Studies Of Vortioxetine Research Articles

Efficacy of vortioxetine versus desvenlafaxine in the treatment of functional impairment in patients with major depressive disorder: Results from the multinational VIVRE study.

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 20mg/day) versus desvenlafaxine (50mg/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 8weeks 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.

Safety and effectiveness of vortioxetine in patients with major depressive disorder in a real-life clinical setting in India: results from an interventional, flexible-dose study

Objective Vortioxetine has demonstrated safety and efficacy in improving symptoms of major depressive disorder (MDD), including overall functioning in real-world settings. This is the first study in a real-life clinical setting in India to evaluate effectiveness and safety of vortioxetine in patients with MDD. Methods This interventional, open-label study consisted of a 12-week treatment period with flexible doses of vortioxetine (5–20 mg/day) in adult patients (aged 18–65 years) with a confirmed MDD diagnosis. Effectiveness outcomes included change from baseline to week 12 in Patient Health Questionnaire-9 (PHQ-9) and Clinical Global Impression–Severity (CGI-S) scores, along with CGI-Improvement (CGI-I) scores at week 12, using a mixed model for repeated measures. Adverse events (AEs) were recorded for safety outcome assessments. Results Of 395 patients who received vortioxetine, 42.3% were women mean age 38.9 years; 322 patients completed the study. Significant improvement in depressive symptoms was observed in change from baseline to week 12 least squares (LS) mean (SE) PHQ-9 total score (−9.36 [0.276]; p<.0001) and CGI-S score (−2.14 [0.065]; p<.0001). LS mean (SE) CGI-I score showed significant improvement at week 12 (1.93 [0.067]; p<.0001). Subgroup analysis across age, sex, disease severity, and body mass index showed significant improvements in depression symptoms and severity. A total of 35.4% (n = 140) of patients experienced treatment-emergent AEs (mostly mild-moderate); nausea and pruritus were the most frequent (6.6%, n = 26 each). Conclusion Safety and effectiveness of vortioxetine in improving symptoms of MDD over a 12-week period was demonstrated in a real-life clinical setting in India. Clinical trial registration information Open-label, flexible-dose study of vortioxetine in patients with major depressive disorder in India; Clinical Trials.gov ID: NCT04288895; https://www.clinicaltrials.gov/study/NCT04288895

Effectiveness of vortioxetine in elderly patients with major depressive disorder in real-world clinical practice: Results from the RELIEVE study.

Data demonstrating the real-world, long-term effectiveness of vortioxetine in elderly patients with major depressive disorder (MDD) are clinically useful to confirm findings from randomized trials. RELIEVE was a multinational, 24-week, observational, prospective study in outpatients with MDD initiating vortioxetine treatment in routine care settings (NCT03555136). Here, we report data from a subgroup of 130 patients aged ⩾ 65 years. The primary study outcome was changed from baseline in patient functioning assessed using the Sheehan Disability Scale (SDS). Other clinical outcomes included depression severity (Patient Health Questionnaire-9 [PHQ-9] and Clinical Global Impressions-Severity [CGI-S]), cognitive performance (Digit Symbol Substitution Test [DSST]) and symptoms (Perceived Deficits Questionnaire - Depression-5 item [PDQ-D-5]), and health-related quality of life (HRQoL) (EuroQoL 5 Dimensions 5 Levels [EQ-5D-5L]). Clinically meaningful and statistically significant improvements in patient functioning, depressive symptoms, cognitive function, and HRQoL were observed at week 24. Least squares mean SDS, PHQ-9, CGI-S, PDQ-D-5, DSST, and EQ-5D-5L scores improved from baseline by 6.5, 5.7, 1.2, 3.2, 4.4, and 0.11 points, respectively (p < 0.01 for all). Adverse events were observed in 23.1% of patients. Consistent with previous clinical studies of vortioxetine, this study supports the effectiveness and safety of vortioxetine in treating elderly patients with MDD in a real-world setting over a 6-month period. Patients showed clinically relevant and sustained improvements in psychosocial functioning, depressive symptoms, and cognitive function after receiving vortioxetine, which was generally well tolerated. Main study limitations include the open-label study design and lack of a placebo or comparator group.

