Back to Browse Journals » Neuropsychiatric Disease and Treatment » Volume 9

Adjunctive agomelatine therapy in the treatment of acute bipolar II depression: a preliminary open label study

Authors Fornaro M, McCarthy MJ, De Berardis D, De Pasquale C, Tabaton M, Martino M, Colicchio S, Cattaneo CI, D'Angelo E, Fornaro P

Received 13 December 2012

Accepted for publication 18 January 2013

Published 15 February 2013 Volume 2013:9 Pages 243—251


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Michele Fornaro,1 Michael J McCarthy,2,3 Domenico De Berardis,4 Concetta De Pasquale,1 Massimo Tabaton,5 Matteo Martino,6 Salvatore Colicchio,7 Carlo Ignazio Cattaneo,8 Emanuela D'Angelo,9 Pantaleo Fornaro6

Department of Formative Sciences, University of Catania, Catania, Italy; 2Department of Psychiatry, Veteran's Affairs San Diego Healthcare System, 3University of California San Diego, La Jolla, CA, USA; 4Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, "ASL 4", Teramo, Italy; 5Department of Internal Medicine and Medical Specialties, University of Genova, Genoa, Italy; 6Department of Neurosciences, Section of Psychiatry, University of Genova, Genoa, Italy; 7Unit of Sleep Medicine, Department of Neuroscience, Catholic University, Rome, Italy; 8National Health System, "ASL 13", Novara, Italy; 9National Health System, "ASL 3", Genoa, Italy

Purpose: The circadian rhythm hypothesis of bipolar disorder (BD) suggests a role for melatonin in regulating mood, thus extending the interest toward the melatonergic antidepressant agomelatine as well as type I (acute) or II cases of bipolar depression.
Patients and methods: Twenty-eight depressed BD-II patients received open label agomelatine (25 mg/bedtime) for 6 consecutive weeks as an adjunct to treatment with lithium or valproate, followed by an optional treatment extension of 30 weeks. Measures included the Hamilton depression scale, Pittsburgh Sleep Quality Index, the Clinical Global Impression Scale–Bipolar Version, Young Mania Rating Scale, and body mass index.
Results: Intent to treat analysis results demonstrated that 18 of the 28 subjects (64%) showed medication response after 6 weeks (primary study endpoint), while 24 of the 28 subjects (86%) responded by 36 weeks. When examining primary mood stabilizer treatment, 12 of the 17 (70.6%) valproate and six of the 11 (54.5%) lithium patients responded by the first endpoint. At 36 weeks, 14 valproate treated (82.4%) and 10 lithium treated (90.9%) subjects responded. At 36 weeks, there was a slight yet statistically significant (P = 0.001) reduction in body mass index and Pittsburgh Sleep Quality Index scores compared to respective baseline values, regardless of mood stabilizer/outcome. Treatment related drop-out cases included four patients (14.28%) at week 6 two valproate-treated subjects with pseudo-vertigo and drug-induced hypomania, respectively, and two lithium-treated subjects with insomnia and mania, respectively. Week 36 drop outs were two hypomanic cases, one per group.
Conclusion: Agomelatine 25 mg/day was an effective and well-tolerated adjunct to valproate/lithium for acute depression in BD-II, suggesting the need for confirmation by future double blind, controlled clinical trials.

Keywords: bipolar disorder type-II, acute bipolar depression, agomelatine, adjunctive treatment

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]


Other articles by this author:

Prevalence and clinical features associated with bipolar disorder polypharmacy: a systematic review

Fornaro M, De Berardis D, Koshy AS, Perna G, Valchera A, Vancampfort D, Stubbs B

Neuropsychiatric Disease and Treatment 2016, 12:719-735

Published Date: 31 March 2016

Cognitive functioning and subjective quality of life in relapsing-remitting multiple sclerosis patients before and after percutaneous transluminal angioplasty: a preliminary report

De Pasquale C, Pistorio ML, Veroux M, Giaquinta A, Veroux P, Fornaro M

Neuropsychiatric Disease and Treatment 2014, 10:1039-1044

Published Date: 11 June 2014

Electroretinographic modifications induced by agomelatine: a novel avenue to the understanding of the claimed antidepressant effect of the drug?

Fornaro M, Bandini F, Cestari L, Cordano C, Ogliastro C, Albano C, De Berardis D, Martino M, Escelsior A, Rocchi G, Fornaro P, De Pasquale C

Neuropsychiatric Disease and Treatment 2014, 10:907-914

Published Date: 20 May 2014

Prevalence and diagnostic distribution of medically unexplained painful somatic symptoms across 571 major depressed outpatients

Fornaro M, Maremmani I, Canonico PL, Carbonatto P, Mencacci C, Muscettola G, Pani L, Torta R, Vampini C, Parazzini F, Dumitriu A, Perugi G

Neuropsychiatric Disease and Treatment 2011, 7:217-221

Published Date: 21 April 2011

Increase in IL-6 levels among major depressive disorder patients after a 6-week treatment with duloxetine 60 mg/day: a preliminary observation

Michele Fornaro, Matteo Martino, Florinda Battaglia, et al

Neuropsychiatric Disease and Treatment 2011, 7:51-56

Published Date: 10 February 2011

Tinnitus psychopharmacology: A comprehensive review of its pathomechanisms and management

Michele Fornaro, Matteo Martino

Neuropsychiatric Disease and Treatment 2010, 6:209-218

Published Date: 1 June 2010

Readers of this article also read:

Green synthesis of water-soluble nontoxic polymeric nanocomposites containing silver nanoparticles

Prozorova GF, Pozdnyakov AS, Kuznetsova NP, Korzhova SA, Emel’yanov AI, Ermakova TG, Fadeeva TV, Sosedova LM

International Journal of Nanomedicine 2014, 9:1883-1889

Published Date: 16 April 2014

Single- and multiple-dose pharmacokinetics, pharmacodynamics, and safety of apixaban in healthy Chinese subjects [Corrigendum]

Cui Y, Song Y, Wang J, Yu Z, Schuster A, Barrett YC, Frost C

Clinical Pharmacology: Advances and Applications 2014, 6:61-62

Published Date: 27 March 2014

Methacrylic-based nanogels for the pH-sensitive delivery of 5-Fluorouracil in the colon

Ashwanikumar N, Kumar NA, Nair SA, Kumar GS

International Journal of Nanomedicine 2012, 7:5769-5779

Published Date: 15 November 2012

A novel preparation method for silicone oil nanoemulsions and its application for coating hair with silicone

Hu Z, Liao M, Chen Y, Cai Y, Meng L, Liu Y, Lv N, Liu Z, Yuan W

International Journal of Nanomedicine 2012, 7:5719-5724

Published Date: 12 November 2012

Cross-linked acrylic hydrogel for the controlled delivery of hydrophobic drugs in cancer therapy

Deepa G, Thulasidasan AK, Anto RJ, Pillai JJ, Kumar GS

International Journal of Nanomedicine 2012, 7:4077-4088

Published Date: 27 July 2012

Particle size reduction to the nanometer range: a promising approach to improve buccal absorption of poorly water-soluble drugs

Rao S, Song Y, Peddie F, Evans AM

International Journal of Nanomedicine 2011, 6:1245-1251

Published Date: 20 June 2011

Crystallization after intravitreal ganciclovir injection

Pitipol Choopong, Nattaporn Tesavibul, Nattawut Rodanant

Clinical Ophthalmology 2010, 4:709-711

Published Date: 14 July 2010