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Clinical Pharmacogenomics Of Human Cyp2d6
Published in Shufeng Zhou, Cytochrome P450 2D6, 2018
Vortioxetine, indicated as a treatment for major depressive disorder (Dhir 2013; Pearce and Murphy 2014; Sanchez et al. 2015), is mainly metabolized by CYP2D6 (Hvenegaard et al. 2012). Individuals who are CYP2D6 PMs have approximately twice the plasma concentration of vortioxetine, as compared to those who are CYP2D6 EMs. The FDA-approved drug label for vortioxetine notes that the maximum recommended dose in patients who are known CYP2D6 PMs is 10 mg/day. Additionally, patients receiving a strong inhibitor of CYP2D6 (e.g., bupropion or paroxetine) should have their dose reduced by one-half. In patients receiving concomitant CYP inducers (e.g., rifampicin, phenytoin), a dose increase can be considered, but the maximum dose is not recommended to exceed three times the original dose.
Neurotransmitters and pharmacology
Published in Mark J. Ashley, David A. Hovda, Traumatic Brain Injury, 2017
Ronald A. Browning, Richard W. Clough
Vortioxetine (Brintellix) is a drug with multiple actions on the serotonergic synapse that has been approved recently (2013) for the treatment of major depressive disorder. Vortioxetine has been referred to as a serotonin modulator and a serotonin stimulator. Its actions include inhibition of SERT (like the SSRIs), partial agonist activity at the 5-HT1A and 5-HT1B receptors, and antagonist activity at the 5-HT1D, 5-HT7, and 5-HT3 receptors. There is also some evidence that vortioxetine can inhibit NE reuptake, giving it some SNRI activity. Whether effects other than its inhibition of SERT and NET contribute to the antidepressant action of vortioxetine remains to be determined.127
The Management of Treatment-Resistant Depression
Published in Dr. Ather Muneer, Mood Disorders, 2018
This chapter summarizes the current conventional pharmacological strategies available for managing TRD. The diversity of treatments reflects the complexity of MDD, in which a single approach cannot account for the varied facets of the disorder. Due to this intricacy, the management of TRD should ideally target the alternate factors relevant to each patient. The paucity of strong evidence to guide clinical decision reflects the need for larger and well-designed studies in TRD. Switching from an SSRI to venlafaxine is a strategy supported by the literature, although the advantage of switching to venlafaxine over other SSRIs is not clear. However, in more severe cases of TRD, venlafaxine was shown to be on the whole useful. The combination of antidepressants, especially mirtazapine, may be beneficial for some patients with TRD, although further studies are needed to establish the superiority of this regimen. Augmentation of antidepressants with lithium or T3 has received wide support in the literature, but in most of the studies they have been evaluated as adjunctive drugs to TCAs and the effect sizes are usually small. AAPs have shown good efficacy as augmentation agents in several well-designed studies and meta-analyses, but metabolic side effects may limit their use. Moreover, the lack of independent trials is a limitation of the studies on AAP. While there are some promising results on the use of modafinil as an augmentation strategy, the role of psychostimulants in TRD is not yet established. Vortioxetine is a promising new antidepressant with effects on core depressive symptoms as well as cognition. Recently, it has been shown to be effective as a switch agent in patients who have failed to respond to an adequate trial of a conventional drug.
Considerations when selecting an antidepressant: a narrative review for primary care providers treating adults with depression
Published in Postgraduate Medicine, 2023
C. Brendan Montano, W. Clay Jackson, Denise Vanacore, Richard Weisler
In a meta-analysis of 3 RCTs, vilazodone was found to be superior to placebo in the short-term treatment of GAD [104]. However, a later meta-analysis demonstrated poor tolerability, highlighting the need for additional studies to confirm overall benefit [105]. Recently published data from an 8-week, open-label study of vortioxetine in 100 adult patients with severe MDD and comorbid severe GAD demonstrated clinically meaningful and statistically significant improvements in patient- and clinician-assessed symptoms of depression and anxiety. In the trial, vortioxetine was administered as a first-line therapy or in patients switching to vortioxetine due to inadequate response to another antidepressant [106]. Significant improvements in overall functioning and health-related quality of life were also noted [106]. In the trial, treatment with vortioxetine was initiated at 10 mg/day and titrated up to 20 mg/day after one week, with dose reductions permitted based on individual tolerability [106].
Long-term safety and efficacy, including anhedonia, of vortioxetine for major depressive disorder: findings from two open-label studies
Published in Current Medical Research and Opinion, 2023
Gregory W. Mattingly, Oscar Necking, Simon Nitschky Schmidt, Elin Reines, Hongye Ren
Both studies were long-term (52 week), open-label, flexible-dose extension studies to evaluate the safety, tolerability, and efficacy of vortioxetine in adult patients with MDD. The first study examined the effect of vortioxetine given at dose of 5 or 10 mg per day in patients who completed an earlier six-week venlafaxine-referenced study (followed by a two week, double-blind, down-tapering period)6 and the second study examined the effect of vortioxetine given at dose of 15 or 20 mg per day in patients who completed an earlier eight-week duloxetine-referenced study11. Both open-label studies began with one week of fixed-dose treatment with vortioxetine 10 mg/day before patients entered a 52-week flexible dose period (where patients received vortioxetine 5–10 mg and 15–20 mg, respectively).
Vortioxetine for Depression in Adults
Published in Issues in Mental Health Nursing, 2019
The results of this review are mixed and a firm stance on the use of vortioxetine for the treatment of major depressive disorder is not clear. The data suggest vortioxetine may be more efficacious than placebo when comparing response, remission and symptoms of depression. However, the clinical relevance of these factors cannot be fully determined based on the overall low quality of evidence. When compared to SNRIs, the evidence did not support vortioxetine as being superior. Vortioxetine was less effective than duloxetine; however, limited evidence suggests fewer individuals reported adverse effects from vortioxetine than duloxetine. A major limitation of the review of the evidence for vortioxetine was a lack of comparison to SSRIs (usual first line of treatment for depression). Studies which compare vortioxetine to SSRIs would address this evidence gap and assist in clarifying the evidence for the use of this new pharmaceutical in the treatment of major depression.