To the Editor: Pramipexole, a dopamine receptor agonist, is currently indicated for treatment of idiopathic Parkinson’s disease. There is also preliminary evidence suggesting that it may have a role in the treatment of bipolar depression (1–3). Pramipexole is generally well tolerated, but there are occasional reports of induction of hypomania. Singh et al. (4) described a case of mania in a patient with Parkinson’s disease with no personal or family history of bipolar disorder. We report the case of a woman with bipolar II disorder who developed a manic episode following treatment of depression with pramipexole. Written informed consent was obtained from the patient after the procedure had been fully explained.
“Ms. B” was a 41-year-old woman with a history of bipolar II disorder that began with an episode of depression at the age of 16. During the early illness course, she received several serotonin reuptake inhibitors alone or in combination with lithium, valproic acid, and carbamazepine that led to the development of hypomania and rapid cycling. She had also experienced spontaneous hypomanic spells over the past 3 years. Her usual duration of hypomania was 2 days (range 1–7 days).
Because of the refractory nature of depression over the previous couple of years that had failed to respond to adequate trials of medications, including lamotrigine, oxcarbazepine, and modafinil, we decided to add pramipexole to valproic acid 750 mg b.i.d. (serum level 110 μg /ml). The starting dose of 0.125 mg was escalated over a 3-week period to 1.5 mg a day, to which there was a partial response. As the dosage was increased to 2 mg, Ms. B developed mania characterized by symptoms of euphoria, irritability, paranoia, decreased requirement of sleep, poor judgment, increased libido, and excessive spending of money. The manic symptoms lasted 2 months, but subsided within a week of discontinuation of pramipexole.
The temporal association of mania with the use of pramipexole and the absence of prior manic or mixed episodes in this patient who had a well-documented history of bipolar II disorder would strongly suggest a causal role for pramipexole in the induction of mania. Close monitoring of patients with bipolar depression is required during treatment with pramipexole. Studies are needed to assess the effect of pramipexole on the long-term course of bipolar disorder.
1.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; 161:564–566
2.Zarate CA Jr, Payne JL, Singh J, Quiroz JA, Luckenbaugh DA, Denicoff KD, Charney DS, Manji HK: Pramipexole for bipolar II depression: a placebo-controlled proof of concept study. Biol Psychiatry 2004; 56:54–60
3.Sporn J, Ghaemi SN, Sambur MR, Rankin MA, Recht J, Sachs GS, Rosenbaun JF, Fava M: Pramipexole augmentation in the treatment of unipolar and bipolar depression: a retrospective chart review. Ann Clin Psychiatry 2000; 12:137–140
4.Singh A, Althoff R, Martineau RJ, Jacobson J: Pramipexole, ropinirole, and mania in Parkinson’s disease. Am J Psychiatry 2005; 162:814–815
The authors report no competing interests.
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