In VIVRE (NCT04448431), vortioxetine was associated with significantly higher rates of symptomatic and functional remission, better daily and social functioning, and greater treatment satisfaction than desvenlafaxine in patients with major depressive disorder (MDD) and partial response to selective serotonin reuptake inhibitor (SSRI) therapy. This analysis further explored the relative improvement in patient functioning with vortioxetine versus desvenlafaxine.

VIVRE was a randomized, double-blind study of vortioxetine (10 or 20 mg/day) versus desvenlafaxine (50 mg/day) in adults with MDD and partial response to initial SSRI monotherapy. Mean percentage changes from baseline to week 8 in Functioning Assessment Short Test (FAST) total and domain scores were analyzed by treatment group in the overall population and in working patients.

In the overall population, the mean reduction in FAST total score from baseline after 8 weeks of treatment was 37.2% in vortioxetine-treated patients versus 31.8% in desvenlafaxine-treated patients (P = 0.04). Significantly greater improvements versus desvenlafaxine were seen in vortioxetine-treated patients for FAST autonomy, cognitive functioning, and interpersonal-relationships scores (all P < 0.05). In working patients, the mean reduction in FAST total score from baseline at week 8 was 38.7% versus 32.1% in the vortioxetine and desvenlafaxine groups, respectively (P = 0.04). Significant correlations were seen between absolute changes in patient functioning, and those in depression severity and health-related quality of life.

Vortioxetine was significantly better than desvenlafaxine in improving overall functioning as well as daily, social, and cognitive functioning in patients with MDD with inadequate response to prior SSRI therapy.

Vortioxetine has demonstrated dose-dependent efficacy in patients with major depressive disorder (MDD), with the greatest effect observed with vortioxetine 20 mg/day. This analysis further explored the clinical relevance of the more rapid and greater improvement in depressive symptoms observed with vortioxetine 20 mg/day vs 10 mg/day.

Analysis of pooled data from six short-term (8-week), randomized, placebo-controlled, fixed-dose studies of vortioxetine 20 mg/day in patients with MDD (N = 2620). Symptomatic response (≥50% decrease in Montgomery–Åsberg Depression Rating Scale [MADRS] total score), sustained symptomatic response, and remission (MADRS total score ≤10) were assessed by vortioxetine dosage (20 or 10 mg/day).

After 8 weeks, 51.4% of patients receiving vortioxetine 20 mg/day had achieved symptomatic response vs 46.0% of those receiving vortioxetine 10 mg/day (P < .05). Significantly more patients achieved symptomatic response vs placebo from week 2 onwards for vortioxetine 20 mg/day and from week 6 onwards for vortioxetine 10 mg/day (both P ≤ .05). Sustained response was achieved from week 4 for 26.0% of patients receiving vortioxetine 20 mg/day vs 19.1% of those receiving vortioxetine 10 mg/day (P < .01), increasing to 36.0% and 29.8%, respectively, over the 8-week treatment period (P < .05). At week 8, 32.0% of patients receiving vortioxetine 20 mg/day were in remission vs 28.2% of those receiving vortioxetine 10 mg/day (P = .09). Rates of adverse events and treatment withdrawal were not increased during the week following vortioxetine dose up-titration to 20 mg/day.

Vortioxetine 20 mg/day provides more rapid and more sustained symptomatic response than vortioxetine 10 mg/day in patients with MDD, without compromising tolerability.

Major depressive disorder (MDD) is a debilitating disease in Italy affects 5.4% of people over 15 and 11.6% for the elderly. Efficacy of vortioxetine in adult patients with MDD was demonstrated in randomised controlled trials, there is a need for data on treatment in daily practice in Italy.

To present the effectiveness and safety data of vortioxetine in real-world setting from patients enrolled from Italy in the RELIEVE study.

RELIEVE was a prospective, multi-national, observational study of outpatients initiating vortioxetine treatment for MDD at physician’s discretion. Data and outcomes of treatment of patients were collected at routine clinical visits. The primary outcome was functioning measured by SDS. Secondary outcomes included depressive symptoms measured by PHQ-9, cognitive funcion measured by PDQ-5, quality of life measured by EQ-5D-5L. Changes from baseline to month 6 were estimated with a linear mixed model of repeated measures approach.

