Pramipexole, Ropinirole, and Mania in Parkinson?s Disease

[John Cottingham <jcott@xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx>]

The source of this article is The American Journal of Psychiatry:
http://tinyurl.com/6dnol

Pramipexole, Ropinirole, and Mania in Parkinson?s Disease
ABHAY SINGH, M.B.B.S., ROBERT ALTHOFF, M.D., PH.D., R. JARED MARTINEAU,
M.D., and JAMES JACOBSON, M.D.
Burlington, Vt.
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.

References


Maj J, Rogoz Z, Skuza G, Kolodziejczyk K: The behavioural effects of
pramipexole, a novel dopamine receptor agonist. Eur J Pharmacol 1997;
324:31?37[CrossRef][Medline]
Willner P: The mesolimbic dopamine system as a target for rapid
antidepressant action. Int Clin Psychopharmacol 1997; 12(3 suppl):S7-S14
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[Abstract/Free Full Text]

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