Pramipexole for bipolar II depression: a placebo-controlled proof of concept study

Biol Psychiatry. 2004 Jul 1;56(1):54-60. doi: 10.1016/j.biopsych.2004.03.013.


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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antidepressive Agents / administration & dosage*
  • Antimanic Agents / therapeutic use*
  • Benzothiazoles
  • Bipolar Disorder / drug therapy*
  • Dopamine Agonists / administration & dosage*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Humans
  • Lithium / therapeutic use
  • Male
  • Middle Aged
  • Nerve Growth Factors / administration & dosage
  • Pilot Projects
  • Pramipexole
  • Receptors, Dopamine D2 / agonists*
  • Receptors, Dopamine D3
  • Thiazoles / administration & dosage*
  • Valproic Acid / therapeutic use


  • Antidepressive Agents
  • Antimanic Agents
  • Benzothiazoles
  • DRD3 protein, human
  • Dopamine Agonists
  • Nerve Growth Factors
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Thiazoles
  • Valproic Acid
  • Pramipexole
  • Lithium