A total of 231 patients (mean age, 55.5 years, 27.3% over 65 years, 62% female) were enrolled from Italy and included in the analysis. Mean(SD) SDS total score, PHQ-9, PDQ-5 scores at baseline were 17.8(7.58), 15.7(5.97) and 9.8(4.99), the scores(SE) decreased by 6.6(0.64), 5.9(0.47) and 3.6(0.36) from baseline to last visit. Mean(SE) EQ-5D-5L utility index increased by 0.13(0.01). Safety and tolerability profile of vortioxetine was in line with the established profile.

Improvements in overall functioning, depressive symptoms, cognitive function and quality of life were observed in patients treated with vortioxetine, including a wide proportion of elderly patients in a real-world setting.

A. Pugliese is an employee of Lundbeck Italy. K. Simonsen and H. Ren are employees of H. Lundbeck A/S.

Major depressive disorder (MDD) affects around 10% of the French population annually and significantly impacts patient functioning. Efficacy of vortioxetine was demonstrated in randomised controlled trials, data on its real-world performance is needed.

To describe the effectiveness and safety of vortioxetine in real-world setting from patients enrolled from France in the global RELIEVE study.

RELIEVE was a prospective, multi-national, observational study of outpatients initiating vortioxetine treatment for MDD at physician’s discretion. Data were collected at routine clinical visits. Here we present the outcomes of treatment of patients in France. The primary outcome was functioning measured by SDS. Secondary outcomes included depressive symptoms measured by PHQ-9, cognitive symptoms measured by PDQ-5 and DSST. Changes from baseline to month 6 were estimated with a linear mixed model of repeated measures approach.

A total of 184 patients (mean age, 50.2 years, 65% female, 67.9% of patients had at least one comorbidity) were enrolled from France and included in the analysis. Mean(SD) SDS total score, PHQ-9, PDQ-5 scores at baseline were 21.1(5.4), 17.5(4.7) and 11.7(4.4), the scores(SE) decreased by 10.9(0.59), 9.3(0.48) and 6.1(0.37) from baseline to month 6. Mean(SD) DSST improved from 41.6(15.2) at baseline to 49.1(19.0) at month 6. Safety and tolerability profile of vortioxetine was in line with previous studies.

Sustained improvements in overall functioning, depressive symptoms, cognitive function were observed in patients treated with vortioxetine in a real-world setting, which provided further evidence of effectiveness and safety of vortioxetine in a broad MDD population in France.

M. Rabbani is an employee of Lundbeck France. K. Simonsen and H. Ren are employees of H. Lundbeck A/S.

This study is about the clinical uses of three antidepressants( escitalopram, desvenlafaxine, vortioxetine) in the treatment of anxioun depression.

The purpose of this study was to compare the efficacy and safety of escitalopram, desvenlafaxine, vortioxetine, and aripiprazole augmentation with escitalopram in the acute treatment of anxious depression.

Patients (n=189) with DSM5 major depression and high levels of anxiety were evenly randomized to escitalopram, desvenlafaxine, vortioxetine, and aripiprazole augmentation with escitalopram in a six-week, randomized, rater-blinded, head to head comparative trial. Changes in overall depressive and anxiety symptoms were assessed.

Patients demonstrated similar baseline-to-endpoint improvement in HAMD and HAMA total scores. Patients also demonstrated similar response rate and remission rate in HAMD and HAMA. In analysis of individual HAMD and HAMA items, desvenlafaxine had greatly reduced scores for anxiety somatic (p=0.013), hypochondriasis (p=0.014), cardiovascular symptoms (p=0.005), respiratory symptoms (p=0.013) compared to escitalopram or vortioxetine. Each treatment were well tolerated with no significant differences.

These results showed no significant differences in efficacy and tolerability of escitalopram, desvenlafaxine, vortioxetine, and aripiprazole augmentation with escitalopram in this subtype of patients with anxious depression during the acute phase treatment.

No significant relationships.

