Vortioxetine Treatment Research Articles

Vortioxetine treatment decreases cocaine-induced locomotor sensitization in rats

Vortioxetine is a serotoninergic multi-target antidepressant, approved to treat major depressive disorder, and carries out its behavioral, pharmacological, and physiological effects through the blocking of serotonin 5-HT1D, 5-HT3, and 5-HT7 receptors and by activating 5-HT1A receptors. Some studies report that the simultaneous activation of the 5-HT1A serotonin receptors or blockade of 5-HT3 serotonin receptors decreased cocaine-induced locomotor activity and cocaine self-administration. Recent studies showed that vortioxetine decreased alcohol consumption. This studio aimed to evaluate the effects of vortioxetine dosing on cocaine-induced behavioral (cocaine-induced locomotor activity and cocaine-induced locomotor sensitization) and neurochemical (dopamine levels) effects.Male Wistar rats received cocaine during the induction and expression of locomotor sensitization. Vortioxetine was administered 30 min before cocaine. After each treatment, the locomotor activity was recorded for 30 min. Dopamine levels were determined in the ventral striatum, the prefrontal cortex (PFC), and the ventral tegmental area (VTA) by high-performance liquid chromatographic (HPLC) in animals treated with vortioxetine and cocaine.In this study, we found that vortioxetine decreased cocaine-induced locomotor activity, as well as the induction and expression of locomotor sensitization. As well as the amount of cocaine-induced dopamine decreased.Vortioxetine can be a useful therapeutic agent to reduce cocaine abuse.

Magnesium Potentiates the Vortioxetine's Effects on Physical Performances and Biological Changes in Exercise-Induced Stress in Rats.

Background and objectives: Vortioxetine (VRT) is a relatively new selective serotonin reuptake inhibitor (SSRI) antidepressant and serotonin receptor modulator, approved for the treatment of major depression and generalized anxiety disorder. Depression has been linked with psychomotor disengagement, oxidative stress burden and decreased blood levels of brain-derived neurotrophic factor (BDNF). In our study we performed the experimental investigation of VRT, magnesium and of their association on the rats’ endurance capacity, motor behavior and blood biological disturbances in rats subjected to forced exercise in treadmill test. Materials and Methods: The substances were administered orally for 14 consecutive days, as follows: group 1 (control): distilled water 0.3 mL/100 g body; group 2 (Mg): magnesium chloride 200 mg/kg body; group 3 (VRT): VRT 20 mg/kg body; group 4 (VRT+Mg): VRT 20 mg/kg body + magnesium chloride 200 mg/kg body. Magnesium was used as positive control substance with known effects in treadmill test. The consequences of VRT treatment on glucose, cortisol, BDNF and oxidative stress biomarkers (superoxide-dismutase, malondialdehyde, glutathione-peroxidase, lactate dehydrogenase) were also assessed. Results and conclusions: The use of VRT resulted in an improvement in motor capacity and an increase of the rats’ endurance to physical effort. The administration of VRT increased the serum BDNF levels and reduced the oxidative stress in rats subjected to physical effort. The association of magnesium potentiated the effects of VRT on physical performances, the antioxidant activity and the decreasing in serum stress markers in treadmill test in rats.

Real-world effectiveness of vortioxetine in outpatients with major depressive disorder: functioning and dose effects

BackgroundFunctional recovery is an important treatment goal in major depressive disorder (MDD). This study assessed the real-world effectiveness of vortioxetine in patients with MDD, with particular focus on functioning; dose–response was also assessed.MethodsThis was a non-interventional, prospective, multicenter study conducted in Greece. Adult outpatients with MDD (n = 336) initiating vortioxetine (5–20 mg/day flexible dosing) as treatment for a current major depressive episode were followed for 3 months. Analyses were stratified according to vortioxetine dosage at 3 months: 5–10 mg/day versus 15–20 mg/day. Functioning was assessed using the Sheehan Disability Scale (SDS).ResultsMean ± standard error SDS total score decreased (improved) from 18.7 ± 0.3 at baseline to 12.9 ± 0.3 after 1 month of vortioxetine treatment and 7.8 ± 0.4 after 3 months (p < 0.001 vs. baseline for all comparisons). Functional recovery (SDS score ≤ 6) was achieved in 14.6% of patients after 1 month of treatment and 48.4% of patients after 3 months. Improvement from baseline in SDS total and domain scores at 3 months was more pronounced in patients receiving vortioxetine 15–20 mg/day than in those receiving vortioxetine 5–10 mg/day. The mean ± standard error change in SDS total score from baseline was 9.2 ± 0.8 in the 5–10 mg/day group and 12.1 ± 0.4 in the 15–20 mg/day group (p < 0.001). Limitations of this study include its non-interventional study design and lack of a control group or active comparator.ConclusionsStatistically significant and clinically relevant improvements in functioning were seen in patients with MDD treated with vortioxetine in a real-world setting. Higher doses of vortioxetine were associated with significantly greater improvements in functioning.

