Vortioxetine 20 mg/day in patients with major depressive disorder: updated analysis of efficacy, safety, and optimal timing of dose adjustment.

BACKGROUND: Analysis of efficacy and tolerability of vortioxetine 20 mg/day, and optimal timing of dose adjustment, in patients with major depressive disorder (MDD). METHODS: Pooled analysis of six randomized, fixed-dose studies of vortioxetine 5 to 20 mg/day. Mean change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score was analyzed by vortioxetine dose using a mixed model for repeated measures. Tolerability was assessed over the 8-week treatment period and from day 8 (ie, following dose increase to 20 mg/day). Data from three randomized, flexible-dose studies were examined for frequency and timing of dose adjustment. RESULTS: A clear dose-response relationship for vortioxetine was confirmed in terms of improvement in MADRS total score. Significant differences vs placebo were seen for vortioxetine 20 mg/day from week 2 onwards; vortioxetine 10 mg did not separate from placebo until week 4. At week 8, mean change in MADRS total score from baseline was significantly greater for vortioxetine 20 mg/day vs 10 mg/day (difference, -1.03 points; P < .05). Incidence of adverse events was not increased in patients who received vortioxetine 20 mg/day vs 10 mg/day. In flexible-dose studies, dosage was increased to 20 mg/day after 1 week in 48.0% of patients; final dosage was 20 mg/day in 64.3% of patients. CONCLUSIONS: Vortioxetine 20 mg is significantly more effective than vortioxetine 10 mg in patients with MDD, with a similar tolerability profile. In flexible-dose studies, almost half of all patients received 20 mg/day after 1 week and two-thirds received 20 mg/day as their final dosage.

Emotional blunting in patients with depression. Part IV: differences between patient and physician perceptions.

BACKGROUND: Emotional blunting is common in patients with depression. An online survey was undertaken to assess the experience of emotional blunting, and its impact on functioning and quality of life, in the acute and remission phases of depression from the perspective of patients and healthcare providers (HCPs). This paper presents data on the level of concordance between patient and HCP perspectives. METHODS: This was a cross-sectional, observational study. Patient respondents were adults with a diagnosis of depression, who were currently using a prescribed antidepressant, and who reported emotional blunting during the past 6 weeks. HCPs completed the survey for the last two eligible patients they had seen, one in each phase of depression. Assessments included the Oxford Depression Questionnaire (ODQ) 'antidepressant as cause' domain and the Functioning Assessment Short Test (FAST). RESULTS: Mean ODQ 'antidepressant as cause' domain scores were significantly higher in the patient-reported cohort (n = 752) than in the HCP-assessed cohort (n = 766) in both the acute (18.0 vs 12.5, respectively; p < 0.01) and remission phases (17.6 vs 12.6; p < 0.01). Overall, 45% of patients believed that their antidepressant medication was negatively affecting their emotions and 39% were considering stopping or had stopped their antidepressant because of perceived emotion-related side effects. In the HCP-assessed cohort, the antidepressant was considered responsible for emotional blunting in 30% of patients and only 18% of patients were believed to be considering stopping their medication due to emotional blunting. Patients reported a greater impact of emotional blunting on activities of daily living than HCPs. Mean FAST score was significantly higher in each phase of depression in the patient-reported cohort than in the HCP-assessed cohort (acute phase, 47.0 vs 39.1; remission phase, 33.5 vs 19.4; both p < 0.01). CONCLUSIONS: Compared with previous studies, our results suggest that HCPs may underestimate the prevalence of emotional blunting in patients with depression. HCPs also appear to underestimate the severity and impact of emotional blunting on patient functioning and treatment adherence compared with patients' own perspectives. Differences between patient and HCP perspectives were most pronounced during the acute phase of the disease.

Emotional blunting in patients with depression. Part I: clinical characteristics.

