vortioxetine and Anxiety-Disorders

The currently accepted psychopharmacological treatment for generalised anxiety disorder in adults is associated with several adverse effects which threaten its acceptability. In this line, vortioxetine has been proposed as an alternative with less adverse effects in the treatment of this pathology.. We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach.. We identified seven systematic reviews including five primary studies, all corresponding to randomized trials evaluating the effectiveness of vortioxetine in adult patients with generalized anxiety disorder without current treatment. We conclude that there is uncertainty whether vortioxetine increases the response to treatment or improves anxious symptoms, because the certainty of the existing evidence has been assessed as very low. Furthermore, vortioxetine may increase nausea (low certainty evidence).. El tratamiento psicofarmacológico actualmente aceptado para el trastorno de ansiedad generalizada en adultos está asociado a efectos adversos que amenazan su aceptabilidad. En esta línea, se ha propuesto a la vortioxetina como una alternativa con un mejor perfil de efectos adversos en el tratamiento de dicha patología.. Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE.. Identificamos siete revisiones sistemáticas que en conjunto incluyeron cinco estudios primarios, todos correspondientes a ensayos aleatorizados que evaluaron la efectividad de la vortioxetina en pacientes adultos con trastorno de ansiedad generalizada sin tratamiento actual. Concluimos que no es posible establecer con claridad si la vortioxetina aumenta la respuesta a tratamiento o mejora los síntomas ansiosos, debido a que la certeza de la evidencia existente ha sido evaluada como muy baja. Además, la vortioxetina podría aumentar los efectos adversos (náuseas) (certeza de la evidencia baja).

Topics: Adult; Anti-Anxiety Agents; Anxiety Disorders; Humans; Systematic Reviews as Topic; Treatment Outcome; Vortioxetine

The aim of this study was to investigate the efficacy, tolerability, safety, and impact on quality of life (QoL) and functional status of vortioxetine treatment for patients with generalised anxiety disorder (GAD) by performing a meta-analysis of randomised controlled trials (RCTs).. Systematic review and meta-analysis.. Data mining was conducted in January 2019 across PubMed, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials Cochrane Library, Web of science and ClinicalTrials.gov.. All published RCTs, which assessed the effect of vortioxetine treatment for patients with GAD when compared with a placebo group, were included.. Relevant data were extracted and synthesised narratively. Results were expressed as standardised mean differences or ORs with 95% CIs.. Our meta-analysis showed that multiple doses (2.5, 5 and 10 mg/day) of vortioxetine did not significantly improve the response rates, compared with placebo (OR 1.16, 95% CI 0.84 to 1.60, p=0.38; OR 1.41, 95% CI 0.82 to 2.41, p=0.21; and OR 1.05, 95% CI 0.76 to 1.46, p=0.75). Moreover, there was no statistically significant difference regarding the remission rates, discontinuation for any reason rates, discontinuation due to adverse events rates, Short-Form 36 Health Survey scores or Sheehan Disability Scale scores between administration of multiple doses (2.5, 5 and 10 mg/day) of vortioxetine and placebo.. Although our results suggest that vortioxetine did not improve the GAD symptoms, QoL and functional status impairment of patients with GAD, it was safe and well tolerated. Clinicians should interpret and translate our data with caution, as the meta-analysis was based on a limited number of RCTs.

Topics: Adult; Anti-Anxiety Agents; Anxiety Disorders; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quality of Life; Randomized Controlled Trials as Topic; Remission Induction; Vortioxetine

Vortioxetine is a multimodal antidepressant that has been developed for the treatment of major depressive and anxiety disorders. The aim of this review is to quantitatively synthesize all data of the efficacy, safety and tolerability of Vortioxetine in treating anxiety disorder.. Terms of "Vortioxetine" OR "LuAA21004" AND "anxiety" OR "fear" OR "panic" OR "phobia" were searched. A total of two phase II and five phase III clinical trials were found.. Vortioxetine was overall superior to placebo in terms of the mean change from baseline in HAM-A total score at week 8 with the pool effect size of -2.95, 95% CIs, -4.37 to -1.53, p<0.01. The patients who received 5 mg of Vortioxetine had higher response rate when compared to placebo (pooled odds ratio=1.4, 95% CI = 1.08 to 1.82, p=0.01). However, the pooled odds ratio of the HAMA remission rate was not statistically significant for both Vortioxetine and placebo (pooled odds ratio= 1.06, 95% CI = 0.86 to 1.30, p=0.62). Although the discontinuation due to adverse effects was higher in Vortioxetine than placebo group (pooled OR= 1.55, 95% CI = 1.04 to 2.31, P= 0.037), the lack of efficacy (pooled OR= 0.39, 95% CI = 0.27 to 0.57, P<0.01) was higher in placebo than Vortioxetine group. Most of the adverse effects were mild and moderate. Overall, Vortioxetine displayed a good safety and tolerability profile.. This review supports the use of Vortioxetine for anxiety disorder. However, further longterm placebo-control observational study or a post market survey would help in strengthening the evidence for this treatment modality.