Effectiveness of Vortioxetine in Patients with Major Depressive Disorder in Real-World Clinical Practice: French Cohort Results from the Global RELIEVE Study.

AimFunctional recovery is an important treatment goal in patients with major depressive disorder (MDD). The Real-Life Effectiveness of Vortioxetine in Depression (RELIEVE) study assessed the effectiveness of vortioxetine in patients with MDD receiving treatment in routine clinical care settings in France, Italy, Canada, and the United States. This paper presents the study data for the cohort enrolled in France.MethodsRELIEVE was a 6-month, international, observational, prospective cohort study in outpatients initiating vortioxetine treatment for MDD at their physician’s discretion (NCT03555136). Patients were assessed at routine clinic visits at study entry (baseline) and after 12 and 24 weeks of vortioxetine treatment. The primary study outcome was patient functioning, assessed by the Sheehan Disability Scale (SDS). Secondary outcomes included depression severity (assessed by the Patient Health Questionnaire [PHQ-9]), cognitive symptoms (assessed by the Perceived Deficits Questionnaire-Depression [PDQ-D-5]), and cognitive performance (Digit Symbol Substitution Test [DSST]). Changes from baseline to week 24 were assessed using mixed models for repeated measures, adjusted for relevant confounders. Adverse events spontaneously reported by the patient or observed by the investigator were recorded.ResultsData are available for 184 patients in France (mean age, 50.2 years; 65.2% female). Overall, 67.9% of patients had at least one comorbidity and 46.2% reported current anxiety symptoms at baseline. Adjusted least-squares mean (standard error) change in SDS score from baseline to week 24 was −10.9 (0.6) points (P < 0.001). Respective changes for PHQ-9, PDQ-D-5 and DSST scores were −9.3 (0.5), −6.1 (0.4), and +6.9 (1.0) points (all P < 0.0001). Adverse events were reported by 29 patients (15.8%), most commonly nausea (11 patients, 6.0%).ConclusionClinically relevant and sustained improvements in overall functioning, depressive symptoms, cognitive symptoms, and cognitive performance were observed in patients with MDD treated with vortioxetine for 6 months in routine clinical practice settings in France.

Effectiveness of Vortioxetine in Patients with Major Depressive Disorder in Real-World Clinical Practice in Italy: Results from the RELIEVE Study.

PurposeVortioxetine has demonstrated efficacy in randomized controlled trials and is approved for the treatment of major depressive disorder (MDD); however, data are limited concerning its effectiveness when used in routine clinical care. The Real-Life Effectiveness of Vortioxetine in Depression (RELIEVE) study aimed to assess the effectiveness and tolerability of vortioxetine for the treatment of MDD in routine clinical practice in Canada, France, Italy, and the USA. This paper presents findings for the patient cohort in Italy.Patients and MethodsRELIEVE was a 6-month, international, observational, prospective cohort study in outpatients initiating vortioxetine treatment for MDD in routine care settings at their physician’s discretion (NCT03555136). Patient functioning was assessed using the Sheehan Disability Scale (SDS). Secondary outcomes included depression severity (9-item Patient Health Questionnaire [PHQ-9]), cognitive symptoms (5-item Perceived Deficits Questionnaire-Depression [PDQ-D-5]), and quality of life (EuroQol 5-Dimensions 5-Levels questionnaire [EQ-5D-5L]). Changes from baseline to month 6 were assessed using mixed models for repeated measures, adjusted for relevant confounders.ResultsData are available for 231 patients enrolled in Italy (mean age, 55.5 years; 27% >65 years). Overall, 69% of patients reported at least one comorbidity, 55% were overweight/obese, and 47% had current anxiety symptoms. Adjusted least-squares mean (standard error) change in SDS score from baseline to week 24 was −6.6 (0.6) points (P < 0.001). Respective changes in PHQ-9, PDQ-D-5, and EQ-5D-5L scores were −5.9 (0.5), −3.6 (0.4), and +0.13 (0.01) points (all P < 0.0001). Adverse events were reported by 29 patients (13%), most commonly nausea (n = 14, 6%). Eleven patients (5%) discontinued treatment due to adverse events.ConclusionClinically relevant and sustained improvements in overall functioning, symptoms of depression, cognitive symptoms, and health-related quality of life were observed in patients with MDD treated with vortioxetine over a period of 6 months in routine care in Italy, including a high proportion of elderly patients.

