現在位置 : 醫療 > 帕金森氏症與睡眠失常- Parkinson Disease and Sleep Disorder

AA

Sleep and Parkinson's Disease
Parkinson's Disease Clinic and Research Center
Introduction/Background
Sleep-Wake Cycle
       Sleep is characterized by two alternating phases, rapid eye movement (REM) sleep and non-rapid eye movement sleep (NREM).  These phases are defined by brain wave activity, muscle activity, and eye movements.  As people start to fall asleep they enter into the lightest of the four stages of NREM sleep, Stage 1.  As sleep continues, people descend into the deeper states of sleep down through Stages 2 and 3.  Then, people move back up through these stages and enter a REM episode.  When people are awakened during REM sleep, they often report having been dreaming.
Circadian Rhythms
       This term refers to things that occur rhythmically roughly every 24 hours.  The sleep-wake cycle is one of the most obvious of our body’s circadian rhythms.  Other circadian rhythms include body temperature and secretion of many hormones.  These rhythms are controlled by a time-keeping mechanism (or clock) in our brains.  This clock can be influenced by a variety of internal and external parameters, including aging, time-zone shifts, exercise, melatonin and the light-dark cycle.  The light-dark cycle is the strongest external parameter affecting this clock.
Changes in Sleep with Aging
       As people age, they experience a number of changes in their circadian rhythms, and among the most noticeable are the changes in the sleep-wake cycle.  Older people tend to wake up earlier and go to bed earlier than they did when they were younger.  They wake up more often during the night and have more difficulty going back to sleep than younger people.  They also tend to sleep more during the daytime hours.  Therefore, if one looks at total sleep time over the 24-hour day, the total time spent sleeping changes very little but the distribution of sleep may be quite different.  Younger people experience a consolidated nighttime episode with little or no daytime sleep, whereas older individuals experience sleep episodes throughout the 24-hour day.  Daytime sleepiness is affected by two major factors:  the amount and quality of nighttime sleep, and the strength of the circadian rhythm.  In addition, older people tend to have a reduced amount of N3 or deep slow wave sleep.
Sleep Disturbances in Parkinson's Disease
       In general, research seems to indicate that people with Parkinson's disease have more sleep disruptions than similarly aged people without the disease.  The most commonly reported sleep-related problems are the inability to sleep through the night and difficulty returning to sleep after awakening, generally referred to as maintenance insomnia.  Unlike many older adults, patients with Parkinson’s disease often find that they have no trouble initiating sleep, but often wake up within a few hours and find sleeping through the rest of the night to be difficult. People with Parkinson's disease also report daytime sleepiness, nightmares, vivid dreams, nighttime vocalizations, leg movements/jerking while asleep, restless legs syndrome, inability to or difficulty turning over in bed, and awakenings to go to the bathroom.
       Although all the reasons for these sleep changes are unknown, potential explanations include reactions to/side effects of medications (e.g. dopamine agonists, levodopa) and awakening due to symptoms such as pain, stiffness, urinary frequency, tremor, dyskinesia, depression and/or disease effects on the internal clock.
Insomnia
       Insomnia is the inability to fall asleep or maintain sleep. The first step in treating insomnia is to initiate a “sleep hygiene program” as described below.  Not all of these behaviors will be appropriate for everyone.  Choose appropriate behaviors that fit your type of sleep problem:  getting to sleep, staying asleep, moving in bed, or waking to go to the bathroom.  Behaviors should be initiated one at a time, and their effect monitored over a week or more by using a diary (see evaluation, below).
Vivid Dreams and Nightmares
       Vivid dreams or nightmares can be the result of a nighttime dose of dopamine medication.  If the dreams are bothersome, the dose can be reduced or possibly eliminated.  Other medications that can cause vivid dreams are hypnotics, especially triazolam.  Some tricyclic antidepressants prescribed for depression or as a sleep aid can also cause nightmares.  If acting-out dreams by movement or vocalization is present, REM behavior disorder (RBD) must be considered.  RBD is very common in PD patients..  Evaluation may include referral for a nighttime sleep study.  Treatment is considered for safety reasons and RBD can usually be controlled with medication.
Periodic Leg Movements of Sleep (PLMS) and Restless Legs Syndrome (RLS)
       Leg movements are common in the elderly and even more so in people with Parkinson’s disease.  RLS typically occurs while at rest, and typically consists of an uncomfortable sensation in the legs that is relieved with movement.    PLMS are jerking movements of the legs during sleep that are not uncomfortable but can result in nighttime awakenings.  PLMS often do not bother an individualbut can rarely be associated with sleep disruption. The movements are often reported by a bed partner.  Both PLMS and RLS can result from medication side effects or medical conditions other than Parkinson's disease.  After medical evaluation, treatment can include continuous release levodopa, dopamine agonists, and clonazepam.
Sleep Apnea
       Although not necessarily more common in people with Parkinson's disease, sleep apnea is common in older adults.  Obstructive sleep apnea (period of time with no or little breathing) is usually associated with snoring and complaints of excessive daytime sleepiness.  Evaluation for apnea is by a nighttime sleep study and treatment is implemented by a sleep specialist.

