improvements across measures of cognition, functioning and mood symptoms generally favored vortioxetine. Most adverse events were mild or moderate, with nausea being the most common adverse event.. This was an exploratory study with small sample sizes implying limited statistical power.. Although this explorative study did not meet primary endpoints, the results confirm vortioxetine in doses of 10-20mg/day as an efficacious and well-tolerated antidepressant switch treatment. The overall direction of numerical effect sizes across cognition endpoints support previous findings that vortioxetine specifically benefits cognitive function in MDD.

Topics: Adult; Antidepressive Agents; Citalopram; Cognition; Cognitive Dysfunction; Depressive Disorder, Major; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Piperazines; Sulfides; Treatment Outcome; Vortioxetine; Young Adult

This post hoc analysis investigates the effect of vortioxetine on cognitive functioning and depressive symptoms in working adults with major depressive disorder (MDD).. Population data from FOCUS, a double-blind, randomized, placebo-controlled study investigating the efficacy of vortioxetine versus placebo on cognitive functioning and depression in patients with MDD, were used to analyze mean change from baseline scores for the Digit Symbol Substitution Test (DSST), Trail Making Test A/B (TMT-A/B), Stroop, and Perceived Deficits Questionnaire (PDQ). FOCUS, conducted from December 2011 through May 2013, included adult patients with recurrent MDD according to DSM-IV-TR criteria. Change in depression severity (Montgomery-Asberg Depression Rating Scale [MADRS] total score) was analyzed using data from 3 additional short-term placebo-controlled studies (2 of which included duloxetine) and 1 relapse prevention study. Analyses were done according to patients' working status at baseline and workplace position. All analyses were made versus placebo.. In FOCUS, the effect versus placebo on the DSST was 5.6 for 10 mg and 5.0 for 20 mg (P < .001 for both doses) in working patients; the effect was 4.0 (P < .001 for both doses) in total study population. The effect remained significant when adjusting for change in MADRS. In patients with "professional" positions, the effect was 9.2 for 10 mg (P = .006) and 9.0 for 20 mg (P = .001). A similar pattern of results was also observed for TMT-A/B, Stroop, PDQ, and MADRS total score. The efficacy of duloxetine was not different in working patients (MADRS).. The beneficial effects of vortioxetine on objective and subjective measures of cognitive functioning are greater in working patients with MDD; the observed benefits were independent of improvement in depressive symptoms.. This study is a secondary analysis of data from 5 registered trials: ClinicalTrials.gov identifiers: NCT01422213, NCT00635219, NCT00735709, NCT01140906, NCT00596817​.

Topics: Adult; Cognitive Dysfunction; Depressive Disorder, Major; Dose-Response Relationship, Drug; Double-Blind Method; Efficiency; Female; Humans; Male; Neuropsychological Tests; Piperazines; Psychometrics; Sulfides; Treatment Outcome; Vortioxetine

Clinical and preclinical studies suggest that alterations in the peripheral and brain immune system are associated with the pathophysiology of depression, also leading to changes in local glucose metabolism in the brain. Here, the authors identified Yin-Yang 1 (YY1), a transcription factor closely associated with central and peripheral inflammation.. Plasma levels of YY1, interleukin (IL) 6, and IL-1β in major depressive disorder (MDD) were collected before and after treatment with vortioxetine, and correlation with clinical and cognitive scores was studied. Chronic unpredictable mild stress was treated with vortioxetine. Micropositron emission tomography (microPET) was used to analyze glucose metabolism and mRNA, and the protein level of the YY1-nuclear factor κB (NF-κB)-IL-1β inflammatory pathway were measured in related brain regions.. Plasma levels of YY1 and IL-1β were significantly increased in MDD and decreased after treatment with vortioxetine. Meanwhile, the level of YY1 in plasma was negatively correlated with cognitive functions in patients with MDD and positively correlated with the level of IL-1β in plasma. Compared with the control group, in chronic unpredictable mild stress rats, (microPET) analysis showed that the decrease of glucose metabolism in the hippocampus, entorhinal cortex, amygdala, striatum, and medial prefrontal cortex was reversed after treatment. mRNA and protein level of related molecular in YY1-NF-κB-IL-1β inflammatory pathway decreased in the hippocampus and was reversed by vortioxetine.. The current study suggests that the YY1-NF-κB-IL-1β inflammatory pathway may play an essential role in both mood changes and cognitive impairment in depression, and may be associated with changes in glucose metabolism in emotion regulation and cognition. These findings provide new evidence for the inflammatory mechanisms of depression.

