Vortioxetine (Lu AA21004) in generalized anxiety disorder: Results of an 8-week, multinational, randomized, double-blind, placebo-controlled clinical trial

Bidzan, Leszek; Mahableshwarkar, Atul R.; Jacobsen, Paula; Yan, Mingjin; Sheehan, David V.

doi:10.1016/j.euroneuro.2012.07.012

Cited by 65 publications

(73 citation statements)

References 27 publications

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“…All studies were financially supported by the manufacturer. Regarding the primary endpoint analysis, only one study showed a robust efficacy of vortioxetine for treating GAD (Bidzan, 2012), whereas the other three RCTs (Mahableshwarkar, 2014a(Mahableshwarkar, , 2014bRothschild, 2012) failed to separate it from placebo treatment. Such trend was also observed in the analyses of response and remission rates.…”

Section: Description Of Studies Included In the Meta-analysismentioning

confidence: 95%

“…The additional endpoints included in the four RCTs were various outcomes such as Hospital Anxiety and Depression (HAD), Clinical Global Impression-Improvement of Illness (CGI-I), and Sheehan Disability Scale (SDS). The study by Bidzan et al (Bidzan, 2012) has shown a superiority of vortioxetine over placebo in all such additional efficacy endpoints, and the others (Mahableshwarkar, 2014a(Mahableshwarkar, , 2014bRothschild, 2012) completely failed to separate it from placebo. Across all of the studies, the most frequently reported AEs were nausea, headache, dizziness, and dry mouth.…”

Section: Description Of Studies Included In the Meta-analysismentioning

confidence: 95%

“…Of these four RCTs, only one study (Mahableshwarkar, 2014a) included an active control for assay sensitivity (duloxetine 60 mg/d) as well as a placebo arm. The other three RCTs compared vortioxetine with a placebo (Bidzan, 2012;Mahableshwarkar, 2014b;Rothschild, 2012). Two RCTs included different doses of vortioxetine (2.5e10 mg/d) in the treatment arm (Mahableshwarkar, 2014a(Mahableshwarkar, , 2014b, whereas the other two studies included one fixed dose of vortioxetine (5 mg/d) in the treatment arm (Bidzan, 2012;Rothschild, 2012).…”

Section: Description Of Studies Included In the Meta-analysismentioning

confidence: 99%

“…Four short-term RCTs (Bidzan et al, 2012;Mahableshwarkar et al, 2014aMahableshwarkar et al, , 2014bRothschild et al, 2012) met the inclusion criteria, and one long-term trial was a relapse prevention study (Baldwin et al, 2012b). Of the 38 records obtained from ClinicalTrials.gov, all five trials were duplicates of those identified by the aforementioned search (Fig.…”

Section: Description Of Studies Included In the Meta-analysismentioning

confidence: 99%

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Vortioxetine, a multimodal antidepressant for generalized anxiety disorder: A systematic review and meta-analysis

Pae

Wang

Han

et al. 2015

Journal of Psychiatric Research

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Section: Description Of Studies Included In the Meta-analysismentioning

confidence: 95%

Section: Description Of Studies Included In the Meta-analysismentioning

confidence: 95%

Section: Description Of Studies Included In the Meta-analysismentioning

confidence: 99%

Section: Description Of Studies Included In the Meta-analysismentioning

confidence: 99%

See 2 more Smart Citations

Vortioxetine, a multimodal antidepressant for generalized anxiety disorder: A systematic review and meta-analysis

Pae

Wang

Han

et al. 2015

Journal of Psychiatric Research

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“…There is significant variability both in types of MDD and severity of symptoms. Most antidepressant therapies act on the serotonergic system, and the most common fall into the categories of selective serotonin reuptake inhibitors, such as fluoxetine; serotonin and norepinephrine reuptake inhibitors, such as venlafaxine; and norepinephrine and dopamine reuptake inhibitors, such as bupropion.Vortioxetine (Lu AA21004) is a new antidepressant extensively studied in the treatment of MDD [3][4][5][6][7][8][9][10][11][12][13] and in generalized anxiety disorder (GAD) [14][15][16][17][18]. Vortioxetine received marketing authorization for use in MDD in the United States of America (USA) in October 2013, and in the European Union (EU) in December 2013 [19,20].…”

mentioning

confidence: 99%

A Population Pharmacokinetic–Pharmacodynamic Meta‐Analysis of Vortioxetine in Patients with Major Depressive Disorder

