+ Clinical Trial, Review, Last 10 Years, Humans, English = 37

Six articles selected

+ Article, Review, Last 5 Years = 96

One article selected

+ Review Article, Research Articles = 117

No articles selected

I: Vortioxetine

C: Duloxetine

O: [Blank]

No articles selected

One article selected

No articles selected

No articles selected

+ Since 2015, – Include Citations, Include Patents = 1,140 (But only searched first 3 pages or 30 items)

Sorted by Relevance

Two articles selected

BACKGROUND:

Major depressive disorder is a common mental disorder affecting a person’s mind, behaviour and body. It is expressed as a variety of symptoms and is associated with substantial impairment. Despite a range of pharmacological and non-pharmacological treatment options, there is still room for improvement of the pharmacological treatment of depression in terms of efficacy and tolerability. The latest available antidepressant is vortioxetine. It is assumed that vortioxetine‘s antidepressant action is related to a direct modulation of serotonergic receptor activity and inhibition of the serotonin transporter. The mechanism of action is not fully understood, but it is claimed to be novel. Vortioxetine was placed in the category of “Other” antidepressants and may therefore provide an alternative to existing antidepressant drugs.

OBJECTIVES:

To assess the efficacy and acceptability of vortioxetine compared with placebo and other antidepressant drugs in the treatment of acute depression in adults.

SEARCH METHODS:

We searched Cochrane’s Depression, Anxiety and Neurosis Review Group’s Specialised Register to May 2016 without applying any restrictions to date, language or publication status. We checked reference lists of relevant studies and reviews, regulatory agency reports and trial databases.

SELECTION CRITERIA:

We included randomised controlled trials comparing the efficacy, tolerability, or both of vortioxetine versus placebo or any other antidepressant agent in the treatment of acute depression in adults.

DATA COLLECTION AND ANALYSIS:

Two review authors independently selected the studies and extracted data. We extracted data on study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy, acceptability and tolerability. We analysed intention-to-treat (ITT) data only and used risk ratios (RR) as effect sizes for dichotomous data and mean differences (MD) for continuous data with 95% confidence intervals (CI). Meta-analyses used random-effects models.

MAIN RESULTS:

We included 15 studies (7746 participants) in this review. Seven studies were placebo controlled; eight studies compared vortioxetine to serotonin-norepinephrine reuptake inhibitors (SNRIs). We were unable to identify any study that compared vortioxetine to antidepressant drugs from other classes, such as selective serotonin reuptake inhibitors (SSRIs).Vortioxetine may be more effective than placebo across the three efficacy outcomes: response (Mantel-Haenszel RR 1.35, 95% CI 1.22 to 1.49; 14 studies, 6220 participants), remission (RR 1.32, 95% CI 1.15 to 1.53; 14 studies, 6220 participants) and depressive symptoms measured using the Montgomery-Åsberg Depression Scale (MADRS) (score range: 0 to 34; higher score means worse outcome: MD -2.94, 95% CI -4.07 to -1.80; 14 studies, 5566 participants). The quality of the evidence was low for response and remission and very low for depressive symptoms. We found no evidence of a difference in total dropout rates (RR 1.05, 95% CI 0.93 to 1.19; 14 studies, 6220 participants). More participants discontinued vortioxetine than placebo because of adverse effects (RR 1.41, 95% CI 1.09 to 1.81; 14 studies, 6220 participants) but fewer discontinued due to inefficacy (RR 0.56, 95% CI 0.34 to 0.90, P = 0.02; 14 studies, 6220 participants). The quality of the evidence for dropouts was moderate.The subgroup and sensitivity analyses did not reveal factors that significantly influenced the results. In comparison with other antidepressants, very low-quality evidence from eight studies showed no clinically significant difference between vortioxetine and SNRIs as a class for response (RR 0.91, 95% CI 0.82 to 1.00; 3159 participants) or remission (RR 0.89, 95% CI 0.77 to 1.03; 3155 participants). There was a small difference favouring SNRIs for depressive symptom scores on the MADRS (MD 1.52, 95% CI 0.50 to 2.53; 8 studies, 2807 participants). Very low quality evidence from eight studies (3159 participants) showed no significant differences between vortioxetine and the SNRIs as a class for total dropout rates (RR 0.89, 95% CI 0.73 to 1.08), dropouts due to adverse events (RR 0.74, 95% CI 0.51 to 1.08) and dropouts due to inefficacy (RR 1.52, 95% CI 0.70 to 3.30). Against individual antidepressants, analyses suggested that vortioxetine may be less effective than duloxetine in terms of response rates (RR 0.86, 95% CI 0.79 to 0.94; 6 studies, 2392 participants) and depressive symptoms scores on the MADRS scale (MD 1.99, 95% CI 1.15 to 2.83; 6 studies; 2106 participants). Against venlafaxine, meta-analysis of two studies found no statistically significant differences (response: RR 1.03, 95% CI 0.85 to 1.25; 767 participants; depressive symptom scores: MD 0.02, 95% CI -2.49 to 2.54; 701 participants). In terms of number of participants reporting at least one adverse effect (tolerability), vortioxetine was better than the SNRIs as a class (RR 0.90, 95% CI 0.86 to 0.94; 8 studies, 3134 participants) and duloxetine (RR 0.89, 95% CI 0.84 to 0.95; 6 studies; 2376 participants). However, the sensitivity analysis casts some doubts on this result, as only two studies used comparable dosing. We judged none of the studies to have a high risk of bias for any domain, but we rated all studies to have an unclear risk of bias of selective reporting and other biases.