BACKGROUND: Emotional blunting-inability to feel positive or negative emotions, detachment, or reduced emotional responsiveness-is common in people with depression. However, there is a paucity of studies comprehensively investigating this symptom and its functional impact. This study investigated the experience of emotional blunting, and its impact on overall functioning and quality of life, in the acute and remission phases of depression from the perspective of patients and healthcare providers. This paper presents data on the clinical presentation of emotional blunting in depression from the patient perspective. METHODS: Cross-sectional, observational study conducted in Brazil, Canada, and Spain between April 15 and May 18, 2021. Data were collected via a self-completed online survey. Respondents were adults with depression (acute or remission phase), who were currently using a prescribed antidepressant, and who reported emotional blunting during the past 6 weeks. Emotional blunting was assessed using the Oxford Depression Questionnaire (ODQ; total score range 26-130, higher scores indicate greater emotional blunting). RESULTS: In all, 752 patients completed the survey (62% female; mean age, 45 years). Overall, 44% of patients rated their emotional blunting as extremely severe (acute phase [n = 300], 72%; remission phase [n = 452], 25%; difference, p < 0.01). In all, 56% of patients considered their emotional blunting to be caused by their depression (acute phase, 62%; remission phase, 52%). Mean ODQ total score was 94.8 for patients in the acute phase of depression and 85.7 for those in remission (difference, p < 0.01). Mean score for the ODQ 'antidepressant as cause' domain (maximum possible score, 30) was 18.0 in patients in the acute phase and 17.6 in those in remission. Overall, 45% of patients believed that their antidepressant medication was blunting their emotions and 39% were considering stopping or had already stopped their antidepressant because of perceived emotion-related side effects. CONCLUSIONS: Almost three-quarters of patients in the acute phase of depression and one-quarter of those in remission reported severe emotional blunting. Approximately 56% of patients considered their emotional blunting to be caused by their depression, while 45% believed that their antidepressant medication was negatively affecting their emotions. Just over one-third of patients were considering stopping or had stopped their antidepressant as a result.

Emotional blunting in patients with depression. Part II: relationship with functioning, well-being, and quality of life.

BACKGROUND: Emotional blunting is a common symptom in people with depression and an important factor preventing full functional recovery. This international survey investigated the experience of emotional blunting in the acute and remission phases of depression from the perspective of patients and healthcare providers. This paper presents data on the impact of emotional blunting on overall functioning and health-related quality of life from the patient perspective. METHODS: Respondents were adults diagnosed with depression by a physician, currently prescribed an antidepressant, and reporting emotional blunting during the past 6 weeks. Assessments included the Oxford Depression Questionnaire (ODQ), the Functioning Assessment Short Test (FAST), and the World Health Organization-Five Well-being Index (WHO-5). Pearson correlation and multivariate regression analyses were applied to examine the relationship between ODQ and FAST scores. RESULTS: Data are available for 752 patients (62% female; mean age, 45 years). Mean ODQ total score was 94.8 in patients in the acute phase of depression (n = 300) and 85.7 in those in remission (n = 452; possible maximum, 130). Mean FAST total scores were 47.0 and 33.5, respectively (possible maximum, 72). Patients in the acute phase of depression had significantly greater impairment in functioning across all FAST domains than those in the remission phase (all differences, p < 0.01). Mean WHO-5 scores were 6.4 and 9.8 in the acute and remission phases, respectively (lower scores indicate poorer well-being). Overall, 65% of patients in the acute phase and 36% of those in remission reported that emotional blunting had a significant impact on their quality of life. Pearson correlation analysis showed a moderate positive correlation between ODQ and FAST total scores (r = 0.52) and a weak negative correlation between ODQ total score and WHO-5 score (r = - 0.26; both p < 0.01). In multivariate regression analysis, ODQ total score (in combination with other covariates) was the strongest significant predictor of poor patient functioning. CONCLUSIONS: Emotional blunting has a substantial negative impact on patients' daily functioning, well-being, and quality of life in both the acute and remission phases of depression. These findings highlight the importance of recognizing and treating emotional blunting in patients with major depressive disorder in order to achieve full functional recovery.

Emotional blunting in patients with depression. Part III: relationship with psychological trauma.

