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Pramipexole Effective Treatment For Depression In Parkinson's Disease

Dopamine receptor agonist pramipexole (PPX), but not pergolide (PRG), shows a significant antidepressant effect for patients with Parkinson's disease.

As many as 40% of patients with Parkinson's disease are reported to experience depression, which is thought to be related to dopaminergic, serotonergic and noradrenergic deficits.

PPX and PRG have been shown to alleviate motor complications associated with Parkinson's disease when used as adjuvant therapy with L-dopa. To date, however, neither of these medications has been evaluated as antidepressant treatments for this disease.

Irena Rektorova, MD, of Masaryk University, Brno, Czech Republic, and colleagues conducted an 8-month multi-centre prospective randomised study to characterize and compare the effects of PPX and PRG administered in combination with L-dopa in patients with advanced stage Parkinson's disease.

Forty-one patients (15 females, 25 males) with advanced idiopathic Parkinson's disease, fluctuations and/or dyskinesias and mild or moderate depression were randomised to receive either PPX (N=22;mean age, 59.7 years) or PRG (N=19; mean age, 63.5 years) in combination with L-dopa. The recommended daily dosage of PPX and PRG was 3 mg, and the allowed dosage ranged from 1.5-4.5 mg/day. It was recommended that the total daily dose of L-dopa be decreased gradually during the study.

Changes in depressive symptoms were evaluated objectively by an independent, blinded observer using the Montogomery-Asberg Depression Rating Scale (MADRS) and subjectively using the Zung Self-Rating Depression Scale. The standardized Unified Parkinson's Disease Rating Scale (UPDRS) was used to evaluate activities of daily living, motor complications and motor symptoms in an open-label design.

Both groups showed a statistically significant decrease in all of the average UPDRS and Zung scores (significance level [SI] =1%), with no significant difference observed between the two treatments. While both groups also showed decreases in the average MADRS score value, this was only significant for the PPX subjects (SI=5%).

The researchers also report a significant decrease in the total daily dose of L-dopa for the both the PPX (22%) and the PRG (28%) groups, although this was statistically more pronounced in the PRG group (SI=5%). Sleep disturbances were the only adverse effect that differed significantly between the two groups (4 PPX patients, 10 PRG patients, SI=5%).

Based on this study, Dr. Rektorova and colleagues conclude that PPX is an effective treatment for mild and moderate depression associated with Parkinson's disease.

Because the PRG group showed a significant decrease in the Zung score but not MADRS, the researchers speculate that "milder depressive symptoms may be less responsive or the MADRS may not be sensitive enough to pick up an improvement of milder symptoms." However, they add, "we can't make any conclusions with regard to the antidepressant effect of PRG," and recommend further investigations to assess the efficacy of this treatment.
Eur J Neurol 2003 Jul;10:4:399-406. "Pramipexole and pergolide in the treatment of depression in Parkinson's disease: a national multicentre prospective randomized study"

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