Goal attainment scaling (GAS) is a method to assess the patient experience of whether a treatment is successful and capture outcomes across a diverse range of goal areas. However, this approach has not yet been used in assessing the treatment of Major Depressive Disorder (MDD) in Japan. GAS was first developed by Kiresuk and Sherman in the 1968, it is increasingly recognised as a sensitive method for recording patient-centred outcomes throughout the course of treatment.

To demonstrate the effectiveness of vortioxetine on patient’s goal achievement and depressive symptoms, emotional, cognitive, overall function and quality of life.

VGOAL-J is a prospective, multi-center, observational cohort study of outpatients initiating vortioxetine treatment for MDD in Japan. Patients with a diagnosis of MDD according to DSM-5 who are 18 to 65 years will be enrolled from 20 sites in Japan and followed for 24 weeks. A total number of 120 patients is planned for enrolment. Primary outcome measures are GAS-D, WPAI, secondary outcome measures include Montgomery – Åsberg Depression Rating Scale (MADRS), Sheehan Disability Scale (SDS), Perceived Deficits Questionnaire-Depression 5-item (PDQ-D-5), Oxford Depression Questionnaire (ODQ), EuroQol-5 Dimension (EQ-5D). Safety will be also assessed with Adverse Events collected during the study.

The results will be disseminated in late 2022 and provide new insights on GAS-D as an effective strategy to assess MDD treatment in Japan.

We expect to observe patients treated with vortioxetine achieving their treatment goals as assessed by GAS-D and improvements on patient- and clinician-reported measures in real-world settings.

Prof. K. Watanabe reports consultancies undertaken for Eli Lilly, Otsuka Pharmaceutical, Sumitomo Dainippon Pharma, Taisho Toyama Pharmaceutical, and Takeda Pharmaceutical, honoraria received from Daiichi Sankyo, Eisai, Eli Lilly, GlaxoSmithKline, J

Analysis of efficacy and tolerability of vortioxetine 20 mg/day, and optimal timing of dose adjustment, in patients with major depressive disorder (MDD).

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.

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.

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.

Vortioxetine has demonstrated sustained efficacy and favorable safety profile in multiple clinical trials.

This study aims to describe the effectiveness and safety of vortioxetine in real-world clinical practice.

RELIEVE is a prospective, multi-national, observational cohort study of outpatients initiating vortioxetine treatment for MDD at physician’s discretion and followed for 6 months. Data were collected at routine clinical visits. The primary outcome was functioning measured by Sheehan Disability Scale (SDS). Depressive symptoms measured by Patient Health Questionnaire 9-item (PHQ-9), cognitive symptoms measured by PDQ-5 and DSST were key secondary outcomes. Safety outcomes including adverse events were reported. This interim analysis presents results of 527 patients who completed the study and were followed for 6 months. Mixed models of repeated measures were used to assess improvements between baseline and month 6, adjusted for relevant confounders.

A total of 527 patients (mean age, 50.2 years, 65% female) were enrolled from US, Canada, France and Italy, and included in the analysis. Mean SDS total score, PHQ-9, PDQ-5 scores decreased by 8.6, 7.4 and 4.7 respectively from baseline to last visit. Mean DSST score improved by 6.5 from baseline to last visit. Patients’ overall functioning and quality of life significantly improved, sick leave days and underproductive days (both absenteeism and presenteeism) decreased over the entire follow up period. The overall incidence of adverse events(AE) was 25%, with the most common AEs being nausea and headache.

The results confirm the effectiveness and good tolerability of vortioxetine in a broad range of patients in routine clinical practice.

Dr. Mattingly has served as researcher, consultant or speaker for Akili, Alcobra, Alkermes, Allergan, Axsome, Boehringer, Forum, Genentech, Jansen, Lundbeck, Medgenics, Merck, Neos, NLS Pharma, Otsuka, Reckitt Benckiser, Roche, Sage, Shire, Sunovion, Supe

Functional recovery is the contemporary treatment goal in Major Depressive Disorder (MDD). Although consistency among physician and patient expectations may influence the therapeutic result (Demyttenaere K et al, 2011), patients’ perceptions are not always fully captured. Vortioxetine,a multimodal antidepressant, has shown encouraging data in achieving functional recovery, improving both mood and cognitive symptoms (Mahableshwarkar AR et al, 2015).

