A review of the clinical efficacy, safety and tolerability of the antidepressants vilazodone, levomilnacipran and vortioxetine

Bibliography

• World Health Organization. The global burden of disease: 2004 update. WHO Press, Geneva; 2008
   Google Scholar
• Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006;3(11):e442
   PubMed Web of Science ®Google Scholar
• Thase ME. The small specific effects of antidepressants in clinical trials: what do they mean to psychiatrists? Curr Psychiatry Rep 2011;13(6):476-82
   Google Scholar
• Blier P. The well of novel antidepressants: running dry. J Psychiatry Neurosci 2010;35(4):219-20
   PubMed Web of Science ®Google Scholar
• Kessler RC, Berglund P, Demler O, et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 2003;289(23):3095-105
   PubMed Web of Science ®Google Scholar
• Stahl SM, Lee-Zimmerman C, Cartwright S, Morrissette DA. Serotonergic drugs for depression and beyond. Curr Drug Targets 2013;14(5):578-85
   PubMed Web of Science ®Google Scholar
• Warden D, Rush AJ, Trivedi MH, et al. The STAR*D Project results: a comprehensive review of findings. Curr Psychiatry Rep 2007;9(6):449-59
   PubMedGoogle Scholar
• Hansen RA, Gartlehner G, Lohr KN, et al. Efficacy and safety of second-generation antidepressants in the treatment of major depressive disorder. Ann Intern Med 2005;143(6):415-26
   PubMed Web of Science ®Google Scholar
• Heinrich T, Bottcher H, Gericke R, et al. Synthesis and Structure-Activity Relationship in a Class of Indolebutylpiperazines as Dual 5-HT1A Receptor Agonists and Serotonin Reuptake Inhibitors Journal of Medicinal Chemistry. 2004;47:4684-92
   Google Scholar
• US Food and Drug Administration. Drug Approval Package. Viibryd (vilazodone hydrochloride) Tablets. 2011. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022567Orig1s000TOC.cfm [Accessed 01 June 2014]
   Google Scholar
• Bartoszyk GD, Hegenbart R, Ziegler H. EMD 68843, a serotonin reuptake inhibitor with selective presynaptic 5-HT1A receptor agonistic properties. Eur J Pharmacol 1997;322(2-3):147-53
   PubMed Web of Science ®Google Scholar
• van Amsterdam C, Seyfried CA. Mechanism of action of the bimodal antidepressant vilazodone: evidence for serotonin1A-receptor-mediated auto-augmentation of extracellular serotonin output. Psychopharmacology (Berl) 2014;231(12):2547-58
   Google Scholar
• Page ME, Cryan JF, Sullivan A, et al. Behavioral and neurochemical effects of 5-(4-[4-(5-Cyano-3-indolyl)-butyl)-butyl]-1-piperazinyl)-benzofuran-2-carboxamide (EMD 68843): a combined selective inhibitor of serotonin reuptake and 5-hydroxytryptamine(1A) receptor partial agonist. J Pharmacol Exp Ther 2002;302(3):1220-7
   PubMed Web of Science ®Google Scholar
• Hughes ZA, Starr KR, Langmead CJ, et al. Neurochemical evaluation of the novel 5-HT1A receptor partial agonist/serotonin reuptake inhibitor, vilazodone. Eur J Pharmacol 2005;510(1-2):49-57
   PubMed Web of Science ®Google Scholar
• Kehne JH, Bartoszyk GD, Greiner HE, et al. In vitro characterization of vilazodone as a dual-acting serotonin reuptake receptor and 5-HT1A receptor partial agonist. Poster, 65th Annual Meeting of the Society of Biological Psychiatry Meeting; New Orleans, LA; 2010
   Google Scholar
• Millan MJ. Multi-target strategies for the improved treatment of depressive states: conceptual foundations and neuronal substrates, drug discovery and therapeutic application. Pharmacol Ther 2006;110(2):135-370
   PubMed Web of Science ®Google Scholar
• Auclair AL, Martel JC, Assié MB, et al. Levomilnacipran (F2695), a norepinephrine-preferring SNRI: profile in vitro and in models of depression and anxiety. Neuropharmacology 2013;70:338-47
   PubMed Web of Science ®Google Scholar
• Kasper S, Meshkat D, Kutzelnigg A. Improvement of the noradrenergic symptom cluster following treatment with milnacipran. Neuropsychiatr Dis Treat 2011;7(Suppl 1):21-7
   Google Scholar
