title: Methodological approaches and magnitude of the clinical unmet need associated with amotivation in mood disorders.
abstract: BACKGROUND
  There is growing research interest in studying motivational deficits in different neuropsychiatric disorders because these symptoms appear to be more common than originally reported and negatively impact long-term functional outcomes. However, there is considerable ambiguity in the terminology used to describe motivational deficits in the scientific literature. For the purposes of this manuscript, the term "amotivation" will be utilised in the context of mood disorders, since this is considered a more inclusive/appropriate term for this patient population. Other challenges impacting the study of amotivation in mood disorders, include: appropriate patient population selection; managing or controlling for potential confounding factors; the lack of gold-standard diagnostic criteria and assessment scales; and determination of the most appropriate study duration.
  
  
  METHODS
  This paper summarises the search for a consensus by a group of experts in the optimal approach to studying amotivation in mood disorders.
  
  
  RESULTS
  The consensus of this group is that amotivation in mood disorders is a legitimate therapeutic target, given the magnitude of the associated unmet needs, and that proof-of-concept studies should be conducted in order to facilitate subsequent larger investigations. The focus of this manuscript is to consider the study of amotivation, as a residual symptom of major depressive disorder (MDD) or bipolar depression (BD), following adequate treatment with a typical antidepressant or mood stabiliser/antipsychotic, respectively.
  
  
  CONCLUSIONS
  There is a paucity of data studying amotivation in mood disorders. This manuscript provides general guidance on the most appropriate study design(s) and methodology to assess potential therapeutic options for the management of residual amotivation in mood disorders.
authors.affiliation: University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Bipolar Disorders Research Center, 10524 Euclid Avenue, 12th Floor, Cleveland, Ohio 44106, USA. Electronic address: Joseph.Calabrese@UHhospitals.org.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Calabrese
authors.affiliation: Massachusetts General Hospital, Boston, USA.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
authors.affiliation: F. Hoffman-La Roche AG, Basel, Switzerland.
authors.forename: George
authors.initials: G
authors.lastname: Garibaldi
authors.affiliation: Newcastle University, Tyne & Wear, UK.
authors.forename: Heinz
authors.initials: H
authors.lastname: Grunze
authors.affiliation: Duke University School of Medicine, Durham, N.C., USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Krystal
authors.affiliation: Laughren Psychopharm Consulting, Rockville, Maryland, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Laughren
authors.affiliation: F. Hoffman-La Roche AG, Basel, Switzerland.
authors.forename: Wayne
authors.initials: W
authors.lastname: Macfadden
authors.affiliation: University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Marin
authors.affiliation: Massachusetts General Hospital, Boston, USA.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Nierenberg
authors.affiliation: University of New Mexico, Albuquerque, NM, USA.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Tohen
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000627:therapeutic use; D057565:Apathy; D001714:Bipolar Disorder / Q000523:psychology*; D003865:Major Depressive Disorder / Q000523:psychology*; D006801:Humans; D009042:Motivation; D012107:Research Design
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents
keywords: Amotivation; Apathy; Mood disorders; Motivational deficits