Parkinson's and the Night

PARKINSON'S AND THE NIGHT

by Johan Samanta, MD, PC

For most people night is a time of rest and renewal, however, for many people with Parkinson's disease (PD) night all too often brings anything but. The reasons for nighttime difficulties are multiple and complex, and, until recently, were not well understood. Fortunately, a number of important factors have come to light, which may allow better understanding and more effective therapies for nighttime problems in PD.

Ask a group of people with PD how many hours of sleep they get per night and you may be in for a surprise. One study found that persons with PD averaged just over 5 hours of sleep per night, and woke up twice as many times as adults of similar age without PD did. Reasons for decreased sleep are varied but include sleep apnea, difficulty falling asleep (insomnia), frequent awakening (sleep fragmentation), nighttime urinary frequency, vivid dreams/nightmares often accompanied by physical action (REM behavioral disorder), nighttime confusion, and even hallucinations and delusions.

Sleep apnea (or obstructive sleep apnea) is the most common sleep-related breathing disorder. The prevalence (the number of persons with this condition in a given group) of sleep apnea increases with age and it is a known cause of mortality in the elderly. Ironically, older adults (and their spouses) are less likely to complain about their sleep apnea symptoms such as snoring, gasping, choking, and shortness of breath. At least one study has suggested that up to 20% of persons with PD have significant sleep apnea compared to less than 5% of older adults without PD. The primary treatment for sleep apnea is the nightly use of continuous positive airway pressure (CPAP), which provides a continuous flow of air through the upper airways, preventing obstruction and improving oxygenation during sleep. Polysomnography ("a sleep study") is used to confirm the diagnosis of sleep apnea and may be repeated to confirm the effectiveness of CPAP. Many adults have difficulty tolerating a CPAP device at first and may require repeat adjustment and instruction for optimal fit and correct use.

Sleep-onset insomnia (primary insomnia) and sleep fragmentation (secondary insomnia) together occur in more than 30% of persons with PD. Insomnia often is related to anxiety and can be a sign of depression, which should then be the focus of treatment. The initiation of L-dopa therapy may be associated with a period of insomnia and may require adjustment of the medication schedule. Treatment of chronic sleep-onset insomnia begins with learning good sleep hygiene (remember, the bed is for sleeping, not reading or watching tv), but may include use of melatonin 1-2 hours before bedtime, a shortacting non-benzodiazepine drug such as zolpidem (Ambien), zaleplon (Sonata), or eszopiclone (Lunesta), a benzodiazepine such as temazepam (Restoril), or alprazolam (Xanax) or a low dose of a sedating antidepressant medication such as amitriptyline or trazodone. These medications should be used with some caution as they may cause increased confusion in elderly and/or demented patients.

Sleep fragmentation is probably the most common nocturnal complaint in PD. Several studies analyzing sleep patterns in PD have found that the sleep pattern is more frequently interrupted and that the amount of time spent in slow-wave and REM sleep (the deepest and most restorative phases of sleep) is significantly less than that of age-matched adults without PD. This type of sleep disturbance may be associated with a greater susceptibility to medication-induced hallucinations as well as excessive daytime sleepiness. Sleep fragmentation is best treated by the use of the long-acting sedative clonazepam (Klonopin) taken at bedtime. Clonazepam, rather than being immediately sedating tends to help regulate sleep and allow for a more normal nighttime sleeping pattern. Another alternative is to try and treat excessive daytime sleepiness, which often goes hand-inhand with sleep disturbance. This may involve alterations in anti-PD drugs (as many of them can cause sedation when taken during the day or disrupt sleep patterns when taken at night) or the addition of a stimulant medication. One such medication is modafinil (Provigil), which is used in narcolepsy and has been found to help daytime sleepiness and fatigue in PD. True stimulants such as methylphenidate (Ritalin) have been used for excessive daytime sleepiness in persons with PD as well, but should be used with particular care in persons with cardiovascular disease.

