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BackgroundHerein, we sought to determine the sensitivity to change in cognitive function, as measured by the THINC-it tool, in a sample of adults with major depressive disorder (MDD) receiving standardized antidepressant therapy.MethodsAdults meeting the DSM-5 criteria for MDD with at least moderate depressive symptom severity [i.e., Montgomery Åsberg Depression Rating Scale (MADRS) total score ≥ 20] were treated with open-label vortioxetine (10–20 mg/day, flexibly-dosed) for 8 weeks. The previously validated THINC-it tool was the primary dependent measure. The THINC-it tool was validated against the paper and pencil version of the Digit Symbol Substitution Test (DSST) and the Trails Making Test B (TMTB).ResultsAfter 8 weeks of treatment, adults with MDD exhibited improvement in cognitive function relative to healthy controls (e.g., processing speed) (p = 0.031). A subdomain measure of working memory (i.e., symbol check; SC) exhibited significant improvement at Weeks 2 and 8 in latency (p = 0.032), SC accuracy (p = 0.046), and objective z-score (p = 0.001) independent of depressive symptoms. A linear regression analysis determined that the THINC-it tool measures of processing speed, as well as executive function were significantly associated with changes observed on the pencil and paper version the Digit Symbol Substitution Test (DSST) (p = 0.002) and in Trails Making Test B (TMTB) (p = 0.003), respectively.ConclusionThe THINC-it tool demonstrates sensitivity to change in adults with MDD and is highly correlated with improvements on pencil and paper versions of DSST and TMTB.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT03053362.

Background: Anhedonia is a common, persistent, and disabling phenomenon in treated adults with Major Depressive Disorder (MDD). Hitherto, relatively few antidepressant agents have been evaluated with respect to their effect on anhedonia in MDD.Methods: This is a post-hoc analysis of a primary study that sought to evaluate the sensitivity to change of the THINC-integrated tool (THINC-it) in MDD (ClinicalTrials.gov Identifier: NCT03053362). Adults meeting DSM-5 criteria for MDD with at least moderate depressive symptom severity [i.e., Montgomery Åsberg Depression Rating Scale (MADRS) total score ≥20] were eligible. Subjects were recruited between October 2017 and August 2018 in Toronto, Ontario at the Brain and Cognition Discovery Foundation. All subjects received open-label vortioxetine (10–20 mg/day, flexibly-dosed) for 8 weeks. Herein, the primary outcome of interest was the change from baseline to endpoint in the Snaith-Hamilton Pleasure Scale (SHAPS) total score, as well as the MADRS anhedonia factor. The mediational effects of improvements in anhedonia on general function and quality of life, as measured by the Sheehan Disability Scale (SDS) and the 5-Item World Health Organization Well-Being Index (WHO-5), were secondarily assessed.Results: A total of 100 subjects with MDD were enrolled in the primary study and began treatment with vortioxetine. Vortioxetine significantly improved anhedonia as evidenced by significant baseline to endpoint improvements in SHAPS and MADRS anhedonia factor scores (p < 0.0001). Improvements in the SHAPS and the MADRS anhedonia factor correlated with improvements in general function (i.e., SDS) and quality of life (i.e., WHO-5) (p < 0.0001). Notably, improvements in anhedonia were found to mediate the association between improvements in overall depressive symptom severity (i.e., MADRS total score) and social functioning (i.e., social life component of the SDS) (p = 0.026).Conclusion: The unmet need in depression is to improve patient functioning and other patient-reported outcomes (e.g., quality of life). Antidepressant interventions capable of attenuating anhedonia as well as cognitive dysfunction in MDD may help in this regard, as improvement in these domains have been associated with improvement in psychosocial function and quality of life.