Excessive Daytime Sleepiness and Unintended Sleep Episodes
       For people with Parkinson's disease, daytime sleepiness may be caused by the many problems that interfere with nighttime sleep, resulting in sleep deprivation, or from the sedating effects of antiparkinsonian medications.  People with excessive daytime sleepiness tend to fall asleep during the day, and depending on the situation, can pose a safety hazard to themselves and others.  Often the sleep episode is very short, and the person is unaware of having fallen asleep.  Unintended sleep episodes have been attributed to dopamine agonist medication.  However, research has shown that these episodes are not unique to the use of these medications.  The unintended sleep episodes can be seen with any of the dopamine medications, including levodopa, and typically are evident with high doses.
       Treatment for excessive daytime sleepiness should be discussed the individual's physician.  A thorough evaluation of all medications, their side effects, and interactions must be considered.  Sleep apnea, PLMS, and RLS need to be treated if present.  PD medications can be changed or doses adjusted.  For a significant minority of patients with Parkinson's disease, daytime fatigue is related to the disease process itself and even when other causes are excluded and medications are adjusted, they may still feel tired or fatigued during the daytime.  Scheduled naps prior to 3pm and/or alerting medications such as modafinil and methylphenidate can be considered and are sometimes helpful.  Caffeine may be an appropriate treatment, if not taken too late in the day.

Steps to Better Sleep Hygiene:  Behavioral Changes
Getting to sleep
● Regular risetime and bedtime—by doing this every day, you can help your internal clock by providing regular cues, thereby improving your sleep-wake cycle.  This should help in getting to sleep faster and reduce the number of nighttime awakenings.
● Get plenty of bright natural light exposure, preferably in the morning along with exercise. This will give your internal clock a strong cue to run on time.
● Avoid stimulants, such as caffeine and nicotine.  Avoid caffeine-containing drugs, drinks, and foods for eight hours before bedtime.  Avoid tobacco in the evening. This will help with getting to sleep and staying asleep.
● Avoid thoughts or discussions about topics that cause anxiety, anger, and frustration before bedtime.  This will help with getting to sleep.
● Institute and maintain a definite bedtime routine that is relaxing to help signal the body that sleep is to occur soon.  Examples might include: a bath, brushing teeth, a small glass of warm milk (4-6 oz.), or a light snack. This will help with getting to sleep and will reduce the need to awaken due to hunger.
● Reserve the bedroom and especially the bed for sleeping. Avoid activities like reading and watching television in bed. Your body needs cues to associate the bed with sleeping and not other activities.
● If you nap, try to do so at the same time every day and for no more than 1 hour, and ending by 3pm.
● Don't spend more than 15 minutes trying to sleep—if you cannot sleep after 15 minutes get out of bed and engage in a quiet activity.  Ideally, the activity should be in low light and sedentary, for example, listening to soft relaxing music or meditating, not reading with a bright light or watching television.  Return to bed only when you are sleepy.

Staying asleep
● Minimize light and noise at bedtime and throughout the night. This will reduce stimulation and promote normal function of the body’s melatonin rhythm that helps to promote and maintain sleep. Ear plugs may be helpful if the environment is noisy. Avoid alcohol within 4-6 hours of bedtime.  When taken at bedtime, alcohol may help induce sleep but disrupts sleep later in the night.
● Avoid heavy exercise within 6 hours of bedtime.  Exercise increases the body temperature. Sleep onset normally occurs as the core body temperature is decreasing. Artificially increasing body temperature can therefore give the wrong cue to the brain and contribute to sleep disruption.
● Avoid heavy late night meals. They can interfere with the ability to fall and stay asleep. A light snack at bedtime, however, may promote sleep.  Good bedtime snacks include dairy products and carbohydrates.
● Assure the bedroom environment is right for sleep: comfortable bed, dark, quiet, and a cool temperature for sleeping.
● Avoid looking at the bedroom clock if you awaken. If necessary, face the clock to the wall.

