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Mark J Millan, Jean-Michel Rivet, Alain Gobert
The highly-interconnected and neurochemically-rich frontal cortex plays a crucial role in the regulation of mood and cognition, domains disrupted in depression and other central nervous system disorders, and it is an important site of action for their therapeutic control. For improving our understanding of the function and dysfunction of the frontal cortex, and for identifying improved treatments, quantification of extracellular pools of neuromodulators by microdialysis in freely-moving rodents has proven indispensable...
October 17, 2016: Journal of Psychopharmacology
K W Miskowiak, C V Ott, J Z Petersen, L V Kessing
Cognitive impairment is a core feature of Major Depressive Disorder (MDD) but treatments targeting cognition are lacking. Numerous pre-clinical and clinical studies have investigated potential cognition treatments, but overall the evidence is conflicting. We conducted a systematic search following the PRISMA guidelines on PubMed and PsychInfo to evaluate the extant evidence and methodological challenges in randomized controlled trials (RCTs) of biological, psychological and behavioural candidate treatments targeting cognition in MDD...
October 13, 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Christian Borch Jacobsen, Morten Meldal, Frederik Diness
A general method for transition metal-free N-arylation of amines has been developed. Mechanistic studies have revealed that the ability of the base to facilitate the desired amination without promoting unwanted side reactions is the guiding factor. By employing lithium bis(trimethylsilyl)amide as a base the resultant deprotonated amines readily react with a range of unactivated fluorobenzene derivatives. This new arylation method is utilized for the simple two-step synthesis of the antidepressant Vortioxetine...
October 14, 2016: Chemistry: a European Journal
Edward C Lauterbach
Dextromethorphan (DM) may have ketamine-like rapid-acting, treatment-resistant, and conventional antidepressant effects.(1,2) This reports our initial experience with DM in unipolar Major Depressive Disorder (MDD). A patient with treatment-resistant MDD (failing adequate trials of citalopram and vortioxetine) with loss of antidepressant response (to fluoxetine and bupropion) twice experienced a rapid-acting antidepressant effect within 48 hours of DM administration and lasting 7 days, sustained up to 20 days with daily administration, then gradually developing labile loss of antidepressant response over the ensuing 7 days...
August 15, 2016: Psychopharmacology Bulletin
Atul R Mahableshwarkar, John Zajecka, William Jacobson, Yinzhong Chen, Richard Se Keefe
No abstract text is available yet for this article.
November 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Xinbo Zhou, Xiurong Hu, Suxiang Wu, Jiali Ye, Mengying Sun, Jianming Gu, Jianrong Zhu, Zhongliang Zhang
In the present work, novel salts of the multimodal antidepressant drug vortioxetine (VT) were crystallized with pharmaceutically acceptable acids, aiming to improve the solubility of VT. The acids for VT were selected based on ΔpKa being greater than 2 or 3. Salts of hydrobromic acid (HBr), hydrochloric acid (HCl), p-hydroxybenzoic acid (PHBA), saccharin (SAC) and L-aspartic acid (ASP) were reported. All salts were characterized by single-crystal X-ray diffraction, FT-IR, powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC)...
October 1, 2016: Acta Crystallographica Section B, Structural Science, Crystal Engineering and Materials
Erkki Soini, Taru Hallinen, Mélanie Brignone, Rosanne Campbell, Françoise Diamand, Sandrine Cure, Maria Aalto-Setälä, Natalya Danchenko, Hannu J Koponen, Katarzyna Kolasa
OBJECTIVES: To assess the cost-utility of vortioxetine versus relevant comparators (agomelatine, bupropion SR, sertraline, and venlafaxine XR) in the Finnish setting in major depressive disorder (MDD) patients with inadequate response to selective serotonin- /serotonin-norepinephrine reuptake inhibitors. METHODS: A one-year analysis was conducted using a decision tree with a Markov state transition component. The health states were remission, relapse and recovery...
September 29, 2016: Expert Review of Pharmacoeconomics & Outcomes Research
Pirathiv Kugathasan, Jessica Waller, Ligia Westrich, Aicha Abdourahman, Joseph A Tamm, Alan L Pehrson, Elena Dale, Maria Gulinello, Connie Sanchez, Yan Li
Neuroplasticity is fundamental for brain functions, abnormal changes of which are associated with mood disorders and cognitive impairment. Neuroplasticity can be affected by neuroactive medications and by aging. Vortioxetine, a multimodal antidepressant, has shown positive effects on cognitive functions in both pre-clinical and clinical studies. In rodent studies, vortioxetine increases glutamate neurotransmission, promotes dendritic branching and spine maturation, and elevates hippocampal expression of the activity-regulated cytoskeleton-associated protein (Arc/Arg3...
