vortioxetine and Alzheimer-Disease

Despite the better understanding of the mechanisms underlying Alzheimer's Disease (AD) and launched clinical trials, no AD-modifying treatment based on a synthetic drug has been introduced for almost twenty years. The serotonin 5-HT

Topics: Alzheimer Disease; Animals; Humans; Nootropic Agents; Receptors, Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists

Pharmacotherapy for the treatment of depressive disorders in Alzheimer's Disease (AD) represents a clinical challenge. pharmacological options are often attempted after a period of watchful waiting (8-12 weeks). monoaminergic antidepressant drugs have shown only modest or null clinical benefits, maybe because the etiology of depressive symptoms in ad patients is fundamentally different from that of nondemented subjects.. The following article looks at the selective serotonin reuptake inhibitor sertraline, which is one of the most frequently studied antidepressant medications in randomized controlled trials (RCTs). It also discusses many other pharmacological approaches that have proven to be inadequate (antipsychotics, acetylcholinesterase inhibitors, anticonvulsants, hormone replacement therapy) and new drug classes (mainly affecting glutamate transmission) that are being studied for treating depression in AD. It also gives discussion to the phase II RCT on the alternative drug S47445 and the potential effect on cognition of the multimodal antidepressant vortioxetine in older depressed patients. Finally, it discusses the N-methyl-D-aspartate antagonist ketamine.. The present RCT methodologies are too disparate to draw firm conclusions. Future studies are required to identify effective and multimodal pharmacological treatments that efficiently treat depression in AD. Genotyping may boost antidepressant treatment success.

Topics: Alzheimer Disease; Antipsychotic Agents; Calcium Channel Blockers; Clinical Trials as Topic; Depressive Disorder, Treatment-Resistant; Humans; Nimodipine; Piperazines; Selective Serotonin Reuptake Inhibitors; Sertraline; Sulfides; Vortioxetine

depressive symptoms are common in Alzheimer's disease(AD). Aim of the study was to investigate the efficacy of vortioxetine compared with other conventional antidepressants on cognitive functions in AD patients with depressive symptoms.. Prospective, randomized, 12 month, parallel-group study.. All participants were evaluated on-site at Neurodegenerative Disorders Unit, ASP2 Caltanissetta(Italy).. 108(71 female, 37 male) AD patients with depression(mean age 76.7 ± 4.3).. Randomized subjects received vortioxetine, 15 mg/day(n=36) or other common antidepressants(n=72).. Primary outcome was change from baseline in the MMSE; secondary outcomes were change in Attentive Matrices, Raven Coloured Progressive Matrices, Digit Span, HAM-D and Cornell scale.. Statistically significant improvement vs. controls was observed for vortioxetine on most of the cognitive tests and showed significantly baseline-to-endpoint reduction in both HAM-D and Cornell total scores.The most commonly reported adverse events were nausea and headache for votioxetine; nausea in the control group.. Vortioxetine had a beneficial effect on cognition and mood in elderly AD patients and was safe and well tolerated.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antidepressive Agents; Depression; Female; Humans; Male; Neuropsychological Tests; Prospective Studies; Treatment Outcome; 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