Moving in bed
       Use of satin sheets on the bed or pajamas to help with moving in bed can minimize the effects of stiffness or pain. (Also, see antiparkinsonian medications, below)
Waking to go to the bathroom
•Decrease evening fluids (3-4 hours before bedtime) to lessen the chance of waking up to go to the bathroom.  Make sure that you drink plenty of fluids in the morning hours.  If you often get dizzy when you stand, sit on the side of the bed for a moment or two while flexing your leg muscles before you stand up.
•Go to the bathroom immediately before retiring.
•A commode placed at the bedside will minimize the activity and necessary light needed for nighttime toileting.

 Evaluation of Sleep Hygiene Program: Sleep Diary
       Monitoring the effectiveness of behavior changes is best done by keeping a diary.  The table below depicts a sample diary that could be kept by the bedside and filled out upon arising by the patient or caregiver.  If daytime sleepiness and napping are problems, items can be added to record the number, time, and duration of napping episode. The diary can be carried with the patient.

Medications for Sleep
Sleeping pills
       Historically, medications known as benzodiazepines have been widely used for insomnia in all ages.  These medications are classified as short-, intermediate-, or long-acting.  Short-acting benzodiazepines (e.g., triazolam) are useful when getting to sleep is the primary concern.  However, their side effects include confusion, agitation, impaired motor performance, and amnesia.  Intermediate-acting benzodiazepines (e.g., temazepam) are useful when sleep maintenance and/or early morning awakening are the primary symptoms.  Long-acting benzodiazepines (e.g., flurazepam) are useful for getting to sleep and sleep maintenance, and when insomnia occurs with daytime anxiety.  However, these drugs are often associated with daytime sleepiness and confusion.  Newer, nonbenzodiazepine drugs, zolpidem (Ambien®), zolpidem CR (Ambien CR®), zaleplon (Sonata®) and ezopiclone (Lunesta®) have recently become available.  These newer drugs seem to have a better safety profile, fewer complications with long-term use, and produce fewer daytime symptoms than the older sleeping medications.
Antidepressants
       Tricyclic antidepressants and trazadone are frequently prescribed for sleep disturbances.  Since depression is a common cause of sleep disturbances in patients with Parkinson's disease, these drugs can help treat both problems.  The more sedating tricyclics (e.g., amitryptiline) are used to assist in sleep initiation and maintenance.  These drugs must be monitored carefully as they have a high incidence of side effects such as constipation and dry mouth.
Antiparkinsonian medications
       All of the antiparkinsonian medications can either help or hinder sleep depending on the problem.  If symptoms of Parkinson's disease are causing the sleeping problem, the longer acting levodopa formula at bedtime may help.  Adding an agonist or COMT inhibitor may also maximize levodopa activity to prevent breakthrough symptoms during the hours of sleep.  Levodopa can also have an alerting effect, and may need to be reduced at bedtime.  Selegiline is also known to cause insomnia.
Bladder medications
       To reduce the frequency of urination, medications such as oxybutynin and tolterodine are often used.  These prescription medications work by relaxing the bladder.
Other insomnia interventions
       In addition to a sleep hygiene program, other interventions may also be useful.  These include sleep restriction programs, chronotherapy, bright light therapy, relaxation training, meditation, biofeedback, and cognitive therapy.