Vortioxetine Modulates the Regional Signal in First-Episode Drug-Free Major Depressive Disorder at Rest.

BackgroundPrevious studies on brain functional alterations associated with antidepressants for major depressive disorder (MDD) have produced conflicting results because they involved short treatment periods and a variety of compounds.MethodsResting-state functional magnetic resonance imaging scans were obtained from 25 first-episode drug-free patients with MDD and 25 healthy controls. The patients, who were treated with vortioxetine for 8 weeks, were scanned at two-time points (baseline and week 8 of treatment). The amplitude of low-frequency fluctuation (ALFF) in the imaging data was used to analyze local brain signal alterations associated with antidepressant treatment.ResultsCompared with the controls, the patients at baseline showed decreased ALFF values in the right inferior temporal gyrus and increased ALFF values in the left inferior cerebellum, right cingulate gyrus and postcentral gyrus. After 8 weeks of vortioxetine treatment, patients showed increased ALFF values in the bilateral cingulate gyrus, middle temporal gyrus, medial superior frontal gyrus, and inferior cerebellum.ConclusionThis study provided evidence that vortioxetine modulates brain signals in MDD sufferers. These findings contribute to the understanding of how antidepressants effect brain function.

Effectiveness and Tolerability of Supratherapeutic Dosing of Vortioxetine in Patients With Treatment-Resistant Depression.

Objective: To evaluate the effectiveness and tolerability of vortioxetine at supratherapeutic dosages in patients with treatment-resistant depression.Methods: A retrospective observational naturalistic study was conducted in 56 depressed patients resistant to standard care treatment from September 2020 to April 2021. Effectiveness of the vortioxetine treatments was evaluated through Clinical Global Impressions (CGI) score, comparing CGI values at the beginning (T0) of the vortioxetine treatment with CGI values at the earliest of these 2 time points (T1): (1) 8 weeks of treatment with supratherapeutic dosages and (2) day of vortioxetine discontinuation or daily dosage reduction to ≤ 20 mg due to side effects. The tolerability and safe of vortioxetine were also monitored.Results: Fifty-six patients (32 females and 24 males, mean ± SD age of 51.1 ± 9.3 years) were included in the study. Thirty-seven patients received vortioxetine 30 mg/d, while 19 patients were treated with a 40-mg/d dosage. CGI scores significantly decreased (P < .001) in patients treated with 30 mg/d and 40 mg/d, respectively. No severe side effects were reported. Weight gain and nausea were the most common reported side effects. Nausea and limited efficacy were recorded as the most frequent reasons for vortioxetine dose reduction. None of the patients required vortioxetine discontinuation.Conclusions: Supratherapeutic doses of vortioxetine were relatively well-tolerated and effective in patients with treatment-resistant depression.

Effectiveness of vortioxetine in real-world clinical practice: Italian cohort results from the global RELIEVE study

IntroductionMajor 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.ObjectivesTo present the effectiveness and safety data of vortioxetine in real-world setting from patients enrolled from Italy in the RELIEVE study.MethodsRELIEVE 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.ResultsA 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.ConclusionsImprovements 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.DisclosureA. Pugliese is an employee of Lundbeck Italy. K. Simonsen and H. Ren are employees of H. Lundbeck A/S.