The aim of the study was to assess the effectiveness of vortioxetine on mood symptoms, cognitive symptoms and functionality, assessed by patient-rated tools, in MDD outpatients in Greece.

In this non-interventional study, vortioxetine was administered as flexible dosing (5-20 mg/d). Mood symptoms, cognitive symptoms and functioning were assessed by the patient-rated scales PHQ-9, PDQ-D and SDS respectively, at baseline, 1 and 3 months. Repeated measures analysis of variance and t-test were used for the statistical analyses.

336 patients participated in the study. PHQ-9 score ±SD decreased from 16.1±5.3, to 10.0±5.7 and 4.6±4.5, PDQ-D score ±SD decreased from 37.3±16.6 to 23.1±14.8 and 12.0±10.6, SDS Score ±SD decreased from 18.7±5.3 to 12.9±5.9 and to 7.8±6.5, at baseline, 1 and 3 months, respectively. The 3 SDS subscales: work/school life improved from 5.8±2.4 to 4.2±2.2 and 2.6±2.2, social life improved from 6.6±2.0 to 4.5±2.2 and 2.7±2.3 and family life improved from 6.3±2.0 to 4.3±2.1 and 2.6±2.3 -baseline, 1 and 3 months, respectively (p<0.001 for all paired comparisons).

MDD patients in Greece treated with vortioxetine significantly improved on mood symptoms, cognitive symptoms and functioning, enriching the already published efficacy data which is mostly based on clinician-rated scales.

A. Galanopoulos and E. Papalexi are full-time employees in Lundbeck Hellas.

Antidepressants in older people have experienced their increase in medical prescriptions in recent decades whit comorbidity with other pathologies and drug polytherapies. With the use of antidepressants, can be observed side and unwanted effects (e.g. emotional blunting). Vortioxetine is a new antidepressant agent which promises fewer side effects.

To evaluate the clinical efficacy, safety, side effects (e.g emotional blunting) and cognitive profile

45 elderly patients affected by MDD (DSM-5) were recruited in our observational study. All patients were treated with vortioxetine for 12 months. Physiological and pathological parameters were collected at baseline (T0), after 3 months (T1), 6 months (T2); 12 months (T3). All patients were administered the following scales: GDS; MMSE; QLi; ODQ. The statistical data were processed with EZAnalyze.

33.33% of patients had a score in the “unlikely depression” GDS group. The ANOVA ODQ “Total” results indicate that at least two of the repeated measures differ significantly. Data of the “antidepressant as cause” dimension are interesting [T0 vs T3 (P-Unadjusted .000; P-Bonferroni .000; T-value 5.687. MMSE scores are indicative of one small but not significant difference. Mean QLIndex scores did not show statistically significant changes, but are indicative of positive changes from the baseline score

Vortioxetine resulted in partial reduction of depression. There was a moderate non-statistically significant increase in body weight, glycidic and lipid profiles. Overall data highlight the importance and role that vortioxetine can have in the management of depressive symptoms in elderly subjects. The handling, effectiveness and reduced side effects of the molecule are emphasized.

The current treatment goal in Major Depressive Disorder (MDD) is functional recovery (Zimmerman M et al, 2012). However, finding the “right dose for the right patient” may be challenging and the dose-response relationship for antidepressant efficacy remains controversial (Hieronymus F et al, 2016). Efficacy evaluated by MADRS increases with higher vortioxetine doses, based on meta-analysis data (Thase ME et al, 2016).

The aim of this exploratory analysis was to assess the impact of different doses on vortioxetine effectiveness in clinical practice in Greece.

In this non-interventional study, open-label vortioxetine was administered at a flexible dosage (5-20 mg/d). Patients receiving 5/10 mg vortioxetine (group A), at the end of the study, were compared to patients receiving 15/20mg vortioxetine (group B). At baseline, 1 and 3 months, depressive symptoms and functioning were assessed by MADRS and SDS. Multiple regression was used for the statistical analyses.