Particularly when dealing with issues such as difficulty maintaining sleep at night and excessive sleepiness during the day the concept of sleep hygiene is crucial. Sleep hygiene refers to the behaviors and habits that we can control that affect our bodies day-night cycling and readiness to go to sleep or be alert at a given time of day. It is especially important for individuals with sleep difficulties to set and follow regular bed/sleep and wake times with a goal of spending at least 7 but not much more than 8 hours in bed each night. Bedtimes should be chosen based on a target waking time (i.e. don't go to bed at 8 pm if you don't want to be up at 4 am!). The bed should be used only as a place of sleeping, reading and watching television should be done elsewhere. Daytime napping should be limited to one nap of no greater than 30 minutes, as longer naps do not seem to provide any greater benefit to daytime fatigue but do disrupt sleep drive for the coming night. Lastly it is vital that persons with these sleep disorders are exposed to as much light (preferably real daylight) and physical/mental stimulation during the day as possible. Light is an important synchronizer of the sleep-wake cycle and many elderly individuals and individuals with chronic illness have reduced exposure to bright light. Physical and mental activity stimulates the alerting and wakefulness centers in the brain and increase blood and oxygen flow to the brain. Most importantly, maintaining good sleep and wake habits can improve many sleep issues without the need of medications.

REM behavioral disorder (RBD), often described by patients and family members as "thrashing about" in sleep or "acting out" of dreams, is a result of impaired sleep paralysis that can manifest in patients with PD and other neurodegenerative conditions. It is more frequently encountered in males with PD than females. Patients often describe vivid dreams that can range from friendly and pleasant to being quite menacing and frightening. It is theorized that excess nighttime levels of dopaminergic medications (L-dopa and dopamine agonists) may exacerbate this phenomenon. The treatment of choice is clonazepam, which is effective in 75-90 percent of cases in the general population. Alternatively certain antidepressants, such as bupropion (Wellbutrin) and sertraline (Zoloft) may be helpful in some individuals. Conversely, individuals with newly diagnosed PD who have RBD symptoms often report resolution of this sleep disturbance when they begin treating their PD with dopaminergic medications.

Nighttime hallucinations and confusion (also referred to as psychosis) may result from any combination of cognitive impairment, dopaminergic medications, age and PD-related vision changes and lack of sleep. Psychosis may develop in up to 15 percent of persons with PD, and is most closely associated with the chronic use of PD medications. It may first appear after infection, trauma, surgery or prolonged hospitalization. Symptoms may range from a sensation that someone or something is standing at the side of or behind the person, to very detailed and often frightening visions as well as (often paranoid) delusions.

Thankfully, psychosis in PD is for the most part, mild and infrequent. The approach to treatment involves simplification of the anti-PD medication regimen and adjusting dose timing (decreasing or eliminating end of day doses), treating other sleep disturbances, providing a consistent and familiar sleep environment (the use of a night light is often very helpful), and in more severe cases, the use of atypical antipsychotic drugs. The most common drugs used are quetiapine (Seroquel) and clozapine (Clozaril). Both have been found to effectively treat psychosis without adversely affecting PD symptoms. Because clozapine carries a risk of aplastic anemia, weekly blood counts are required. As quetiapine has no such risk or requirement it is often the first choice for treating psychosis in PD. Olanzapine (Zyprexa) may be used as a third choice but is more likely to worsen PD symptoms. Medications such as haloperidol, risperidone, and chlorpromazine should be avoided as they carry a significant risk of exacerbating PD symptoms.

Nighttime urinary frequency is usually a result of autonomic dysfunction, which nearly all PD patients experience in one form or another. It is characterized by an increased sense of urgency, hesitancy and increased frequency, particularly at night. In new cases, other treatable and potentially serious causes such as infections, prostate difficulties (in men), and other renal or circulatory dysfunction should be ruled out first. For simple nighttime urinary frequency, anticholinergic medications such as darifenacin (Enablex), solifenacin (Vesicare), tolterodine (Detrol) and oxybutinin (ditropan) are often helpful. In some cases the hormone ddAVP taken as a nasal spray at bedtime has been used with good effects. If the problem persists a formal urologic evaluation may be necessary. While the causes of nighttime difficulties in PD are varied and often complex, it is important to know that potential solutions do exist, and that no one should have to "just live with it".

Johan Samanta, MD, Director-Movement Disorders Research, Banner Good Samaritan Medical Center, Clinical Associate Professor-Neurology, University of Arizona College of Medicine.

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