Sleep Disorders and Parkinson's Disease

By David B. Rye, Md, Ph.D., Associate Professor of Neurology, Medical Directory, Emory Sleep Disorders Laboratory, Atlanta, GA

Sleep disorders in Parkinson's disease (PD) have long been recognized, however their causes remain ill-defined and treatment strategies not well established. These deficiencies derive from the heterogeneity of PD and coincident factors such as medication, again, and cognitive and mood disturbances, each of which are independently known to affect sleep. The sleep of PD patients is profoundly disturbed, even relative to other neurodegenerative conditions. One survey has estimated that prevalence of sleep disturbance in PD at 98%.

For discussion purposes it is convenient to consider sleep complaints in three broad categories: sleep onset insomnia, sleep maintenance problems, and daytime sleepiness. It should be stressed that these complaints are not mutually exclusive; i.e., many patients suffer from two or more of these symptoms.
Sleep onset insomnia

Difficulties with sleep onset, surprisingly, seem no greater a problem in the PD patient than in the general population. In most instances, sleep onset problems can be related to anxiety or to agitated depression, which if identified, should then be the focus of treatment. On occasion, I have seen anxiety related to anticipation of an "off" period severely interferes with sleep onset, and in such an instance more attention must be paid to optimizing anti-parkinsonian medications. Additional contributors to sleep onset insomnia in small subpopulations of PD patients include restless legs syndrome (which, incidentally, appears no more common in PD than in the general population) and akathisia (i.e., inner restlessness) and dyskinesias usually reflective of overmedication with anti-parkinsonian drugs. When treatment with L-dopa is instituted, some patients may experience sleep onset insomnia that typically resolves with time. In such an instance it is best to administer medication earlier and to wait patiently. When insomnia is severe enough to produce a significant and persistent delay of sleep onset (viz., delayed sleep phase syndrome).

The use of fairly rapidly absorbed and/or short acting benzodiazepines such as Restoril®, Xanax®, Prosom®, or Halcion® seem warranted. We have been most satisfied with Halcion® with the comment that it should be used with caution in elderly and cognitively affected patients. Our own attempts to treat advanced patients with AmbienÆ, a very rapidly absorbed and commonly prescribed medication, have met with limited success even at therapeutic doses. Many patients are prescribed sedating, antidepressant medications to enhance sleep onset and in many cases these seem effective. We have been less inclined to employ these medications due to: 1) fear of morning "hangover" effects; and 2) the potential to enhance nocturnal movement and thereby further fragment sleep (see below).
Sleep maintenance insomnia

Sleep maintenance insomnia, i.e., sleep fragmentation, is the most common nocturnal complaint in PD patients. In many instances it can precede the waking manifestations of the disease (e.g., in the form of dream sleep behavior disorder) or more commonly be apparent at initial presentation/diagnosis. The complaint of sleep fragmentation, as correlated with objective findings during recording of sleep in the laboratory, represents a continuum from unexplained awakenings to awakenings associated with quite specific night-time motor disturbances. Early in the course of treatment of PD, daytime administration of L-dopa improves motor symptoms and may not disrupt sleep. Frequent awakenings, for the most part unassociated with nighttime movements, are treated with sedating antidepressants. Some caution is warranted in anti-depressant use as they are known to precipitate confusion/hallucinations, exacerbate arousing movements at night and even worsen daytime PD in some patients. As PD progresses, patients may experience "off" periods during the night. Immobility with subsequent inability to rise to use the bathroom is therefore a common complaint. In this instance, L-dopa dosing may need to be moved closer to bedtime, particularly in the sustained release form, because this is felt to diminish sleep fragmentation. It may also be prudent to consider use of a dopamine agonist, e.g., Permax®, Mirapex® or Requip® in such instances as they tend to be sedating. Unfortunately, these agents, like some antidepressants, may precipitate hallucinations although they are preferred in that they diminish nocturnal movement.

It is increasingly recognized that many—an estimated 15% PD patients—experience exaggerated nocturnal movements and dream-enactment (viz. Dream-sleep behavior disorder) behaviors. Treatment is usually in the form of KlonopinÆ and precautions should be taken in insuring that injury is not incurred by the patient or bed partner (e.g., bed rails, and removal of breakable objects from nearby the bed). Finally, it is important to respect proper sleep hygiene so as to not worsen the quality of sleep. Measures should include abstinence from caffeinated beverages or foods (e.g. chocolates) within 4-5 hours of bedtime. Alcohol, while promoting sleep onset, is well known to fragment sleep once achieved, and thereby should be avoided.
Daytime sleepiness

Daytime sleepiness, and even near instances of sudden onset sleep, are increasingly recognized in the PD patient population. Unfortunately, because of its insidious nature, many patients and caregivers do not endorse sleepiness as a significant complaint and most physicians fail to inquire about this symptom. Sleepiness should be taken very seriously as it can contribute to significant morbidity and even mortality (e.g., automobile accidents). Most importantly, quality of life can be significantly improved if it is identified and properly treated.

Sleepiness in PD has many potential causes. First, dopamine deficiency itself or other brain pathologies in PD render some patients sleepy. Some, may even approach the level of excessive sleepiness seen in narcolepsy. Such a diagnosis requires careful assessment and exclusion of other contributors to sleepiness by a trained sleep specialist. Treatments include activating antidepressants such as Wellbutrin®, the new wake promoting agent Provigil® or even classic amphetamine like stimulants (e.g., Ritalin®, Dexedrine®). Second, the dopamine agonists such as Permax®, Mirapex®, or Requip® are themselves sedating and recently have been reported to precipitate excessive somnolence and sudden onset of sleep in some PD patients. If sleepiness coincides with dosing of any of these medications, the dose should be lowered or discontinued. Third, insufficient quantity or quality of prior nights sleep can contribute to daytime sleepiness. In this instance, any disorder delaying sleep onset or interfering with sleep maintenance needs to be identified and properly treated (see above). In so saying, it has been surprising in our practice that this third instance is actually quite rare. We have made the somewhat counterintuitive observation that PD patients that sleep less and have more fragmented sleep actually tend to be the most alert group of patients in the day.

In closing, there is much yet we need to learn about the effect of PD and anti-parkinsonian medications upon sleep/daytime alertness. The above is meant to provide just a brief guide to some of the more common sleep complaints of PD patients and treatments. It should be emphasized, however, that each patient is unique. When straight forward solutions, such as those preferred, fail to significantly improve the quality of sleep or daytime alertness, examination by a sleep specialist trained in managing patients with brain disorders is recommended.

Note: Dr. Rye was an APDA Cotzias Fellow

Reprinted with permission from the American Parkinson Disease Association, Inc. Newsletter Spring 2000