Naik

Chan

Vakilynejad

et al. 2015

Basic Clin Pharma Tox

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Vortioxetine is approved for the treatment of major depressive disorder (MDD). This analysis aimed to develop pharmacokinetic (PK) and PK/Efficacy models to evaluate the exposure-response relationship for vortioxetine in patients with MDD. PK data from 10 MDD and two generalized anxiety disorder studies of vortioxetine (3160 patients), and efficacy data [Montgomery-Asberg Depression Rating Scale (MADRS)] from seven MDD studies (2537 patients), were used for the development of PK and PK/Efficacy models. One-and two-compartment models were evaluated as structural PK models, and linear and nonlinear (E max ) models were used to describe the relationship between average vortioxetine concentration at steady-state (C av ) and change in MADRS score from baseline (DMADRS). The impact of selected covariates on the PK and efficacy parameters of vortioxetine was also investigated. PK of vortioxetine was best characterized by a two-compartment model with first-order absorption and elimination. Mean estimates for oral clearance (CL/F) and volume of distribution for the central compartment of vortioxetine were 42 L/hr and 2920 L. Creatinine clearance, height and geographic region had statistically significant effects on vortioxetine CL/F, but the effect of each of these covariates was not considered clinically relevant, as they lead to AE26% change in area under the curve or C max of vortioxetine. An E max model best described the relationship between DMADRS and C av . Half-maximal effective concentration (EC 50 ) and E max estimates were 24.9 ng/mL and 7.0. No identified covariates, except region, had clinically meaningful effects on vortioxetine efficacy. These PK/Efficacy models adequately characterized the vortioxetine exposure-response relationship.A recent systematic review reported a global prevalence of major depressive disorder (MDD) of 4.7% [1], and according to the World Health Organization it is the leading cause of disability globally in middle-to high-income countries [2]. There is significant variability both in types of MDD and severity of symptoms. Most antidepressant therapies act on the serotonergic system, and the most common fall into the categories of selective serotonin reuptake inhibitors, such as fluoxetine; serotonin and norepinephrine reuptake inhibitors, such as venlafaxine; and norepinephrine and dopamine reuptake inhibitors, such as bupropion.Vortioxetine (Lu AA21004) is a new antidepressant extensively studied in the treatment of MDD [3][4][5][6][7][8][9][10][11][12][13] and in generalized anxiety disorder (GAD) [14][15][16][17][18]. Vortioxetine received marketing authorization for use in MDD in the United States of America (USA) in October 2013, and in the European Union (EU) in December 2013 [19,20]. The mechanism of action of vortioxetine is thought to be related to multimodal activity [21], through direct modulation of receptor activity, and modulation of the serotonin transporter (SERT). In vitro and in vivo studies have shown that vortioxetine is a 5-hydroxytryptamine (HT) 3 , ...

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Differential Outcomes of Placebo Treatment Across 9 Psychiatric Disorders

Bschor,

Nagel,

Unger

et al. 2024

JAMA Psychiatry

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ImportancePlacebo is the only substance systematically evaluated across common psychiatric diagnoses, but comprehensive cross-diagnostic comparisons are lacking.ObjectiveTo compare changes in placebo groups in recent high-quality randomized clinical trials (RCTs) across a broad spectrum of psychiatric disorders in adult patients.Data SourcesMEDLINE and the Cochrane Database of Systematic Reviews were systematically searched in March 2022 for the latest systematic reviews meeting predetermined high-quality criteria for 9 major psychiatric diagnoses.Study SelectionUsing these reviews, the top 10 highest-quality (ie, lowest risk of bias, according to the Cochrane Risk of Bias tool) and most recent placebo-controlled RCTs per diagnosis (totaling 90 RCTs) were selected, adhering to predetermined inclusion and exclusion criteria.Data Extraction and SynthesisFollowing the Cochrane Handbook, 2 authors independently carried out the study search, selection, and data extraction. Cross-diagnosis comparisons were based on standardized pre-post effect sizes (mean change divided by its SD) for each placebo group. This study is reported following the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline.Main Outcome and MeasureThe primary outcome, pooled pre-post placebo effect sizes (dav) with 95% CIs per diagnosis, was determined using random-effects meta-analyses. A Q test assessed statistical significance of differences across diagnoses. Heterogeneity and small-study effects were evaluated as appropriate.ResultsA total of 90 RCTs with 9985 placebo-treated participants were included. Symptom severity improved with placebo in all diagnoses. Pooled pre-post placebo effect sizes differed across diagnoses (Q = 88.5; df = 8; P &lt; .001), with major depressive disorder (dav = 1.40; 95% CI, 1.24-1.56) and generalized anxiety disorder (dav = 1.23; 95% CI, 1.06-1.41) exhibiting the largest dav. Panic disorder, attention-deficit/hyperactivity disorder, posttraumatic stress disorder, social phobia, and mania showed dav between 0.68 and 0.92, followed by OCD (dav = 0.65; 95% CI, 0.51-0.78) and schizophrenia (dav = 0.59; 95% CI, 0.41-0.76).Conclusion and RelevanceThis systematic review and meta-analysis found that symptom improvement with placebo treatment was substantial in all conditions but varied across the 9 included diagnoses. These findings may help in assessing the necessity and ethical justification of placebo controls, in evaluating treatment effects in uncontrolled studies, and in guiding patients in treatment decisions. These findings likely encompass the true placebo effect, natural disease course, and nonspecific effects.

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Vortioxetine (Lu AA21004) in generalized anxiety disorder: Results of an 8-week, multinational, randomized, double-blind, placebo-controlled clinical trial

Cited by 65 publications

References 27 publications

Vortioxetine, a multimodal antidepressant for generalized anxiety disorder: A systematic review and meta-analysis

Vortioxetine, a multimodal antidepressant for generalized anxiety disorder: A systematic review and meta-analysis

A Population Pharmacokinetic–Pharmacodynamic Meta‐Analysis of Vortioxetine in Patients with Major Depressive Disorder

Differential Outcomes of Placebo Treatment Across 9 Psychiatric Disorders

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