Topics: Animals; Cognitive Dysfunction; Depression; Depressive Disorder, Major; Glucose; Inflammation; Interleukin-6; NF-kappa B; Rats; RNA, Messenger; Transcription Factors; Vortioxetine; Yin-Yang; YY1 Transcription Factor

Advances in prostate cancer treatment have significantly improved survival, but quality of life for survivors remains an under-studied area of research. Androgen deprivation therapy (ADT) is a foundational treatment for advanced prostate cancer and is used as an adjuvant for prolonged periods in many high-risk, localized tumors. More than half of patients treated with ADT experience debilitating cognitive impairments in domains such as spatial learning and working memory. In this study, we investigated the effects of androgen deprivation on hippocampal-mediated cognition in rats. Vortioxetine, a multimodal antidepressant, has been shown to improve cognition in depressed patients. Thus, we also tested the potential efficacy of vortioxetine in restoring impaired cognition after ADT. We further investigated mechanisms that might contribute to these effects, measuring changes in the circuitry and gene expression within the dorsal hippocampus. ADT via surgical castration induced impairments in visuospatial cognition on the novel object location test and attenuated afferent-evoked local field potentials recorded in the CA1 region of the dorsal hippocampus. Chronic dietary administration of vortioxetine effectively reversed these deficits. Castration significantly altered gene expression in the hippocampus, whereas vortioxetine had little effect. Pathway analysis revealed that androgen depletion altered pathways related to synaptic plasticity. These results suggest that the hippocampus may be vulnerable to ADT, contributing to cognitive impairment in prostate cancer patients. Further, vortioxetine may be a candidate to improve cognition in patients who experience cognitive decline after androgen deprivation therapy for prostate cancer and may do so by restoring molecular and circuit-level plasticity-related mechanisms compromised by ADT.

Topics: Androgen Antagonists; Androgens; Animals; Cognitive Dysfunction; Hippocampus; Humans; Male; Prostatic Neoplasms; Quality of Life; Rats; Vortioxetine

Cognitive impairments are frequent in patients suffering from major depressive disorders. They are among the first symptoms, often persist independently of improvement even after remission of the affective symptoms and are an important predictor of psychosocial functioning. In the clinical practice it is mandatory to ask about subjective complaints of the patient as well as to assess the cognitive abilities with the help of a standardized neuropsychological test battery. Cognitive remediation, selective serotonin reuptake inhibitors (SSRI) and vortioxetine as well as repetitive transcranial magnetic stimulation have proven their effectiveness as treatment options.. Kognitive Störungen bei Patienten mit Depressionen sind häufig. Sie treten bereits zu Beginn der Erkrankung auf, persistieren auch nach Remission der affektiven Symptome und sind wichtiger Prädiktor für das psychosoziale Leistungsniveau. In der klinischen Praxis sollten sowohl die subjektiv wahrgenommenen Defizite erfragt, als auch die tatsächliche kognitive Leistungsfähigkeit mittels standardisierter Diagnostik erfasst werden. In der Behandlung haben sich neuropsychologische Verfahren der kognitiven Remediation, psychopharmakologisch SSRIs („selective serotonin reuptake inhibitors“) sowie Vortioxetin und neuromodulatorisch die repetitive transkranielle Magnetstimulation als wirksam erwiesen.

Topics: Antidepressive Agents; Cognitive Dysfunction; Depression; Depressive Disorder, Major; Humans; Neuropsychological Tests; Vortioxetine

Patients with major depressive disorder (MDD) show impairments in cognitive functioning, including deficits on performance-based measures of functional capacity. A proportion of patients with MDD may achieve higher scores at baseline, and may not show a detectable response to treatment. How to identify these cases is the goal of this investigation.. Retrospective analyses of data from the CONNECT study with vortioxetine were performed to determine whether the Work Limitations Questionnaire (WLQ) can be used to exclude very high-performing patients on the functional capacity outcome measure, University of California San Diego Performance-Based Skills Assessment (UPSA), in studies evaluating cognitive function impairment in MDD, to identify those with greater potential for treatment response. The post-hoc analyses included data on cognitive function assessed with a Digit Symbol Substitution Test (DSST) from vortioxetine-treated patients.. WLQ score >13 identified patients with greater impairments in UPSA-Brief (UPSA-B). Patients with WLQ scores >13, but not with scores ≤13, showed statistically significant improvements with vortioxetine treatment in UPSA-B and DSST compared with placebo.. Study limitations include small sample size and use of post-hoc analyses. The generalizability of this analysis is limited to working patients with MDD.. The WLQ can be used to identify patients with MDD with high potential for treatment response in studies evaluating cognitive function impairment while excluding patients likely to achieve ceiling scores on UPSA. This approach helps identify higher performers on potential outcomes measures without biasing the study by requiring a specific UPSA cutoff score for eligible participants.

