No abstract

In addition to treating the motor symptoms of Parkinson's disease, the dopamine agonist pramipexole has shown an antidepressant effect. The trials, however, included patients with motor complications, raising the question of whether the antidepressant benefit represented only a treatment-related motor improvement. To address this issue, we have conducted a 14-week randomized trial comparing pramipexole with an established antidepressant in patients without motor complications. At seven Italian centers, 67 Parkinsonian outpatients with major depression but no history of motor fluctuations and/or dyskinesia received open-label pramipexole (at 1.5 to 4.5 mg/day) or sertraline (at 50 mg/day). In both groups, the Hamilton Depression Rating Scale (HAM-D) score decreased throughout 12 weeks of treatment, but in the pramipexole group the proportion of patients who recovered, as defined by a final HAM-D score

Parkinson's disease is characterized by heterogeneity of clinical presentations, association of signs and symptoms, rate of progression, and response to therapy. The aim of this prospective 5-year study was to evaluate whether clinical features at onset were predictive of the subsequent progression. Two courses were identified which differed in the characteristics at onset. Slow course was characterized by earlier age at onset, lateralization of motor signs, rest tremor, and absence of gait disturbance. Rapid course presented older age, less evident lateralization of signs, predominance of bradykinesia-rigidity and gait disturbance. Our results confirmed that PD is clinically heterogeneous and specific patterns of onset seem to be associated with different rates of disease progression. Predictive models based on these clinical characteristics have a good sensitivity in indicating a slow disease progression but are not reliable in indicating a rapid evolution.

Cabergoline is a potent D2 receptor agonist with a half-life of 65 hours that may provide continuous dopaminergic stimulation administered once daily. In this study, we randomized de novo Parkinson's disease (PD) patients to treatment with increasing doses of cabergoline (0.25 to 4 mg/d) or levodopa (100 to 600 mg/d) up to the optimal or maximum tolerated dose. Decreases of > 30% in motor disability (Unified Parkinson's Disease Rating Scale Factor III) versus baseline were considered indicative of clinical improvement. If 30% improvement was not achieved, levodopa/ carbidopa could be added on an open basis. Of the 208 patients entered in the cabergoline group, 175 remained in the study for 1 year at a mean dose of 2.8 mg/d; in the levodopa group, 176 of the 205 patients entered were still on study after 1 year at a mean dose of 468 mg/d. The proportion of patients requiring additional levodopa/carbidopa increased in the cabergoline group from 18% at 6 months to 38% at 1 year versus 10% (p = 0.05) at 6 months and 18% (p < 0.01) at 1 year in the levodopa group. The proportion of patients showing clinical improvement did not differ significantly between the two groups, or between the subgroups on monotherapy, at any endpoint. Irrespective of levodopa/carbidopa addition, 81% of patients in the cabergoline group and 87% of patients in the levodopa group were clinically improved at 1 year (p = 0.189); the corresponding figures for the subgroup on monotherapy were 79% in the cabergoline-treated patients and 86% in the levodopa-treated patients (p = 0.199). The mean difference versus baseline in Unified Parkinson's Disease Rating Scale Factor III scores in patients who remained on monotherapy up to 1 year was 12.6 (95% confidence interval [CI]: 10.8, 14.3) in the cabergoline group and 16.4 (95% CI: 14.8, 18.0) in the levodopa group. Adverse events occurred in 76% of patients on cabergoline and in 66% of patients on levodopa. The severity profile for reported events was similar for the two agents. The results of this study indicate that cabergoline treatment for up to 1 year is only marginally less effective than levodopa in the proportion of patients who can be treated in monotherapy. More than 60% of de novo PD patients could be managed on cabergoline alone up to 1 year. In the patients in whom levodopa/carbidopa was needed, the combination therapy provided efficacy similar to that obtained with levodopa alone, with a relevant sparing of levodopa.

Parkinson's disease (PD) is a chronic, progressive, disabling movement disorder with a clear impact on Health-Related Quality of Life (HRQoL). We investigated the correlations between HRQoL and sleep disorders measured with the Parkinson's disease Sleep Scale (PDSS) and the motor and non-motor aspects of the disease. A correlation was found between HRQoL and the scores from PDSS, motor and depression scales. We conclude that more attention should be paid to the non-motor aspects of PD to attempt to improve HRQoL.