AUTHORS’ CONCLUSIONS:

The place of vortioxetine in the treatment of acute depression is unclear. Our analyses showed vortioxetine may be more effective than placebo in terms of response, remission and depressive symptoms, but the clinical relevance of these effects is uncertain. Furthermore, the quality of evidence to support these findings was generally low. In comparison to SNRIs, we found no advantage for vortioxetine. Vortioxetine was less effective than duloxetine, but fewer people reported adverse effects when treated with vortioxetine compared to duloxetine. However, these findings are uncertain and not well supported by evidence. A major limitation of the current evidence is the lack of comparisons with the SSRIs, which are usually recommended as first-line treatments for acute depression. Studies with direct comparisons to SSRIs are needed to address this gap and may be supplemented by network meta-analyses to define the role of vortioxetine in the treatment of depression.

Comment in

• Network meta-analysis of antidepressants. [Lancet. 2018]

PMID: 28677828

PMCID: PMC6483322

DOI: 10.1002/14651858.CD011520.pub2

[Indexed for MEDLINE]

Free PMC Article

BACKGROUND AND OBJECTIVE:

Vortioxetine and duloxetine are two new antidepressant drugs that have been used clinically in the treatment of major depressive disorder (MDD). The objectives of this meta-analysis were to evaluate the efficacy and tolerability of vortioxetine compared with duloxetine in MDD.

METHODS:

Randomized controlled trials (RCTs) published in PubMed, EMBASE, Web of Science, and ClinicalTrials.gov were systematically reviewed to compare vortioxetine with duloxetine in terms of efficacy and tolerability in patients with MDD. Results were expressed as the risk ratio (RR) with 95 % confidence intervals (CIs), and weighted mean difference (WMD). Pooled estimates were calculated by using a fixed-effects model or a randomized-effects model, depending on the heterogeneity among studies.

RESULTS:

A total of five RCTs involving 2287 patients met the inclusion criteria and were included in this meta-analysis. Pooled results showed that duloxetine was associated with a higher response rate than vortioxetine, as well as showing a similar remission rate with vortioxetine. The changes from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS), 24-item Hamilton Rating Scale for Depression (HAM-D24), Clinical Global Impression-Improvement scale (CGI-I), CGI-Severity scale (CGI-S), Sheehan Disability Scale (SDS), and Hamilton Anxiety Rating Scale (HAM-A) scores were significantly greater in the duloxetine group than in the vortioxetine group. The incidence of treatment-emergent adverse events was significantly higher in the duloxetine group than in the vortioxetine group.

CONCLUSION:

Duloxetine was more effective but less well-tolerated than vortioxetine in MDD. Considering the potential limitations of this meta-analysis, more large-scale RCTs are needed to confirm these findings.

