Vortioxetine treatment for generalised anxiety disorder: a meta-analysis of anxiety, quality of life and safety outcomes

Qin, Bin; Huang, Guangsu; Yang, Qian; Zhao, Mingjun; Chen, Hong; Gao, Wen; Yang, Mingxiu

doi:10.1136/bmjopen-2019-033161

Cited by 16 publications

(7 citation statements)

References 45 publications

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“…Vortioxetine, a multimodal antidepressant, has been licensed for major depressive disorder since 2013. In a systematic review and meta-analysis of four placebo-controlled trials including GAD patients vortioxetine exhibited no superiority over placebo in terms of remission, and it was well tolerated (Qin et al, 2019), which is consistent with the results of the present analysis. Agomelatine and venlafaxine were better than vortioxetine in the current analysis.…”

Section: Discussionsupporting

confidence: 90%

Comparative Remission Rates and Tolerability of Drugs for Generalised Anxiety Disorder: A Systematic Review and Network Meta-analysis of Double-Blind Randomized Controlled Trials

et al. 2020

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Background: Generalized anxiety disorder (GAD) is one of the most common psychiatric disorders associated with substantial dysfunction and socioeconomic burden. Pharmacotherapy is the first choice for GAD. Remission [Hamilton Anxiety Scale (HAM-A) score ≤7] is regarded as a crucial treatment goal for patients with GAD. There is no up-to-date evidence to compare remission rate and tolerability of all available drugs by using network meta-analysis. Therefore, the goal of our study is to update evidence and determine the best advantageous drugs for GAD in remission rate and tolerability profiles.Method: We performed a systematic review and network meta-analysis of double-blind randomized controlled trials (RCTs). We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, wanfang data, China Biology Medicine and ClinicalTrials.gov from their inception to March 2020 to identify eligible double-blind, RCTs reporting the outcome of remission in adult patients who received any pharmacological treatment for GAD. Two reviewers independently assessed quality of included studies utilizing the Cochrane Collaboration’s risk of bias tool as described in Cochrane Collaboration Handbook and extracted data from all manuscripts. Our outcomes were remission rate (proportion of participants with a final score of seven or less on HAM-A) and tolerability (treatments discontinuations due to adverse events). We calculated summary odds ratios (ORs) and 95% confidence intervals (CIs) of each outcome via pairwise and network meta-analysis with random effects.Results: Overall, 30 studies were included, comprising 32 double-blind RCTs, involving 13,338 participants diagnosed as GAD by DSM-IV criteria. Twenty-eight trials were rated as moderate risk of bias, four trials as low. For remission rate, agomelatine (OR 2.70, 95% CI 1.74–4.19), duloxetine (OR 1.88, 95% CI 1.47–2.40), escitalopram (OR 2.03, 95% CI 1.48–2.78), paroxetine (OR 1.74, 95% CI 1.25–2.42), quetiapine (OR 1.88, 95% CI 1.39–2.55), and venlafaxine (OR 2.28, 95% CI 1.69–3.07) were superior to placebo. For tolerability, sertraline, agomelatine, vortioxetine, and pregabalin were found to be comparable to placebo. However, the others were worse than placebo in terms of tolerability, with ORs ranging between 1.86 (95% CI 1.25–2.75) for tiagabine and 5.98 (95% CI 2.41–14.87) for lorazepam. In head-to-head comparisons, agomelatine, duloxetine, escitalopram, quetiapine, and venlafaxine were more efficacious than tiagabine in terms of remission rate, ORs from 1.66 (95% CI 1.04–2.65) for duloxetine to 2.38 (95% CI 1.32–4.31) for agomelatine. We also found that agomelatine (OR 2.08, 95% CI 1.15–3.75) and venlafaxine (OR 1.76, 95% CI 1.08–2.86) were superior to vortioxetine. Lorazepam and quetiapine were poorly tolerated when compared with other drugs.Conclusions: Of these interventions, only agomelatine manifested better remission with relatively good tolerability but these results were limited by small sample sizes. Duloxetine, escitalopram, venlafaxine, paroxetine, and quetiapine showed better remission but were poorly tolerated.

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Section: Discussionsupporting

confidence: 90%

Comparative Remission Rates and Tolerability of Drugs for Generalised Anxiety Disorder: A Systematic Review and Network Meta-analysis of Double-Blind Randomized Controlled Trials

et al. 2020

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“…In the largest meta-analyses for anxiety disorders, pharmacotherapies achieved SMDs in comparison to placebo between 0.33 and 0.45 53,56,64 (see Figure 2). Overall, effect sizes for pharmacotherapy were between 0.01 and 0.56, with the majority of effect sizes being small 53,[55][56][57][58][59][60][61][62][63][64]66,67,69,70 (see supplementary information). RR ranged between 1.20 and 4.03, with most values being small, one medium (monoamine oxidase inhibitors), and one large (benzodiazepines, RR=4.03) 69 .…”