BACKGROUND: This international online survey investigated the experience and impact of emotional blunting in the acute and remission phases of depression from the perspective of patients and healthcare providers (HCPs). This paper presents data on the history and severity of psychological trauma and its potential impact on emotional blunting in major depressive disorder (MDD); differences between patient and HCP perceptions are explored. METHODS: Patient respondents (n = 752) were adults with a diagnosis of depression who were currently taking antidepressant therapy and reported emotional blunting during the past 6 weeks. HCPs provided details on two eligible patients: one in the acute phase of depression and one in remission from depression (n = 766). Trauma was assessed using questions based on the Childhood Trauma Questionnaire; emotional blunting was assessed using the Oxford Depression Questionnaire (ODQ). Multivariate regression analyses were applied to examine the relationship between trauma and ODQ score. RESULTS: A history of any childhood or recent traumatic event was reported by 97% of patients in the self-assessed cohort and for 83% of those in the HCP-assessed cohort (difference, p < 0.01). Patients were more likely than HCPs to feel that this trauma had contributed to their/the patient's depression (58% vs 43%, respectively; p < 0.01) and that the depression was more severe because of trauma (70% vs 61%, respectively; p < 0.01). Emotional blunting was significantly worse in patients who reported severe trauma than in those who had not experienced severe trauma (mean total ODQ score, 90.1 vs 83.9, respectively; p < 0.01). In multivariate regression analyses, experiencing both severe childhood and recent trauma had a statistically significant impact on ODQ total score (p = 0.001). CONCLUSIONS: A high proportion of patients with depression and emotional blunting self-reported exposure to childhood and/or recent traumatic events, and emotional blunting was more severe in patients who reported having experienced severe trauma. However, history of psychological trauma in patients with MDD appeared to be under-recognized by HCPs. Improved recognition of patients who have experienced psychological trauma and are experiencing emotional blunting may permit more targeted therapeutic interventions, potentially resulting in improved treatment outcomes.

Efficacy of vortioxetine in working patients with generalized anxiety disorder.

BACKGROUND: Vortioxetine is an approved antidepressant that has also demonstrated positive effects on anxiety symptoms in subjects with generalized anxiety disorder (GAD). This post-hoc analysis evaluates the efficacy of vortioxetine in GAD subjects who are working and/or pursuing an education. METHODS: In study NCT00744627, 301 GAD subjects were randomized to vortioxetine 5 mg or placebo for 8 weeks. Efficacy measures included the Hamilton Anxiety Rating Scale (HAM-A) total score, response/remission, global functioning (Sheehan Disability Scale [SDS]), and quality of life (Short Form-36 Health Survey). In study NCT00788034, 687 GAD subjects were treated open-label with vortioxetine 5 or 10 mg for 20 weeks, after which subjects in remission were randomized to fixed-dose of vortioxetine (5 or 10 mg) or placebo for at least 24 weeks. The primary endpoint was time to relapse. Analyses were completed in subjects working and/or pursuing an education at study entry and the full analysis set. RESULTS: In study NCT00744627, the effect of vortioxetine versus placebo on HAM-A total score was -4.3 (p=0.0005) in working subjects (60% of total), while the effect in the total population was -3.8 (p=0.0001). The effect was greatest in subjects in professional (-4.5, p=0.0130) and associate professional positions (-7.6, p=0.0086). Greater effects in terms of response, remission, and the SDS and SF-36 were also observed. In NCT00788034, working subjects (69% of total) randomized to placebo were significantly more likely to relapse than subjects treated with vortioxetine (hazard ratio=2.9; p<0.001), while the hazard ratio in the total population was 2.7 (p<0.0001). CONCLUSIONS: The beneficial effects of vortioxetine on anxiety symptoms, functioning, and quality of life are greater in adults with GAD who are working and/or pursuing an education versus the full GAD study population.

A Subgroup Analysis of the Impact of Vortioxetine on Functional Capacity, as Measured by UPSA, in Patients with Major Depressive Disorder and Subjective Cognitive Dysfunction.

Background: We evaluated vortioxetine's effects on functional capacity in demographic and clinical subgroups of patients with major depressive disorder. Methods: This was an exploratory analysis of the CONNECT study (NCT01564862) that evaluated changes in functional capacity using University of California San Diego Performance-based Skills Assessment data, categorized by sex, age, education, employment status, and baseline disease severity (Montgomery-Åsberg Depression Rating Scale, Clinical Global Impressions-Severity of Illness). Results: Greater changes in University of California San Diego Performance-based Skills Assessment composite scores were observed with vortioxetine vs placebo in specific subgroups: males (∆+3.2), females (∆+2.9), 45-54 or ≥55 years (∆+5.6, ∆+3.4), working (∆+2.8), high school or greater education (∆+2.7, ∆+2.8), disease severity (Montgomery-Åsberg Depression Rating Scale, <30, ∆+3.5; ≥30, ∆+2.5; Clinical Global Impressions-Severity of Illness ≤4, ∆+2.8; >4, ∆+3.0), major depressive episodes (≤2, >2 [∆+2.7,+3.3]), and episode duration (≤22, >22 weeks [∆+3.7,+2.4]). Conclusions: Our findings support the need for additional studies to assess whether vortioxetine improves functional capacity within specific patient subgroups. Clinical Trial Registry: clinicaltrials.gov: NCT01564862.

The Functioning Assessment Short Test (FAST): Clinically meaningful response threshold in patients with major depressive disorder receiving antidepressant treatment.

