Pramipexole, Ropinirole, and Mania in Parkinson’s Disease
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.
Ms. A was a 37-year-old white woman with a 4-year history of Parkinson’s disease. Her family history revealed a paternal grandmother with a single major depressive episode and a sibling with anorexia nervosa. Her Parkinson’s disease symptoms had been treated with levodopa and selegiline with moderate response. Because of episodic rigidity and dyskinesia, pramipexole was added to her treatment regimen and increased to 1.5 mg b.i.d., with improvement of motor symptoms. However, in the first week after its addition, she developed symptoms of elevated mood, increased sex drive, energy, psychomotor activity, and decreased need for sleep. After 6 months on this regimen, she developed irritability, paranoia, and delusions of jealousy. Selegiline and pramipexole were discontinued, and she began taking quetiapine, titrated to 50 mg, at bedtime. Her psychotic symptoms resolved in 1 month. Quetiapine was discontinued without symptom recurrence. Two months later, her levodopa dose was decreased because of tremors and dyskinesias, and ropinirole was added and titrated to 0.75 mg t.i.d. She rapidly developed insomnia, increased energy, and agitation. Consequently, ropinirole was discontinued, which led to symptom resolution. She remained stable taking levodopa alone for several months. Ropinirole was reinstituted but led to reemergence of manic symptoms, necessitating discontinuation, which resulted in amelioration of mania.
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.
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3. Goldberg JF, Burdick KE, Endick CJ: Preliminary randomized, double-blind, placebo-controlled trial of pramipexole added to mood stabilizers for treatment-resistant bipolar depression. Am J Psychiatry 2004; 161:564–566Link, Google Scholar
