Tolcapone improves sleep in patients with advanced Parkinson's disease (PD)
Introduction
The majority of patients with PD suffers from sleep disorders (Tandberg et al., 1998, Poewe and Hogl, 2000, Garcia-Borreguero et al., 2003, Comella, 2007). Disturbance of sleep in PD can be caused by various factors including primary sleep-wake dysregulation, symptoms of PD, medication-induced insomnia and effects of co-morbid conditions (Comella, 2007). The most common night-time sleep complaint is frequent nocturnal awakening (Factor et al., 1990). A further feature closely related to sleep disturbance is daytime sleepiness, which is often induced by medication but is also related to night-time sleep-deprivation (Rye, 2006, Comella, 2007).
Although sleep disturbances have a significant impact on quality of life in patients with PD (Scaravilli et al., 2003, Martinez-Martin et al., 2004), only few trials have specifically assessed the medical management of nocturnal problems in PD (Poewe and Seppi, 2008). Long-acting dopamine agonists have been shown to improve sleep (Chaudhuri et al., 2001, Poewe et al., 2007), but side effects are more frequent compared to levodopa, particularly in elderly patients (Poewe, 2003). Controlled release preparations of levodopa have been reported to relieve night-time problems in PD (Pahwa et al., 1993, Stocchi et al., 1998), but improvement of nocturnal disability was not superior with slow-release levodopa compared to standard preparations in a double-blind study (The U.K. Madopar CR Study Group, 1989).
Due to the limited duration of levodopa effects, the second half of the night is particularly critical for hypodopaminergic fluctuations (Poewe and Seppi, 2008). Tolcapone is an inhibitor of COMT providing increased bio-availability and longer plasma half-life of levodopa (Jorga et al., 1998). Although co-administration of tolcapone at bed-time should result in a longer nocturnal maintenance of therapeutic plasma-levels of levodopa and thus overcome the above mentioned limitations of levodopa use during night-time, there are no data available on the effects of tolcapone on sleep quality in PD. The present prospective open-label multicenter non-interventional trial, therefore, investigates the effects of tolcapone on sleep quality in PD assessing the PDSS before and after treatment with tolcapone.
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Study design and patients
The present prospective open-label multicenter non-interventional trial was conducted in Germany from July 2008 to February 2009. 21 centers (mainly physicians in private practice) participated, with a total of 61 patients with PD who had not responded to or did not tolerate entacapone. Eligible individuals were men or women, aged 30–80 years old, with a diagnosis of idiopathic PD responsive to levodopa treatment, Hoehn & Yahr stage II-IV (Fahn et al., 1987) and were on stable medication for at
Demographics and baseline characteristics
Documentation forms of 61 patients: 22 women (36%) and 39 men (64%) from 21 centers were available for evaluation. Demographical data and baseline characteristics are summarized in Table 1. Mean Hoehn & Yahr stage was 2.9 ± 0.9 with most patients (36%) in stage III. All patients were regularly taking levodopa (mean ± S.D. daily dose: 639 ± 276 mg), 36 patients were on slow-release levodopa (in 29 patients, slow-release levodopa was given once only as bed-time medication). 86.9% of patients experienced
Discussion
In this study, tolcapone was shown to improve quality of sleep in patients with advanced PD. Sub-analysis of different items of the PDSS suggests that reduction of nocturnal akinesia was the key factor responsible for this effect. It is important to note that improvements were achieved in patients who already underwent optimized levodopa treatment including slow-release levodopa and/or the COMT-inhibitor entacapone in the majority of subjects.
Conflict of interest statement
Georg Ebersbach received honoraries for presentations and advisory board activities from Axxonis Pharma, Boehringer Ingelheim Pharma, Cephalon, Desitin Pharma, GlaxoSmithKline, MEDA, Novartis, Orion, und Schwarz Pharma (UCB).
Kirsten Hahn received honoraries for presentations from Novartis.
Michael Lorrain received honoraries for presentations and advisory board activities from Boehringer, Solvay, Cephalon, Meda, Orion, Eisai, Trommsdorf, GSK, UCB-Schwarz, Temmler, Serono-Merck, Novartis.
Acknowledgements
The statistical support of med:unit GmbH, Köln is gratefully acknowledged. This study was supported by a research grant of MEDA Pharmaceuticals Germany GmbH, Bad Homburg, Germany.
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