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Updated: Aug 23, 2026
Developing a Rat Model for Bipolar Disorder
Published on: May 2, 2025
Pramipexole for bipolar II depression: a placebo-controlled proof of concept study
Carlos A Zarate1, Jennifer L Payne, Jaskaran Singh
1Laboratory 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.
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.