The study included 336 MDD patients. At the end of the study, 64.3% (n=200) of patients were receiving 15/20 mg vortioxetine. Higher vortioxetine dose at month 3 was significantly correlated with higher MADRS total score at baseline (p<0.001). SDS total score change from baseline to month 3 was significantly associated with vortioxetine dose (p<0.001), with group A and group B showing improvements of -9.2±8.2 and -12.1±6.0, respectively- whereas such association was not observed for MADRS total score.

In conclusion, patients with more severe depressive symptoms were treated with higher antidepressant doses. However, beyond symptom improvement, vortioxetine effectiveness on patient functioning seems to increase with higher doses.

A. Galanopoulos and E. Papalexi are full-time employees in Lundbeck Hellas. A. Ettrup is a full-time employee in H. Lundbeck A/S.

This study aimed to evaluate the risk of suicidal ideation and behavior associated with vortioxetine treatment in adults with major depressive disorder (MDD).

Suicide-related events were evaluated post hoc using 2 study pools: one short-term pool of 10 randomized, placebo-controlled studies (6–8 weeks) and another long-term pool that included 3 open-label extension studies (52 weeks). Evaluation of suicide-related events was performed using Columbia-Suicide Severity Rating Scale (C-SSRS) scores and treatment-emergent adverse events (TEAEs) data.

At baseline, the percentage of patients reporting any C-SSRS ideation or behavior events in short-term studies was similar between placebo (14.7%), vortioxetine (19.8%, 13.0%, 11.2%, and 13.7% for 5-, 10-, 15-, and 20-mg groups, respectively), and duloxetine active reference (13.2%) and did not change throughout the 6- to 8-week treatment period for placebo (17.0%), vortioxetine (19.3%, 13.5%, 12.6%, and 15% for 5-, 10-, 15-, and 20-mg groups, respectively), or duloxetine (11.3%). The incidence of suicide-related events for TEAEs in the short-term pool was 0.4% for placebo, 0.2% or 1.0% for vortioxetine 5 mg or 10 mg, and 0.7% each for vortioxetine 15 mg and 20 mg, as well as duloxetine. After 52-week treatment with vortioxetine, suicidal ideation based on C-SSRS was 9.8%, C-SSRS suicidal behavior was 0.2%, and the incidence of suicide-related events based on TEAEs was <1%. There were no completed suicides in any study.

Vortioxetine is not associated with increased risk of suicidal ideation or behavior in MDD patients.

The AtWoRC study is an interventional, open-label Canadian study that demonstrated significant improvements in cognitive function and workplace productivity in patients with major depressive disorder (MDD) treated with vortioxetine for a current major depressive episode. The objective of the present analysis was to assess the Canadian economic impact of improved workplace productivity based on the AtWoRC study results.

The economic impact of improved productivity in patients with MDD treated with vortioxetine was assessed over a 52-week period considering productivity loss due to absenteeism and presenteeism using the standard human capital approach and an employer’s perspective. Absenteeism was measured with the Work Productivity and Activity Impairment questionnaire; and presenteeism with the Work Limitation Questionnaire. Productivity gains following treatment initiation with vortioxetine were estimated using the difference from baseline.

In the AtWoRC study, patients at baseline reportedly missed, in the past 7 days, an average of 8.1 h due to absenteeism and 3.0 h due to presenteeism. Following 52 weeks of treatment with vortioxetine, patients reportedly missed an average of 4.9 h due to absenteeism and 2.0 h due to presenteeism. This improved workplace productivity translated into savings of C$110.64 for 1 week of work following 52 weeks of treatment. The cumulative 52-week economic impact showed potential savings of C$4,550 when factoring in the cost of therapy.

This study suggested that workplace productivity gain due to an improvement in symptoms of MDD following treatment with vortioxetine will lead to substantial cost savings for the Canadian economy.

The objective of this work was to describe treatment-emergent sexual dysfunction (TESD) and tolerability following a switch from selective serotonin reuptake inhibitor (SSRI: citalopram, paroxetine, or sertraline) monotherapy to vortioxetine or escitalopram monotherapy in adults with well-treated major depressive disorder (MDD) and SSRI-induced sexual dysfunction.