September 26, 2016: Journal of Psychopharmacology
Maurizio S Riga, Vicent Teruel-Martí, Connie Sánchez, Pau Celada, Francesc Artigas
Vortioxetine (VOR) is a multimodal antidepressant drug. VOR is a 5-HT3-R, 5-HT7-R and 5-HT1D-R antagonist, 5-HT1B-R partial agonist, 5-HT1A-R agonist, and serotonin transporter (SERT) inhibitor. VOR shows pro-cognitive activity in animal models and beneficial effects on cognitive dysfunction in major depressive patients. Here we compared the effects of 14-day treatments with VOR and escitalopram (ESC, selective serotonin reuptake inhibitor) on neuronal activity in the medial prefrontal cortex (mPFC). Ten groups of rats (5 standard, 5 depleted of 5-HT with p-chlorophenylalanine -pCPA-, used as model of cognitive impairment) were fed with control food or with two doses of VOR-containing food...
September 23, 2016: Neuropharmacology
Louise K Refsgaard, Kia Haubro, Darryl S Pickering, Sarah A Stuart, Emma S J Robinson, Jesper T Andreasen
RATIONALE: Affective biases seemingly play a crucial role for the onset and development of depression. Acute treatment with monoamine-based antidepressants positively influences emotional processing, and an early correction of biases likely results in repeated positive experiences that ultimately lead to improved mood. OBJECTIVES: Using two conventional antidepressants, sertraline and duloxetine, we aimed to forward the characterization of a newly developed affective bias test (ABT) for rats...
October 2016: Psychopharmacology
Phillip Raphael Kyle, Ole Michael Lemming, Nina Timmerby, Susan Søndergaard, Kate Andreasson, Per Bech
Our objective was to validate the different versions of the Hamilton Depression Scale (HAM-D) both psychometrically (scalability) and clinically in discriminating antidepressants from placebo in terms of remission rates in an 8-week clinical trial in the acute treatment of major depression. The traditional HAM-D17 version was compared with the shorter HAM-D6 and the longer HAM-D21 or HAM-D24 in a fixed-dose placebo-controlled vortioxetine study. Clinical Global Impression of Severity scores were used to establish standardized cutoff scores for remission across each scale...
October 2016: Journal of Clinical Psychopharmacology
André F Carvalho, Manu S Sharma, André R Brunoni, Eduard Vieta, Giovanni A Fava
Newer generation antidepressant drugs (ADs) are widely used as the first line of treatment for major depressive disorders and are considered to be safer than tricyclic agents. In this critical review, we evaluated the literature on adverse events, tolerability and safety of selective serotonin reuptake inhibitors, serotonin noradrenaline reuptake inhibitors, bupropion, mirtazapine, trazodone, agomelatine, vilazodone, levomilnacipran and vortioxetine. Several side effects are transient and may disappear after a few weeks following treatment initiation, but potentially serious adverse events may persist or ensue later...
2016: Psychotherapy and Psychosomatics
David S Baldwin, Ioana Florea, Paula L Jacobsen, Wei Zhong, George G Nomikos
BACKGROUND: Coexisting anxiety is common in major depressive disorder (MDD) and more difficult to treat than depression without anxiety. This analysis assessed the efficacy, safety, and tolerability of vortioxetine in MDD patients with high levels of anxiety (baseline Hamilton Anxiety Rating Scale [HAM-A] total score ≥20). METHODS: Efficacy was assessed using an aggregated, study-level meta-analysis of 10 randomized, placebo-controlled, 6/8-week trials of vortioxetine 5-20mg/day in adults (18-75 years), with a study in elderly patients (≥65 years) analyzed separately...
July 7, 2016: Journal of Affective Disorders
Alan L Pehrson, Todd M Hillhouse, Nasser Haddjeri, Renaud Rovera, Joseph H Porter, Arne Mørk, Gennady Smagin, Dekun Song, David Budac, Manuel Cajina, Connie Sanchez
Major depressive disorder (MDD) is a common psychiatric disorder that often features impairments in cognitive function, and these cognitive symptoms can be important determinants of functional ability. Vortioxetine is a multimodal antidepressant that may improve some aspects of cognitive function in patients with MDD, including attention, processing speed, executive function, and memory. However, the cause of these effects is unclear, and there are several competing theories on the underlying mechanism, notably including regionally-selective downstream enhancement of glutamate neurotransmission and increased acetylcholine (ACh) neurotransmission...