• Mørk A, Pehrson A, Brennum LT, et al. Pharmacological effects of Lu AA21004: a novel multimodal compound for the treatment of major depressive disorder. J Pharmacol Exp Ther 2012;340(3):666-75
   PubMed Web of Science ®Google Scholar
• Adell A. Lu-AA21004, a multimodal serotonergic agent, for the potential treatment of depression and anxiety. IDrugs 2010;13(12):900-10
   PubMedGoogle Scholar
• Bétry C, Etiévant A, Oosterhof C, et al. Role of 5-HT3 receptors in the antidepressant response. Pharmaceuticals 2011;4(4):603-29
   Google Scholar
• Hedlund PB. The 5-HT7 receptor and disorders of the nervous system: an overview. Psychopharmacology (Berl) 2009;206(3):345-54
   Google Scholar
• Pehrson A, Li Y, Haddjeri N, et al. Vortioxetine, a novel multimodal antidepressant, modulates GABA and glutamate neurotransmission via serotonergic mechanisms. Eur Neuropsychopharmacol 2013;23(Suppl 2):S196-7
   Google Scholar
• Pehrson AL, Sanchez C. Serotonergic modulation of glutamate neurotransmission as a strategy for treating depression and cognitive dysfunction. CNS Spectr 2014;19(2):121-33
   PubMed Web of Science ®Google Scholar
• Pehrson AL, Cremers T, Bétry C, et al. Lu AA21004, a novel multimodal antidepressant, produces regionally selective increases of multiple neurotransmitters – a rat microdialysis and electrophysiology study. Eur Neuropsychopharmacol 2013;23(2):133-45
   PubMed Web of Science ®Google Scholar
• Bang-Andersen B, Ruhland T, Jørgensen M, et al. Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J Med Chem 2011;54(9):3206-21
   PubMed Web of Science ®Google Scholar
• Sanchez C, Asin KE, Artigas F. Vortioxetine, a novel antidepressant with multimodal activity: Review of preclinical and clinical data. Pharmacol Ther 2014. [Epub ahead of print]
   Google Scholar
• Montgomery SA, Möller HJ. Is the significant superiority of escitalopram compared with other antidepressants clinically relevant? Int Clin Psychopharmacol 2009;24(3):111-18
   PubMed Web of Science ®Google Scholar
• Cohen J. Statistical power analysis for the behavioral sciences. 2nd edition. Lawrence Erlbaum Associates, New York; 1988
   Google Scholar
• Turner EH, Matthews AM, Linardatos E, et al. Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med 2008;358(3):252-60
   PubMed Web of Science ®Google Scholar
• Laughren TP, Gobburu J, Temple RJ, et al. Vilazodone: clinical basis for the US Food and Drug Administration’s approval of a new antidepressant. J Clin Psychiatry 2011;72(9):1166-73
   PubMed Web of Science ®Google Scholar
• Khan A. Vilazodone, a novel dual-acting serotonergic antidepressant for managing major depression. Expert Opin Investig Drugs 2009;18(11):1753-64
   PubMed Web of Science ®Google Scholar
• Rickels K, Athanasiou M, Robinson DS, et al. Evidence for efficacy and tolerability of vilazodone in the treatment of major depressive disorder: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 2009;70(3):326-33
   PubMed Web of Science ®Google Scholar
• Reed CR, Kajdasz DK, Whalen H, et al. The efficacy profile of vilazodone, a novel antidepressant for the treatment of major depressive disorder. Curr Med Res Opin 2012;28(1):27-39
   PubMed Web of Science ®Google Scholar
• Khan A, Cutler AJ, Kajdasz DK, et al. A randomized, double-blind, placebo-controlled, 8-week study of vilazodone, a serotonergic agent for the treatment of major depressive disorder. J Clin Psychiatry 2011;72(4):441-7
   PubMed Web of Science ®Google Scholar
• Kennedy SH, Andersen HF, Lam RW. Efficacy of escitalopram in the treatment of major depressive disorder compared with conventional selective serotonin reuptake inhibitors and venlafaxine XR: a meta-analysis. J Psychiatry Neurosci 2006;31(2):122-31
   Google Scholar
• Khan A, Sambunaris A, Edwards J, et al. Vilazodone in the treatment of major depressive disorder: efficacy across symptoms and severity of depression. Int Clin Psychopharmacol 2014;29(2):86-92
   Google Scholar