Data were analyzed from the primary study, an 8-week, randomized, double-blind, head-to-head study in which participants with well-treated depressive symptoms but experiencing TESD with SSRIs were directly switched to flexible doses (10/20 mg) of vortioxetine or escitalopram. Sexual functioning was assessed by the Changes in Sexual Functioning Questionnaire-14 (CSFQ-14), efficacy by the Montgomery–Åsberg Depression Rating Scale scores (MADRS) and Clinicians Global Impression of Severity/Improvement (CGI-S/CGI-I), and tolerability by adverse events. Efficacy and tolerability were assessed by pre-switch SSRI therapy where possible, and by participant characteristics.

Greater improvements in TESD were seen in the vortioxetine compared with escitalopram groups based on: participant demographics (≤45 years, women; P = 0.045), prior SSRI treatment (P = 0.044), number of prior major depressive episodes (MDEs) (1–3; P = 0.001), and duration of prior SSRI therapy (>1 year; P = 0.001). Prior SSRI treatment did not appear to influence the incidence or severity of TEAEs, except for nausea. Regardless of prior SSRI, both treatments maintained antidepressant efficacy after 8 weeks.

Results suggest that vortioxetine is a safe and effective switch therapy for treating SSRI-induced sexual dysfunction in adults with well-treated MDD. Also, improvement in sexual dysfunction with vortioxetine or escitalopram may be influenced by prior SSRI usage, sex, age, and history of MDEs.

AtWoRC (Assessment in Work productivity and the Relationship with Cognitive symptoms) was an interventional, open-label, Canadian study (NCT02332954) designed to assess the association between cognitive symptoms and workplace productivity in working patients with major depressive disorder (MDD) receiving vortioxetine.

Eligible patients with MDD received vortioxetine (10–20 mg/day) and were assessed over 52 weeks at visits emulating a real-life setting (n = 199). Partial correlation between changes in patient-reported cognitive symptoms (20-item Perceived Deficits Questionnaire–Depression; PDQ-D-20) and workplace productivity (Work Limitations Questionnaire; WLQ) was assessed at 12 and 52 weeks. Additional assessments included depression severity, cognitive performance, and patient-reported functioning. Structural equations model (SEM) analyses assessed causal relationships between changes in measures of cognition and functioning over time, adjusted for improvements in depressive symptoms.

Statistically significant improvements in all outcomes from baseline to week 52 were seen in the overall population and both subgroups (first treatment and switch). Response and remission rates were 77% and 56%, respectively. Improvements in PDQ-D-20 and WLQ productivity loss scores at weeks 12 and 52 were significantly correlated. SEM analyses found patient-rated cognitive symptoms (PDQ-D-20) at weeks 12 and 26 were significantly predictive (p < 0.05) of patient-reported functioning (Sheehan Disability Scale) at the subsequent visit. Depression severity and objectively measured cognitive performance did not significantly predict functional outcomes at any timepoint.

These results demonstrate the long-term benefits of vortioxetine treatment in working patients with MDD and emphasize the strong association between cognitive symptoms and functioning in a real-world setting.

The Assessment in Work Productivity and the Relationship with Cognitive Symptoms (AtWoRC) study aimed to assess the association between cognitive symptoms and work productivity in gainfully employed patients receiving vortioxetine for a major depressive episode (MDE).

Patients diagnosed with major depressive disorder (MDD) and treated with vortioxetine independently of study enrollment were assessed over 52 weeks at visits that emulated a real-life setting. Patients were classified as those receiving vortioxetine as the first treatment for their current MDE (first treatment) or having shown inadequate response to a previous antidepressant (switch). The primary endpoint was the correlation between changes in patient-reported cognitive symptoms (20-item Perceived Deficits Questionnaire [PDQ-D-20]) and changes in work productivity loss (Work Limitations Questionnaire [WLQ]) at week 12. Additional assessments included changes in symptom and disease severity, cognitive performance, functioning, work loss, and safety.

