Udine Special Section
Dopamine agonists and sleepiness in PD: review
of the literature and personal findings
Raffaele Manni
a,
*
, Michele Terzaghi
a
, Ivana Sartori
a
, Francesca Mancini
b
, Claudio Pacchetti
b
a
Unit of Sleep Medicine and Epilepsy, IRCCS ‘C. Mondino’ Institute of Neurology, Pavia, Italy
b
Unit of Parkinson’s Disease and Movement Disorders, IRCCS ‘C. Mondino’ Institute of Neurology, Pavia, Italy
Received 1 December 2002; received in revised form 1 January 2003; accepted 15 January 2003
Abstract
Background and purpose: This study is aimed at evaluating daytime sleepiness in a series of Parkinson’s disease (PD) patients
chronically treated with dopamine agonists (DAs) alone or in combination with
L
-Dopa.
Patients and methods: A preliminary series of 22 non-demented, adult PD patients (mean age 68.9, 13 men and 9 women) were evaluated
by means of structured sleep interview, Epworth sleepiness scale (ESS) and 24-h ambulatory polysomnography (A-PSG).
Results: Sleep attacks (SAs) were reported by 32% of the patients, in three of them (43%) after DA treatment was initiated (alone or in
addition to
L
-Dopa). In two patients, both with chronic use of ropinirole, we documented NREM SAs during a continuous ambulatory
polysomnography (A-PSG) performed in the patients’ real-life settings. The subjects experiencing SAs showed a higher degree of daytime
sleep propensity than those without SA, having higher ESS scores and a higher proportion of microsleeps and intentional naps on A-PSG.
Interestingly, we found that nocturnal total sleep time is higher in PD patients with SAs than in the others.
Conclusions: All in all, our data indicate that SAs are an extreme manifestation of increased daytime sleepiness. The occurrence of SAs in
our series of PD patients is unlikely to depend simply on the demands of homeostatic mechanisms.
q 2004 Elsevier B.V. All rights reserved.
Keywords: Parkinson’s disease; Daytime sleepiness; Sleep attacks; Dopamine agonists
1. Introduction
In 1999, the scientific community was alerted to the
sedating effect of non-ergot dopamine agonists (DAs) in
Parkinson’s disease (PD) patients [1].
Several studies [2–6] indicate that DAs play a role in the
genesis of excessive daytime sleepiness (EDS) in PD, most
indicating that the sedating effect of DAs is related to the
stimulation of the inhibitory D
2
-like autoreceptors at the
level of the ventral tegmental area (VTA). The sedating
effect is not unique to a subgroup of DAs and seems to
depend on the dose administered and on the functional state
of the central dopaminergic pathways.
The mechanisms by which DAs cause daytime sleepiness
in PD and the clinical phenomenology of the somnolence
they induce are still a matter of debate [7]. Sleep attacks
(SAs) have been reported in PD patients under treatment
with DAs [8–14]. However, to date SAs had been
documented during polysomnographic (PSG) recording in
only two patients, in one of which sleep onset REM
(SOREM) was detected [15,16].
2. Dopamine agonists and excessive sleepiness in PD:
pathophysiological basis
In spite of several methodological research limitations
met in exploring the mechanisms by which DAs influence
vigilance in animals and humans, some facts have become
established and further evidences are emerging [2].
Studies in animals indicate that the effect of DAs on
vigilance and on the sleep –wake cycle depends strictly on
whether D
1
or D
2
receptor is stimulated, on the site of action
of the DA (pre-synaptic or post-synaptic), and on the DA
1389-9457/$ - see front matter q 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.sleep.2003.01.001
Sleep Medicine 5 (2004) 189–193
www.elsevier.com/locate/sleep
*
Corresponding author. Address: Unita
`
Medicina del Sonno ed Epilessia,
Via Palestro 3, 27100 Pavia, Italy. Tel.: þ39-382-380316; fax: þ 39-382-
380286.
E-mail address: raffaele.manni@mondino.it (R. Manni).