Effects of dopaminergic treatment on striatal dopamine turnover in de novo Parkinson disease

Objective: To evaluate the effects of levodopa and the dopamine D2 agonist cabergoline on striatal dopamine turnover estimated as the inverse of the effective dopamine distribution volume ratio (EDVR) measured by 18 F-dopa PET in de novo Parkinson disease (PD). Methods: Single-center, parallel-group, randomized, observer-blinded study of cabergoline (3 mg/day) and levodopa (300 mg/day) over 12 weeks in patients with de novo PD. Primary efficacy measure was the change of the side-to-side averaged putaminal EDVR comparing baseline and end-of-maintenance period. Results: Thirty-five out of 39 randomized patients were assigned to the primary efficacy analysis (cabergoline, n = 17; levodopa, n = 18). At the end of treatment period, mean EDVRs were significantly lower compared to baseline solely in the levodopa group (relative change −1.0 ± 13.0% in cabergoline [ p = 0.525 when compared to baseline], −8.3 ± 11.8% in levodopa group [ p = 0.006]) with a nonsignificant trend between groups (mean relative difference: 7.3% (95% confidence interval −1.2% to 15.8%; p = 0.091). There was significant clinical improvement in both groups at 12 weeks compared to baseline, but no significant differences between groups in clinical and PET secondary outcome measures. Both pharmacologic treatments and PET scanning were well-tolerated and safe. Conclusion: Putaminal dopamine turnover is increased by levodopa treatment in de novo PD. The nonsignificant trend toward a larger influence by levodopa compared to cabergoline is supported by ancillary statistical analyses. This augmentation of early compensatory events by levodopa might contribute not only to its symptomatic effects, but also to its induction of motor complications.