Is pramipexole better than placebo for the treatment of mildly to moderately depressed, nondemented people with Parkinson disease (PD)? To find out, researchers conducted a 12-week, double blind, placebo-controlled, multicenter, manufacturer-sponsored trial involving 296 patients with mild-to-moderate depressive symptoms and PD without motor fluctuations.

Pramipexole was statistically superior to placebo in reducing scores on the Beck Depression Inventory (the primary outcome) and on two other depression scales, while also improving motor function. Path analysis suggested that depression benefit was mostly independent of improved motor function. Although improvements on two quality-of-life (QOL) measures correlated with reduced depression, the QOL improvements did not differ significantly between the treatment groups, nor did changes on two measures of pleasure and pain. The drug was well tolerated.

Comment: This is the largest study ever done of drug therapy for depression in PD and appears to have been well designed and well performed. The results showed a surprisingly good tolerance of pramipexole, with scant hallucinations and a suspiciously low incidence of impulse-control problems. The depression benefits were not large but appeared to correlate with improvement in QOL. These results suggest that pramipexole has antidepressant effects, which may explain puzzling observations of reduced depressive symptoms in other blinded studies in which pramipexole was underdosed for treating motor dysfunction. In the current study, the benefits may have been dampened by the exclusion of severely depressed patients. However, even in antidepressant trials in the general population, effects are generally only mildly better than those of placebo.

As of this writing, some evidence suggests that tricyclics are helpful in treating depression in patients with PD, but very little evidence supports the use of selective serotonin reuptake inhibitors. These new results suggest that using pramipexole to treat depression in the setting of PD is reasonable, but only for appropriate patients who are at lowest risk for the common adverse effects of this drug.

— Joseph H. Friedman, MD

Dr. Friedman is Director, Movement Disorders Program, Butler Hospital, and Professor and Chief, Division of Movement Disorders, Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI. He has received funds for lectures from the manufacturer that sponsored this trial.

Published in Journal Watch Neurology June 29, 2010