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.

Clinical benefits of vortioxetine 20 mg/day in patients with major depressive disorder.

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.

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

BackgroundPatients 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. MethodsThe 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. ResultsThe 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. LimitationsShort-term trials. ConclusionsVortioxetine 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 registrationNCT01140906, NCT01153009, NCT01163266, NCT01255787, NCT01488071.

Vortioxetine for Major Depressive Disorder in Adolescents: 12-Week Randomized, Placebo-Controlled, Fluoxetine-Referenced, Fixed-Dose Study

To evaluate the efficacy and safety of vortioxetine in adolescents with major depressive disorder (MDD). After 4 weeks of single-blind lead-in treatment with a Brief Psychosocial Intervention (BPI) plus placebo, patients (aged 12-17 years) with MDD (DSM-5) who did not meet response criteria (Children's Depression Rating Scale-Revised [CDRS-R]; total score≥40 plus<40% reduction and a Parent Global Assessment score >2) were randomized 1:1:1:1 to 8 weeks of BPI plus double-blind treatment with vortioxetine 10 mg, vortioxetine 20 mg, fluoxetine 20 mg, or placebo. The primary endpoint was change from randomization in CDRS-R total score at week 8; the primary comparison was the average effect of 2 vortioxetine doses vs placebo. Of 784 patients enrolled in the lead-in, 616 were randomized. At week 8, the mean change in CDRS-R total score averaged for vortioxetine doses was -18.01 (SE= 0.98) and the mean difference vs placebo was 0.21 (P = .878; not significant). For fluoxetine, the mean change in CDRS-R total score was -21.95 and the mean difference vs placebo was -3.73 (P = .015). Treatment-emergent adverse events occurring in≥5% of patients in either vortioxetine arm and at least twice more frequently than placebo were nausea, headache, vomiting, and dizziness. Patients in all groups showed reduction in CDRS-R scores by the end of the study, with no difference between combined doses of vortioxetine and placebo. The primary endpoint was not met, thereby rendering the study negative. The overall favorable safety profile of vortioxetine in an adolescent patient population was consistent with that seen in adults. Active Reference (Fluoxetine) Fixed-Dose Study of Vortioxetine in Paediatric Patients Aged 12 to 17 Years With Major Depressive Disorder (MDD); http://clinicaltrials.gov; NCT02709746.

Therapeutic Potential of Vortioxetine for Anhedonia-Like Symptoms in Depression: A Post Hoc Analysis of Data from a Clinical Trial Conducted in Japan.

AimAnhedonia 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.MethodsThis 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).ResultsData 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).ConclusionThis 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.

A comparison of real-world effectiveness of vortioxetine along the treatment algorithm for major depressive disorder

Objective To evaluate the effectiveness of vortioxetine in major depressive disorder (MDD) when used as a first-line versus second-line treatment or later. Methods This was a post-hoc analysis of three 3-month non-interventional, prospective studies of vortioxetine in MDD – REVIDA (Malaysia, Philippines, Singapore, Thailand), PREVIDA (Pakistan) and TREVIDA (Taiwan). Improvements in depressive symptoms (PHQ-9, CGI-S), cognitive function (PDQ-D) and work productivity (WPAI) were compared between studies, and in a pooled analysis of patients using vortioxetine as first line versus second-line treatment or later. Safety was compared between studies. Results Overall, 798 patients were analyzed (PREVIDA =425, REVIDA =130, TREVIDA =243). Most patients in PREVIDA (60.5%)/REVIDA (57.4%) used vortioxetine as first-line treatment versus TREVIDA (21.8%). Generally, greater improvements from baseline were observed across outcome measures in PREVIDA/REVIDA versus TREVIDA (Month 3, p < 0.0001). Vortioxetine as first-line treatment was associated with greater improvements in depression severity, cognition, functioning outcomes compared to second-line or later users (PHQ-9: -16.1 [6.4] vs -10.8 [8.9]; CGI-S: -2.7 [1.1] vs -2.0 [1.4]; PDQ-D: -29.5 [17.7] vs -18.5 [21.4]; p < 0.0001 at Month 3) as well as greater response (PHQ-9: 88.6% vs 61.5%; p < 0.0001) and remission rates (PHQ-9: 75.4% vs 47.7%; p < 0.0001). No new adverse events were reported outside of the product label. Conclusions In the Asian real-world setting, vortioxetine showed greater improvements in depressive and cognitive symptoms, work functioning, and response and remission rates when used as first-line versus second-line treatment or later. Vortioxetine was well-tolerated irrespective of the study population across Asia.

