Question: In patients with early, mild Parkinson disease (PD), does the long-term effectiveness of levodopa alone differ from that of levodopa plus selegiline or initial bromocriptine monotherapy?
Design: Randomized {allocation concealed*}†, blinded {data safety and monitoring committee}†,* controlled trial with a mean 9.2-year follow-up.
Setting: United Kingdom.
Patients: 782 patients with a clinical diagnosis of PD. Exclusion criteria were failure to respond to an adequate trial of dopaminergic drugs or incapacitating cognitive impairment.
Intervention: 249 patients were allocated to levodopa alone, 271 to levodopa plus selegiline, and 262 to initial bromocriptine. 104 patients in the bromocriptine group were rerandomized to 1 of the other 2 treatment groups after bromocriptine was withdrawn, but all patients were analyzed in the groups to which they were initially randomized.
Main outcome measures: Mortality, disability, and adverse effects.
Main results: Analysis was by intention to treat. The groups did not differ for mortality (Table). At 3 years, those assigned to initial bromocriptine had worse disability scores than those assigned to levodopa alone (difference in adjusted mean Webster score 1.3, 95% CI 0.4 to 2.1). This difference was no longer statistically significant at 9 years (0.2, CI −1.5 to 1.5). At a mean of 9.2 years of follow-up, a lower incidence of dyskinesia occurred in patients initially assigned to bromocriptine than in those in the levodopa-alone group (relative risk 0.73, CI 0.57 to 0.93). However, when only moderate-to-severe dyskinesias were analyzed, this difference was no longer statistically significant. The groups did not differ for incidence of dystonia or on-off fluctuations.
Conclusions: In patients with mild, early Parkinson disease, initial treatment with bromocriptine did not reduce mortality more than levodopa. Disability scores were worse during the first 3 years of treatment with initial bromocriptine.
Initial bromocriptine (IB) vs levodopa alone (L) and levodopa plus selegiline (LS) in early, mild Parkinson disease at a mean 9.2 years
| Outcome | Comparisons | Event rates (person-yr at risk) | Unadjusted hazard ratios (95% CI) |
| Mortality | IB vs L | 58% (140) vs 51% (118) | 1.15 (0.90 to 1.47)‡ |
| LS vs IB | 61% (148) vs 58% (140) | 1.06 (0.84 to 1.34)‡ |
| LS vs L | 61% (148) vs 51% (118) | 1.22 (0.95 to 1.55)‡ |