Major Depressive Disorder
Measuring Cognitive Dysfunction: The Digit Symbol Substitution Test
Patients with major depressive disorder (MDD) may experience cognitive impairments not only before and during depressive episodes but also after mood symptoms have remitted. Such impairments contribute to missed workdays, poor academic performance, and a reduced ability to carry out day-to-day tasks. The Digit Symbol Substitution Test (DSST) is the most extensively used and validated cognitive test in neuropsychology. Here, Charles Debattista, MD, Professor of Psychiatry and Behavioral Sciences at Stanford University, discusses the measurement of cognitive dysfunction in patients with MDD.
Professor of Psychiatry and Behavioral Sciences
"The NMA using the DSST showed that vortioxetine was the only antidepressant that improved cognitive dysfunction on the DSST versus placebo."
It is a very interesting range of cognitive dysfunctions you see in patients with mood disorders and especially the group of patients for whom symptoms are getting better but the cognitive performance is not. In our practice, we see many people who used to be high-functioning workers (eg, Silicon Valley executives) who have had 1 or more episodes of depression and who with treatment may achieve significant improvement in their depressive symptoms, allowing for a return to work—but not at the same level of functioning as before.
A big factor driving disability in patients with MDD—and even partial disability, in the population that we work with—is cognitive impairment, which may certainly outlive the emotional aspects of the depressive episode.
Many studies have investigated cognitive function in depression in a variety of cognitive domains, including attention, processing speed, executive function, and memory. However, data are limited on the comparative effectiveness of antidepressants on cognitive symptoms. The diversity of tools used in clinical trials to assess cognition tends to cloud this picture, creating heterogeneous outcomes. Recently, Baune and colleagues were able to compare the effects of various antidepressant classes on the DSST (ie, across 72 randomized clinical trials from 103 publications, the DSST was the only test that was used in 12 of the included trials) allowing for construction of a stable network suitable for the network meta-analysis (NMA).
The NMA using the DSST showed that vortioxetine was the only antidepressant that improved cognitive dysfunction on the DSST versus placebo. Compared with 3 other antidepressants, vortioxetine was statistically more efficacious on the DSST versus escitalopram, nortriptyline, and the selected serotonin reuptake inhibitor and tricyclic antidepressant classes.
This study highlighted the fact that so many different measures have been used to assess cognitive functioning. The findings on the DSST support the notion that there may be different effects of various antidepressants on improving cognitive function in patients with MDD. Certainly, more studies are required to better understand cognitive deficits associated with MDD and the response of these deficits to various procognitive strategies.
Baune BT, Brignone M, Larsen KG. 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. Int J Neuropsychopharmacol. 2017. doi: 10.1093/ijnp/pyx070. [Epub ahead of print].
Baune BT, Miller R, McAfoose J, Johnson M, Quirk F, Mitchell D. The role of cognitive impairment in general functioning in major depression. Psychiatry Res. 2010;176(2-3):183-189.
Jaeger J, Zaragoza Domingo S. The digit symbol substitution test (DSST): psychometric properties and clinical utility in major depressive disorder. 2016. Abstract presented at the 29th ECNP Congress, Vienna, Austria.
Trivedi MH, Greer TL. Cognitive dysfunction in unipolar depression: implications for treatment. J Affect Disord. 2014;152-154:19-27.
Trivedi MH, Morris DW, Wisniewski SR, et al. Increase in work productivity of depressed individuals with improvement in depressive symptom severity. Am J Psychiatry. 2013;170(6):633-641.