The memory study: an effectiveness study of vortioxetine in patients with major depressive disorder and early dementia

The memory study: an effectiveness study of vortioxetine in patients with major depressive disorder and early dementia

Early Improvement with Vortioxetine Predicts Response and Remission: A Post Hoc Analysis of Data from a Clinical Trial Conducted in Japan.

AimSeveral 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.MethodsThis 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.ResultsRelevant 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.ConclusionImprovement 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.

Therapeutic Potential of Vortioxetine for Anxious Depression: A Post Hoc Analysis of Data from a Clinical Trial Conducted in Japan.

AimAntidepressants, 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.MethodsThis 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.ResultsData 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.ConclusionVortioxetine 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 RegistrationClinicalTrials.gov identifier for primary study: NCT02389816.

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

Analysis of efficacy and tolerability of vortioxetine 20mg/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 20mg/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 day8 (ie, following dose increase to 20mg/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 20mg/day from week2 onwards; vortioxetine 10mg did not separate from placebo until week4. At week8, mean change in MADRS total score from baseline was significantly greater for vortioxetine 20mg/day vs 10mg/day (difference, -1.03 points; P<.05). Incidence of adverse events was not increased in patients who received vortioxetine 20mg/day vs 10mg/day. In flexible-dose studies, dosage was increased to 20mg/day after 1week in 48.0% of patients; final dosage was 20mg/day in 64.3% of patients. Vortioxetine 20mg is significantly more effective than vortioxetine 10mg in patients with MDD, with a similar tolerability profile. In flexible-dose studies, almost half of all patients received 20mg/day after 1week and two-thirds received 20mg/day as their final dosage.

Efficacy of Vortioxetine on Anhedonia: Results from a Pooled Analysis of Short-Term Studies in Patients with Major Depressive Disorder.

PurposeAnhedonia is a core symptom of major depressive disorder (MDD), which has important functional consequences for the patient. This post hoc analysis investigated the relationship between anhedonia and functioning in patients with MDD treated with vortioxetine.Patients and MethodsWe conducted a pooled analysis of all 11 short-term, double-blind, randomized, placebo-controlled studies of vortioxetine (fixed dose, 5–20 mg/day) in patients with MDD which included Montgomery–Åsberg Depression Rating Scale (MADRS) and Sheehan Disability Scale (SDS) assessments. A short-term, randomized, active-controlled trial of flexible-dose treatment with vortioxetine (10–20 mg/day) versus agomelatine (25–50 mg/day) was also analyzed. Mean changes from baseline to study endpoint in MADRS total, MADRS anhedonia subscale, SDS total, and SDS social-functioning scores were analyzed by a mixed model for repeated measures. The relationship between treatment effects on anhedonia and functioning was investigated using path analysis.ResultsA total of 4988 patients with MDD were included in the placebo-controlled studies and 495 in the active-comparator study. Significant dose-dependent improvements in overall depressive symptoms, anhedonia, and measures of functioning were seen in vortioxetine-treated patients compared with those who received placebo or agomelatine. Results of the path analysis for the placebo-controlled studies suggested that the effect on functioning was mostly driven by the effect of treatment on MADRS anhedonia factors.ConclusionVortioxetine showed significant short-term efficacy against anhedonia in this large population of patients with MDD. In the placebo-controlled studies, improvements in functioning associated with vortioxetine appeared to be mostly driven by the effect of treatment on MADRS anhedonia factors.

