Objective: Investigate safety, feasibility and efficacy of switching therapy in patients with advanced-stage Parkinson’s disease (PD) inadequately controlled with pramipexole (≤ 3.5 mg/day) or ropinirole (≤ 14 mg/day) to rotigotine transdermal system (≤ 14 mg/24 h; dose adjustments ≤ 16 mg/24 h permitted).
Methods: PD0009 (ClinicalTrials.gov: NCT01711866) was an open-label study in patients with advanced-stage PD receiving levodopa, and experiencing sleep disturbance or early-morning motor impairment. Pramipexole/ropinirole was switched to equivalent dose rotigotine overnight or in two stages. During the 4-week treatment period rotigotine dose adjustments were permitted (up to 16 mg/24 h). Primary variable: Clinical Global Impressions (CGI) item 4: side effects (assessing safety) at end of treatment.
Results: 79/87 (91%) patients completed the study; 2 (2%) withdrew due to adverse events (AEs). Most (84; 97%) had CGI item 4 score < 3 indicating switch did not interfere with functioning; three experienced drug-related AEs interfering with functioning (score = 3). 62% patients improved on Patient Global Impression of Change, assessing effectiveness. AEs occurring ≥ 5%: application site pruritus (10%), application site erythema (7%), dizziness (7%), dyskinesia (7%), erythema (6%), pruritus (6%). Unified Parkinson’s Disease Rating Scale II and III, Parkinson’s Disease Sleep Scale-2 and Pittsburgh Sleep Quality Index were unchanged. Numerical improvements in ‘off’ time, awakenings and nocturias were observed.
Conclusions: Switch from pramipexole or ropinirole to rotigotine (up to 14 mg/24 h) was feasible and possibly associated with some benefit. 相似文献
Dopaminergic dysfunction is implicated in the pathophysiology of treatment‐resistant depression. In this review, we describe the putative role of dopamine in depression, summarize the evidence for the efficacy of dopamine receptor agonists in the treatment of treatment‐resistant depression, and discuss the underlying mechanisms by which these medications work. Both preclinical and clinical data suggest that adjunctive dopamine agonists could be a promising option for the treatment of such a condition, indicating that there is a dopamine agonist‐responsive subgroup of depression. Future clinical studies are warranted to clarify unresolved issues regarding dopamine agonists such as long‐term efficacy, efficacy as a monotherapy, and efficacy for juvenile and senile depression. Further basic research is also necessary to fully understand how dopamine acts in the brain of depressed patients. 相似文献
Background and purpose: In chronic diseases including Parkinson’s disease (PD), complex pharmacotherapy dosing schedules are reported to reduce adherence, perhaps leading to less‐effective symptom control and, in PD, more erratic stimulation of dopamine receptors. However, blinded clinical‐trial designs preclude direct comparisons of adherence to various schedules. Methods: In two double‐blind (DB) studies of early PD and one of advanced PD, subjects received three‐times‐daily (t.i.d.) pramipexole or placebo. In open‐label (OL) extensions, subjects took extended‐release, once‐daily (q.d.) pramipexole. At 24 or 32 OL weeks, q.d. versus t.i.d. dosing preference was surveyed by questionnaire. Results: Of 590 DB‐trial completers with early PD, 511 entered the OL extension. Of 374 survey respondents, 94.4% preferred q.d. dosing (72.2% of them found it ‘very much more convenient’ and 27.8%‘more convenient’), 2.7% preferred t.i.d., and 2.9% chose ‘no difference’. Of 465 DB‐trial completers with advanced PD, 391 entered its OL extension. Of 334 survey respondents, 88.9% preferred q.d. dosing (59.9% of them found it ‘very much more convenient’ and 40.1%‘more convenient’), 5.7% preferred t.i.d., and 5.4% chose ‘no difference’. Results excluding DB‐placebo recipients were highly similar. Conclusions: In this first direct comparison of patient preference for q.d. versus t.i.d. dopamine‐agonist dosing, patients with early or advanced PD had a strong preference for q.d. rather than t.i.d. pramipexole. The high proportion of advanced‐PD patients declaring this preference indicates that it does not depend on whether a patient is taking concomitant PD medications dosed more frequently than q.d.相似文献