title: Pramipexole for bipolar II depression: a placebo-controlled proof of concept study.
abstract: BACKGROUND
  The original serotonergic and noradrenergic hypotheses do not fully account for the neurobiology of depression or mechanism of action of effective antidepressants. Research implicates a potential role of the dopaminergic system in the pathophysiology of bipolar disorder. The current study was undertaken as a proof of the concept that dopamine agonists will be effective in patients with bipolar II depression.
  
  
  METHODS
  In a double-blind, placebo-controlled study, 21 patients with DSM-IV bipolar II disorder, depressive phase on therapeutic levels of lithium or valproate were randomly assigned to treatment with pramipexole (n = 10) or placebo (n = 11) for 6 weeks. Primary efficacy was assessed by the Montgomery-Asberg Depression Rating Scale.
  
  
  RESULTS
  All subjects except for one in each group completed the study. The analysis of variance for total Montgomery-Asberg Depression Rating Scale scores showed a significant treatment effect. A therapeutic response (>50% decrease in Montgomery-Asberg Depression Rating Scale from baseline) occurred in 60% of patients taking pramipexole and 9% taking placebo (p =.02). One subject on pramipexole and two on placebo developed hypomanic symptoms.
  
  
  CONCLUSIONS
  The dopamine agonist pramipexole was found to have significant antidepressant effects in patients with bipolar II depression.
authors.affiliation: Laboratory of Molecular Pathophysiology, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institute of Health, Department of Human and Health Services, Bethesda, Maryland, USA.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Zarate
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Payne
authors.forename: Jaskaran
authors.initials: J
authors.lastname: Singh
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Quiroz
authors.forename: David A
authors.initials: DA
authors.lastname: Luckenbaugh
authors.forename: Kirk D
authors.initials: KD
authors.lastname: Denicoff
authors.forename: Dennis S
authors.initials: DS
authors.lastname: Charney
authors.forename: Husseini K
authors.initials: HK
authors.lastname: Manji
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage*; D018692:Antimanic Agents / Q000627:therapeutic use*; D052160:Benzothiazoles; D001714:Bipolar Disorder / Q000188:drug therapy*; D018491:Dopamine Agonists / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008094:Lithium / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000008:administration & dosage; D010865:Pilot Projects; D000077487:Pramipexole; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D050637:Receptors, Dopamine D3; D013844:Thiazoles / Q000008:administration & dosage*; D014635:Valproic Acid / Q000627:therapeutic use
chemical_list: D000928:Antidepressive Agents; D018692:Antimanic Agents; D052160:Benzothiazoles; C493593:DRD3 protein, human; D018491:Dopamine Agonists; D009414:Nerve Growth Factors; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013844:Thiazoles; D014635:Valproic Acid; D000077487:Pramipexole; D008094:Lithium