title: Newer treatment studies for bipolar depression.
abstract: OBJECTIVE
  Depressive symptoms of bipolar disorder have more negative impact on a patient's life than manic symptoms. This review focused on the emerging efficacy data for treatments in bipolar depression.
  
  
  METHODS
  English-language literature cited in Medline was searched with terms bipolar depression, clinical trial, and trial. Randomized, placebo-controlled trials of newer studies with older agents and all studies with newer or novel agents were prioritized. Open-label studies of novel agents presented at major scientific meetings were also included.
  
  
  RESULTS
  Olanzapine, olanzapine-fluoxetine combination (OFC), and quetiapine were superior to placebo in the acute treatment of bipolar depression. Lamotrigine only significantly reduced core symptoms of depression compared with placebo. Pramipexole, a dopamine D2/D3 receptor agonist and omega-3 fatty acids, a polyunsaturated fatty acid, augmentation to mood stabilizer (MS) had superiority to placebo in reducing depressive symptoms. Topiramate augmentation of an MS was equally as effective as Bupropion-SR. Patients treated with an MS responded well to the addition of agomelatine, a melatonin receptor agonist with 5-HT2C antagonist properties. However, inositol and repetitive transcranial magnetic stimulation did not separate from placebo. Lamotrigine and olanzapine, and to a lesser extent, divalproex, are superior to placebo in preventing depressive relapses. All agents were relatively well tolerated.
  
  
  CONCLUSIONS
  Olanzapine, OFC, and quetiapine are effective in the acute treatment of bipolar depression. Compared with lithium and divalproex, lamotrigine is more effective in preventing bipolar depression. Larger controlled studies of the other agents in the acute and maintenance treatment of bipolar depression are warranted.
authors.affiliation: NIMH Bipolar Research Center, Mood Disorders Program, University Hospitals of Cleveland/Case Western Reserve University School of Medicine, Cleveland, OH, USA. keming.gao@uhhs.com
authors.forename: Keming
authors.initials: K
authors.lastname: Gao
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Calabrese
mesh_terms: D000081:Acetamides / Q000627:therapeutic use; D000927:Anticonvulsants / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy*; D003987:Dibenzothiazepines / Q000627:therapeutic use; D018491:Dopamine Agonists / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use; D000077213:Lamotrigine; D000077152:Olanzapine; D000069348:Quetiapine Fumarate; D016032:Randomized Controlled Trials as Topic; D055502:Secondary Prevention; D050781:Transcranial Magnetic Stimulation; D014227:Triazines / Q000627:therapeutic use; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000927:Anticonvulsants; D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D001569:Benzodiazepines; D003987:Dibenzothiazepines; D018491:Dopamine Agonists; D006993:Hypnotics and Sedatives; D000077213:Lamotrigine; D000077152:Olanzapine; D000069348:Quetiapine Fumarate; D014227:Triazines; C084711:agomelatine; D009281:Naphthalenes