Topics: Anti-Anxiety Agents; Anxiety Disorders; Humans; Vortioxetine

Efficacy has been proven for vortioxetine in short-term and long-term treatment of major depressive disorder (MDD), with broad beneficial effects on emotional, physical and cognitive symptoms. Limited specific data on the effects of vortioxetine on depression-related physical symptoms have been published.. A meta-analysis was carried out of five short-term multinational, double-blind, placebo-controlled studies. These studies were conducted in a total of 2105 adult MDD outpatients (18-75 years) with a major depressive episode of ⩾3 months' duration. Only patients treated with a dose of 5 or 10 mg vortioxetine (therapeutic doses) or placebo were included in this analysis. Efficacy assessment of vortioxetine on the physical symptoms of depression included all items of the Hamilton Depression Scale (HAM-D) assessing physical symptoms, and all somatic items in the Hamilton Anxiety Scale (HAM-A). A subgroup analysis in MDD patients with coexisting anxiety symptoms (i.e. those with a HAM-A ⩾20 at baseline) was also performed.. A significant improvement ( p<0.05) of vortioxetine versus placebo was observed on all HAM-D items measuring physical symptoms, except for the somatic gastrointestinal symptoms and loss of weight items. Significant effects were also observed on the HAM-A somatic items: general somatic symptoms, gastrointestinal symptoms, and autonomic symptoms. In patients with a high baseline level of anxiety, a significant effect of vortioxetine was also observed on the physical symptoms of depression.. These analyses indicate that patients with MDD, including those with a high level of anxiety symptoms, have significant improvements in MDD-associated physical symptoms when treated with vortioxetine.

Topics: Antidepressive Agents; Anxiety Disorders; Depressive Disorder, Major; Dose-Response Relationship, Drug; Humans; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Treatment Outcome; Vortioxetine

Generalized Anxiety Disorder (GAD) is a persistent condition characterized by chronic anxiety, exaggerated worry and tension, mainly comorbid with Major Depressive Disorder (MDD). Currently, selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors are recommended as first-line treatment of GAD. However, some patients may not respond to the treatment or discontinue due to adverse effects. Vortioxetine (VRX) is a multimodal antidepressant with a unique mechanism of action, by acting as 5-HT3A, 5-HT1D and 5-HT7 receptor antagonist, partial agonist at the 5-HT1A and 5-HT1B receptors and inhibitor at the 5-HT transporter. Preliminary clinical trials showed contrasting findings in terms of improvement of the anxiety symptomatology and/or cognitive impairment. Here, we aim to systematically review the evidence currently available on the efficacy, safety and tolerability of VRX in the treatment of GAD. The generalizability of results on the efficacy of VRX in patients with anxiety symptomatology and GAD is limited due to few and contrasting RCTs so far available. Only two studies, of which one prevention relapse trial, reported a significant improvement in anxiety symptomatology compared to three with negative findings.

Topics: Antidepressive Agents; Anxiety Disorders; Depressive Disorder, Major; Humans; Piperazines; Sulfides; Vortioxetine

Vortioxetine has a beneficial pharmacological profile for reducing anxiety and depression. Recently, a number of randomized, double-blind, placebo-controlled clinical trials (RCTs) of vortioxetine have been conducted in patients with generalized anxiety disorder (GAD); however, the results from GAD RCTs are inconsistent. With an extensive search of databases and clinical trial registries, four published short-term RCTs were identified and included in the present meta-analysis. The mean change in total scores on the Hamilton Anxiety Rating Scale (HAMA) from baseline was the primary endpoint. The secondary endpoints included the response and remission rates, as defined by a ≥50% reduction in HAMA total scores and a ≤7 change in the HAMA total score at the end of treatment. In addition, the mean change in the HAMA total score from baseline in the subgroup with a HAMA total score ≥25 at baseline was included. Vortioxetine was significantly more effective than was placebo, with a standardized mean difference (SMD) of -0.118 (95% CIs, -0.203 to -0.033, P = 0.007). In particular, those with severe GAD (HAMA total score ≥25 at baseline) had a significantly greater benefit from vortioxetine than those without (SMD = -0.338, 95% CIs = -0.552 to -0.124, p = 0.002). The odds ratios (ORs) for vortioxetine for response and remission were 1.221 (95% CIs, 1.027 to 1.452, P = 0.024) and 1.052 (95% CIs, 0.853 to 1.296, P = 0.637), respectively. Discontinuation due to adverse events (AEs) (OR = 1.560, 1.006 to 2.419, p = 0.047) was marginally higher in vortioxetine than placebo treatment, whereas discontinuation due to any reason (OR = 0.971, 0.794 to 1.187, p = 0.771) and inefficacy (OR = 0.687, 0.380 to 1.243, p = 0.215) were not significantly different among treatment groups. Although our results suggest that vortioxetine may have a potential as an another treatment option for GAD (especially for severe GAD), they should be interpreted and translated into clinical practice with caution, as the meta-analysis was based on a limited number of RCTs.

