title: New advances in the treatment of generalized anxiety disorder: the multimodal antidepressant vortioxetine.
abstract: Generalized Anxiety Disorder (GAD) is a persistent condition characterized by chronic anxiety, exaggerated worry and tension, mainly comorbid with Major Depressive Disorder (MDD). Currently, selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors are recommended as first-line treatment of GAD. However, some patients may not respond to the treatment or discontinue due to adverse effects. Vortioxetine (VRX) is a multimodal antidepressant with a unique mechanism of action, by acting as 5-HT3A, 5-HT1D and 5-HT7 receptor antagonist, partial agonist at the 5-HT1A and 5-HT1B receptors and inhibitor at the 5-HT transporter. Preliminary clinical trials showed contrasting findings in terms of improvement of the anxiety symptomatology and/or cognitive impairment. Here, we aim to systematically review the evidence currently available on the efficacy, safety and tolerability of VRX in the treatment of GAD. The generalizability of results on the efficacy of VRX in patients with anxiety symptomatology and GAD is limited due to few and contrasting RCTs so far available. Only two studies, of which one prevention relapse trial, reported a significant improvement in anxiety symptomatology compared to three with negative findings.
authors.affiliation: a School of Life and Medical Sciences , University of Hertfordshire , Hatfield , UK.|b Villa San Giuseppe Hospital , Hermanas Hospitalarias , Ascoli Piceno , Italy.|c Polyedra Research Group , Teramo , Italy.|d Department of Psychiatry and Neuropsychology , University of Maastricht , Maastricht , The Netherlands.
authors.forename: Laura
authors.initials: L
authors.lastname: Orsolini
authors.affiliation: c Polyedra Research Group , Teramo , Italy.|e NHS, Department of Mental Health ASL Teramo, Psychiatric Service of Diagnosis and Treatment , Hospital 'Maria SS dello Splendore' , Giulianova , Italy.|f Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, Reproductive and Odontostomatogical Sciences , University of Naples 'Federico II' , Napoli , Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Tomasetti
authors.affiliation: b Villa San Giuseppe Hospital , Hermanas Hospitalarias , Ascoli Piceno , Italy.|c Polyedra Research Group , Teramo , Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Valchera
authors.affiliation: c Polyedra Research Group , Teramo , Italy.|f Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, Reproductive and Odontostomatogical Sciences , University of Naples 'Federico II' , Napoli , Italy.
authors.forename: Felice
authors.initials: F
authors.lastname: Iasevoli
authors.affiliation: c Polyedra Research Group , Teramo , Italy.|f Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, Reproductive and Odontostomatogical Sciences , University of Naples 'Federico II' , Napoli , Italy.
authors.forename: Elisabetta Filomena
authors.initials: EF
authors.lastname: Buonaguro
authors.affiliation: c Polyedra Research Group , Teramo , Italy.|g NHS, Department of Mental Health ASL Teramo, Psychiatric Service of Diagnosis and Treatment , Hospital 'G. Mazzini' , Teramo , Italy.|h Department of Neuroscience and Imaging , University 'G. d'Annunzio' , Chieti , Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Vellante
authors.affiliation: c Polyedra Research Group , Teramo , Italy.|i New York Psychiatric Institute , Columbia University , New York , NY , USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Fornaro
authors.affiliation: c Polyedra Research Group , Teramo , Italy.
authors.forename: Annastasia
authors.initials: A
authors.lastname: Fiengo
authors.affiliation: c Polyedra Research Group , Teramo , Italy.|j Department of Life, Health and Environmental Sciences , University of L'Aquila , L'Aquila , Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Mazza
authors.affiliation: b Villa San Giuseppe Hospital , Hermanas Hospitalarias , Ascoli Piceno , Italy.|c Polyedra Research Group , Teramo , Italy.|d Department of Psychiatry and Neuropsychology , University of Maastricht , Maastricht , The Netherlands.
authors.forename: Roberta
authors.initials: R
authors.lastname: Vecchiotti
authors.affiliation: d Department of Psychiatry and Neuropsychology , University of Maastricht , Maastricht , The Netherlands.|k Hermanas Hospitalarias, FoRiPsi, Department of Clinical Neurosciences , Villa San Benedetto Menni , Albese con Cassano , Como , Italy.|l Department of Psychiatry and Behavioral Sciences , Leonard Miller School of Medicine, University of Miami , Coral Gables , Florida , USA.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Perna
authors.affiliation: f Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, Reproductive and Odontostomatogical Sciences , University of Naples 'Federico II' , Napoli , Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: de Bartolomeis
authors.affiliation: i New York Psychiatric Institute , Columbia University , New York , NY , USA.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinotti
authors.affiliation: i New York Psychiatric Institute , Columbia University , New York , NY , USA.
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Giannantonio
authors.affiliation: c Polyedra Research Group , Teramo , Italy.|g NHS, Department of Mental Health ASL Teramo, Psychiatric Service of Diagnosis and Treatment , Hospital 'G. Mazzini' , Teramo , Italy.|i New York Psychiatric Institute , Columbia University , New York , NY , USA.
authors.forename: Domenico
authors.initials: D
authors.lastname: De Berardis
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000188:drug therapy; D003865:Major Depressive Disorder / Q000188:drug therapy*; D006801:Humans; D010879:Piperazines / Q000627:therapeutic use*; D013440:Sulfides / Q000627:therapeutic use*; D000078784:Vortioxetine
chemical_list: D000928:Antidepressive Agents; D010879:Piperazines; D013440:Sulfides; D000078784:Vortioxetine
keywords: Lu AA21004; Vortioxetine; antidepressant; anxiety; brintellix; generalized anxiety disorder