Study design of VGOAL-J: an observational, prospective cohort study to assess effectiveness of vortioxetine on goal achievement and work productivity in patients with MDD in Japan

IntroductionGoal 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.ObjectivesTo demonstrate the effectiveness of vortioxetine on patient’s goal achievement and depressive symptoms, emotional, cognitive, overall function and quality of life.MethodsVGOAL-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.ResultsThe results will be disseminated in late 2022 and provide new insights on GAS-D as an effective strategy to assess MDD treatment in Japan.ConclusionsWe 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.DisclosureProf. 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

Effectiveness of vortioxetine in real-world clinical practice: French cohort results from the global RELIEVE study

IntroductionMajor 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.ObjectivesTo describe the effectiveness and safety of vortioxetine in real-world setting from patients enrolled from France in the global RELIEVE study.MethodsRELIEVE 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.ResultsA 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.ConclusionsSustained 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.DisclosureM. Rabbani is an employee of Lundbeck France. K. Simonsen and H. Ren are employees of H. Lundbeck A/S.

Vortioxetine Treatment for Depression in Alzheimer's Disease: A Randomized, Double-blind, Placebo-controlled Study.

ObjectiveVortioxetine, a new antidepressant, has been demonstrated to have effects on depression and cognitive function. This study aimed to investigate the anti-depressive efficacy of vortioxetine through a well-designed double-blind, placebo-controlled study in Alzheimer’s disease (AD) patients, and to confirm the presence of secondary benefits, including the improvement of cognitive function and activities of daily living (ADL).MethodsThe present study included 100 AD patients with depression who were assigned randomly to 12 weeks of daily treatment with either vortioxetine or placebo. The primary efficacy measure was the change in the Cornell Scale for Depression in Dementia score from baseline to 12 weeks. Several secondary efficacy measures were evaluated, including the Korean version of the Short form of Geriatric Depression Scale and several cognitive function domains. The safety and tolerability of vortioxetine were also assessed. We performed modified intention-to-treat analysis using mixed modeling (the Mixed Models for Repeated Measures).ResultsThere was no statistically significant difference between the two groups in terms of depressive symptoms, cognitive functions, and ADL. Further, the percentage of adverse events and drug discontinuation between the vortioxetine and placebo groups was similar.ConclusionOur results suggest that vortioxetine might not be effective in reducing depressive symptoms or cognitive impairment in AD patients with depression. However, general drug tolerance and patient safety were similar to those of placebo. Thus, additional studies are needed to replicate the effectiveness and tolerability of vortioxetine in AD patients with depression.

Efficacy and safety of vortioxetine in treatment of patients with major depressive disorder and common co-morbid physical illness

BackgroundThe multimodal antidepressant vortioxetine is effective in reducing somatic symptoms in patients with major depressive disorder (MDD), but little is known about its effects in reducing depressive symptoms in patients with common comorbid physical illnesses. MethodsThis was a pooled analysis of 13 randomized, placebo-controlled trials which evaluated the efficacy (using the Montgomery–Åsberg Depression Rating Scale [MADRS]) and safety of vortioxetine (5-20 mg/day) in adult patients with MDD. We evaluated stable somatic comorbid conditions that were verified by a diagnosis and had sufficient database representation. ResultsOf the 5982 patients included in the database, 963 (16.1%) patients had a diagnosis of cardiovascular disease, 152 (2.5%) had diabetes mellitus and 26 (0.4%) had chronic obstructive pulmonary disorder (COPD). At Week 8, adjusted mean[95%CI] treatment differences (vortioxetine vs. placebo) on MADRS total scores were −2.7[−4.2, −1.3] (p = 0.0002) points for the cardiovascular disease, −4.0[−7.7, −0.4] (p = 0.03) for the diabetes, and −6.2[−21.3, 8.9] (p = 0.36) for the COPD groups. The rate and pattern of adverse events were similar across the sub-groups with comorbidities and was consistent with that expected for vortioxetine treatment. LimitationsThe primary studies were not designed to investigate the relationship between vortioxetine and comorbidities, nor were the post hoc analyses powered to detect group differences. ConclusionsPatients with MDD and comorbid cardiovascular disease or diabetes respond to vortioxetine in a similar way to the broader MDD population. Vortioxetine was generally safe and well tolerated and without unexpected adverse events in these subpopulations, most of whom are taking multiple concomitant medications.