Topics: Anti-Anxiety Agents; Anxiety Disorders; Humans; Piperazines; Sulfides; Vortioxetine

Modest response and remission rates for the selective serotonin reuptake inhibitors and the serotonin-norepinephrine reuptake inhibitors, coupled with mounting evidence that the tolerability of the antidepressants (ADs) may have been overstated in the literature, has contributed to changes in prescribing patterns for generalized anxiety disorder (GAD). New interest in the absence of evidence that supports these standard therapies as superior to benzodiazepines stimulated a review of the literature.. A literature search was conducted in the MedLine database with search terms 'generalized anxiety disorder' and 'treatment' for purposes of including relevant literature related to pharmacologic treatment of GAD. Aside from a review of pivotal literature, the authors also included newer studies that evaluated novel drug treatments. Last, the database was searched for benzodiazepine comparisons to standard therapy secondary to concerns that such literature is sparse. The review of newer modalities and the decision to include related literature was also based on the strength of the evidence and the status of their approval for the treatment of GAD.. Although ADs remain the most frequently prescribed medications for GAD, alternative and off-label therapies such as pregabalin, the atypical antipsychotics and vortioxetine are garnering interest. Based on the evidence available to us, it is our recommendation that along with the ADs, benzodiazepines be considered a possible first-line therapy in eligible patients based on the discretion and clinical judgment of the treating physician.

Topics: Adrenergic Uptake Inhibitors; Anti-Anxiety Agents; Antidepressive Agents; Antipsychotic Agents; Anxiety Disorders; Benzodiazepines; Humans; Off-Label Use; Piperazines; Selective Serotonin Reuptake Inhibitors; Sulfides; Vortioxetine

Major depressive disorder (MDD), one of the most common disorders in medical practice and one of the leading causes of disability worldwide, is frequently comorbid with anxiety disorders. Vortioxetine (Lu AA21004) is a new antidepressant that combines a number of neurotransmitter reuptake and receptor effects that have been thought to predict efficacy as a treatment for depressive and anxiety disorders.. This review summarizes the pharmacology and neurobiology of vortioxetine. Studies of its efficacy and tolerability in major depression and generalized anxiety disorder are critically reviewed.. Despite the fact that industry-sponsored studies are more likely than other clinical trials to support efficacy of the experimental drug, results have been mixed. Some studies supported that vortioxetine is superior to placebo in the treatment of MDD and some do not. Two studies supported the efficacy of vortioxetine in the treatment of generalized anxiety disorder and two do not. The incidence of sexual dysfunction has varied considerably in different studies, but cardiac effects and psychomotor impairment seem to be minimal. Advantages of vortioxetine over existing antidepressants are not yet clear.

Topics: Anti-Anxiety Agents; Antidepressive Agents; Anxiety Disorders; Brain; Depressive Disorder, Major; Drug Resistance; Humans; Neurons; Neurotransmitter Agents; Piperazines; Sulfides; Vortioxetine

Lu-AA21004, an oral, multimodal serotonergic agent, is currently under development by H Lundbeck and Takeda Pharmaceutical, for the potential treatment of depression and anxiety. Lu-AA21004 belongs to a novel chemical class of antidepressant agents, the bisarylsulfanyl amines, and possesses a novel pharmacological profile, with activity at serotonergic receptors 5-HT3, 5-HT7 and 5-HT1A, and also at the 5-HT transporter. Acute administration of Lu-AA21004 in rats inhibited the firing activity of serotonergic neurons of the dorsal raphe nucleus through 5-HT3 receptor blockade, with rapid recovery of firing activity upon cessation of treatment compared with an antidepressant of the SSRI class. Results from phase II clinical trials have reported improvement in depression and anxiety symptoms after 6 weeks of treatment. Lu-AA21004 was generally well tolerated, with adverse events related to sexual dysfunction occurring in a lower number of patients receiving Lu-AA21004 compared with venlafaxine. Phase III clinical trials with Lu-AA21004 in patients with major depressive disorder are underway and phase III trials in patients with generalized anxiety disorder have been completed. If initial outcomes from these clinical trials prove positive, Lu-AA21004 may pave the way for new multimodal therapies for the treatment of depression and anxiety.

