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

Carlos A. Zarate, Jennifer L. Payne, Jaskaran Singh, Jorge A. Quiroz, David A. Luckenbaugh, Kirk D. Denicoff, Dennis S. Charney, Husseini K. Manji

Research output: Contribution to journalArticlepeer-review

280 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)54-60
Number of pages7
JournalBiological psychiatry
Issue number1
StatePublished - Jul 1 2004
Externally publishedYes


  • Antidepressant
  • bipolar depression
  • dopaminergic
  • pramipexole

ASJC Scopus subject areas

  • Biological Psychiatry


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