 ---- 2014, The Regents of the University of California
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Sleep Disturbances
Parkinson Disease Foundation
       Most people with Parkinson's find it difficult to sleep through the night. Rigid muscles, tremors or stiffness at night, or not being able to roll over in bed can all interfere with sleep, as can the frequent urge to urinate.  In addition, many people with Parkinson's experience vivid dreams or hallucinations and act out their dreams, violent nightmares, a problem called “REM sleep behavior disorder.” Recent research suggests that REM sleep behavior disorder sometimes begins even before motor symptoms are diagnosed in Parkinson's.
       Medicine, such as clonazepam, is available for this problem. For some people, an extra dose of anti-Parkinson medications or a sleeping medication can help alleviate sleep disturbances. In other cases, sleep disturbances may be caused by medical conditions not related to PD. For example, a disruption in breathing called sleep apnea can also interfere with sleep, and can be treated separately from PD. Getting a good night's sleep is essential for people with Parkinson's, so if you are having any of these symptoms you should discuss them with your doctor.
       Not sleeping well at night often causes people with Parkinson's to feel drowsy during the day. Anti-Parkinson medications and the disease itself can also contribute to excessive daytime sleepiness. A pattern of falling asleep suddenly for short periods of time, similar to narcolepsy, can interfere with daily life. Adjusting antiparkinson medications, or taking a stimulant during the day—under a doctor's supervision, of course—may help alleviate sleepiness during the day.
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商品名 : RISPERDAL  (1mg or 2mg)
中文名 : 理思必妥錠  (1mg or 2mg)
學名 : Risperidone 
藥品許可證 : 衛署藥輸字第022768號
健保局藥理類別 : 281608   抗精神病藥 
類別 : PHR      劑量 : TAB
藥理作用 :  本品為benzisoxazole衍生物，具選擇性之單胺拮抗作用，對Serotoninergic 5-HT及Dopaminergic D2接受體具高度親和力。本品亦可與 α-adrenergic接受體結合，對H1-histaminergic及α-adrenergic接受體之親和力較低，而對Cholinergic接受體則無親和力。本品為強效之D2拮抗劑，可改善精神分裂症之活性症狀，並較其他典型之精神阻斷劑不易引起運動功能抑制及強直性昏厥(catalepsy)。
適應症 :  本品適用於急慢性精神分裂症與其他精神病狀態之活性症狀(如幻覺、妄想、思考障礙、敵意、多疑)與負性症狀(如情感遲滯、情結與社交退縮、缺乏言談)。本品亦可減輕伴隨精神分裂症產生之情感症狀(如憂鬱、愧疚感、焦慮)。
精神異常引起之相關症狀。
用法用量 :
1. 病患應於三天內逐漸調整劑量至每天兩次，每次3mg。無論急性或慢性病人，服用本品之劑量為第一天兩次，每次1mg；第二天兩次，每次2mg；第三天兩次，每次增加至3mg。第三天以後，劑量可持續不變或視個別情況而加以調整。一般最適當之劑量為每天兩次，每次2～4mg。投與劑量超過每天兩次5mg時，其療效未必優於較低劑量，且可能導致錐體外徑副作用。由於每天兩次，每次服用8mg以上之安全性未經評估，請勿超過此劑量。如需加強鎮靜作用，可添加benzodiazepine 與本品併用。
2. 老年：建議起始劑量為每天兩次，每次0.5mg。此劑量可視個體差異調整，維持每天兩次，每次增加0.5mg至每天兩次，每次1.2mg。在得到進一步治療經驗以前，老年患老使用本品時應特別小心。
3. 孩童：小於15歲孩童之治療經驗尚不足。
4. 腎或肝臟疾病：建議起始劑量為每天兩次，每次0.5mg。此劑量可視個體差異調整，維持每天兩次每次增加0.5mg至每天兩次，每次1～2mg。
5. RISPERDAL CONSTA每兩週使用一次,使用內附之安全針注射深層臀部肌肉。兩臀須交替注射。不能靜脈注射。本藥限由醫師使用。
藥動力學 : 
1. 本品經口服後可完全吸收，於1～2小時後達血中最高濃度。本品之吸收不會受食物影響，故可單獨服藥或與食物併服。
2. 本品部份代謝成具類似藥理作用之9-hydroxy-risperidone，此代謝物與 risperidone共同形成有效之抗精神病成份。本品另一代謝途徑為N-去羥基化。精神病患者口服本品後，本品之排除半衰期為30小時。9-hydroxy-risperidone與有效抗精神病成份之排除半衰期則為24小時。多數病患血中之risperidone濃度可於一天內達穩定狀態，而9-hydroxy-risperidone約需4～5天方可達穩定狀態。
副作用 :
本品耐受性極佳，在許多情況下很難分辨是副作用或疾病本身之症狀、於臨床試驗中使用本品所觀察到的副作用如下：
常見：失眠、精神激動、焦慮、頭痛、光敏感、體温調節能力降低。
罕見：嗜眠、疲倦、眩暈、注意力受損、便秘、消化不良、噁心、腹痛、視力模糊、異常勃起、勃起困難、無法射精、無高潮、小便失禁、鼻炎、皮疹及其他過敏反應、本品較傳統抗精神分裂症藥物少引起錐體外徑作用、然而，少數病例仍可能產生下列錐體外徑症狀：震顫、肌肉僵直、多唾液流症、運動徐緩、靜坐不能、急性肌緊張不足、這些症狀通常極為輕微，如降低劑量或必要時投與抗巴金森藥物，症狀可消除。
交互作用 : 
1. 本品併用其他藥物之危險性尚未經系統性評估。由於本品主要作用於中樞神經系統，故併用其他作用於中樞之藥物時應小心。
2. 本品可能拮抗Levodopa及其他多巴胺作用劑之效應。
3. Carbamazepine含降低血漿中本品的有效抗精神病藥成份C其他會產生誘導肝酵素合成的化合物也會有相同的效應。因此，當Carbamazepine及會產生誘導肝酵素合成的藥物停止服用時，本品的服用劑量需重新評估，必要時須減量。
4. Phenothiazines、三環抗抑鬱劑與某些β-阻斷劑可能提高risperidone之血中濃度，但並不是屬於抗精神病作用的部份，本品與蛋白結合率高之藥物併服時，不會影響彼此與血漿蛋白結合。
禁忌 : 已知對RISPERDAL或其任一成份過敏之病人禁用。