• Citrome L, Gommoll C, Mathews M, et al. The efficacy of vilazodone in achieving remission in patients with major depressive disorder: post hoc analyses of a Phase IV trial. Poster NR6-090, American Psychiatric Association 167th Annual Meeting; 3 – 7 May 2014; New York, NY
   Google Scholar
• Safety, efficacy, and tolerability of vilazodone in major depressive disorder. ClinicalTrials.gov. U.S. National Institutes of Health. Available from: http://clinicaltrials.gov/show/NCT01473394 [Last accessed 9 July 2014]
   Google Scholar
• Thase ME, Gommoll C, Mathews M, et al. Effects of vilazodone on depression symptoms: category shift analysis of MADRS items from a randomized, double-blind, placebo-controlled trial. Poster NR8-057, American Psychiatric Association 167th Annual Meeting; 3 – 7 May 2014; New York, NY
   Google Scholar
• Thase ME, Chen D, Edwards J, Ruth A. Efficacy of vilazodone on anxiety symptoms in patients with major depressive disorder. Int Clin Psychopharmacol 2014. [Epub ahead of print]
   Google Scholar
• Fava M, Rush AJ, Alpert JE, et al. Difference in treatment outcome in outpatients with anxious versus nonanxious depression: a STAR*D report. Am J Psychiatry 2008;165(3):342-51
   PubMed Web of Science ®Google Scholar
• Gommoll C, Chen D, Khan A, et al. Efficacy and safety of vilazodone 20 mg and 40 mg in major depressive disorder: A randomized, double-blind, placebo- and active-controlled trial. Poster NR6-103, American Psychiatric Association 167th Annual Meeting; 3 – 7 May 2014; New York, NY
   Google Scholar
• US Food and Drug Administration. Drug Approval Package. Fetzima (levomilnacipran) Extended-Release Capsules. 2013. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204168Orig1s000TOC.cfm [Accessed 01 June 2014]
   Google Scholar
• Montgomery SA, Mansuy L, Ruth A, et al. Efficacy and safety of levomilnacipran sustained release in moderate to severe major depressive disorder: a randomized, double-blind, placebo-controlled, proof-of-concept study. J Clin Psychiatry 2013;74(4):363-9
   PubMed Web of Science ®Google Scholar
• Montgomery SA, Mansuy L, Ruth AC, et al. The efficacy of extended-release levomilnacipran in moderate to severe major depressive disorder: secondary and post-hoc analyses from a randomized, double-blind, placebo-controlled study. Int Clin Psychopharmacol 2014;29(1):26-35
   Google Scholar
• Asnis GM, Bose A, Gommoll CP, et al. Efficacy and safety of levomilnacipran sustained release 40 mg, 80 mg, or 120 mg in major depressive disorder: a phase 3, randomized, double-blind, placebo-controlled study. J Clin Psychiatry 2013;74(3):242-8
   PubMed Web of Science ®Google Scholar
• Bakish D, Bose A, Gommoll C, et al. Levomilnacipran ER 40 mg and 80 mg in patients with major depressive disorder: a phase III, randomized, double-blind, fixed-dose, placebo-controlled study. J Psychiatry Neurosci 2014;39(1):40-9
   PubMed Web of Science ®Google Scholar
• Sambunaris A, Bose A, Gommoll CP, et al. A phase III, double-blind, placebo-controlled, flexible-dose study of levomilnacipran extended-release in patients with major depressive disorder. J Clin Psychopharmacol 2014;34(1):47-56
   PubMed Web of Science ®Google Scholar
• Gommoll C, Greenberg WM, Chen C. A randomized, double-blind, placebo-controlled study of flexible doses of levomilnacipran ER (40-120 mg/day) in patients with major depressive disorder. J Drug Assess 2014;3:10-19
   PubMedGoogle Scholar
• Montgomery SA, Gommoll CP, Chen C, Greenberg WM. Efficacy of levomilnacipran extended-release in major depressive disorder: pooled analysis of 5 double-blind, placebo-controlled trials. CNS Spectr 2014. [Epub ahead of print]
   Google Scholar
• Nelson JC, Delucchi K, Schneider LS. Efficacy of second generation antidepressants in late-life depression: a meta-analysis of the evidence. Am J Geriatr Psychiatry 2008;16(7):558-67
   PubMed Web of Science ®Google Scholar
• US Food and Drug Administration. Drug Approval Package. Brintellix (vortioxetine) Tablets. 2013. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000TOC.cfm [Accessed 01 June 2014]
   Google Scholar