BACKGROUND: Functional impairment is common in patients with major depressive disorder (MDD). The Functioning Assessment Short Test (FAST) provides a detailed clinician-rated assessment of functioning across multiple aspects of daily life. This study aimed to establish clinically relevant response thresholds for the FAST in patients with MDD receiving antidepressant treatment. METHODS: Data were derived from three 8-week clinical trials of antidepressant therapy in patients with MDD that included assessment of functioning using the FAST as a pre-specified endpoint. The minimal clinically important difference (MCID) and threshold for response in terms of change in FAST total score were determined using anchor-based methods. RESULTS: After 8 weeks of antidepressant treatment, the mean reduction in FAST total score in patients considered clinically minimally improved (Clinical Global Impression-Improvement [CGI-I] score of 3) was 7-9 points (~20 % reduction). The threshold for functional response (reduction in FAST total score from baseline in patients with a CGI-I score of ≤2 at week 8) was 16-19 points (~50 % reduction). The threshold for functional response was higher in patients with MDD and comorbid generalized anxiety disorder than in those with MDD alone (mean reduction in FAST total score at 8 weeks: 26 points [63 %]). LIMITATIONS: Short-term studies. CONCLUSIONS: These results provide further validation of the FAST for assessing functioning in patients with MDD. In patients with MDD, the suggested MCID for FAST total score is 7-9 points and the proposed threshold for response is a reduction from baseline of approximately 50 %.

Effectiveness of Vortioxetine in Working Patients with Major Depressive Disorder in China: A Subgroup Analysis of the RELIEVE China Study.

Background: Major depressive disorder (MDD) causes significant functional impairments that impact on all aspects of patients' daily lives, including their ability to work, work productivity, and social life. Purpose: To assess the real-world effectiveness of the multimodal antidepressant vortioxetine in working patients with MDD in China. Patients and methods: RELIEVE China was an observational, prospective cohort study. Patients (aged ≥18 years) with MDD initiating treatment with vortioxetine in routine clinical practice settings were followed for 24 weeks. In this subgroup analysis, functioning was assessed using the Sheehan Disability Scale (SDS) in patients in full- or part-time work or education at baseline who remained on treatment at all follow-up visits (n=424). Depressive, cognitive, and anxiety symptoms were also assessed. For all endpoints, mean change from baseline at weeks 8 and 24 was analyzed using mixed models for repeated measures. Results: Clinically relevant and sustained improvements in patient functioning and measures of work productivity were observed over the 24 weeks of vortioxetine treatment. The adjusted mean (standard error) reduction in SDS total score from baseline was 5.4 (0.3) points at week 8 and 8.7 (0.3) points at week 24 (both P<0.001 vs baseline). Significant improvements were observed across all SDS domains and in levels of absenteeism and presenteeism (P<0.001 vs baseline for all endpoints at both time points). Significant improvements in depressive, cognitive, and anxiety symptoms were also observed over the study period (all P<0.001 vs baseline). The proportion of patients in remission (ie, 17-item Hamilton Depression Rating Scale score ≤7) after 24 weeks of vortioxetine treatment was 65.4%. Vortioxetine was well tolerated; nausea was the most common adverse event, reported by 18.6% of patients. Conclusion: These findings support the effectiveness and tolerability of vortioxetine in working patients with MDD receiving treatment in routine clinical practice settings in China.

Effectiveness of Vortioxetine for the Treatment of Emotional Blunting in Patients with Major Depressive Disorder Experiencing Inadequate Response to SSRI/SNRI Monotherapy in Spain: Results from the COMPLETE Study.