A Feasibility Study of Patients with Major Depression and Substance Use Disorders: Vortioxetine as Maintenance Treatment.

BackgroundLimited studies have evaluated the effectiveness of vortioxetine in real-world settings, and none of them has involved patients with dual depression (major depressive disorder [MDD] and substance use disorder [SUD]). The objective of the study was to describe the effectiveness of vortioxetine in clinical practice and determine its effect on affective symptoms, cognitive function, quality of life, and substance use in patients with MDD and SUD.MethodsPost-authorization, retrospective, multicenter, descriptive, and observational study in 80 patients with MDD and SUD receiving a maintenance treatment with vortioxetine for six months between January 2017 and April 2021.ResultsCompared with baseline, scores significantly decreased after 3 and 6 months of treatment in the Montgomery-Åsberg Depression Rating Scale total (from 28.9 to 17.7 and 12.0), and global functional impairment of the Sheehan Disability Inventory (from 26.3 to 19.1 and 16.7). The number of correct answers in the symbol digit modalities test significantly improved during vortioxetine treatment (from 40.4 to 43.8 and 48.4). Regarding the clinical global impression scale, the score for disease severity significantly decreased from 3.8 to 3.0 and 2.4. Compared with baseline, there was a significant reduction in consumption of practically all substances, especially of alcohol, cannabis, and cocaine.ConclusionVortioxetine was effective in clinical practice for alleviating depressive symptoms and functional impairment, and in improving cognitive and executive functions and disease severity in patients with MDD and SUD. Moreover, the treatment with vortioxetine favored a reduction in substance use and the severity of the SUDs.

Vortioxetine ameliorates motor and cognitive impairments in the rotenone-induced Parkinson's disease via targeting TLR-2 mediated neuroinflammation

Parkinson's disease (PD) is characterized by motor and non-motor symptoms associated with dopaminergic and non-dopaminergic injury. Vortioxetine is a multimodal serotonergic antidepressant with potential procognitive effects. This study aimed to explore the effects of vortioxetine on motor functions, spatial learning and memory, and depression-like behavior in the rotenone-induced rat model of PD. Male Sprague-Dawley rats were daily administered with the rotenone (2 mg kg−1, s.c.) and/or vortioxetine (10 mg kg−1, s.c.) for 28 days. Motor functions (rotarod, catalepsy, open-field), depression-like behaviors (sucrose preference test), anxiety (elevated plus maze), and spatial learning and memory abilities (novel object recognition and Morris water maze) were evaluated in behavioral tests. Then immunohistochemical, neurochemical, and biochemical analysis on specific brain areas were performed. Vortioxetine treatment markedly reduced rotenone-induced neurodegeneration, improved motor and cognitive dysfunction, decreased depression-like behaviors without affecting anxiety-like parameters. Vortioxetine also restored the impaired inflammatory response and affected neurotransmitter levels in brain tissues. Interestingly, vortioxetine was thought to trigger a sort of dysfunction in basal ganglia as evidenced by increased Toll-like receptor-2 (TLR-2) and decreased TH immunoreactivity only in substantia nigra tissue of PD rats compared to the control group. The present study indicates that vortioxetine has beneficial effects on motor dysfunction as well as cognitive impairment associated with neurodegeneration in the rotenone-induced PD model. Possible mechanisms underlying these beneficial effects cover TLR-2 inhibition and neurochemical restoration of vortioxetine.

Vortioxetine as adjunctive therapy in the treatment of schizophrenia.

