vortioxetine and Anhedonia

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

Depression-associated cognitive impairments are among the most prevalent and persistent symptoms during remission from a depressive episode and a major risk factor for relapse. Consequently, development of antidepressant drugs, which also alleviate cognitive impairments, is vital. One such potential antidepressant is vortioxetine that has been postulated to exhibit both antidepressant and pro-cognitive effects. Hence, we tested vortioxetine for combined antidepressant and pro-cognitive effects in male Long-Evans rats exposed to the chronic mild stress (CMS) paradigm. This well-established CMS paradigm evokes cognitive deficits in addition to anhedonia, a core symptom of depression. Learning and memory performance was assessed in the translational touchscreen version of the paired-associates learning task. To identify the mechanistic underpinning of the neurobehavioural results, transcriptional profiling of genes involved in the stress response, neuronal plasticity and genes of broad relevance in neuropsychiatric pathologies were assessed. Vortioxetine substantially relieved the anhedonic-like state in the CMS rats and promoted acquisition of the cognitive test independent of hedonic phenotype, potentially due to an altered cognitive strategy. Minor alterations in gene expression profiling in prefrontal cortex and hippocampus were found. In summary, our findings suggest that vortioxetine exhibits an antidepressant effect as well as behavioural changes in a translational learning task.

Topics: Anhedonia; Animals; Antidepressive Agents; Cerebral Cortex; Cognition; Gene Expression; Hippocampus; Learning; Male; Rats, Long-Evans; Stress, Physiological; Vortioxetine

Vortioxetine is a novel antidepressant capable of improving depressive and cognitive symptoms associated with major depressive disorder (MDD). This study established whether treatment with vortioxetine, fluoxetine or vehicle alters the modulation of brain-derived neurotrophic factor (BDNF) under the 21-day chronic unpredictable mild stress (CUMS) condition in 54 Sprague-Dawley rats. Vortioxetine mitigated the reduction in rearing behavior by CUMS in the OFT on day 7 and 21, as well as sucrose preference on day 21. Histological examination by H&E staining showed that most hippocampal neurons in the CUMS + FLU and CUMS + VOR groups were intact, although some of them demonstrated karyopyknosis. The mean optical density value of hippocampal BDNF was significantly higher in the CUMS + VOR group than the CUMS and CUMS + FLU groups. There was a trend towards a higher number of hippocampal BDNF-positive cells in the CUMS + VOR group, although it did not reach statistical significance. In conclusion, vortioxetine, but not fluoxetine, increased hippocampal BDNF levels in rats subject to CUMS.

Topics: Anhedonia; Animals; Antidepressive Agents; Brain-Derived Neurotrophic Factor; Depressive Disorder, Major; Disease Models, Animal; Fluoxetine; Hippocampus; Male; Neurons; Random Allocation; Rats, Sprague-Dawley; Stress, Psychological; Vortioxetine