Background: The multinational, open-label COMPLETE study (NCT03835715) investigated the effectiveness of vortioxetine in alleviating emotional blunting in patients with major depressive disorder (MDD) experiencing inadequate response and emotional blunting while being treated with a selective serotonin reuptake inhibitor (SSRI) or serotonin-noradrenaline reuptake inhibitor (SNRI). This paper presents results for the subgroup of patients enrolled in Spain. Methods: Patients with MDD (n = 67) experiencing partial response and emotional blunting during monotherapy with an SSRI or SNRI were switched to vortioxetine (10-20 mg/day) for 8 weeks. The primary study outcome was emotional blunting, assessed by the Oxford Depression Questionnaire (ODQ). Results: After 8 weeks of vortioxetine, the mean (SE) change in ODQ total score from baseline was -26.0 (2.9) (P < 0.001). Respective changes in Montgomery-Åsberg Depression Rating Scale (MADRS), Motivation and Energy Inventory, Digit Symbol Substitution Test, and Sheehan Disability Scale (SDS) total scores were -14.9 (0.8), +34.2 (4.5), +6.3 (1.6), and ‒9.0 (1.3) (all P < 0.001 vs baseline). At week 8, 70.4% of patients no longer reported emotional blunting and 53.7% had achieved remission from their depressive symptoms (defined as a MADRS total score ≤10). Mediation analysis showed 77.1% of the change in SDS total score to be a direct effect of the improvement in ODQ total score after switching to vortioxetine. Adverse events were reported by 35 patients (52.2%), most commonly nausea (14 patients, 20.9%). At week 8, 33/54 patients (61.1%) were receiving vortioxetine 20 mg/day. Conclusion: In this study investigating the effectiveness of vortioxetine in Spanish patients with MDD who experienced inadequate response and emotional blunting on SSRI/SNRI monotherapy, significant improvements in emotional blunting, core depressive symptoms (including anhedonia), sleep duration, motivation and energy, cognitive performance, and overall patient functioning were observed during the 8 weeks of treatment. Two-thirds of patients no longer reported emotional blunting and over half were in remission from their depressive symptoms at week 8.

Clinical benefits and bioequivalence of vortioxetine oral drop solution versus oral tablets.

BACKGROUND: Vortioxetine is efficacious and well tolerated in patients with major depressive disorder (MDD) and is available as an immediate-release tablet and oral drop solution. The oral drop solution may offer clinical benefits versus a tablet, such as the reduced risk of nausea, personalised dosing and ease of administration. AIMS: To investigate the bioequivalence of vortioxetine 20 mg/mL oral drop solution versus a 20 mg immediate-release tablet. METHODS: Healthy adults were randomised 1:1 to receive vortioxetine 20 mg oral drop solution or immediate-release 20 mg tablet after fasting on days 1 and 29 in an open-label, single-centre, single-dose crossover study. The area under the plasma concentration-time curve from 0 to 72 h (AUC0-72h) and maximum plasma concentration (Cmax) were analysed. Bioequivalence was concluded if the 90% CI for the oral drop solution-to-immediate-release tablet ratio for AUC0-72h and Cmax were contained within a range of 0.80-1.25. RESULTS: Vortioxetine oral drop solution was bioequivalent to the tablet (n = 26; estimated AUC0-72h ratio 1.06 (90% CI: 1.03-1.10); Cmax ratio 1.01 (90% CI: 0.97-1.05)). A similar proportion of participants reported adverse events in each study arm but more headache events (7 vs 1) were reported with the oral drop solution versus tablet. The most common adverse event was nausea (16-23% of participants; all mild intensity). CONCLUSIONS: Vortioxetine oral drop solution is bioequivalent to immediate-release tablets. Oral drop solution provides an alternative to tablets and facilitates clinical benefit through individualised treatment, including gradual dose up-titration, for patients with MDD.

Goal Attainment Scaling for Depression: Validation of the Japanese GAS-D Tool in Patients with Major Depressive Disorder.

Purpose: Goal attainment scaling (GAS) has been proposed as a person-centric, semi-quantitative measure that assimilates achievement of individually set goals into a single standardized "goal attainment score" that can be compared at the population level. We aimed to examine the reliability and validity of the Japanese version of the GAS for depression (GAS-D) tool in assessing goal attainment in people living with major depressive disorder (MDD). Patients and Methods: This was a prespecified analysis of a prospective, 24-week, multicenter, observational cohort study of employed Japanese outpatients with MDD initiating treatment with vortioxetine according to the Japanese label (JRCT1031210200). Participants were assessed using the Japanese version of the GAS-D and other clinical rating scales at baseline and Weeks 8, 12 and 24. Results: Goal attainment was significantly associated with symptom severity as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS) scale, confirming convergent validity. In particular, GAS-D scores were significantly related to MADRS total score at Weeks 12 and 24, indicating that improvements in overall symptom severity with vortioxetine treatment were likely to be reflected in the achievement of individualized treatment goals. With an intraclass correlation coefficient of 0.67 (95% CI 0.45-0.82), the GAS-D also showed moderate test-retest reliability between Weeks 8 and 12 while proving independent of demographic characteristics. Conclusion: The results of this open-label study support the use of the GAS-D as a valid and sensitive outcome measure in the assessment of treatment response in MDD.

Effectiveness of vortioxetine in patients with major depressive disorder and early-stage dementia: The MEMORY study.