Background:The evidence for safe and effective interventions to treat the negative and cognitive symptoms of schizophrenia is lacking.Objectives:Vortioxetine is a novel antidepressant that has been used as adjunctive therapy for the treatment of psychosis; however, its effectiveness in clinical practice is relatively unknown. In this study, we aimed to determine the potential clinical effectiveness and safety and tolerability of vortioxetine in psychosis.Design:This is a non-interventional, retrospective study on the add-on use of vortioxetine in a group of people with schizophrenia-spectrum disorders in a large UK NHS mental health trust.Methods:Clinical effectiveness of vortioxetine was retrospectively assessed through the Clinical Global Impression – Severity (CGI-S) scale at 3 months. Safety and tolerability were evaluated through treatment discontinuation rates at 3, 6, and 12 months, and clinical reasons were evaluated at the primary endpoint of 3 months.Results:Data were available for 40 subjects with a diagnosis of schizophrenia or schizoaffective disorder–prescribed vortioxetine treatment; 30 (75%) remained on treatment at 3 months. At CGI-S assessment, 15 of the 35 evaluated subjects reported at least a 1-point improvement, from 5 at baseline to 4 after 3 months of treatment. Twenty-six (65%) remained on treatment at 1-year follow-up. The main reasons for those discontinuing treatment were inadequate response (10%) and manic switch (7.5%), while one subject refused treatment. Tolerability to treatment was good, and 36 subjects (90%) reported no adverse events specific to vortioxetine treatment.Conclusion:Schizophrenia is a complex illness, and there is insufficient treatment response in many individuals. A significant proportion of whom may require adjunctive treatments depending on the nature of the residual symptoms. Vortioxetine could be a potentially safe and effective option in such people, but further controlled studies are required.

Improved cognitive function in patients with major depressive disorder after treatment with vortioxetine: A EEG study.

IntroductionVortioxetine has a positive effect on cognitive function in patients with major depressive disorder (MDD). This study aimed to examine the changes in cognitive function and EEG (spectral power and mismatch negativity (MMN)) in patients with MDD pre‐ and postvortioxetine treatment.MethodsThirty patients with MDD were included in the study. They were given vortioxetine (10‐20mg po per day) for eight weeks. Depression and anxiety severities, social function (Korean version of the social adjustment scale (K‐SAS)), and cognitive function (digit‐symbol substitution Test (DSST), Korean version of the attentional control questionnaire (K‐ACQ), and Korean version of the perceived deficits questionnaire for depression (K‐PDQD)) were evaluated. Spectral power of EEG and MMN was also measured pre‐ and postvortioxetine treatment.ResultsDepression and anxiety severity, social function, and cognitive functioning significantly improved after vortioxetine treatment. Also, there was a significant decrease in the right central delta band and an increase in the right central beta 2 band following vortioxetine treatment. The changes in EEG spectral power were not related to changes in cognitive functions. Baseline MMN significantly predicted changes in DSST score after controlling for the baseline clinical variables.ConclusionVortioxetine treatment improved cognitive function and induced changes in EEG (decreased theta power and increased beta power) in patients with MDD. Our results suggest that greater negative MMN amplitude is associated with greater potential for cognitive improvement following vortioxetine treatment.

Validation of the Oxford Depression Questionnaire: Sensitivity to change, minimal clinically important difference, and response threshold for the assessment of emotional blunting

The Oxford Depression Questionnaire (ODQ) is a patient-reported scale for assessing emotional blunting in patients with major depressive disorder (MDD). This analysis was undertaken to further validate the scale in patients experiencing emotional blunting while receiving antidepressant treatment. Patients with MDD who experienced inadequate depressive-symptom resolution 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. ODQ total scores were assessed excluding and including the "antidepressant-as-cause" domain (ODQ-20 and ODQ-26, respectively). Anchor- and distribution-based methods were used to determine the minimal clinically important difference in ODQ scores in terms of change from baseline to week 8 of antidepressant treatment. After 8 weeks of vortioxetine treatment, the mean change in ODQ-20 and ODQ-26 scores from baseline was -24.8 and -30.1 points, respectively. Greater mean changes from baseline in ODQ-20 and ODQ-26 scores were seen in patients reporting no emotional blunting vs those still experiencing emotional blunting after 8weeks of vortioxetine treatment (ODQ-20: -27.0 vs -22.6 points; ODQ-26: -32.8 vs -27.5 points, respectively). In patients considered clinically minimally improved (Clinical Global Impression-Improvement score, 3) after 8 weeks of vortioxetine treatment, respective mean (standard deviation) change in ODQ-20 and ODQ-26 score from baseline was -15.5 (18.1) and -20.0 (20.5) points. Short study duration. These results provide further validation of the clinical utility of the ODQ for assessing emotional blunting in patients with MDD. The suggested minimal clinically important difference for change in ODQ-20 and ODQ-26 scores is 16 and 20 points, respectively, after 8 weeks of antidepressant treatment. ClinicalTrials.gov identifier: NCT03835715.

