Vortioxetine reduces BOLD signal during performance of the N-back working memory task: a randomised neuroimaging trial in remitted depressed patients and healthy controls

Abstract

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.

Assessing and addressing cognitive impairment in bipolar disorder: the International Society for Bipolar Disorders Targeting Cognition Task Force recommendations for clinicians

“…Specifically, beneficial effects of a single dose (200 mg) of modafinil over placebo were observed on episodic memory and working memory (but not on executive function or sustained attention) in these remitted patients . Further, the antidepressant vortioxetine was found in several RCTs to improve some aspects of cognition in unipolar disorder, which seemed to be partially independent of its antidepressant actions and was also recently shown in remitted patients . Studies are therefore warranted to investigate the ability of these compounds to improve cognitive function in BD.…”

Neuronal underpinnings of cognitive impairment and - improvement in mood disorders

“…In contrast to the above-mentioned studies, Smith et al 25 found that 2 weeks of treatment with the monoaminergic antidepressant vortioxetine reduced working memory-related dlPFC activity in remitted UD in the absence of changes in working memory performance. Notably, these patients displayed no objective impairment in working memory performance in Performance: No effect of treatment (similar performance in UD and HC).…”

“…Nine fMRI studies investigated the neural correlates of cognitive improvement in mood disorders, of which 5 focused on specific mood-independent cognitive improvement in response to candidate cognition treatments, [22][23][24][25]123 and 4 investigated nonspecific cognitive improvement following symptom reduction 106,[124][125][126] (see Table 4).…”

“…14,21 In keeping with these findings, emerging evidence from a few recent intervention trials in mood disorders indicates that cognitive improvements are accompanied by neural activity changes in similar fronto-parietal, temporal, and DMN networks. [22][23][24][25] However, the precise location(s) and direction of the neural activity changes underlying cognitive impairments and cognitive improvements are unclear. The aims of the present systematic review were therefore to delineate (a) the most reliable neural underpinnings of cognitive impairments in mood disorders and (b) the emerging neural basis for direct or indirect cognitive improvements in response to candidate cognition treatments or reduction in mood symptoms, respectively.…”

Quantum Analysis of the Interaction of Vortioxetine vs. Neurotransmitters.

“…[13] Vx inhibits serotonin reuptake, in addition it is a 5-HT 1D, 5-HT 3, 5-HT 7 receptor antagonist, a 5-HT 1B receptor agonist and a 5-HT 1A receptor agonist. [14][15][16][17] Vx increases serotonergic, noradrenergic, dopaminergic, cholinergic, histaminergic and glutamatergic neurotransmission in brain structures associated with MDD. [21] The Japanese Takamine and Uenaka settled in New York on August 5, 1900, crystallizing AD by a different procedure to that used.…”