PMID:  27067232

DOI: 10.1007/s40261-016-0396-9

[Indexed for MEDLINE]

BACKGROUND:

Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide in adults. Pharmacological and non-pharmacological treatments are available; however, because of inadequate resources, antidepressants are used more frequently than psychological interventions. Prescription of these agents should be informed by the best available evidence. Therefore, we aimed to update and expand our previous work to compare and rank antidepressants for the acute treatment of adults with unipolar major depressive disorder.

METHODS:

We did a systematic review and network meta-analysis. We searched Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS database, MEDLINE, MEDLINE In-Process, PsycINFO, the websites of regulatory agencies, and international registers for published and unpublished, double-blind, randomised controlled trials from their inception to Jan 8, 2016. We included placebo-controlled and head-to-head trials of 21 antidepressants used for the acute treatment of adults (≥18 years old and of both sexes) with major depressive disorder diagnosed according to standard operationalised criteria. We excluded quasi-randomised trials and trials that were incomplete or included 20% or more of participants with bipolar disorder, psychotic depression, or treatment-resistant depression; or patients with a serious concomitant medical illness. We extracted data following a predefined hierarchy. In network meta-analysis, we used group-level data. We assessed the studies’ risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions, and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. Primary outcomes were efficacy (response rate) and acceptability (treatment discontinuations due to any cause). We estimated summary odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with PROSPERO, number CRD42012002291.

FINDINGS:

We identified 28 552 citations and of these included 522 trials comprising 116 477 participants. In terms of efficacy, all antidepressants were more effective than placebo, with ORs ranging between 2·13 (95% credible interval [CrI] 1·89-2·41) for amitriptyline and 1·37 (1·16-1·63) for reboxetine. For acceptability, only agomelatine (OR 0·84, 95% CrI 0·72-0·97) and fluoxetine (0·88, 0·80-0·96) were associated with fewer dropouts than placebo, whereas clomipramine was worse than placebo (1·30, 1·01-1·68). When all trials were considered, differences in ORs between antidepressants ranged from 1·15 to 1·55 for efficacy and from 0·64 to 0·83 for acceptability, with wide CrIs on most of the comparative analyses. In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants (range of ORs 1·19-1·96), whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious drugs (0·51-0·84). For acceptability, agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were more tolerable than other antidepressants (range of ORs 0·43-0·77), whereas amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine had the highest dropout rates (1·30-2·32). 46 (9%) of 522 trials were rated as high risk of bias, 380 (73%) trials as moderate, and 96 (18%) as low; and the certainty of evidence was moderate to very low.

INTERPRETATION:

All antidepressants were more efficacious than placebo in adults with major depressive disorder. Smaller differences between active drugs were found when placebo-controlled trials were included in the analysis, whereas there was more variability in efficacy and acceptability in head-to-head trials. These results should serve evidence-based practice and inform patients, physicians, guideline developers, and policy makers on the relative merits of the different antidepressants.

FUNDING:

National Institute for Health Research Oxford Health Biomedical Research Centre and the Japan Society for the Promotion of Science.

Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Comment in

• Effectiveness of antidepressants. [BMJ. 2018]
• Review: In major depressive disorder, antidepressant drugs improve short-term response compared with placebo. [Ann Intern Med. 2018]
• The benefits of antidepressants: news or fake news? [Br J Psychiatry. 2018]
• Network meta-analysis of antidepressants. [Lancet. 2018]
• Network meta-analysis of antidepressants. [Lancet. 2018]
• Network meta-analysis of antidepressants. [Lancet. 2018]
• Network meta-analysis of antidepressants. [Lancet. 2018]
• Network meta-analysis of antidepressants. [Lancet. 2018]
• Which first-line antidepressant? [Br J Gen Pract. 2019]

PMID: 29477251

PMCID: PMC5889788

DOI: 10.1016/S0140-6736(17)32802-7

[Indexed for MEDLINE]

Free PMC Article

Appendix (Includes Statistical Analysis Important to my Clinical Question: Y_mmc1.pdf

BACKGROUND:

Second-generation antidepressants dominate the medical management of major depressive disorder (MDD). Levomilnacipran, vilazodone and vortioxetine are the latest therapeutic options approved for the treatment of MDD. This systematic review aims to compare the benefits and harms of vilazodone, levomilnacipran, and vortioxetine with one another and other second-generation antidepressants.