Topics: Animals; Anti-Anxiety Agents; Antidepressive Agents; Anxiety Disorders; Depressive Disorder, Major; Drugs, Investigational; Humans; Piperazines; Serotonin Antagonists; Sulfides; Vortioxetine

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

Topics: Anxiety Disorders; Cognition; Depressive Disorder, Major; Double-Blind Method; Humans; Treatment Outcome; Vortioxetine

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.

Topics: Adult; Anti-Anxiety Agents; Anxiety Disorders; Double-Blind Method; Female; Humans; Male; Middle Aged; Secondary Prevention; Treatment Outcome; Vortioxetine

In this 6-month open-label extension (OLE) of NCT01491035 (a 14-day, open-label, pharmacokinetic/safety lead-in study), the long-term safety and tolerability of vortioxetine (5-20 mg/day) were investigated in children and adolescents with a DSM-IV-TR™ diagnosis of depressive or anxiety disorder in the United States or Germany. The study also was designed to provide data to inform dose selection and titration in future pediatric studies with vortioxetine.. Safety evaluations included spontaneously reported adverse events (AEs), the Columbia Suicide Severity Rating Scale (C-SSRS), and the Pediatric Adverse Events Rating Scale (PAERS; clinician administered). Clinical effectiveness was determined by Clinical Global Impressions. Comorbid attention-deficit/hyperactivity disorder was permitted, including concomitant use of stimulant medication (US sites only).. Of the 47 patients who completed the lead-in period, 41 continued into the OLE. Most patients (n = 39 [95%]) continued their previous dose regimen. Twenty-one patients (51%) withdrew during the OLE; the most common primary reasons were administrative [n = 8], AEs [n = 4], and lack of efficacy [n = 3]. Thirty-five patients (85%) had ≥1 AE, 86% of which were mild or moderate in severity. Five patients (12%) reported a severe AE, none of which was considered related to study medication. The most common AEs (≥10%) were headache (27%), nausea (20%), dysmenorrhea (females; 19%), and vomiting (15%), with no relationship between AE intensity and age or dose. Five patients reported instances of suicidal ideation during the OLE, one of whom also reported this during the lead-in period. Two patients had nonsuicidal self-injurious behavior; one had a nonfatal suicide attempt. Throughout the study, there was a decrease over time in the incidence and intensity of AEs collected using the PAERS. Effectiveness assessment indicated a trend toward improvement based on numeric results.. This OLE confirms the findings from the lead-in study, which concluded that a dosing strategy of 5-20 mg/day is safe, well tolerated, and suitable for future clinical studies of vortioxetine in pediatric patients.

Topics: Adolescent; Anti-Anxiety Agents; Antidepressive Agents; Anxiety Disorders; Child; Depressive Disorder, Major; Dose-Response Relationship, Drug; Female; Germany; Humans; Male; Prospective Studies; Psychiatric Status Rating Scales; Treatment Outcome; United States; Vortioxetine

The primary objectives of this study were to evaluate the pharmacokinetics (PK) and tolerability of single and multiple doses of vortioxetine in children and adolescents with a depressive or anxiety disorder and to provide supportive information for appropriate dosing regimens for pediatric clinical trials.. This prospective, open-label, multinational, multisite, multiple-dose trial enrolled 48 patients (children and adolescents; 1:1 ratio) divided into 8 cohorts (4 adolescent and 4 child), with each cohort including 6 patients. The cohorts in each age group were assigned to receive one of four dosing regimens: vortioxetine 5, 10, 15, or 20 mg q.d. for 14 days. The total treatment period lasted 14-20 days with patients in the higher dose cohorts uptitrated over 2-6 days. Plasma samples for PK analysis were obtained on the first and last days of dosing.. Among children and adolescents, respectively, 62% and 92% had depression and 58% and 33% had anxiety disorder. Comorbid attention-deficit/hyperactivity disorder (ADHD) was present in 50% of children and 38% of adolescents. After 14 days q.d. at the target dose, the PK of vortioxetine concentrations was generally proportional to the dose in both age groups. Exposure, as assessed by maximum plasma concentrations and area under the plasma concentration-time curve from time 0 to 24 hours, was 30%-40% lower in adolescents than in children. There was no significant relationship between sex, height, or ADHD diagnosis and PK parameters. Most adverse events were mild in severity and consistent with those seen in adults.. The results suggest that the dosages of vortioxetine evaluated (5-20 mg q.d.; approved for treatment in adults) and the uptitration schedule used are appropriate for pediatric efficacy and safety trials.

