The effects of vortioxetine versus placebo on cognitive functioning in mild cognitive impairment: a placebo-controlled, randomized, double-blind study

IntroductionThis study investigates the effects of vortioxetine on cognitive performance in patients with mild cognitive impairment (MCI) in a randomized controlled trial (RCT). MCI is characterized by memory impairment and deficits in other cognitive domains and has been found to progress into Alzheimers dementia (AD) in some cases. In a recent open-label, single-arm study, vortioxetine, an antidepressant, was associated with improved cognitive function in patients with MCI, however, no placebo-controlled studies have been conducted to support these findings. MethodsForty-seven subjects diagnosed with MCI were randomly assigned to receive treatment with either 10 mg vortioxetine, 20 mg vortioxetine, or placebo over 12 weeks, in a randomized, double-blind study design. Neuropsychological tests were conducted several times during the trial, including at a baseline screening visit, consisting of the Alzheimers Disease Assessment Scale - Cognitive Subscale (ADAS-cog), a German version of the Rey Auditory Verbal Learning Test ("Verbaler Lern-und Merkfahigkeitstest", VLMT), the Digit Symbol Substitution Test (DSST), the Mini-Mental State Examination (MMSE), and the Quality of Life Scale (QOLS). Statistical analysis of neuropsychological data was performed using linear mixed models (LMM) and subsequent post-hoc testing to account for multiple comparisons. ResultsLMM results showed a significant increase in VLMT test scores from baseline to week 12 in the 10 mg (p = 0.02) and 20 mg vortioxetine groups (p = 0.017). The placebo group showed a significant increase in test scores from baseline to week 4 (p = 0.009), followed by a significant decrease in test performance observed from week 4 to week 8 (p = 0.006). Both the vortioxetine and placebo groups showed statistically significant DSST test score changes over 12 weeks (10mg: p = 0.004; 20mg: p <.0001; placebo: p <.0001). Similarly, ADAS-Cog test performance significantly increased from baseline to week 12 in both the 10 mg vortioxetine group (p = 0.02) and the placebo group (p = 0.002). MMSE test results showed significant improvement over 8 weeks in the 20 mg vortioxetine group (p = 0.011), compared to no significant findings in the 10 mg and placebo groups. A significant improvement of QOLS scores was observed from week 8 to week 12 in the 10 mg vortioxetine group only (p = 0.033). ConclusionThe results of this study indicate a potential treatment effect of vortioxetine on verbal learning and memory processes in patients with MCI. However, the effects of vortioxetine could not be found at the group level; thus, further research and larger RCTs are needed to elucidate its underlying mechanisms and potential in MCI and early AD treatment.