Dopamine Agonists

From a phenomenological point of view, bipolar depression presents as an opposite to mania. Whereas bipolar depression shows retarded activity, slow thinking, and low mood, mania shows enhanced activity, rapid thinking, and heightened or irritable mood. Such dichotomous presentation of a disorder is rare in nature. Himmelhoch (2000) suggested that bipolar depression is centered around volitional inhibition and that there is a relationship between bipolar depression and involuntary motor disorders. Pharmacological agents effective in Parkinson's disease may be useful in bipolar depression. Such agents are mainly drugs affecting dopaminergic systems.


Pramipexole, a dopamine agonist used to treat Parkinson's disease, was reported in two double-blind studies to be effective in bipolar depression (Goldberg et al. 2004; Zarate et al. 2004). Zarate et al. (2004) reported on the efficacy of pramipexole in bipolar type II depression. These authors conducted a double-blind, placebo-controlled study in 21 patients with DSM-IV-TR bipolar type II disorder, depressive phase. Patients were taking lithium or valproate at therapeutic levels and were randomly assigned to treatment with pramipexole (n = 10) or placebo (n = 11) for 6 weeks. All subjects, except for one in each group, completed the study. A therapeutic response (> 50% decrease in MADRS

from baseline) occurred in 60% of patients taking pramipexole and 9% taking placebo, a statistically significant difference. One subject taking pramipexole and two receiving placebo developed hypomanic symptoms.

Goldberg et al. (2004) conducted a randomized, double-blind, placebo-controlled trial of pramipexole added to mood stabilizers for treatment-resistant bipolar depression. In this study, 22 depressed outpatients with DSM-IV-TR, nonpsychotic bipolar disorder were randomly assigned to receive placebo or a flexible dose of pramipexole added to existing mood stabilizers for 6 weeks. More patients given pramipexole (10 of 12) than patients given placebo (6 of 10) completed the study. Sixty-six percent patients taking pramipexole and only 20% taking placebo had an improvement of at least 50% in their Ham-D scores: the mean percentage of improvement from baseline was greater for patients taking pramipexole than for those taking placebo (48% vs. 21%). One patient developed hypomania while taking pramipexole.

These two studies suggest that pramipexole may have antidepressive effects in patients with bipolar depression. Larger randomized, controlled trials are needed to affirm these observations.

Understanding And Treating Bipolar Disorders

Understanding And Treating Bipolar Disorders

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