title: Current landscape, unmet needs, and future directions for treatment of bipolar depression.
abstract: BACKGROUND
  Depression is the predominant pole of illness disability in bipolar disorder and, compared with acute mania, has less systematic research guiding treatment development. The aim of this review is to present the therapeutic options currently available for managing bipolar depression and to highlight areas of unmet need and future research.
  
  
  METHODS
  Literature search of PubMed, PsycINFO, and Cochrane databases and bibliographies from 2000 to August 2013 for treatments that have regulatory approval for bipolar depression or early controlled preliminary data on efficacy.
  
  
  RESULTS
  Treatment options for bipolar depression have increased over the last decade, most notably with regulatory approval for olanzapine/fluoxetine combination, quetiapine, and lurasidone. Conventional mood stabilizers lamotrigine and divalproex have meta-analyses suggesting acute antidepressant response. Manual-based psychotherapies also appear to be effective in treating bipolar depression. The therapeutic utility of unimodal antidepressants, as a class, for the treatment of patients with bipolar depression, as a group, remains to be confirmed. There is a substantially unmet need to develop new interventions that are efficacious, effective, and have low side effect burden.
  
  
  CONCLUSIONS
  Additional compounds are currently being developed that may ultimately be applicable to the treatment of bipolar depression and early open-trial data encourage further studies, but both of these topics are beyond the scope of this review.
  
  
  CONCLUSIONS
  Future registrational trials will need to establish initial efficacy, but increasing interest for personalized or individualized medicine will encourage further studies on individual predictors or biomarkers of response.
authors.affiliation: Mayo Clinic Depression Center, Department of Psychiatry & Psychology, Mayo Clinic College of Medicine, Rochester, MN, USA. Electronic address: mfrye@mayo.edu.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Frye
authors.affiliation: Universidad de los Andes, Facultad de Medicina, Departamento de Psiquiatría, Santiago, Chile.
authors.forename: Miguel L
authors.initials: ML
authors.lastname: Prieto
authors.affiliation: Mayo Clinic Depression Center, Department of Psychiatry & Psychology, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: William V
authors.initials: WV
authors.lastname: Bobo
authors.affiliation: Mayo Clinic Depression Center, Department of Psychiatry & Psychology, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Kung
authors.affiliation: Mayo Clinic Depression Center, Department of Psychiatry & Psychology, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Marin
authors.initials: M
authors.lastname: Veldic
authors.affiliation: Mayo Clinic Depression Center, Department of Psychiatry & Psychology, Mayo Clinic College of Medicine, Rochester, MN, USA; Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: Renato D
authors.initials: RD
authors.lastname: Alarcon
authors.affiliation: Mayo Clinic Depression Center, Department of Psychiatry & Psychology, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Moore
authors.affiliation: Mayo Clinic Depression Center, Department of Psychiatry & Psychology, Mayo Clinic College of Medicine, Rochester, MN, USA; Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Doo-Sup
authors.initials: DS
authors.lastname: Choi
authors.affiliation: Mayo Clinic Depression Center, Department of Psychiatry & Psychology, Mayo Clinic College of Medicine, Rochester, MN, USA; Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Biernacka
authors.affiliation: Mayo Clinic Depression Center, Department of Psychiatry & Psychology, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Susannah J
authors.initials: SJ
authors.lastname: Tye
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy / Q000628:therapy*; D003987:Dibenzothiazepines / Q000627:therapeutic use; D004338:Drug Combinations; D005473:Fluoxetine / Q000627:therapeutic use; D005544:Forecasting; D006301:Health Services Needs and Demand; D006801:Humans; D054833:Isoindoles / Q000627:therapeutic use; D000077213:Lamotrigine; D000069056:Lurasidone Hydrochloride; D011613:Psychotherapy; D000069348:Quetiapine Fumarate; D013844:Thiazoles / Q000627:therapeutic use; D014227:Triazines / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D000928:Antidepressive Agents; D003987:Dibenzothiazepines; D004338:Drug Combinations; D054833:Isoindoles; D013844:Thiazoles; D014227:Triazines; C492572:olanzapine-fluoxetine combination; D005473:Fluoxetine; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D000069056:Lurasidone Hydrochloride; D000077213:Lamotrigine
keywords: Antidepressants; Bipolar; Depression; Mood stabilizers