Vortioxetine Versus Placebo for Major Depressive Disorder: A Comprehensive Analysis of the Clinical Trial Dataset.

Prior meta-analyses have found vortioxetine to be efficacious for depression. Building on those findings, the present meta-analysis examined the effect that placebo response has on drug-placebo effect size in studies of vortioxetine treatment.

Validation of a Population Pharmacokinetic Model of Vortioxetine Using Therapeutic Drug Monitoring Data.

IntroductionVortioxetine is an antidepressant primarily metabolized by the polymorphic enzyme cytochrome P450 (CYP) 2D6. A population pharmacokinetic (popPK) model of vortioxetine and its CYP2D6-dependent metabolite was recently published.ObjectiveThe aim of the current study was to assess the predictive performance of the popPK model using vortioxetine concentration measurements from a clinical setting. Furthermore, the study aimed to evaluate the ability of different CYP2D6 phenotype classification systems to provide accurate concentration predictions.MethodsOverall, 1388 patients receiving vortioxetine treatment were identified from a therapeutic drug monitoring (TDM) database in Oslo, Norway; 334 CYP2D6-genotyped patients with 502 serum concentrations of vortioxetine, analysed by a validated ultra-high-performance liquid chromatography–high-resolution mass spectrometry (UHPLC-HRMS) method, were retrospectively included. The performance of the vortioxetine popPK model was tested on the clinical data from the TDM database.ResultsOverall, the model had a good ability to predict vortioxetine concentrations measured in clinical practice, with a slight tendency to overpredict concentrations. Using simulation-based diagnostics, 76% of the prediction-corrected TDM concentrations were within the 90% prediction interval based on 1000 simulated data sets. Prediction-based diagnostics showed the best performance for CYP2D6 poor and ultrarapid metabolizers, with a median prediction error (MDPE) of 12% and 23%, respectively, while the poorest performance was observed for normal metabolizers, with an MDPE of 66%. In the comparison of different CYP2D6 phenotype classification systems, the use of differentiated activity scores for decreased function alleles did not improve the concentration predictions. Grouping the CYP2D6 genotypes into the four conventional phenotype groups provided predictions closest to the TDM measured concentrations.ConclusionTDM data provide a unique insight into real-world clinical practice with vortioxetine. The tendency of the popPK model to overpredict vortioxetine concentrations measured in TDM may be attributed to several factors, including poor treatment compliance for some patients and, to a lesser extent, lack of information on patient characteristics and misspecified CYP2D6 alleles. To optimize personalized therapy with vortioxetine, real-world clinical data sets originating from different ethnicities need to be studied in the future.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40262-021-01029-7.

Withdrawal Symptoms Following Discontinuation of Vortioxetine—Retrospective Chart Review

The efficacy of vortioxetine has been proven in many studies, but data concerning discontinuation symptoms (DS) after vortioxetine withdrawal is scarce. The aim of our study is to systematically evaluate the prevalence, determinants, and clinical features of vortioxetine DS in a retrospective chart review. Data were obtained from medical records of 263 adult patients with depressive disorders who discontinued former vortioxetine treatment. DS were observed in eight (3%) patients after 71–375 days (median 272) of treatment. DS emerged after median three days following vortioxetine withdrawal and lasted for median seven days. The clinical presentation of DS involved: emotional lability (100% of patients), irritability (75%), sudden worsening of mood (75%), nervousness (37.5%), and agitation (37.5%). Median DESS score was four (range of four to six). DS were significantly more prevalent after accidental vs. planned discontinuation (adjusted p = 0.011) and were less frequent after switching to a different antidepressant vs. ceasing pharmacotherapy (adjusted p = 0.0165). DS appeared more often if patients discontinued therapy without medical consultation (adjusted p = 0.033). The occurrence of DS was not associated with the dose and way of drug discontinuation (sudden vs. gradual). In sum, our results show that clinicians should be aware that vortioxetine withdrawal is associated with the possibility of DS.