Topics: Adult; Cognition; Cognitive Dysfunction; Depressive Disorder, Major; Double-Blind Method; Employment; Female; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Retrospective Studies; Self Report; Vortioxetine

Vortioxetine has been reported to exhibit a variety of neurobiological functions and neuroprotective effects. In the present study, we aimed to investigate the effects of vortioxetine on cognitive performance in a transgenic mouse model of Alzheimer's disease (AD).. We administered vortioxetine (10 mg/kg, i.p., every day, for approximately 6 weeks), which acts on multiple 5-serotonin (5-HT) receptors, to 3.5-month-old 5×FAD mice. Subsequently, we used the open field (OF) test to detect anxiety-like behavior in the mice. The novel object recognition (NOR) test and Morris water maze (MWM) were used to assess the cognitive states of the 5×FAD mice. We also measured the levels of insoluble amyloid plaques and soluble β-amyloid (Aβ) plaques. Finally, we explored the expression levels of postsynaptic density protein 95 (PSD95), synaptophysin (SYP), and synaptotagmin-1 (SYT1) in the hippocampus of the mice.. The administration of vortioxetine effectively reversed the reduction in anxiety-type behaviors in 5×FAD mice and improved the impairment in recognition memory and spatial reference memory. However, we did not find that vortioxetine decreased or delayed the formation of amyloid plaques or Aβ. Interestingly, we found a significant increase in the expression levels of PSD95, SYP, and SYT1 in the 5×FAD mice after vortioxetine treatment compared with the control group.. These results demonstrate that vortioxetine may improve cognitive impairment in 5×FAD mice. The role in cognitive improvement may be related to the beneficial effects of vortioxetine on synaptic function.

Topics: Alzheimer Disease; Animals; Cognitive Dysfunction; Flavin-Adenine Dinucleotide; Hippocampus; Humans; Maze Learning; Mice; Mice, Transgenic; Neuroprotective Agents; Plaque, Amyloid; Synapses; Vortioxetine

Topics: Animals; Antidepressive Agents; Anxiety Disorders; Attention Deficit Disorder with Hyperactivity; Autistic Disorder; Benzodiazepines; Cognitive Aging; Cognitive Behavioral Therapy; Cognitive Dysfunction; Cognitive Remediation; Dementia; Drosophila melanogaster; Female; Humans; Hypnotics and Sedatives; Intellectual Disability; Neural Pathways; Pregnancy; Prenatal Exposure Delayed Effects; Risk Factors; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Sleep; Vortioxetine

Post-traumatic stress disorder (PTSD) can be observed after a traumatic event. The effect of an antidepressant vortioxetine (Vrx) against PTSD is unknown. The aim of this study was to investigate the possible protective effect of Vrx in the predator scent-induced PTSD rat model. The rats were exposed to dirty cat litter for 10 min and the protocol was repeated 1 week later with clean cat litter as a trauma reminder. The rats received Vrx (10 mg/kg/p.o.) or saline (1 ml/kg/p.o.) during 7 days between two exposure sessions. Novel object recognition test, hole board test, and elevated plus maze were performed. The b-cell lymphoma (bcl-2)/bcl-2-associated X protein (bax) ratio, brain-derived neurotrophic factor (BDNF), caspase-3 and -9 expressions were detected using Western blotting in the amygdaloid complex, hippocampus, and frontal cortex. Our results indicate that increased freezing time and anxiety index in the stress-induced group is decreased with Vrx application. Vrx treatment improved deteriorated recognition memory in the stress-induced group. Decreased bcl-2/bax ratio and BDNF level and increased caspase-3 and -9 expressions in the stress group, improved with Vrx in the amygdala, and hippocampus. Decreased bcl-2/bax ratio and increased casp-3 and -9 expressions in the stress group are ameliorated with Vrx in frontal cortex. The level of BDNF was increased with Vrx in the frontal cortex. Increased damage scores in the amygdaloid complex, hippocampal CA3, and frontal cortex in the stress group ameliorated with Vrx treatment. Our results show that if vortioxetine is administered immediately after trauma, it reduces anxiety, cognitive and neuronal impairment and may be protective against the development of PTSD.