Applying the inclusion/exclusion criteria in placebo-controlled studies to a clinical sample: A comparison of medications

BackgroundWe previously compared the inclusion/exclusion criteria in the studies of vortioxetine to other antidepressants and found that they were significantly more restrictive in the vortioxetine studies. In the present study, we tested the hypothesis that the differences in psychiatric inclusion/exclusion criteria used in the studies of some antidepressants resulted in differences in generalizability to clinical samples. MethodsWe applied the inclusion and exclusion criteria used in 161 antidepressant efficacy trials to 1,271 patients presenting to an outpatient practice who received a principal diagnosis of major depressive disorder. The patients underwent a thorough diagnostic evaluation. We compared the percentage of patients that would be excluded in studies of different medications. ResultsThe percentage of patients that would have been excluded was significantly higher in the vortioxetine studies than other medications. For the 15 medications that were included in at least 5 trials, we computed the mean percentage of patients that would be excluded. The values ranged from 76.0% (for fluoxetine) to 99.1% (for quetiapine). LimitationsWhile our calculations were based on the exclusion criteria stated in the published articles, we have no way of knowing how these criteria were actually applied. ConclusionStudies of different medications vary in how representative the samples are of patients in clinical practice. The variability in the inclusion/exclusion criteria used to select samples for antidepressant efficacy trials, and the evidence that studies of different medications vary in their generalizability, makes it more difficult to interpret network analyses comparing the relative efficacy of medications.

A double-blind, placebo-controlled study of vortioxetine in the treatment of binge-eating disorder.

Binge-eating disorder (BED) is associated with impaired quality of life and has a number of untoward public health associations. There are few established pharmacological treatments for BED, and available options are not suitable for all individuals. Vortioxetine is a recently developed pharmacological agent with effects on the serotonergic but also other neurochemical systems, which has yet to be evaluated in this context. Eighty adults with BED were recruited for a double-blind, placebo-controlled study. Participants received 12-week treatment with vortioxetine (10 mg/day for 1 week, then increasing to 20 mg/day) or placebo in a parallel design. The primary efficacy outcome measures were binge-eating frequency and weight. Safety data were collected. Effects of active versus placebo treatment were characterized using linear repeated measures models. Both vortioxetine and placebo treatment were associated with significant reductions in binge-eating frequency. Vortioxetine did not differentiate significantly from placebo on any efficacy measure. Frequency of adverse events did not differ between groups. Vortioxetine was not more effective than placebo in the treatment of BED. The ability to detect pharmacological treatment benefit may have been hindered by the relatively high placebo response and drop out. Future work should seek to better understand and predict placebo response in BED, with a view to more targeted treatment interventions and, potentially, sample enrichment.

Cognitive-functional relationships in major depressive disorder: Crucial data from a Ukrainian open-label study of vortioxetine versus escitalopram

BackgroundMajor depressive disorder (MDD) is one of the most prevalent mental illnesses associated with impairments in different spheres of functioning. Cognitive deficits are currently investigated as a possible factor of functional decline. We aimed: 1) to assess the influence of cognitive domains among other MDD symptoms on functional impairment; 2) to compare effects of eight weeks` vortioxetine versus escitalopram treatments on cognitions and consequent influence on various domains of functioning. MethodsAt baseline, 119 MDD (according to DSM-5, MADRS ≥ 7) patients and 71 healthy controls completed neurocognitive tests (RAVLT, TMT-B, DSST) and Sheehan Disability Scale. After 8 weeks of vortioxetine/escitalopram treatment, 56 patients had repeated clinical and neuropsychological evaluations. Linear regression analyses were performed to find significant predictors of impairment (at baseline) and improvement (after treatment) of functioning. Differences between groups after treatment were analyzed using mixed models for repeated measurements. ResultsCognitive impairments predominantly affected social functioning and were crucial for working productivity and total functioning along with anhedonia, hypothymia. Working memory disturbances impaired all aspects of functioning. Executive dysfunction made an additional contribution to workplace performance disturbances. At week 8, vortioxetine compared with escitalopram greater improved all impaired cognitive parameters and aspects of functioning and had higher remission rates. Cognitive improvement was the most significant factor for total functioning recovery and among crucial contributors to workplace performance recovery. LimitationsNo placebo group. ConclusionCognitions play a key role in social, working, overall functioning in Ukrainian MDD patients. Compared to escitalopram, vortioxetine treatment greater improves all cognitive and functioning domains, which leads to higher remission rates.

