A Network Meta-Analysis Comparing Effects of Various Antidepressant Classes on the Digit Symbol Substitution Test (DSST) as a Measure of Cognitive Dysfunction in Patients with Major Depressive Disorder

摘要

Background Major depressive disorder is a common condition that often includes cognitive dysfunction. A systematic literature review of studies and a network meta-analysis were carried out to assess the relative effect of antidepressants on cognitive dysfunction in major depressive disorder. Methods MEDLINE, Embase, Cochrane, CDSR, and PsychINFO databases; clinical trial registries; and relevant conference abstracts were searched for randomized controlled trials assessing the effects of antidepressants/placebo on cognition. A network meta-analysis comparing antidepressants was conducted using a random effects model. Results The database search retrieved 11337 citations, of which 72 randomized controlled trials from 103 publications met the inclusion criteria. The review identified 86 cognitive tests assessing the effect of antidepressants on cognitive functioning. However, the Digit Symbol Substitution Test, which targets multiple domains of cognition and is recognized as being sensitive to change, was the only test that was used across 12 of the included randomized controlled trials and that allowed the construction of a stable network suitable for the network meta-analysis. The interventions assessed included selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and other non-selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors. The network meta-analysis using the Digit Symbol Substitution Test showed that vortioxetine was the only antidepressant that improved cognitive dysfunction on the Digit Symbol Substitution Test vs placebo {standardized mean difference: 0.325 (95% CI = 0.120; 0.529, P =.009}. Compared with other antidepressants, vortioxetine was statistically more efficacious on the Digit Symbol Substitution Test vs escitalopram, nortriptyline, and the selective serotonin reuptake inhibitor and tricyclic antidepressant classes. Conclusions This study highlighted the large variability in measures used to assess cognitive functioning. The findings on the Digit Symbol Substitution Test indicate differential effects of various antidepressants on improving cognitive function in patients with major depressive disorder. major depressive disorder , vortioxetine , cognitive dysfunction , systematic literature review , network meta-analysis Significance Statement Cognitive dysfunction is a common impairment for patients with major depressive disorder (MDD) and leads to debilitating problems such as missed workdays, poor academic performance, and reduced ability to perform day-to-day tasks. Numerous studies have investigated cognitive function in depression in a variety of domains, including attention, processing speed, executive function, and memory. Nevertheless, there is limited evidence on comparative effectiveness of antidepressants on cognitive symptoms, mainly due to the diversity of tools used in clinical trials. This study compared the effects of antidepressants on a commonly used cognitive outcome, the Digit Symbol Substitution Test (DSST), and showed that vortioxetine had the largest improvement in DSST vs all investigated classes of single antidepressants. It was the only antidepressant demonstrating statistically significant improvement vs placebo and vs specific antidepressants. The findings support the effect of vortioxetine in improving cognitive function in MDD patients measured by the DSST.