• Thase ME, Dragheim M, Loft H, Mahableshwarkar AR. Efficacy of vortioxetine versus placebo in adults with major depressive disorder: Meta-analyses of MADRS single items from 9 short-term studies. Poster NR6-130, American Psychiatric Association 167th Annual Meeting, 3 – 7 May 2014; New York, NY
   Google Scholar
• Citrome L. Vortioxetine for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antidepressant - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed? Int J Clin Pract 2014;68(1):60-82
   PubMed Web of Science ®Google Scholar
• Alvarez E, Perez V, Dragheim M, et al. A double-blind, randomized, placebo-controlled, active reference study of Lu AA21004 in patients with major depressive disorder. Int J Neuropsychopharmacol 2012;15(5):589-600
   PubMed Web of Science ®Google Scholar
• Henigsberg N, Mahableshwarkar AR, Jacobsen P, et al. A randomized, double-blind, placebo-controlled 8-week trial of the efficacy and tolerability of multiple doses of Lu AA21004 in adults with major depressive disorder. J Clin Psychiatry 2012;73(7):953-9
   PubMed Web of Science ®Google Scholar
• Boulenger JP, Loft H, Olsen CK. Efficacy and safety of vortioxetine (Lu AA21004), 15 and 20 mg/day: a randomized, double-blind, placebo-controlled, duloxetine-referenced study in the acute treatment of adult patients with major depressive disorder. Int Clin Psychopharmacol 2014;29(3):138-49
   PubMed Web of Science ®Google Scholar
• Areberg J, Luntang-Jensen M, Søgaard B, Nilausen D. Occupancy of the serotonin transporter after administration of Lu AA21004 and its relation to plasma concentration in healthy subjects. Basic Clin Pharmacol Toxicol 2012;110(4):401-4
   PubMed Web of Science ®Google Scholar
• Jacobsen PL, Mahableshwarkar AR, Serenko M. A randomized, double-blind, placebo-controlled study of the efficacy and safety of vortioxetine 10 mg and 20 mg in adults with major depressive disorder. Poster NR9-06, American Psychiatric Association 166th Annual Meeting; 18 – 22 May 2013; San Francisco, CA
   Google Scholar
• Mahableshwarkar AR, Jacobsen PL, Serenko M, et al. A duloxetine-referenced, fixed-dose study comparing efficacy and safety of 2 vortioxetine doses in the acute treatment of adult MDD patients. Poster NR9-01, American Psychiatric Association 166th Annual Meeting; 18 – 22 May 2013; San Francisco, CA
   Google Scholar
• Katona C, Hansen T, Olsen CK. A randomized, double-blind, placebo-controlled, duloxetine-referenced, fixed-dose study comparing the efficacy and safety of Lu AA21004 in elderly patients with major depressive disorder. Int Clin Psychopharmacol 2012;27(4):215-23
   PubMed Web of Science ®Google Scholar
• Montgomery SA, Nielsen RZ, Poulsen LH, Häggström L. A randomised, double-blind study in adults with major depressive disorder with an inadequate response to a single course of selective serotonin reuptake inhibitor or serotonin-noradrenaline reuptake inhibitor treatment switched to vortioxetine or agomelatine. Hum Psychopharmacol 2014. [Epub ahead of print]
   Google Scholar
• Papakostas G, Dragheim M, Nielsen RZ. Efficacy and tolerability of vortioxetine vs agomelatine is independent of previous treatment in MDD patients switched after an inadequate response. Poster NR6-118, American Psychiatric Association 167th Annual Meeting; 3 – 7 May 2014; New York, NY
   Google Scholar
• Baldwin DS, Loft H, Dragheim M. A randomised, double-blind, placebo controlled, duloxetine-referenced, fixed-dose study of three dosages of Lu AA21004 in acute treatment of major depressive disorder (MDD). Eur Neuropsychopharmacol 2012;22(7):482-91
   PubMed Web of Science ®Google Scholar
• Jain R, Mahableshwarkar AR, Jacobsen PL, et al. A randomized, double-blind, placebo-controlled 6-wk trial of the efficacy and tolerability of 5 mg vortioxetine in adults with major depressive disorder. Int J Neuropsychopharmacol 2013;16(2):313-21
   PubMed Web of Science ®Google Scholar