In the week 12 primary analysis, 196 eligible patients at 26 Canadian sites were enrolled, received at least one treatment dose, and attended at least one postbaseline study visit. This analysis demonstrated a significant, strong correlation between PDQ-D-20 and WLQ productivity loss scores (r=0.634; p<0.001), and this correlation was significant in both first treatment and switch patients (p<0.001). A weaker correlation between Digit Symbol Substitution Test and WLQ scores was found (r=−0.244; p=0.003).

At 12 weeks, improvements in cognitive dysfunction were significantly associated with improvements in workplace productivity in patients with MDD, suggesting a role for vortioxetine in functional recovery in MDD.

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.

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.

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).

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.

These post hoc analyses evaluate the efficacy, safety, and tolerability of vortioxetine versus placebo in patients aged ≥55 years with major depressive disorder (MDD).

Study-level efficacy data from 12 short-term, fixed-dose, randomized, placebo-controlled trials of vortioxetine 5–20 mg/day were assessed using a random-effects meta-analysis. Adverse events (AEs), vital signs, ECG values, liver enzymes, and body weight were pooled from the same studies. Patients had baseline Montgomery–Åsberg Depression Rating Scale (MADRS) total scores ranging from 22–30.

1508 patients (mean age=62.4 years; range, 55–88 years) were included. Mean differences from placebo in change from baseline to study end (6/8 weeks) in MADRS were –2.56 (5 mg, n=324, P=0.035), –2.87 (10 mg, n=222, P=0.007), –1.32 (15 mg, n=90, P=NS), and –4.65 (20 mg, n=165, P=0.012). Odds ratios for response versus placebo were 1.6 (5 mg, P=NS), 1.8 (10 mg, P=0.002), 1.2 (15 mg, P=NS), and 2.5 (20 mg, P<0.001), and for remission versus placebo were 1.5 (5 mg, P=NS), 1.5 (10 mg, P=NS), 1.4 (15 mg, P=NS), and 2.7 (20 mg, P=0.001). The proportion of patients with AEs for placebo and vortioxetine 5–20 mg was 61.5% and 62.3%, respectively, with no increase at increased doses. Vortioxetine demonstrated a placebo-level incidence of serious AEs (1.2%). AEs occurring in ≥5% of any treatment group were nausea, headache, diarrhea, dizziness, dry mouth, constipation, fatigue, vomiting, and anxiety. No clinically significant mean changes in vital signs, ECG values, liver enzymes, or body weight emerged during treatment.

Vortioxetine 5–20 mg/day is efficacious and well tolerated in MDD patients aged ≥55 years, a group that is often comorbid with other conditions and treated with other medications.

Antidepressants are frequently associated with treatment-emergent sexual dysfunction (TESD). Vortioxetine, which was approved for patients with major depressive disorder (MDD), has a receptor profile that suggests limited impact on sexual functioning.

Arizona Sexual Experiences Scale (ASEX) patient-level data were pooled from 7 short-term vortioxetine trials (6 in MDD, 1 in generalized anxiety disorder) and analyzed for incidence of TESD at any post-baseline visit in patients without sexual dysfunction at baseline (defined as ASEX total score ≥19; individual ASEX item score ≥5; or a score ≥4 on any 3 ASEX items). The primary objective was to confirm the non-inferiority of vortioxetine 5–20 mg/day to placebo on the incidence of TESD. Comparisons were based on the common risk difference (95% confidence interval). Additional analyses compared vortioxetine to duloxetine and duloxetine to placebo. A sensitivity analysis, defined as TESD at 2 consecutive post-baseline visits, was conducted.

TESD incidence, relative to placebo, generally increased with vortioxetine dose with vortioxetine 5 mg non-inferior to placebo. Vortioxetine 10, 15, and 20 mg did not meet the non-inferiority criterion, but no dose had a significantly higher risk of developing TESD versus placebo. Changes in ASEX individual item scores supported the similarity of vortioxetine doses to placebo. Significantly higher TESD risk occurred with duloxetine 60 mg/day versus placebo and versus vortioxetine 5 or 10 mg. The sensitivity analysis was generally consistent with the primary analysis. Rates of spontaneously reported sexual adverse events were low.

Vortioxetine was associated with rates of TESD that were not significantly different from placebo in short-term clinical trials.