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Cognitive symptoms in major depressive disorder (MDD) contribute to impaired functional abilities and work productivity, particularly presenteeism. We investigated the association between baseline cognitive symptoms and subsequent presenteeism, and global functional impairment in Japanese patients with MDD from PERFORM-J (Prospective Epidemiological Research on Functioning Outcomes Related to Major Depressive Disorder in Japan) – a 6-month, multicenter, epidemiological study data. A total of 518 patients initiating antidepressant monotherapy (first-line or switched from another drug) were enrolled. Assessments include Perceived Deficits Questionnaire – Depression (PDQ-D) for cognitive complaints, Sheehan Disability Scale (SDS) for global function (analysed n = 318), and Work Productivity and Activity Impairment Questionnaire for presenteeism (analysed n = 122). A strong association between changes in presenteeism and changes in SDS scores (r: total = 0.636; work/school = 0.686) was observed. After adjusting for sociodemographic and MDD-related factors, patients without cognitive complaints at baseline showed lower odds of impaired presenteeism at 6 months versus patients with cognitive complaints (0.243, 95% CI: 0.079 to 0.747, p = 0.014) and also in patients with first episode of MDD against with recurrent MDD (0.327 (95% CI: 0.136 to 0.787). Similarly, patients without cognitive complaints had healthier global functioning (lower mean SDS total score) than patients with cognitive complaints (8.3 vs 11.2; 95% CI, −5.189 to −0.578; p = 0.014). First depressive episode (lower risk of presenteeism), being male, and low baseline SDS total score (better global functioning) were also associated with improved outcomes. These results highlight the potential value of baseline PDQ-D scores in predicting subsequent workplace and global functioning in patients undergoing treatment for MDD. [ABSTRACT FROM AUTHOR]

Aim: Anhedonia in major depressive disorder may be resistant to first-line antidepressants. We examined the effect of vortioxetine, a multimodal antidepressant, on anhedonia-like symptoms in Japanese patients with major depressive disorder. Methods: This was a post hoc analysis of an 8-week, randomized, double-blind, placebo-controlled, phase 3 study of vortioxetine (10 mg or 20 mg) in Japanese patients aged 20– 75 years with recurrent major depressive disorder and a Montgomery–Åsberg Depression Rating Scale (MADRS) total score of at least 26. The primary outcome was the mean change from baseline to week 8 in anhedonia-like symptoms as measured by MADRS anhedonia factor score, composed of: Q1, apparent sadness; Q2, reported sadness; Q6, concentration; Q7, lassitude; and Q8, inability to feel. Mean change in MADRS total score and anhedonia factor score were compared among treatment groups, with data categorized by median baseline anhedonia factor score (0– 17 or ≥ 18). Results: Data were available for 489 patients. The least-squares mean difference in MADRS anhedonia factor score change from baseline to week 8 versus placebo was − 1.34 for vortioxetine 10 mg (P = 0.0300) and − 1.77 for vortioxetine 20 mg (P = 0.0044). The least-squares mean difference between vortioxetine and placebo in MADRS total score change from baseline to week 8 was − 3.11 (10 mg dose) and − 3.37 (20 mg dose) for patients with a higher baseline anhedonia factor score (≥ 18), and − 2.08 (10 mg) and − 2.61 (20 mg) for patients with a lower baseline score (0– 17). Conclusion: This post hoc analysis suggests that vortioxetine may have therapeutic potential in patients with anhedonia-like symptoms of major depressive disorder. ClinicalTrials.gov identifier for primary study: NCT02389816. [ABSTRACT FROM AUTHOR]

Aim: Antidepressants, including selective serotonin reuptake inhibitors, often elicit a poor response in patients with major depressive disorder (MDD) with significant anxiety symptoms. This study investigated the effects of the multimodal antidepressant vortioxetine in patients with MDD and associated anxiety. Methods: This was a post hoc analysis of data from an 8-week, randomized, double-blind, placebo-controlled, Phase 3 study of vortioxetine (10 mg or 20 mg) in Japanese patients aged 20– 75 years with recurrent MDD and a Montgomery–Åsberg Depression Rating Scale (MADRS) score of at least 26. Changes from baseline to week 8 in MADRS total score and Hamilton Depression Rating Scale (HAM-D) anxiety/somatization factor score were assessed in patients with anxious depression (HAM-D anxiety/somatization factor score ≥ 7) and without anxious depression. Results: Data were available for 489 patients. In patients with anxious depression, the least-squares (LS) mean difference (95% confidence interval [CI]) versus placebo in change in MADRS total score was − 3.44 (− 6.10, − 0.77) for vortioxetine 10 mg and − 4.51 (− 7.15, − 1.87) for vortioxetine 20 mg. In patients with non-anxious depression, the LS mean difference (95% CI) versus placebo was − 1.81 (− 4.71, 1.09) and − 1.05 (− 4.00, 1.90) for vortioxetine 10 mg and 20 mg, respectively. Changes from baseline in HAM-D anxiety/somatization factor score were greater in patients treated with vortioxetine 10 mg or 20 mg than in those treated with placebo. Conclusion: Vortioxetine may be effective for patients with anxiety symptoms in MDD. Further research is warranted to investigate these effects in a real-world clinical setting. Clinical Trials Registration: ClinicalTrials.gov identifier for primary study: NCT02389816. [ABSTRACT FROM AUTHOR]