• Mahableshwarkar AR, Jacobsen PL, Serenko M, et al. A randomized, double-blind, parallel-group, placebo-controlled, fixed-dose study comparing the efficacy and safety of 2 doses of vortioxetine (Lu AA21004) in acute treatment of adults with major depressive disorder. Poster NR9-02, American Psychiatric Association 166th Annual Meeting; 18 – 22 May 2013; San Francisco, CA
   Google Scholar
• Mahableshwarkar AR, Jacobsen PL, Chen Y. A randomized, double-blind trial of 2.5 mg and 5 mg vortioxetine (Lu AA21004) versus placebo for 8 weeks in adults with major depressive disorder. Curr Med Res Opin 2013;29(3):217-26
   PubMed Web of Science ®Google Scholar
• Khin NA, Chen YF, Yang Y, et al. Exploratory analyses of efficacy data from major depressive disorder trials submitted to the US Food and Drug Administration in support of new drug applications. J Clin Psychiatry 2011;72(4):464-72
   PubMed Web of Science ®Google Scholar
• Mahableshwarkar A, Baldwin DS, Chen Y, et al. A meta-analysis of the efficacy of vortioxetine in patients with major depressive disorder (MDD) and high levels of anxiety symptoms. Poster NR6-112, American Psychiatric Association 167th Annual Meeting; 3 – 7 May 2014; New York, NY
   Google Scholar
• Baldwin DS, Nutt DJ. On assessing potential efficacy for vortioxetine in generalized anxiety disorder. Eur Neuropsychopharmacol 2012;22(12):841-3
   Google Scholar
• Szegedi A, Jansen WT, van Willigenburg AP, et al. Early improvement in the first 2 weeks as a predictor of treatment outcome in patients with major depressive disorder: a meta-analysis including 6562 patients. J Clin Psychiatry 2009;70(3):344-53
   PubMed Web of Science ®Google Scholar
• Papakostas GI, Perlis RH, Scalia MJ, et al. A meta-analysis of early sustained response rates between antidepressants and placebo for the treatment of major depressive disorder. J Clin Psychopharmacol 2006;26(1):56-60
   PubMed Web of Science ®Google Scholar
• Blier P, Ward NM. Is there a role for 5-HT1A agonists in the treatment of depression? Biol Psychiatry 2003;53(3):193-203
   PubMed Web of Science ®Google Scholar
• Jain R, Chen D, Edwards J, Mathews M. Early and sustained improvement with vilazodone in adult patients with major depressive disorder: post hoc analyses of two phase III trials. Curr Med Res Opin 2014;30(2):263-70
   PubMed Web of Science ®Google Scholar
• Jain R, Chen D, Edwards J, Mathews M. Early improvement and sustained response with vilazodone in patients with major depressive disorder: Pooled analyses from two phase III trials. Poster NR9-37, American Psychiatric Association 166th Annual Meeting; 18 – 22 May 2013; San Francisco, CA
   Google Scholar
• Patkar A, Gommoll C, Mathews M, et al. Early improvement with vilazodone in adults with major depressive disorder: post hoc analysis of a randomized, double-blind, placebo-controlled trial. Poster NR6-120, American Psychiatric Association 167th Annual Meeting; 3 – 7 May 2014; New York, NY
   Google Scholar
• Sambunaris A, Gommoll C, Chen C, Greenberg WM. Efficacy of levomilnacipran extended-release in improving functional impairment associated with major depressive disorder: pooled analyses of five double-blind, placebo-controlled trials. Int Clin Psychopharmacol 2014;29(4):197-205
   Google Scholar
• Cutler A, Chen C, Gommoll C, et al. Clinical relevance of levomilnacipran ER treatment in patients with major depressive disorder: Improvements in functional impairment categories. Poster NR6-091, American Psychiatric Association 167th Annual Meeting; 3 – 7 May 2014; New York, NY
   Google Scholar
• Sheehan DV, Harnett-Sheehan K, Spann ME, et al. Assessing remission in major depressive disorder and generalized anxiety disorder clinical trials with the discan metric of the Sheehan disability scale. Int Clin Psychopharmacol 2011;26(2):75-83
   PubMed Web of Science ®Google Scholar
• McKnight PE, Kashdan TB. The importance of functional impairment to mental health outcomes: a case for reassessing our goals in depression treatment research. Clin Psychol Rev 2009;29(3):243-59