BACKGROUND: Depression and dementia are highly prevalent in older adults and often co-occur. This Phase IV study investigated the effectiveness and tolerability of vortioxetine in improving depressive symptoms, cognitive performance, daily and global functioning and health-related quality of life (HRQoL) in patients with major depressive disorder (MDD) and comorbid early-stage dementia. METHODS: Patients (n = 82) aged 55-85 years with a primary diagnosis of MDD (onset before age 55 years) and comorbid early-stage dementia (diagnosed ≥6 months before screening and after onset of MDD; Mini-Mental State Examination-2 total score, 20-24) received vortioxetine for 12 weeks (initiated at 5 mg/day and up-titrated to 10 mg/day at day 8, with flexible dosing thereafter [5-20 mg/day]). The primary endpoint was change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at week 12. RESULTS: Significant improvement in depressive symptom severity was seen from week 1 onwards (P < 0.0001). At week 12, the least-square mean (standard error) change in MADRS total score from baseline was -12.4 (0.78). Significant improvements in cognitive performance were observed (from week 1 for the Digit Symbol Substitution Test and week 4 for the Rey Auditory Verbal Learning Test). Patients also experienced significant improvements in daily and global functioning, and HRQoL. Vortioxetine was well tolerated. From week 4 onwards, more than 50 % of patients were receiving 20 mg/day. LIMITATIONS: Open-label study. CONCLUSIONS: Vortioxetine demonstrated effectiveness in clinically significantly improving depressive symptoms, cognitive performance, daily and global functioning, and HRQoL in patients with MDD and comorbid early-stage dementia treated for 12 weeks. TRIAL REGISTRATION: ClinicalTrials.gov/ct2/show/NCT04294654.

The Motivation and Energy Inventory (MEI): Analysis of the clinically relevant response threshold in patients with major depressive disorder and emotional blunting using data from the COMPLETE study.

BACKGROUND: The Motivation and Energy Inventory (MEI) is a patient-reported scale for assessment of the impact of mental/cognitive energy, social motivation, and physical energy on daily functioning in patients with major depressive disorder (MDD). This analysis was undertaken to establish the clinically relevant response threshold for the MEI in patients with MDD receiving antidepressant treatment. METHODS: Patients with MDD experiencing inadequate response and emotional blunting on selective serotonin reuptake inhibitor or serotonin-noradrenaline reuptake inhibitor monotherapy (adequate dose for ≥6 weeks) were switched to vortioxetine 10-20 mg/day for 8 weeks. Anchor- and distribution-based methods were used to determine the minimal clinically important difference (MCID) in MEI total score. RESULTS: After 8 weeks of vortioxetine treatment, mean (standard deviation) change in MEI total score from baseline was 33.0 (27.3) points. At week 8, mean change in MEI total score from baseline was 37.5 (27.8) points in patients no longer reporting emotional blunting and 28.3 (26.2) points in those still experiencing emotional blunting. In patients considered minimally improved (i.e. Clinical Global Impression-Improvement [CGI-I] score of 3 after 8 weeks of vortioxetine), mean change in MEI total score from baseline was 14.7 (19.1) points. In patients defined as responders (CGI-I score of 2 at 8 weeks), mean change in MEI total score was 33.0 (24.7) points. LIMITATIONS: Short study duration. CONCLUSIONS: These results provide further validation of the clinical utility of the MEI for assessing treatment response in patients with MDD. The suggested MCID for MEI total score is 15 points. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03835715.

Effectiveness of vortioxetine in patients with major depressive disorder and co-morbid generalized anxiety disorder in routine clinical practice: A subgroup analysis of the RELIEVE study.