Aim: Several weeks of treatment with an antidepressive agent may be required before efficacy is demonstrated in patients with major depressive disorder. This study investigated the predictive value of early partial improvement with vortioxetine for treatment response and remission. Methods: This was a post hoc analysis of an 8-week, randomized, double-blind, placebo-controlled, Phase 3 study of vortioxetine (10 mg or 20 mg) in Japanese patients aged 20– 75 years with recurrent major depressive disorder and a Montgomery–Åsberg Depression Rating Scale (MADRS) score of at least 26. The key outcomes were the predictive value of early partial improvement (reduction in MADRS total score of ≥ 20% from baseline to week 2) with vortioxetine for MADRS response (≥ 50% decrease in score from baseline) and remission (decrease in score to ≤ 10) at week 8. Results: Relevant data were available for 478 patients; 62/158 patients receiving placebo, 71/162 receiving vortioxetine 10 mg, and 66/158 receiving vortioxetine 20 mg were early improvers. Early improvers receiving vortioxetine (10 mg or 20 mg) were more likely than non-early improvers to achieve a week 8 response (71.2– 73.2% vs 29.7– 38.0%) or remission (50.7– 51.5% vs 17.4– 18.7%). Positive predictive values for response and remission with vortioxetine were ∼ 70% and ∼ 50%, respectively; negative predictive values were ∼ 70% and ∼ 80%, respectively. Conclusion: Improvement with vortioxetine may be predicted by early partial improvement in MADRS score. Some patients may benefit from longer-term treatment even without early improvement, another finding that may aid clinical decision-making. ClinicalTrials.gov registration for primary study: NCT02389816. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is highly prevalent in Japan and frequently accompanied by insomnia that may persist even with MDD remission. Hypnotics are used for the pharmacological treatment of insomnia, but their influence on MDD recurrence or residual insomnia following MDD remission is unclear. This retrospective, longitudinal, cohort study utilized a large Japanese health insurance claims database to investigate patterns of hypnotic prescriptions among patients with MDD, and the influence of hypnotic prescription pattern on MDD recurrence. Methods: Eligible patients (20–56 years) were those registered in the Japan Medical Data Center database between 1 January 2005 and 31 December 2018, and prescribed antidepressant and hypnotic therapy after being diagnosed with MDD. Patients who had ceased antidepressant therapy for > 180 days were followed for 1 year to evaluate depression recurrence, as assessed using Kaplan-Meier estimates. Logistic regression modelling was used to analyze the effect of hypnotic prescription pattern on MDD recurrence. Results: Of the 179,174 patients diagnosed with MDD who initiated antidepressant treatment between 1 January 2006 and 30 June 2017, complete prescription information was available for 2946 eligible patients who had been prescribed hypnotics. More patients were prescribed hypnotic monotherapy (70.8%) than combination therapy (29.2%). The most prescribed therapies were benzodiazepine monotherapy (26.2%), non-benzodiazepine monotherapy (28.9%), and combination therapy with two drugs (21.1%). Among patients prescribed multiple hypnotics, concomitant prescriptions for anxiolytics, antipsychotics, mood stabilizers and sedative antidepressants were more common. The 1-year recurrence rate for MDD was approximately 20%, irrespective of hypnotic mono- versus combination therapy or class of hypnotic therapy. Being a spouse (odds ratio [OR], 1.44; 95% confidence interval [CI], 1.03–2.02) or other family member (OR, 1.46, 95% CI, 0.99–2.16) of the insured individual, or being prescribed a sedative antidepressant (OR, 1.50, 95% CI, 1.24–1.82) conferred higher odds of MDD recurrence within 1 year of completing antidepressant therapy. Conclusions: Benzodiazepines are the most prescribed hypnotic among Japanese patients with MDD, though combination hypnotic therapy is routinely prescribed. Hypnotic prescription pattern does not appear to influence real-world MDD recurrence, though hypnotics should be appropriately prescribed given class differences in efficacy and safety. [ABSTRACT FROM AUTHOR]

Background: Residual insomnia is associated with a risk of depression recurrence.Methods: In this retrospective, longitudinal cohort study, the recurrence pattern of depression in patients with or without residual insomnia was assessed using a health insurance claims database. Patients who were diagnosed with major depressive disorder and prescribed antidepressants, between January 2006 and June 2017 in Japan, were enrolled in the study. Residual insomnia was defined by a prescription of hypnotics, and recurrence of depression by prescription of antidepressants. Main outcomes included time to recurrence and the 1-year recurrence rate. Factors associated with recurrence of depression were assessed by multivariate analyses. The effect of residual insomnia on the frequency of recurrence was assessed by Chi-square test.Results: Of the 30,381 patients analyzed, there were 4,166 and 26,215 patients with or without residual insomnia, respectively. Time to recurrence in patients with residual insomnia was significantly shorter compared with those without residual insomnia (p <0.001), with a 1-year recurrence rate (95% CI) of 43.4% (41.9-45.0) and 7.4% (7.1-7.7), respectively. The frequency of recurrence was significantly higher in patients with residual insomnia than in those without (p <0.0001). A higher risk of depression recurrence (odds ratio 9.98, 95% CI 9.22-10.81) was found for residual insomnia compared with other significant factors.Limitations: The diagnosis stated in the receipt data may not accurately reflect the patient's condition, and medication adherence was unknown but assumed.Conclusions: Residual insomnia is a significant risk factor for depression recurrence in Japanese patients. [ABSTRACT FROM AUTHOR]