To the Editor: Dopamine receptor agonists, such as pramipexole and ropinirole, are a safe and effective initial therapy for mild to moderate Parkinson’s disease. There are at least three lines of evidence to suggest that this class of drugs may also be related to mood symptoms. First, at the clinical level, besides ameliorating motor symptoms, pramipexole has shown antidepressant effects in Parkinson’s disease, in major depression, and in treatment-resistant unipolar and bipolar depression. Next, at the basic science level, pramipexole and ropinirole are novel dopamine receptor agonists with a high affinity for all dopamine D₂ subfamily receptors and show highest affinity for the D₃ receptor subtype (1). The antidepressant effect of pramipexole and ropinirole may be related to a resensitization or potentiation of the D₂/D₃ receptors in the mesolimbic system, a region relevant to mood regulation (2). Finally, in a recent clinical trial by Goldberg and colleagues (3), one case of mania was reported in a patient with a personal history of bipolar depression while being treated with pramipexole. Here, we describe a case of mania in a patient with Parkinson’s disease given pramipexole and ropinirole who had no personal or family history of bipolar disorder.

The long-term studies of dopamine receptor agonists support their use instead of levodopa earlier in the treatment of Parkinson’s disease in order to delay levodopa-related motor complications. We provide evidence here that dopamine receptor agonists may induce mood symptoms and that there is potential for the novel agents of this class, pramipexole and ropinirole, to induce manic symptoms necessitating close monitoring and further study.