METHODS:

We searched electronic databases up to September 2017 and reviewed reference lists and pharmaceutical dossiers to detect published and unpublished studies. Two reviewers independently screened abstracts and full text articles, and rated the risk of bias of included studies. Randomized controlled trials (RCTs) and controlled observational studies including adult outpatients with MDD were eligible for inclusion. We conducted network meta-analyses on response to treatment using frequentist multivariate meta-analyses models. Placebo- and active-controlled trials were eligible for network meta-analyses.

RESULTS:

Twenty-four studies met our inclusion criteria. Direct comparisons were limited to vilazodone versus citalopram, and vortioxetine versus duloxetine, paroxetine, or venlafaxine XR (extended release). Results of head-to-head trials and network meta-analyses, overall, indicated similar efficacy among levomilnacipran, vilazodone, or vortioxetine and other second-generation antidepressants. Although rates of overall adverse events and discontinuation due to adverse events were similar, RCTs reported several differences in specific adverse events. For most outcomes the strength of evidence was low.

LIMITATIONS:

Limitations are the focus of literature searches on studies published in English, possible reporting biases, and general methodological limitations of network meta-analyses.

CONCLUSIONS:

Overall, the available evidence does not indicate greater benefits or fewer harms of levomilnacipran, vilazodone, and vortioxetine compared with other second-generation antidepressants.

Copyright © 2017 Elsevier B.V. All rights reserved.

KEYWORDS:

Levomilnacipran; Network meta–analysis; Second-generation antidepressants; Systematic review; Vilazodone; Vortioxetine

PMID: 29197738

DOI: 10.1016/j.jad.2017.11.056

[Indexed for MEDLINE]

INTRODUCTION:

Vortioxetine is an antidepressant with multimodal activity which has shown efficacy in major depressive disorder (MDD) patients in six of ten short-term, randomized, placebo-controlled trials (completed end 2012).

METHODS:

We performed meta-regression analyses to indirectly compare vortioxetine to seven marketed antidepressants with different mechanisms of action. To ensure study comparability, only experimental drug and placebo arms from placebo-controlled registration studies were included in primary analyses. The main outcomes were efficacy (standardized mean difference in change from baseline to 2 months on primary endpoint [MADRS/HAM-D]), and tolerability (withdrawal rate due to adverse events).

RESULTS:

For efficacy, estimates of treatment effect (negative estimates favor vortioxetine) for vortioxetine versus comparators were: agomelatine, -0.16 (p = 0.11); desvenlafaxine, 0.03 (p = 0.80); duloxetine, 0.09 (p = 0.42); escitalopram, -0.05 (p = 0.70); sertraline, -0.04 (p = 0.83); venlafaxine IR/XR, 0.12 (p = 0.33); and vilazodone, -0.25 (p = 0.11). For tolerability, all but one combination was numerically in favor of vortioxetine (odds ratio < 1), although not all differences were statistically significant: agomelatine, 1.77 (p = 0.03); desvenlafaxine, 0.58 (p = 0.04); duloxetine, 0.75 (p = 0.26); escitalopram, 0.67 (p = 0.28); sertraline, 0.30 (p = 0.01); venlafaxine, 0.47 (p = 0.01); and vilazodone, 0.64 (p = 0.18). Sensitivity analyses did not significantly alter antidepressant effect estimates or relative ranking.

CONCLUSION:

These meta-regression data show that vortioxetine offers a comparable or favorable combination of efficacy (measured by MADRS/HAM-D) and tolerability (measured by withdrawal rate due to adverse events) versus other antidepressants in registration studies in MDD. Alternative methods like mixed-treatment comparison and inclusion of all randomized studies and active reference arms may provide complementary information to this analysis (more evidence but also more heterogeneity). Key messages: Indirect comparisons based on registration studies allow a useful comparison between a recently approved antidepressant and an approved drug. Vortioxetine offers a comparable or favorable combination of efficacy (measured by MADRS/HAM-D assessments) and tolerability (measured by withdrawal rate due to adverse events) versus other antidepressants in registration studies in MDD.

KEYWORDS:

Antidepressants; Comparative evidence; Major depressive disorder; Vortioxetine

PMID: 25249164

DOI: 10.1185/03007995.2014.969566

[Indexed for MEDLINE]