Treatment effects on residual cognitive symptoms among partially or fully remitted patients with major depressive disorder: A randomized, double-blinded, exploratory study with vortioxetine

Background: Residual cognitive symptoms in major depressive disorder (MDD) are common, yet poorly investigated. We explored the effectiveness of vortioxetine as adjunctive treatment to selective serotonin reuptake inhibitors (SSRI) and as monotherapy versus continued SSRI, in patients with MDD who achieved full or partial remission with SSRI, but report residual cognitive symptoms. Methods: Patients (18-65 years old, N = 151) diagnosed with MDD, with a Hamilton Depression Rating Scale 17-items total score <= 10 and a Perceived Deficits Questionnaire-Depression total score >25, were randomized 1: 1: 1 to 8 weeks of double-blind treatment with current SSRI + placebo, SSRI + vortioxetine (10-20 mg/day), or vortioxetine (10-20 mg/day) + placebo. The primary efficacy measure was the Digit Symbol Substitution Test (DSST), analyzed using a mixed model for repeated measurements. Secondary outcomes comprised cognitive functioning, subjectively-rated cognitive symptoms, patient functioning, and mood symptoms. Results: From baseline to week 8, all treatment groups improved DSST performance, with statistically nonsignificant treatment differences. Similar results were seen for secondary endpoints. Improvement in cognitive performance tended to be numerically larger with vortioxetine monotherapy than with SSRI monotherapy, while vortioxetine as adjunctive treatment tended to perform numerically better in further improving depressive symptoms. Most adverse events were mild or moderate. Nausea was the most common adverse event for vortioxetine. Limitations: Small sample sizes limited statistical power. Conclusion: In this explorative study, remitted patients with MDD improved their cognitive performance with no treatment differences. Secondary results indicate numerical benefits for cognitive performance with vortioxetine monotherapy, and for depressive symptoms with vortioxetine augmentation.