Cabergoline versus pergolide in levodopa-treated Parkinson's disease patients with nocturnal disabilities: a randomised, double-blind crossover trial to evaluate efficacy, tolerability, and quality of life

Sleep disorders in PD patients often are caused by complications of levodopa therapy like motor fluctuations in response or abnormal involuntary movements. These may appear as early morning dystonia, pain and spasm at night, nocturnal akinesia, nocturia and nocturnal treatment-related psychotic episodes, namely hallucinations.

Method: In a double-blind, randomised, bi-centre, crossover design, patients with idiopathic PD and nocturnal disabilities were up-titrated in the first crossover period (2 weeks) to an individually optimised dose of CBG (maximum dose: 6mg) or PGL (maximum dose: 5mg, given in 3 doses). After week 12, patients were switched to the other treatment and treated for 8 weeks. Assessments were performed at the end of the first (week 12) and the second (week 20) crossover period. Primary efficacy parameters were two items of the Parkinson Disease Sleep Scale (PDSS, 1: quality of sleep, 12: early morning dystonia), and UPDRS item „bradykinesia“ of subscale 3. Secondary outcome criteria were the UPDRS subscales 3, 4a and b, and the PDQ-39 quality of life scale

Results: Of 32 patients (median age 70 years, 54% females) from 2 centers (UK: 16, Germany: 16), 23 completed both crossover periods. No statistical differences could be observed between the two crossover sequences in PDSS item 1 (p=.1090); therefore. Patients improved under both treatments although in PDSS items „urge to move“, „restlessless“, „nocturia“, „pain in arms and legs“, „tiredness after awakening“, PGL numerically showed more favorable effects than CBG. Similar severity ratings in both treatment groups were observed in the UPDRS total score (subscale 3) and in the „bradykinesia“ item. No differences between CGB and PGL were found in the PDQ-39, all items of UPDRS subscale IV, the CGI, and the ESS.

Slightly more patients dropped out unter PGL (n=5) than under CBG treatment. In addition. more AEs of severe intensity occurred in the PGL (n=12) than in the CBG (n=6) group.

Conclusion: CBG and PGL were not different with regard to improvements in efficacy and quality of life in the treatment of PD patients with nocturnal disabilities, although cabergoline was given only once a day compared with three dosages of pergolide application. Tolerability of CBG was slightly better than of PGL.