title: Drugs under early investigation for the treatment of bipolar disorder.
abstract: BACKGROUND
  Despite the availability of several treatment options for bipolar disorder (BD), patients suffer from chronic, subsyndromal symptoms, quite frequent polarity shifts, cognitive impairment and poor community function. Overall, the current treatment outcomes for BD highlight the need to develop targeted, more effective and safe treatments.
  
  
  METHODS
  This review focuses on compounds currently under investigation for BD, covering compounds tested through animal studies to those in Phase II clinical trials over the past 5 years. These drugs concern all phases of BD treatment, that is, mania, depression, maintenance, and cognitive dysfunction.
  
  
  CONCLUSIONS
  Limitations exist in applying valid preclinical bipolar models and study designs. Research emphasis is given mainly on bipolar depression, with few compounds showing some evidence of efficacy. Non-effectiveness in current studies of mania and maintenance treatment reflects the need for novel compounds. Glycogen synthase kinase 3, casein kinase 1, inositol monophosphatase inhibition, histone deacetylase inhibition pathways are known targets that should proceed from preclinical to the clinical trial level.
authors.affiliation: University of Athens, Eginition Hospital, First Department of Psychiatry , 72-74 Vas. Sofias Avenue, 11528, Athens , Greece +0030 210 7289137 ; +0030 210 7242020 ; gekonst@otenet.gr ; george.konstantakopoulos@kcl.ac.uk.
authors.forename: George
authors.initials: G
authors.lastname: Konstantakopoulos
authors.forename: Stefanos
authors.initials: S
authors.lastname: Dimitrakopoulos
authors.forename: Panayiota G
authors.initials: PG
authors.lastname: Michalopoulou
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D015195:Drug Design; D015507:Drugs, Investigational / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D058990:Molecular Targeted Therapy
chemical_list: D014150:Antipsychotic Agents; D015507:Drugs, Investigational
keywords: bipolar disorder; cognitive deficits; drug development; target; treatment