title: Agomelatine or placebo as adjunctive therapy to a mood stabiliser in bipolar I depression: randomised double-blind placebo-controlled trial.
abstract: BACKGROUND
  Adjunctive antidepressant therapy is commonly used to treat acute bipolar depression but few studies have examined this strategy.
  
  
  OBJECTIVE
  To examine the efficacy of agomelatine v. placebo as adjuncts to lithium or valproate in bipolar depression.
  
  
  METHODS
  Patients who were currently depressed despite taking lithium or valproate for at least 6 weeks were randomised to treatment with agomelatine (n = 172) or placebo (n = 172) for 8 weeks of acute therapy and 44 weeks of continuation therapy (trial registration: ISRCTN28588282).
  
  
  RESULTS
  No significant differences in improvement of depressive symptoms were observed between the two groups either at 8 weeks or 52 weeks on the primary efficacy measure of change in Montgomery-Åsberg Depression Rating Scale scores from baseline to end-point. Adverse events including switches into mania/hypomania were low and similar in both groups.
  
  
  CONCLUSIONS
  Agomelatine adjunctive therapy was not superior to placebo adjunctive therapy for acute bipolar depression.
authors.affiliation: Lakshmi N. Yatham, MBBS, University of British Columbia, Vancouver, British Columbia, Canada; Eduard Vieta, MD, Bipolar Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain; Guy M. Goodwin, MD, University Department of Psychiatry, Oxford University, Oxford, UK; Michel Bourin, MD, University of Nantes, Nantes, France; Christian de Bodinat, MD, Judith Laredo, PhD, Institut de Recherches Internationales Servier (IRIS), Suresnes, France; Joseph Calabrese, MD, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA yatham@mail.ubc.ca.
authors.forename: Lakshmi N
authors.initials: LN
authors.lastname: Yatham
authors.affiliation: Lakshmi N. Yatham, MBBS, University of British Columbia, Vancouver, British Columbia, Canada; Eduard Vieta, MD, Bipolar Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain; Guy M. Goodwin, MD, University Department of Psychiatry, Oxford University, Oxford, UK; Michel Bourin, MD, University of Nantes, Nantes, France; Christian de Bodinat, MD, Judith Laredo, PhD, Institut de Recherches Internationales Servier (IRIS), Suresnes, France; Joseph Calabrese, MD, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: Eduard
authors.initials: E
authors.lastname: Vieta
authors.affiliation: Lakshmi N. Yatham, MBBS, University of British Columbia, Vancouver, British Columbia, Canada; Eduard Vieta, MD, Bipolar Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain; Guy M. Goodwin, MD, University Department of Psychiatry, Oxford University, Oxford, UK; Michel Bourin, MD, University of Nantes, Nantes, France; Christian de Bodinat, MD, Judith Laredo, PhD, Institut de Recherches Internationales Servier (IRIS), Suresnes, France; Joseph Calabrese, MD, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: Guy M
authors.initials: GM
authors.lastname: Goodwin
authors.affiliation: Lakshmi N. Yatham, MBBS, University of British Columbia, Vancouver, British Columbia, Canada; Eduard Vieta, MD, Bipolar Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain; Guy M. Goodwin, MD, University Department of Psychiatry, Oxford University, Oxford, UK; Michel Bourin, MD, University of Nantes, Nantes, France; Christian de Bodinat, MD, Judith Laredo, PhD, Institut de Recherches Internationales Servier (IRIS), Suresnes, France; Joseph Calabrese, MD, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: Michel
authors.initials: M
authors.lastname: Bourin
authors.affiliation: Lakshmi N. Yatham, MBBS, University of British Columbia, Vancouver, British Columbia, Canada; Eduard Vieta, MD, Bipolar Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain; Guy M. Goodwin, MD, University Department of Psychiatry, Oxford University, Oxford, UK; Michel Bourin, MD, University of Nantes, Nantes, France; Christian de Bodinat, MD, Judith Laredo, PhD, Institut de Recherches Internationales Servier (IRIS), Suresnes, France; Joseph Calabrese, MD, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: de Bodinat
authors.affiliation: Lakshmi N. Yatham, MBBS, University of British Columbia, Vancouver, British Columbia, Canada; Eduard Vieta, MD, Bipolar Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain; Guy M. Goodwin, MD, University Department of Psychiatry, Oxford University, Oxford, UK; Michel Bourin, MD, University of Nantes, Nantes, France; Christian de Bodinat, MD, Judith Laredo, PhD, Institut de Recherches Internationales Servier (IRIS), Suresnes, France; Joseph Calabrese, MD, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: Judith
authors.initials: J
authors.lastname: Laredo
authors.affiliation: Lakshmi N. Yatham, MBBS, University of British Columbia, Vancouver, British Columbia, Canada; Eduard Vieta, MD, Bipolar Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain; Guy M. Goodwin, MD, University Department of Psychiatry, Oxford University, Oxford, UK; Michel Bourin, MD, University of Nantes, Nantes, France; Christian de Bodinat, MD, Judith Laredo, PhD, Institut de Recherches Internationales Servier (IRIS), Suresnes, France; Joseph Calabrese, MD, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Calabrese
mesh_terms: D000081:Acetamides / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018692:Antimanic Agents / Q000627:therapeutic use; D001118:Argentina; D001315:Australia; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy*; D001938:Brazil; D002170:Canada; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D006801:Humans; D007194:India; D007391:International Cooperation; D018020:Lithium Compounds / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D015990:Placebo Effect; D011569:Psychiatric Status Rating Scales; D056910:Republic of Korea; D013019:South Africa; D016896:Treatment Outcome; D014635:Valproic Acid / Q000627:therapeutic use; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000928:Antidepressive Agents; D018692:Antimanic Agents; D018020:Lithium Compounds; D014635:Valproic Acid; C084711:agomelatine; D009281:Naphthalenes