September 2016: Journal of Pharmacology and Experimental Therapeutics
Toshi A Furukawa, Georgia Salanti, Lauren Z Atkinson, Stefan Leucht, Henricus G Ruhe, Erick H Turner, Anna Chaimani, Yusuke Ogawa, Nozomi Takeshima, Yu Hayasaka, Hissei Imai, Kiyomi Shinohara, Aya Suganuma, Norio Watanabe, Sarah Stockton, John R Geddes, Andrea Cipriani
INTRODUCTION: Many antidepressants are indicated for the treatment of major depression. Two network meta-analyses have provided the most comprehensive assessments to date, accounting for both direct and indirect comparisons; however, these reported conflicting interpretation of results. Here, we present a protocol for a systematic review and network meta-analysis aimed at updating the evidence base and comparing all second-generation as well as selected first-generation antidepressants in terms of efficacy and acceptability in the acute treatment of major depression...
2016: BMJ Open
Thomas J Tobin, Mary L Tobin
Similar names between two unrelated drugs have led the FDA to issue warnings about and now approve a name change for vortioxetine, which was branded as Brintellix® until recently. While the trade name had been screened prior to the product's launch, the FDA received numerous reports of prescribing and dispensing errors, specifically with regard to the anti-coagulant drug Brilinta® (ticagrelor). Starting 1 June 2016, vortioxetine will be marketed under the name Trintellix™ in an effort to reduce confusion...
July 7, 2016: Issues in Mental Health Nursing
Michal Douša, Jan Doubský, Jan Srbek
An analytical reversed-phase high-performance liquid chromatography (HPLC) method for the detection and quantitative determination of two genotoxic impurities at ppm level present in the vortioxetine manufacturing process is described. Applying the concept of threshold of toxicological concern, a limit of 75 ppm each for both genotoxic impurities was calculated based on the maximum daily dose of active pharmaceutical ingredients. The novel reversed-phase HPLC method with photochemically induced fluorescence detection was developed on XSELECT Charged Surface Hybrid Phenyl-Hexyl column using the mobile phase consisted a mixture of 10 mM ammonium formate pH 3...
July 1, 2016: Journal of Chromatographic Science
Marina Sagud, Matea Nikolac Perkovic, Bjanka Vuksan-Cusa, Anja Maravic, Dubravka Svob Strac, Alma Mihaljevic Peles, Maja Zivkovic, Zorana Kusevic, Nela Pivac
BACKGROUND: Various antidepressants occupy brain serotonin transporter (SERT), decrease platelet serotonin (5-HT) concentration, and normalize reduced plasma brain-derived neurotrophic factor (BDNF) concentrations in depressed patients. Vortioxetine is a recently introduced antidepressant with a multimodal mechanism of action. In addition to SERT inhibition, vortioxetine acts via different 5-HT receptors. To further elucidate its mechanism of action, we have investigated the effects of vortioxetine on platelet 5-HT and plasma BDNF concentrations in patients with major depression...
September 2016: Psychopharmacology
R S McIntyre, J Harrison, H Loft, W Jacobson, C K Olsen
BACKGROUND: Management of cognitive deficits in Major Depressive Disorder (MDD) remains an important unmet need. This meta-analysis evaluated the effects of vortioxetine on cognition in patients with MDD. METHODS: Random effects meta-analysis was applied to three randomized, double-blind, placebo-controlled 8-week trials of vortioxetine (5-20mg/day) in MDD, and separately to two duloxetine-referenced trials. The primary outcome measure was change in Digit Symbol Substitution Test (DSST) score...
June 15, 2016: International Journal of Neuropsychopharmacology
James Lomas, Alexis Llewellyn, Marta Soares, Mark Simmonds, Kath Wright, Alison Eastwood, Stephen Palmer
The National Institute for Health and Care Excellence (NICE) invited the manufacturer of vortioxetine (Lundbeck) to submit clinical and cost-effectiveness evidence for vortioxetine for the treatment of major depressive episodes (MDEs), as part of the Institute's Single Technology Appraisal (STA) process. The Centre for Reviews and Dissemination and Centre for Health Economics at the University of York were commissioned to act as the independent Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and the resulting NICE guidance TA367 issued in November 2015...
September 2016: PharmacoEconomics
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