   PubMed Web of Science ®Google Scholar
• Zimmerman M, McGlinchey JB, Posternak MA, et al. How should remission from depression be defined? The depressed patient’s perspective. Am J Psychiatry 2006;163(1):148-50
   PubMed Web of Science ®Google Scholar
• Hirschfeld RM, Montgomery SA, Keller MB, et al. Social functioning in depression: a review. J Clin Psychiatry 2000;61(4):268-75
   PubMed Web of Science ®Google Scholar
• McIntyre RS, Cha DS, Soczynska JK, et al. Cognitive deficits and functional outcomes in major depressive disorder: determinants, substrates, and treatment interventions. Depress Anxiety 2013;30(6):515-27
   PubMed Web of Science ®Google Scholar
• Greer TL, Kurian BT, Trivedi MH. Defining and measuring functional recovery from depression. CNS Drugs 2010;24(4):267-84
   Google Scholar
• Mørk A, Montezinho LP, Miller S, et al. Vortioxetine (Lu AA21004), a novel multimodal antidepressant, enhances memory in rats. Pharmacol Biochem Behav 2013;105:41-50
   PubMed Web of Science ®Google Scholar
• Guilloux JP, Mendez-David I, Pehrson A, et al. Antidepressant and anxiolytic potential of the multimodal antidepressant vortioxetine (Lu AA21004) assessed by behavioural and neurogenesis outcomes in mice. Neuropharmacology 2013;73:147-59
   PubMed Web of Science ®Google Scholar
• du Jardin KG, Jensen JB, Sanchez C, Pehrson AL. Vortioxetine dose-dependently reverses 5-HT depletion-induced deficits in spatial working and object recognition memory: a potential role for 5-HT1A receptor agonism and 5-HT3 receptor antagonism. Eur Neuropsychopharmacol 2014;24(1):160-71
   PubMed Web of Science ®Google Scholar
• Jensen JB, du Jardin KG, Song D, et al. Vortioxetine, but not escitalopram or duloxetine, reverses memory impairment induced by central 5-HT depletion in rats: evidence for direct 5-HT receptor modulation. Eur Neuropsychopharmacol 2014;24(1):148-59
   PubMed Web of Science ®Google Scholar
• Raskin J, Wiltse CG, Siegal A, et al. Efficacy of duloxetine on cognition, depression, and pain in elderly patients with major depressive disorder: an 8-week, double-blind, placebo-controlled trial. Am J Psychiatry 2007;164(6):900-9
   PubMed Web of Science ®Google Scholar
• McIntyre RS, Lophaven S, Olsen CK. A randomized, double-blind, placebo-controlled study of vortioxetine on cognitive function in depressed adults. Int J Neuropsychopharmacol 2014. [Epub ahead of print]
   Google Scholar
• Harrison JE, Lophaven S, Olsen C. Which cognitive domains are impacted by treatment with vortioxetine? Poster NR6-105, American Psychiatric Association 167th Annual Meeting; 3 – 7 May 2014; New York, NY
   Google Scholar
• McIntyre RS, Lophaven S, Olsen CK. Randomized, double-blind, placebo-controlled study of the efficacy of vortioxetine in adult patients with major depressive disorder (MDD). Poster NR6-114, American Psychiatric Association 167th Annual Meeting; 3 – 7 May 2014; New York, NY
   Google Scholar
• Geddes JR, Carney SM, Davies C, et al. Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review. Lancet 2003;361(9358):653-61
   PubMed Web of Science ®Google Scholar
• Shiovitz T, Greenberg WM, Chen C, et al. A randomized, double-blind, placebo-controlled trial of the efficacy and safety of levomilnacipran ER 40-120mg/day for prevention of relapse in patients with major depressive disorder. Innov Clin Neurosci 2014;11(1-2):10-22
   PubMedGoogle Scholar
• Boulenger JP, Loft H, Florea I. A randomized clinical study of Lu AA21004 in the prevention of relapse in patients with major depressive disorder. J Psychopharmacol 2012;26(11):1408-16
   PubMed Web of Science ®Google Scholar
• Filippov G, Christens PF. Vortioxetine (Lu AA21004) 15 and 20 mg/day: open-label long-term safety and tolerability in major depressive disorder. Eur Neuropsychopharmacol 2013;23(Suppl 2):S325
   Google Scholar
• Alam MY, Jacobsen PL, Chen Y, et al. Safety, tolerability, and efficacy of vortioxetine (Lu AA21004) in major depressive disorder: results of an open-label, flexible-dose, 52-week extension study. Int Clin Psychopharmacol 2014;29(1):36-44
