Major Depressive Disorder and Improving Cognitive Functioning

Young female psychiatrist talking with despair patient
Researchers found data that showed the Work Limitations Questionnaire is a useful tool to identify working patients with major depressive disorder and cognitive impairment.

The Work Limitations Questionnaire (WLQ) can be used to effectively identify working patients with major depressive disorder (MDD) who have considerable potential to respond to treatment in clinical trials evaluating impairment in cognitive functioning so these trials can better evaluate and develop useful antidepressant therapies, according to study results published in the Journal of Affective Disorders.

The prevalence of impaired cognitive functioning in MDD is currently unknown, and the methods used to assess cognitive impairment in working patients with MDD provide diverse results that cannot be easily equated across all studies. Also, working patients with MDD who are evaluated for cognitive functioning often produce high scores on assessments at baseline, but don’t necessarily respond well to antidepressant treatment. The objective of this study was to determine whether the WLQ can identify working patients with MDD who may achieve high scores in cognitive functioning at baseline, but who could still benefit from improvements in symptoms and functioning.

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In this study, researchers performed retrospective analyses of data from the CONNECT study, which evaluated the effects of vortioxetine on cognitive functioning in adults with MDD (n=528). The goal was to identify patients who had greater potential for treatment response.

The CONNECT study used 2 versions of the University of California San Diego Performance-Based Skills Assessment (UPSA): the 5-skill domain UPSA-Validation of Intermediate Measures (UPSA-VIM) for the United States and the UPSA-B, which was used in non-English speaking countries and was developed with the financial and communication subtests that correlated most closely with the total scores on the 5 subtests in the UPSA-VIM. Spearman and Pearson correlation coefficients were calculated to examine the association between UPSA-B and WLQ scores at baseline. The study end points were changes from baseline to week 8 in 3 measures: WLQ scores, Digit Symbol Substitution Test scores, and the UPSA-B using analysis of covariance in the observed cases.

Results revealed that working patients achieved higher UPSA-B scores at baseline compared with patients who didn’t work (79.83 vs 77.49; P =.049). A statistically significant improvement was observed in UPSA-B scores among patients treated with vortioxetine vs placebo in the working patient subgroup (4.12; P =.005), but there was no statistically significant improvement observed in nonworking patients (2.18; P =.071).

Working patients also achieved higher Digit Symbol Substitution Test scores at baseline compared with those who didn’t work (45.19 vs 41.02; P <.001), and exhibited lower improvements in treatment when receiving vortioxetine relative to placebo. Improvement was not statistically significant for the working patient group (1.01; P =.403) although it was for the nonworking group (2.66, P =.008).

Working patients with baseline WLQ scores >13 (n=123) had greater impairments in UPSA-B than those who had baseline WLQ scores ≤13 (n = 84) (78.46 vs 81.83; P =.052). Compared with patients who received placebo, patients with WLQ scores >13 who received vortioxetine treatment experienced statistically significant improvements in UPSA-B and DSST (5.37-point improvement with vortioxetine vs placebo, P =.018). The same effect was not seen in patients with baseline WLQ scores ≤13.

Limitations to this study were its small patient sample size, use of post hoc analysis, and generalizability that was limited to working patients with MDD.

The study researchers concluded that the WLQ can effectively identify working patients with MDD and cognitive impairment who can benefit from improvements in symptoms and functional capacity, and who can participate in clinical trials aimed at developing and improving antidepressant therapies.

Disclosure: This clinical trial was supported by Takeda Pharmaceuticals U.S.A., Inc. Please see the original reference for a full list of authors’ disclosures.


Murthy NV, Xu R, Zhong W, Harvey PD. Using self-reported vocational functioning measures to identify employed patients with impaired functional capacity in major depressive disorder [published online September 4, 2019]. J Affect Disord. doi: 10.1016/j.jad.2019.09.025.