Pharmacokinetic and metabolic studies of Vortioxetine in rats using ultra high performance liquid chromatography with tandem mass spectrometry.

Vortioxetine is a multimodal antidepressant that has been recently utilized globally. Vortioxetine hemi-hydrochloride is a novel salt that was previously reported in our research. However, the pharmacokinetics of this salt and the metabolites of Vortioxetine in vivo remain unknown. In this study, the pharmacokinetics of the Vortioxetine hemi-hydrochloride salt is explored in rats through a newly developed ultra-performance liquid chromatography with tandem mass spectrometry method. In addition, ultra-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry was used to identify the metabolites of Vortioxetine in vivo. The results demonstrate that after a single, 3mg/kg oral dose, the maximum concentration for the Vortioxetine hemi-hydrochloride salt is 14.63 ± 4.00ng/mL, and is attained in 1.00∼4.00 h. The area under the plasma concentration-time curve from time 0 to 24 h is 67.30 ± 23.78ng·h·mL-1 . Additionally, 29 metabolites were identified after the oral administration of 10mg/kg, including 17 metabolites in the plasma, nine in the urine, and 12 in the feces. Eleven metabolites were novel. The major metabolic pathways include methylation, hydroxylation, oxidation, and glucuronidation. In conclusion, this study provides insight for further development of the Vortioxetine hemi-hydrochloride salt.

27.2 Out of the Pediatric Pipeline: Vortioxetine a Multimodal Antidepressant

The goal of this presentation is to review safety and tolerability data from pediatric studies of vortioxetine and to discuss these data with regard to the potential role of this medication in the psychopharmacologic armamentarium for depressive and anxiety disorders in youth.

Task- and Treatment Length-Dependent Effects of Vortioxetine on Scopolamine-Induced Cognitive Dysfunction and Hippocampal Extracellular Acetylcholine in Rats.

Major depressive disorder (MDD) is a common psychiatric disorder that often features impairments in cognitive function, and these cognitive symptoms can be important determinants of functional ability. Vortioxetine is a multimodal antidepressant that may improve some aspects of cognitive function in patients with MDD, including attention, processing speed, executive function, and memory. However, the cause of these effects is unclear, and there are several competing theories on the underlying mechanism, notably including regionally-selective downstream enhancement of glutamate neurotransmission and increased acetylcholine (ACh) neurotransmission. The current work sought to evaluate the ACh hypothesis by examining vortioxetine’s ability to reverse scopolamine-induced impairments in rodent tests of memory and attention. Additionally, vortioxetine’s effects on hippocampal extracellular ACh levels were examined alongside studies of vortioxetine’s pharmacokinetic profile. We found that acute vortioxetine reversed scopolamine-induced impairments in social and object recognition memory, but did not alter scopolamine-induced impairments in attention. Acute vortioxetine also induced a modest and short-lived increase in hippocampal ACh levels. However, this short-term effect is at variance with vortioxetine’s moderately long brain half life (5.1 hours). Interestingly, subchronic vortioxetine treatment failed to reverse scopolamine-induced social recognition memory deficits and had no effects on basal hippocampal ACh levels. These data suggest that vortioxetine has some effects on memory that could be mediated through cholinergic neurotransmission, however these effects are modest and only seen under acute dosing conditions. These limitations may argue against cholinergic mechanisms being the primary mediator of vortioxetine′s cognitive effects, which are observed under chronic dosing conditions in patients with MDD.