Topics: Adolescent; Anti-Anxiety Agents; Anxiety Disorders; Attention Deficit Disorder with Hyperactivity; Child; Comorbidity; Depressive Disorder; Dose-Response Relationship, Drug; Female; Humans; Male; Piperazines; Sulfides; Vortioxetine

This study aims to evaluate the efficacy and tolerability of vortioxetine 2.5-, 5- and 10-mg once-daily doses vs. placebo in the treatment of generalised anxiety disorder (GAD).. In this 8-week, multicentre, double-blind, placebo-controlled, parallel-group, phase 3 study, patients with a primary GAD diagnosis were randomised to receive placebo (n = 157), vortioxetine 2.5 mg, vortioxetine 5 mg, vortioxetine 10 mg or duloxetine 60 mg once daily (n = 156 each). The primary end-point, mean change from baseline in Hamilton Anxiety Scale (HAM-A) total score and key secondary end-points for the 5- and 10-mg vortioxetine doses were analysed in a prespecified sequential testing procedure (all at week 8). Sexual dysfunction was evaluated using the Arizona Sexual Experiences Scale.. Differences from placebo in the primary efficacy end-point were not statistically significant for the vortioxetine groups. The mean difference from placebo was significant in the duloxetine arm. For all secondary efficacy end-points, results were similar among the vortioxetine groups and did not reach statistical significance. The vortioxetine 10-mg group showed separation from placebo on the Hospital Anxiety and Depression anxiety subscore (nominal p = 0.036). Duloxetine 60 mg significantly improved the primary end-point (p < 0.05 vs. placebo), validating the study. Nausea, dry mouth, diarrhoea, nasopharyngitis, headache, dizziness, somnolence, vomiting, dyspepsia, constipation and fatigue were reported in ≥ 5% of patients receiving vortioxetine. Rates of treatment-emergent sexual dysfunction (TESD) in the vortioxetine dosing groups were similar to placebo.. In this study, vortioxetine 2.5-, 5- and 10-mg once-daily doses showed no significant improvement in HAM-A total scores vs. placebo. Vortioxetine was well tolerated at all doses and was not associated with TESD.

Topics: Adolescent; Adult; Aged; Anti-Anxiety Agents; Anxiety Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Duloxetine Hydrochloride; Female; Humans; Male; Middle Aged; Piperazines; Sulfides; Thiophenes; Treatment Outcome; Vortioxetine; Young Adult

Vortioxetine is a recently approved multimodal antidepressant with anxiolytic properties in preclinical studies.. This double-blind, placebo-controlled study assessed the efficacy and tolerability of vortioxetine in subjects with a primary diagnosis of generalized anxiety disorder.. Subjects (n = 457) were randomized 1:1:1 to treatment with placebo or vortioxetine 2.5 or 10 mg once daily. The primary efficacy endpoint was reduction in Hamilton Anxiety Scale (HAM-A) total scores from baseline after 8 weeks of treatment. Key secondary outcomes were changes from baseline in HAM-A total scores for the 2.5 and 10 mg dose, Hospital Anxiety and Depression anxiety subscore, 36-Item Short-Form Health Survey, Sheehan Disability Scale, and Clinical Global Impression-Improvement Scale score, as well as HAM-A response rate at week 8.. Neither vortioxetine dose achieved a statistically significant improvement over placebo on the primary endpoint (least-squares mean difference ± standard error from placebo: -0.87 ± 0.803 [p = 0.279] for 2.5 mg and -0.81 ± 0.791 [p = 0.306] for 10 mg vortioxetine) or on any secondary efficacy endpoints. Common adverse events (≥5% in either vortioxetine group) were nausea, dry mouth, headache, diarrhea, constipation, and vomiting.. Vortioxetine 2.5 and 10 mg treatment did not significantly improve generalized anxiety disorder symptoms versus placebo. Vortioxetine was safe and well tolerated in this patient population.