BACKGROUND: Generalized anxiety disorder (GAD) is commonly co-morbid with major depressive disorder (MDD) and is associated with greater functional impairment and poorer treatment outcomes than MDD alone. However, studies on treatment with drugs for depression in patients with MDD and co-morbid GAD are limited. AIMS: To examine the effectiveness of vortioxetine treatment in patients with MDD and co-morbid GAD in a subgroup analysis of the real-world RELIEVE study. METHODS: The analysis included outpatients diagnosed with MDD and co-morbid GAD who initiated vortioxetine treatment at their physician's discretion in the 24-week, observational RELIEVE study. Primary outcome was patient functioning (Sheehan Disability Scale (SDS)) after 12 and 24 weeks of vortioxetine treatment; secondary outcomes included depression severity (9-item Patient Health Questionnaire (PHQ-9)), cognitive symptoms (5-item Perceived Deficits Questionnaire - Depression (PDQ-D-5)) and cognitive performance (Digit Symbol Substitution Test (DSST)). RESULTS: Overall, 180 patients with MDD and co-morbid GAD were included in the analysis. Following vortioxetine initiation, clinically significant improvements in patient functioning (SDS total score) were observed at week 12 (least-squares (LS) mean reduction from baseline, 7.5 points), sustained through week 24 (9.2 points) (both p < 0.0001). LS mean PHQ-9, PDQ-D-5 and DSST scores improved by 7.9, 4.8 and 7.4 points at week 24, respectively (all p < 0.0001 vs baseline). Adverse events were reported by 33.9% of patients (most commonly nausea, 13.3%). CONCLUSIONS: In routine clinical practice, vortioxetine was associated with clinically meaningful, sustained improvements in functioning, and depressive and cognitive symptoms, in patients with MDD and co-morbid GAD. CLINICAL TRIALS REGISTRY NAME AND IDENTIFIER: Real-life Effectiveness of Vortioxetine in Depression (RELIEVE) (NCT03555136) https://clinicaltrials.gov/ct2/show/NCT03555136.

Vortioxetine in patients with major depressive disorder and high levels of anxiety symptoms: An updated analysis of efficacy and tolerability.

BACKGROUND: Patients with major depressive disorder (MDD) often experience comorbid anxiety symptoms. Vortioxetine has demonstrated efficacy in treating anxiety symptoms in patients with MDD; however, efficacy and tolerability have not been assessed across the entire approved dosage range. METHODS: The efficacy and tolerability of vortioxetine 5-20 mg/day were assessed in patients with MDD and high levels of anxiety symptoms (Hamilton Anxiety Rating Scale [HAM-A] total score ≥ 20) using pooled data from four randomized, fixed-dose, placebo-controlled studies (n = 842). Data from a randomized, double-blind study of vortioxetine 10-20 mg/day versus agomelatine 25-50 mg/day in patients with an inadequate response to prior therapy (n = 299) were analyzed separately. Mean changes from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS), HAM-A, and Sheehan Disability Scale (SDS) total scores were analyzed by vortioxetine dosage. RESULTS: The pooled analysis of fixed-dose studies demonstrated a clear dose-response relationship for vortioxetine 5-20 mg/day for improvements in MADRS, HAM-A, and SDS total scores. Vortioxetine 20 mg/day demonstrated significant effects versus placebo from week 4 onwards. In the post-hoc analysis of the active-controlled study in patients with an inadequate response to prior therapy, vortioxetine 10-20 mg/day was superior to agomelatine across all outcome measures from week 4 onwards. Up-titration of vortioxetine to 20 mg/day was not associated with an increase in adverse events. LIMITATIONS: Short-term trials. CONCLUSIONS: Vortioxetine is efficacious and well tolerated in patients with MDD and high levels of anxiety symptoms, including those with an inadequate response to prior therapy. The greatest therapeutic benefits were observed with vortioxetine 20 mg/day. TRIAL REGISTRATION: NCT01140906, NCT01153009, NCT01163266, NCT01255787, NCT01488071.

Head-To-Head Comparison of Vortioxetine Versus Desvenlafaxine in Patients With Major Depressive Disorder With Partial Response to SSRI Therapy: Results of the VIVRE Study.