   PubMed Web of Science ®Google Scholar
• Baldwin DS, Hansen T, Florea I. Vortioxetine (Lu AA21004) in the long-term open-label treatment of major depressive disorder. Curr Med Res Opin 2012;28(10):1717-24
   PubMed Web of Science ®Google Scholar
• Wade A, Despiegel N, Heldbo Reines E. Escitalopram in the long-term treatment of major depressive disorder. Ann Clin Psychiatry 18(2):83-9
   Google Scholar
• Jacobsen PL, Chan S, Harper L, et al. A phase 3, long-term, open-label extension study evaluating the safety and tolerability of vortioxetine in subjects with major depressive disorder. Poster NR6-106, American Psychiatric Association 167th Annual Meeting; 3 – 7 May 2014; New York, NY
   Google Scholar
• Robinson DS, Kajdasz DK, Gallipoli S, et al. A 1-year, open-label study assessing the safety and tolerability of vilazodone in patients with major depressive disorder. J Clin Psychopharmacol 2011;31(5):643-6
   PubMed Web of Science ®Google Scholar
• Patkar AA, Rele S Millet R, et al. An 8-week randomized, double-blind trial comparing efficacy, safety and tolerability of three different dose initiation strategies with vilazodone. Poster No. 118, American Psychiatric Association 167th Annual Meeting; 3 – 7 May 2014; New York, NY
   Google Scholar
• Williams VS, Baldwin DS, Hogue SL, et al. Estimating the prevalence and impact of antidepressant-induced sexual dysfunction in 2 European countries: a cross-sectional patient survey. J Clin Psychiatry 2006;67(2):204-10
   PubMedGoogle Scholar
• Mathews M, Chen D, Gommoll C, et al. Effects of vilazodone on sexual dysfunction in major depressive disorder: A randomized, double-blind trial with placebo and active controls. Poster NR6-113, American Psychiatric Association 167th Annual Meeting; 3 – 7 May 2014; New York, NY
   Google Scholar
• Thase ME, Greenberg WM, Bose A, et al. Safety and tolerability of levomilnacipran SR in major depressive disorder: analysis of 5 short-term double-blind, placebo-controlled trials. Poster NR10-53, American Psychiatric Association 166th Annual Meeting; 18 – 22 May 2013; San Francisco, CA
   Google Scholar
• Palmer R, Shrestha P, Greenberg WM, et al. Cardiovascular safety profile of levomilnacipran SR in the treatment of major depressive disorder. Poster NR9-12, American Psychiatric Association 166th Annual Meeting; 18 – 22 May 2013; San Francisco, CA
   Google Scholar
• Jacobsen PL, Clayton AH, Mahableshwarkar AR, et al. The effect of vortioxetine on sexual dysfunction during the treatment of adults with major depressive disorder (MDD) or generalized anxiety disorder (GAD). Poster #35, American Society of Clinical Psychopharmacology Annual Meeting; 16 – 19 June 2014; Hollywood, FL
   Google Scholar
• Jacobsen PL, Mahableshwarkar AR, Chen Y, et al. A head-to-head, randomized, comparison study of vortioxetine vs. escitalopram in patients well treated for MDD and experiencing treatment-emergent sexual dysfunction. Poster #41, American Society of Clinical Psychopharmacology Annual Meeting; 16 – 19 June 2014; Hollywood, FL
   Google Scholar
• Trivedi MH, Lin EH, Katon WJ. Consensus recommendations for improving adherence, self-management, and outcomes in patients with depression. CNS Spectr 2007;12(8 Suppl 13):1-27
   PubMed Web of Science ®Google Scholar
• Safety and efficacy of vilazodone in major depressive disorder. ClinicalTrials.gov. U.S. National Institutes of Health. Available from: http://clinicaltrials.gov/show/NCT01573598 [Last accessed 9 July 2014]
   Google Scholar
• Israel JA. Remission in depression: definition and initial treatment approaches. J Psychopharmacol 2006;20(3 Suppl):5-10
   Web of Science ®Google Scholar
• Ashton AK, Jamerson BD, Weinstein W, Wagoner C. Antidepressant-related adverse effects impacting treatment compliance: results of a patient survey. Curr Ther Res Clin Exp 2005;66(2):96-106
   PubMed Web of Science ®Google Scholar