Section: Anxiety Disordersmentioning

confidence: 99%

The efficacy of psychotherapies and pharmacotherapies for mental disorders in adults: an umbrella review and meta‐analytic evaluation of recent meta‐analyses

et al. 2022

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Mental disorders represent a worldwide public health concern. Psychotherapies and pharmacotherapies are recommended as first line treatments. However, evidence has emerged that their efficacy may be overestimated, due to a variety of shortcomings in clinical trials (e.g., publication bias, weak control conditions such as waiting list). We performed an umbrella review of recent meta‐analyses of randomized controlled trials (RCTs) of psychotherapies and pharmacotherapies for the main mental disorders in adults. We selected meta‐analyses that formally assessed risk of bias or quality of studies, excluded weak comparators, and used effect sizes for target symptoms as primary outcome. We searched PubMed and PsycINFO and individual records of the Cochrane Library for meta‐analyses published between January 2014 and March 2021 comparing psychotherapies or pharmacotherapies with placebo or treatment‐as‐usual (TAU), or psychotherapies vs. pharmacotherapies head‐to‐head, or the combination of psychotherapy with pharmacotherapy to either monotherapy. One hundred and two meta‐analyses, encompassing 3,782 RCTs and 650,514 patients, were included, covering depressive disorders, anxiety disorders, post‐traumatic stress disorder, obsessive‐compulsive disorder, somatoform disorders, eating disorders, attention‐deficit/hyperactivity disorder, substance use disorders, insomnia, schizophrenia spectrum disorders, and bipolar disorder. Across disorders and treatments, the majority of effect sizes for target symptoms were small. A random effect meta‐analytic evaluation of the effect sizes reported by the largest meta‐analyses per disorder yielded a standardized mean difference (SMD) of 0.34 (95% CI: 0.26‐0.42) for psychotherapies and 0.36 (95% CI: 0.32‐0.41) for pharmacotherapies compared with placebo or TAU. The SMD for head‐to‐head comparisons of psychotherapies vs. pharmacotherapies was 0.11 (95% CI: –0.05 to 0.26). The SMD for the combined treatment compared with either monotherapy was 0.31 (95% CI: 0.19‐0.44). Risk of bias was often high. After more than half a century of research, thousands of RCTs and millions of invested funds, the effect sizes of psychotherapies and pharmacotherapies for mental disorders are limited, suggesting a ceiling effect for treatment research as presently conducted. A paradigm shift in research seems to be required to achieve further progress.

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“…Vortioxetine, a 5-HT 3 antagonist and 5-HT 1A agonist, was FDA-approved for MDD in 2013, but its efficacy for anxiety is not clear ( 95 ). Despite initial promise in GAD ( 96 , 97 ), and an initial meta-analysis recommending further study ( 95 ), two subsequent meta-analyses failed to show significant efficacy of vortioxetine over placebo in GAD despite fairly good tolerability ( 91 , 98 ) and thus further study and pursuit of FDA approval in GAD was abandoned in 2015. There was one open-label study of vortioxetine in PD reporting improvement in panic symptoms ( 99 ) but no known RCTs.…”

Section: Novel Treatments For Anxiety Disordersmentioning

confidence: 99%

Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options

et al. 2020

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Anxiety disorders are the most prevalent psychiatric disorders and a leading cause of disability. While there continues to be expansive research in posttraumatic stress disorder (PTSD), depression and schizophrenia, there is a relative dearth of novel medications under investigation for anxiety disorders. This review's first aim is to summarize current pharmacological treatments (both approved and off-label) for panic disorder (PD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), and specific phobias (SP), including selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), azapirones (e.g., buspirone), mixed antidepressants (e.g., mirtazapine), antipsychotics, antihistamines (e.g., hydroxyzine), alpha- and beta-adrenergic medications (e.g., propranolol, clonidine), and GABAergic medications (benzodiazepines, pregabalin, and gabapentin). Posttraumatic stress disorder and obsessive-compulsive disorder are excluded from this review. Second, we will review novel pharmacotherapeutic agents under investigation for the treatment of anxiety disorders in adults. The pathways and neurotransmitters reviewed include serotonergic agents, glutamate modulators, GABAergic medications, neuropeptides, neurosteroids, alpha- and beta-adrenergic agents, cannabinoids, and natural remedies. The outcome of the review reveals a lack of randomized double-blind placebo- controlled trials for anxiety disorders and few studies comparing novel treatments to existing anxiolytic agents. Although there are some recent randomized controlled trials for novel agents including neuropeptides, glutamatergic agents (such as ketamine and d-cycloserine), and cannabinoids (including cannabidiol) primarily in GAD or SAD, these trials have largely been negative, with only some promise for kava and PH94B (an inhaled neurosteroid). Overall, the progression of current and future psychopharmacology research in anxiety disorders suggests that there needs to be further expansion in research of these novel pathways and larger-scale studies of promising agents with positive results from smaller trials.

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Vortioxetine treatment for generalised anxiety disorder: a meta-analysis of anxiety, quality of life and safety outcomes

Cited by 16 publications

References 45 publications

Comparative Remission Rates and Tolerability of Drugs for Generalised Anxiety Disorder: A Systematic Review and Network Meta-analysis of Double-Blind Randomized Controlled Trials

Comparative Remission Rates and Tolerability of Drugs for Generalised Anxiety Disorder: A Systematic Review and Network Meta-analysis of Double-Blind Randomized Controlled Trials

The efficacy of psychotherapies and pharmacotherapies for mental disorders in adults: an umbrella review and meta‐analytic evaluation of recent meta‐analyses

Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options

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