Topics: Adult; Anti-Anxiety Agents; Anxiety Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Least-Squares Analysis; Male; Middle Aged; Piperazines; Psychiatric Status Rating Scales; Sulfides; Treatment Outcome; Vortioxetine

The purpose of this study was to investigate the long-term maintenance of the efficacy of Lu AA21004 5 or 10 mg/day in the prevention of relapse in patients with generalized anxiety disorder (GAD). Patients (n = 687) with a primary diagnosis of GAD (DSM-IV criteria) and a baseline Hamilton Anxiety (HAM-A) total score of at least 20 underwent a 20-week, open-label Lu AA21004 treatment. In all, 459 patients responded and were randomized to 24-56 weeks of a double-blind treatment with Lu AA21004 (n = 229) or placebo (n = 230). The predefined primary efficacy endpoint was time to relapse (HAM-A total score ≥ 15) using a Cox model; the key secondary efficacy endpoint under multiplicity control was time to relapse for patients responding to treatment for at least 12 weeks. The primary analysis showed a statistically significant effect of Lu AA21004 relative to the placebo on the time to relapse of GAD, with a hazard ratio of 2.71 (P < 0.001). There was a statistically significant effect of Lu AA21004 in the stable responders (hazard ratio = 3.06, P < 0.001). Lu AA21004 was well tolerated, with withdrawal rates due to adverse events of 9% (open-label) and 3% (placebo) and 4% (Lu AA21004) in the double-blind period. In this study, Lu AA21004 5 or 10 mg/day was efficacious in preventing relapse and was well tolerated in the maintenance treatment of GAD.

Topics: Adolescent; Adult; Aged; Anti-Anxiety Agents; Anxiety Disorders; Double-Blind Method; Female; Humans; Male; Middle Aged; Piperazines; Psychiatric Status Rating Scales; Secondary Prevention; Sulfides; Vortioxetine

Vortioxetine is a multimodal antidepressant, with anxiolytic properties observed in preclinical studies. The goal of the current study was to evaluate the efficacy and tolerability of vortioxetine 5mg vs placebo in adults with generalized anxiety disorder (GAD). Adults with a primary diagnosis of GAD (HAM-A total score ≥20 and MADRS score ≤16) received vortioxetine 5mg or placebo for 8 weeks. The primary efficacy endpoint was reduction in HAM-A total scores from baseline after 8 weeks of treatment compared with placebo. Key secondary measurements were HAD anxiety subscore, CGI-I, SDS total score, HAM-A response rates, HAM-A total score for subjects whose baseline HAM-A total score was ≥25, and SF-36 social functioning subscore. HAM-A remission rates were also measured. Adverse events (AEs) were assessed throughout the study. In total, 301 subjects (mean age, 45.2 years; 31% male) were randomized (1:1) to receive vortioxetine 5mg (n=150) or placebo (n=151). After 8 weeks of treatment, there was a statistically significant difference in reduction from baseline in HAM-A total score for the vortioxetine group (-14.30) compared with placebo recipients (-10.49) (P<0.001). Statistically significant differences were observed for all key secondary outcomes favoring vortioxetine treatment (vs placebo), using a mixed model for repeated measurements (MMRM) analysis. Active treatment resulted in a significantly higher rate of remission. Vortioxetine was well tolerated. The most common treatment-related AEs were nausea, headache, dizziness, and dry mouth. In sum, vortioxetine was safe and effective in treating adults with GAD in this multinational population.

Topics: Adult; Anti-Anxiety Agents; Anxiety Disorders; Double-Blind Method; Female; Humans; Internationality; Male; Middle Aged; Piperazines; Poland; Sulfides; Time Factors; Treatment Outcome; Vortioxetine

The goal of the current clinical study, conducted in the United States (US), was to evaluate the efficacy and tolerability of vortioxetine 5mg vs placebo in adults with a primary diagnosis of generalized anxiety disorder (GAD; HAM-A total score ≥20 and MADRS score ≤16). Subjects were randomized (1:1) to receive vortioxetine 5mg (n=152) or placebo (n=152) for 8 weeks. Efficacy was assessed using change from baseline in HAM-A total scores after 8 weeks of treatment compared with placebo, using mixed-model repeated measures (MMRM) analyses. Adverse events (AEs) were assessed throughout the study. A total of 304 subjects were randomized (mean age, 41.2 years). After 8 weeks of treatment, there was no statistically significant difference in the reduction in HAM-A total score from baseline between the Vortioxetine (n=145) and placebo (n=145) groups. There were no statistically significant differences in any key secondary efficacy outcome between vortioxetine and placebo. Factors potentially contributing to the differences between the results of this study and those of one of identical design conducted outside the US are discussed. The most common treatment-emergent AEs were nausea, headache, dizziness, and dry mouth. Nausea was more frequently reported in the vortioxetine group (25% vs 4.6% for the placebo group). Most AEs were mild to moderate in severity. In conclusion, in this trial, vortioxetine did not improve symptoms of GAD (compared with placebo) over 8 weeks of treatment. Vortioxetine was well tolerated in this study.

