The US Food and Drug Administration’s Perspective on the New Antidepressant Vortioxetine

Zhang, Jing; Mathis, Mitchell; Sellers, Jenn W.; Kordzakhia, George; Jackson, André J.; Dow, Antonia; Yang, Pei‐Ling; Fossom, Linda H.; Zhu, Hao; Patel, Hiren; Unger, Ellis F.; Temple, Robert

doi:10.4088/jcp.14r09164

Cited by 34 publications

(47 citation statements)

References 18 publications

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“…As the current success rate for psychiatric medications in Phase 3 RCTs hovers around 50%, the FDA concluded that the preponderance of the evidence supported the efficacy of vortioxetine 20 mg/day. [26,27] The results of the single longer-term, relapse-prevention study also were consistent with the FDA's appraisal of efficacy. [28] In this trial, a total of 693 depressed outpatients were treated for up to 12 weeks with 5-10 mg of vortioxetine, of which 396 responded and were then blindly randomized to continuation treatment or placebo.…”

Section: Phase 3 Studies and Fdasupporting

confidence: 65%

“…The US FDA review of this body of work is nicely summarized by Zhang and colleagues. [26] All of these studies enrolled adult outpatients with MDD (DSM-IV-TR criteria); one study focused specifically on patients age 65 and older. All studies required that patients were medically stable and were not taking concomitant medications that might complicate study treatment.…”

Section: Phase 3 Studies and Fdamentioning

confidence: 99%

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Vortioxetine: a New Treatment for Major Depressive Disorder

Connolly

Thase

2016

Expert Opinion on Pharmacotherapy

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Results of placebo-controlled trials suggest efficacy and an overall safety profile comparable to existing first-line antidepressants. The most common side effects are nausea, vomiting and constipation. Results of several studies indicate that vortioxetine may have therapeutic effects on cognition (e.g., memory and executive functioning) that exceed that of standard antidepressants. Disadvantages include cost and the current paucity of long-term efficacy data from large clinical trials. The authors suggest that vortioxetine is currently a good second-line antidepressant option and shows promise, pending additional long-term data, to become a first-line antidepressant option.

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Section: Phase 3 Studies and Fdasupporting

confidence: 65%

Section: Phase 3 Studies and Fdamentioning

confidence: 99%

Vortioxetine: a New Treatment for Major Depressive Disorder

Connolly

Thase

2016

Expert Opinion on Pharmacotherapy

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“…There was a relatively low incidence of sexual dysfunction and sleep disruption [88,89]. Overall, vortioxetine showed strong evidence for antidepressant efficacy with good tolerability [90]. In addition, it showed improvement of cognitive dysfunction in patients with MDD.…”

Section: Vortioxetinementioning

confidence: 99%

Emerging mechanisms and treatments for depression beyond SSRIs and SNRIs

Dale

Bang‐Andersen

Sanchéz

2015

Biochemical Pharmacology

201

114

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The monoamine hypothesis has been the prevailing hypothesis of depression over the last several decades. It states that depression is associated with reduced monoamine function. Hence efforts to increase monoamine transmission by inhibiting serotonin (5-HT) and norepinephrine (NE) transporters has been a central theme in depression research since the 1960s. The selective 5-HT reuptake inhibitors (SSRIs) and 5-HT and NE reuptake inhibitors (SNRIs) that have emerged from this line of research are currently first line treatment options for major depressive disorder (MDD). One of the recent trends in antidepressant research has been to refine monoaminergic mechanisms by targeting monoaminergic receptors and additional transporters (e.g. with multimodal drugs and triple re-uptake inhibitors) or by adding atypical antipsychotics to SSRI or SNRI treatment. In addition, several other hypotheses of depression have been brought forward in pre-clinical and clinical research based on biological hallmarks of the disease and efficacy of pharmacological interventions. A central strategy has been to target glutamate receptors (for example, with intravenous infusions of the N-methyl-d-aspartate (NMDA) receptor antagonist ketamine). Other strategies have been based on modulation of cholinergic and γ-aminobutyric acid (GABA)ergic transmission, neuronal plasticity, stress/hypothalamic pituitary adrenal(HPA)-axis, the reward system and neuroinflammation. Here we review the pharmacological profiles of compounds that derived from these strategies and have been recently tested in clinical trials with published results. In addition, we discuss putative treatments for depression that are being investigated at the preclinical level and outline future directions for antidepressant research.

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“…Of course not-the observed differences in efficacy almost certainly pertain to problems with signal detection in contemporary RCTs of antidepressants, which, in the case of the studies of vortioxetine, was more evident in the United States than elsewhere in the world. This has not always been the case; as noted by Zhang et al, 1 the results of an earlier meta-analysis of regulatory submissions across several decades concluded that signal detection used to be better in studies conducted within the United States. 3 However, an opposite pattern was evident in the registration studies of vortioxetine, a point that was nicely illustrated by the findings of the study 4 conducted in late-life depression.…”

mentioning

confidence: 99%

“…1 It is almost certain, for example, that vortioxetine does not have a stronger antidepressant effect than the serotonin-norepinephrine reuptake inhibitors (SNRIs) duloxetine and venlafaxine. 1 However, Sanchez and colleagues 5 marshal evidence to suggest that the receptormediated effects of vortioxetine-which include antagonism of 5-HT 1D , 5-HT 3A , and 5-HT 7 receptors; partial agonism of 5-HT 1B receptors; and agonism of 5-HT 1A receptorsmay convey important differences in side effect profile (eg, fewer sexual side effects) and secondary therapeutic effects (eg, better effects on cognition) when compared to "purer" SSRIs such as escitalopram or the SNRI duloxetine. This difference in perspective is understandable, as the FDA uses a much higher standard to evaluate claims of superiority than is typical for people who are closely tied to a drug's development.…”

mentioning

confidence: 99%