Topics: Animals; Apoptosis; Behavior, Animal; Brain; Brain-Derived Neurotrophic Factor; Cats; Cognitive Dysfunction; Disease Models, Animal; Male; Memory; Neuronal Plasticity; Neuroprotective Agents; Odorants; Rats, Wistar; Stress Disorders, Post-Traumatic; Stress, Psychological; Vortioxetine

Androgen deprivation therapy (ADT) is an effective treatment for prostate cancer, but induces profound cognitive impairment. Little research has addressed mechanisms underlying these deficits or potential treatments. This is an unmet need to improve quality of life for prostate cancer survivors.. We investigated mechanisms of cognitive impairment after ADT in rats and potential utility of the multimodal serotonin-targeting drug, vortioxetine, to improve the impairment, as vortioxetine has specific efficacy against cognitive impairment in depression.. Male Sprague-Dawley rats were surgically castrated. Vortioxetine (28 mg/kg/day) was administered in the diet. The attentional set-shifting test was used to assess medial prefrontal cortex (mPFC) executive function. Afferent-evoked field potentials were recorded in the mPFC of anesthetized rats after stimulating the ventral hippocampus (vHipp) or medial dorsal thalamus (MDT). Gene expression changes were assessed by microarray. Effects of vortioxetine on growth of prostate cancer cells were assessed in vitro.. ADT impaired cognitive set shifting and attenuated responses evoked in the mPFC by the vHipp afferent, but not the MDT. Both the cognitive impairment and attenuated vHipp-evoked responses were reversed by chronic vortioxetine treatment. Preliminary investigation of gene expression in the mPFC indicates that factors involved in neuronal plasticity and synaptic transmission were down-regulated by castration and up-regulated by vortioxetine in castrated animals. Vortioxetine neither altered the growth of prostate cancer cells in vitro nor interfered with the antiproliferative effects of the androgen antagonist, enzalutamide.. These results suggest that vortioxetine may be useful in mitigating cognitive impairment associated with ADT for prostate cancer.

Topics: Androgen Antagonists; Animals; Cognitive Dysfunction; Dose-Response Relationship, Drug; Male; Orchiectomy; Prefrontal Cortex; Prostatic Neoplasms; Rats; Rats, Sprague-Dawley; Vortioxetine

Major depressive disorder (MDD) is a common psychiatric disorder that often features impairments in cognitive function, and these cognitive symptoms can be important determinants of functional ability. Vortioxetine is a multimodal antidepressant that may improve some aspects of cognitive function in patients with MDD, including attention, processing speed, executive function, and memory. However, the cause of these effects is unclear, and there are several competing theories on the underlying mechanism, notably including regionally-selective downstream enhancement of glutamate neurotransmission and increased acetylcholine (ACh) neurotransmission. The current work sought to evaluate the ACh hypothesis by examining vortioxetine's ability to reverse scopolamine-induced impairments in rodent tests of memory and attention. Additionally, vortioxetine's effects on hippocampal extracellular ACh levels were examined alongside studies of vortioxetine's pharmacokinetic profile. We found that acute vortioxetine reversed scopolamine-induced impairments in social and object recognition memory, but did not alter scopolamine-induced impairments in attention. Acute vortioxetine also induced a modest and short-lived increase in hippocampal ACh levels. However, this short-term effect is at variance with vortioxetine's moderately long brain half life (5.1 hours). Interestingly, subchronic vortioxetine treatment failed to reverse scopolamine-induced social recognition memory deficits and had no effects on basal hippocampal ACh levels. These data suggest that vortioxetine has some effects on memory that could be mediated through cholinergic neurotransmission, however these effects are modest and only seen under acute dosing conditions. These limitations may argue against cholinergic mechanisms being the primary mediator of vortioxetine's cognitive effects, which are observed under chronic dosing conditions in patients with MDD.

Topics: Acetylcholine; Animals; Cognitive Dysfunction; Extracellular Space; Hippocampus; Male; Piperazines; Rats; Rats, Wistar; Recognition, Psychology; Scopolamine; Social Behavior; Sulfides; Synaptic Transmission; Vortioxetine