Topics: Adult; Anti-Anxiety Agents; Anxiety Disorders; Double-Blind Method; Female; Humans; Male; Middle Aged; Piperazines; Psychiatric Status Rating Scales; Sulfides; Time Factors; Treatment Outcome; United States; Vortioxetine

Major depressive disorder (MDD) and generalized anxiety disorder (GAD) are frequently comorbid.. To assess the effectiveness of vortioxetine in patients with MDD and comorbid GAD.. Open-label, 8-week study (NCT04220996) in 100 adult outpatients with severe MDD and severe comorbid GAD receiving vortioxetine as first treatment for the current depressive episode or switching to vortioxetine due to inadequate response to another drug for depression. Vortioxetine starting dosage was 10 mg/day, with forced up-titration to 20 mg/day after 1 week. Response was defined as ⩾50% decrease in Montgomery-Åsberg Depression Rating Scale (MADRS) and/or Hamilton Anxiety Rating Scale (HAM-A) total score from baseline; remission defined as MADRS and/or HAM-A total score ⩽10.. Clinically meaningful and statistically significant improvements from baseline in symptoms of depression and anxiety, and overall functioning and health-related quality of life, were observed after 8 weeks' vortioxetine treatment (all changes. Vortioxetine demonstrates effectiveness in significantly reducing symptoms of both depression and anxiety in patients with severe MDD comorbid with severe GAD. Findings support increasing vortioxetine dosage to 20 mg/day early in the course of therapy, and show that this may be achieved without compromising tolerability.

Topics: Adult; Anxiety Disorders; Comorbidity; Depressive Disorder, Major; Humans; Quality of Life; Treatment Outcome; Vortioxetine

Topics: Animals; Antidepressive Agents; Anxiety Disorders; Attention Deficit Disorder with Hyperactivity; Autistic Disorder; Benzodiazepines; Cognitive Aging; Cognitive Behavioral Therapy; Cognitive Dysfunction; Cognitive Remediation; Dementia; Drosophila melanogaster; Female; Humans; Hypnotics and Sedatives; Intellectual Disability; Neural Pathways; Pregnancy; Prenatal Exposure Delayed Effects; Risk Factors; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Sleep; Vortioxetine

Advanced Practice Providers recognize and treat the most common side effects patients bring to our attention with the use of antidepressants, including insomnia, weight gain, emotional flattening, and sexual side effects. (https://www.psychcongress.com/article/top-5-side-effects-psychotropics-and-how-manage-them). We are, however, less intuitive and competent at picking up the high risk and rare, problem prone side effects our patients may experience related to the medications we prescribe, particularly in the more medically complex patients. In addition, the medically complex patient may mask a psychiatric concern as the psychiatric provider finds themselves caught up in the ambiguity of numerous somatic symptoms a patient presents with versus the psychiatric concerns that bear our attention. Autoimmune disorders often blur this line all too well affecting both psychiatric and physical well-being.

Topics: Adult; Antidepressive Agents; Anxiety Disorders; Citalopram; Depression; Edema; Female; Hashimoto Disease; Humans; Vortioxetine

Topics: Aged; Anxiety Disorders; Female; Humans; Hyperhidrosis; Psychotic Disorders; Selective Serotonin Reuptake Inhibitors; Serotonin Syndrome; Vortioxetine

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.

Topics: Adult; Anxiety Disorders; Depressive Disorder, Major; Female; Humans; Male; Middle Aged; Piperazines; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological; Sulfides; Vortioxetine