Objective: To compare the efficacy of vortioxetine and the serotonin-norepinephrine reuptake inhibitor (SNRI) desvenlafaxine in patients with major depressive disorder (MDD) experiencing partial response to initial treatment with a selective serotonin reuptake inhibitor (SSRI).Methods: This randomized, double-blind, active-controlled, parallel-group, 8-week study of vortioxetine (10 or 20 mg/d; n = 309) versus desvenlafaxine (50 mg/d: n = 293) was conducted from June 2020 to February 2022 in adults with a DSM-5 diagnosis of MDD who experienced partial response to SSRI monotherapy. The primary endpoint was mean change from baseline to week 8 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Differences between groups were analyzed using mixed models for repeated measures.Results: Non-inferiority of vortioxetine versus desvenlafaxine was established in terms of mean change from baseline to week 8 in MADRS total score; however, a numeric advantage was observed in favor of vortioxetine (difference, -0.47 MADRS points [95% CI, -1.61 to 0.67]; P = .420). At week 8, significantly more vortioxetine-treated than desvenlafaxine-treated patients had achieved symptomatic and functional remission (ie, Clinical Global Impressions-Severity of Illness scale [CGI-S] score ≤ 2) (32.5% vs 24.8%, respectively; odds ratio = 1.48 [95% CI, 1.03 to 2.15]; P = .034). Vortioxetine-treated patients also experienced significantly greater improvements in daily and social functioning assessed by the Functioning Assessment Short Test (P = .009 and .045 vs desvenlafaxine, respectively) and reported significantly greater satisfaction with their medication assessed by the Quality of Life Enjoyment and Satisfaction Questionnaire (P = .044). Treatment-emergent adverse events (TEAEs) were reported in 46.1% and 39.6% of patients in the vortioxetine and desvenlafaxine groups, respectively; these were mostly mild or moderate in intensity (> 98% of all TEAEs in each group).Conclusions: Compared with the SNRI desvenlafaxine, vortioxetine was associated with significantly higher rates of CGI-S remission, better daily and social functioning, and greater treatment satisfaction in patients with MDD and partial response to SSRIs. These findings support the use of vortioxetine before SNRIs in the treatment algorithm in patients with MDD.Trial Registration: ClinicalTrials.gov Identifier: NCT04448431.

Assessing Reliability and Validity of the Oxford Depression Questionnaire (ODQ) in a Japanese Clinical Population.

Purpose: Originally developed in English, the Oxford Depression Questionnaire (ODQ) is a patient-reported scale specifically developed for assessing emotional blunting in people with major depressive disorder (MDD). We aimed to examine the reliability and validity of the Japanese version of the ODQ. Patients and methods: This was a prespecified analysis of a prospective, 24-week, multicenter, observational cohort study of employed Japanese outpatients with MDD initiating treatment with vortioxetine according to the Japanese label (JRCT1031210200). Participants were assessed using the Japanese version of the ODQ and other clinical rating scales at baseline and Weeks 8, 12 and 24. Results: One hundred and sixteen patients initiated vortioxetine and had ≥1 post-baseline visit. Directionally, the associations between ODQ scores and other clinical measures were as expected and demonstrated good concurrent validity. Factor analysis shows that the scale has a good fit for three factors. The Cronbach's α coefficient was 0.912, and the scale also showed good test-retest reliability with intraclass correlation coefficients for the ODQ total score and domains ranging between 0.69 and 0.82. ODQ scores had strong positive correlations with symptom severity assessed using the Montgomery and Åsberg Depression Rating Scale and were moderately correlated with work productivity, overall functioning, and quality of life scales. Conclusion: Data from this prospective analysis confirm that the Japanese version of the ODQ retains the good validity and reliability of the original English scale and is suitable for use in prospective studies wanting to capture treatment effects on emotional blunting in MDD.

Effectiveness of vortioxetine in patients with major depressive disorder comorbid with generalized anxiety disorder: Results of the RECONNECT study.

BACKGROUND: Major depressive disorder (MDD) and generalized anxiety disorder (GAD) are frequently comorbid. AIMS: To assess the effectiveness of vortioxetine in patients with MDD and comorbid GAD. METHODS: Open-label, 8-week study (NCT04220996) in 100 adult outpatients with severe MDD and severe comorbid GAD receiving vortioxetine as first treatment for the current depressive episode or switching to vortioxetine due to inadequate response to another drug for depression. Vortioxetine starting dosage was 10 mg/day, with forced up-titration to 20 mg/day after 1 week. Response was defined as ⩾50% decrease in Montgomery-Åsberg Depression Rating Scale (MADRS) and/or Hamilton Anxiety Rating Scale (HAM-A) total score from baseline; remission defined as MADRS and/or HAM-A total score ⩽10. RESULTS: Clinically meaningful and statistically significant improvements from baseline in symptoms of depression and anxiety, and overall functioning and health-related quality of life, were observed after 8 weeks' vortioxetine treatment (all changes p < 0.0001 vs baseline). At week 8, rates of MADRS response and remission were 61% and 35%, respectively. Corresponding rates of HAM-A response and remission were 55% and 42%. Response on both the MADRS and HAM-A scales was achieved by 52% of patients; 31% achieved remission on both scales. Vortioxetine dose up-titration was well tolerated; no unexpected adverse events were reported. CONCLUSION: Vortioxetine demonstrates effectiveness in significantly reducing symptoms of both depression and anxiety in patients with severe MDD comorbid with severe GAD. Findings support increasing vortioxetine dosage to 20 mg/day early in the course of therapy, and show that this may be achieved without compromising tolerability.