This article summarizes the US Food and Drug Administration's (FDA's) review of the New Drug Application for vortioxetine, especially the clinical efficacy and safety data. It emphasizes the issues that were important to the FDA's approval decision, particularly the difference in the effective dose in domestic and foreign studies, and notes several new labeling features, specifically, description of time course of treatment response and detailed sexual dysfunction evaluation.. The data sources were the original raw data sets for all clinical trials included in the development program for vortioxetine, as well as the sponsor's original analyses of these data. Data were available from 51 human trials involving vortioxetine, and included a total of 7,666 healthy volunteers and patients with a diagnosis of major depressive disorder (MDD) or generalized anxiety disorder who were exposed to at least 1 dose of vortioxetine for a total of 2,743 patient-years.. Vortioxetine was effective in treating MDD in the United States at a dose of 20 mg/d. The recommended starting dose is 10 mg once daily without regard to food, with increase to 20 mg/d if the 10 mg/d dose is tolerated. For patients who do not tolerate 20 mg/d, 10 mg/d can be used and 5-mg/d dose can be considered. Vortioxetine can be discontinued abruptly, but it is recommended that doses of 15 mg/d or 20 mg/d be reduced to 10 mg/d for 1 week prior to full discontinuation to avoid potential withdrawal symptoms. Although the non-US maintenance study showed that maintenance doses of 5 to 10 mg/d were effective, a clinical judgment needs to be made to decide the maintenance dose in the United States. The applicant has agreed to conduct a US maintenance dose-response study covering the US-approved dose range. Vortioxetine's adverse event profile is similar to that of other selective serotonin reuptake inhibitors (SSRIs). Nausea is the most common adverse event and is dose dependent. No dose adjustment is needed based on age, gender, or the presence of renal or mild to moderate hepatic impairment. The maximum recommended dose is 10 mg/d in known cytochrome P450 2D6 poor metabolizers.. Vortioxetine is a new treatment for MDD, and its adverse event profile is similar to that of other SSRIs.

Topics: Adult; Anxiety Disorders; Controlled Clinical Trials as Topic; Depressive Disorder, Major; Drug Approval; Female; Humans; Male; Middle Aged; Piperazines; Selective Serotonin Reuptake Inhibitors; Sulfides; United States; United States Food and Drug Administration; Vortioxetine

Vortioxetine is an orally administered small molecule developed by Lundbeck A/S for the once-daily treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD). Vortioxetine received its first global approval for MDD in the USA in September 2013 and regulatory approval for its use in this indication in the EU (where it has received a positive opinion) and Canada is awaited. The drug is a bis-aryl-sulphanyl amine compound that combines serotonin (5-HT) reuptake inhibition with other characteristics, including receptor activity modulation. In vitro studies indicate that vortioxetine is an inhibitor of the 5-HT transporter and is a 5-HT(1D), 5-HT₃ and 5-HT₇ receptor antagonist, a 5-HT(1A) receptor agonist and a 5-HT(1B) receptor partial agonist. Animal and in vitro studies indicate that several neurotransmitter systems may be impacted by vortioxetine, with the drug enhancing levels of 5-HT, noradrenaline, dopamine, acetylcholine and histamine in certain areas of the brain, as well as modulating γ-aminobutyric acid and glutamate neurotransmission. Phase III trials of vortioxetine in both MDD and GAD have been conducted worldwide. This article summarizes the milestones in the development of vortioxetine leading to this first approval for MDD.

Topics: Animals; Anti-Anxiety Agents; Antidepressive Agents; Anxiety Disorders; Clinical Trials as Topic; Depressive Disorder, Major; Drug Approval; Drug Interactions; Humans; Piperazines; Sulfides; Vortioxetine

Vortioxetine (Lu-AA-21004; 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine hydrobromide) is a novel orally active molecule that is being investigated by Lundbeck and Takeda for the treatment of major depression and generalized anxiety disorders. Vortioxetine has a unique "multi-modal" mechanism of action. It inhibits the activity of serotonin transporters and is an agonist of serotonin 5-HT1A receptor, partial agonist of 5-HT1B and antagonist of 5-HT3A, 5-HT7 and 5-HT1D receptors. Vortioxetine has been effective in various animal models of depression and anxiety and clinical studies have shown the antidepressant and antianxiety properties of vortioxetine in a dose range of 5-20 mg/day. Vortioxetine reverses cognitive decline in patients with depression making it a unique molecule. The molecule lacks any serious side effects and drug-drug interactions. However, dose adjustments are required if vortioxetine is co-administered with rifampicin or bupropion. The molecule is under review by various regulatory agencies around the world for the treatment of major depression.

Topics: Animals; Anti-Anxiety Agents; Antidepressive Agents; Anxiety Disorders; Depressive Disorder, Major; Dose-Response Relationship, Drug; Drug Interactions; Humans; Piperazines; Sulfides; Vortioxetine

Topics: Anti-Anxiety Agents; Anxiety Disorders; Clinical Trials as Topic; Humans; Piperazines; Sulfides; Treatment Outcome; Vortioxetine