給付規定 :  
1.2.2.1.Clozapine（如Clozaril）
1.限精神科專科醫師使用。
2.前18週使用時，每週需作白血球檢驗，每次處方以七日為限，使用18週後，每月作一次白血球檢驗。
3.申報費用時，應檢附白血球檢驗報告。
1.2.2.2.Second generation antipsychotics (簡稱第二代抗精神病藥品，如clozapine、olanzapine、risperidone、quetiapine、amisulpride、ziprasidone、aripiprazole、paliperidone等)：(91/9/1、92/1/1、92/7/1、94/1/1、95/10/1、97/5/1、99/10/1)
(發文日期：中華民國99年9月9日,發文字號：健保審字第0990074769號)
1.本類製劑之使用需符合下列條件(95/10/1、97/5/1、99/10/1)：
(1)開始使用「第二代抗精神病藥品」時需於病歷記載：
醫療理由或診斷，以及臨床整體評估表 (Clinical Global Impression，簡稱CGI) 之分數。
(2)經規則使用六至八週後，需整體評估其療效，並於病歷記載：臨床整體評估表之分數。
(3)日劑量超過下列治療劑量時，需於病歷記載理由：
clozapine 400 mg/day
risperidone 6 mg/day
olanzapine 20 mg/day
quetiapine 600 mg/day
amisulpride 800mg/day (92/1/1)
ziprasidone120mg/day (92/7/1)
aripiprazole 15mg/day (94/1/1)
paliperidone 12mg/day (97/5/1）
2.本類藥品不得使用於雙極性疾患之鬱症發作。(95/10/1)

注意事項 : 
1. 由於本品之α-阻斷作用，可能產生直立性低血壓，在最初劑量調整期間更應特別注意。本品應小心使用於心臟血管疾病患者(如心臟衰竭、心肌梗塞、傳導異常、脫水、血容積減少或腦血管疾病)。並依(用法用量)欄之建議逐漸調整劑量。如有低血壓現象應考慮降低劑量。
2. 由於具多巴胺接受體拮抗作用之藥物會引起遲發性運動困難，特徵為節奏性不隨意運動，尤以舌頭與面部最為顯著，而本品亦具有此項可能性。會報導錐體外徑症狀為產生遲發性運動困難之危險因子。由於本品較不易產生錐體外徑症狀，故其引發遲發性運動困難之危險性較其他傳統抗精神分裂症藥物低。一旦產生遲發性運動困難之徵兆或症狀，應考慮中止所有抗精神病藥物之治療，使用傳統抗精神分裂症藥物會引起抗精神分裂症藥物惡化症候群，特徵為發熱、肌肉僵直、自主不穩定、改變意念及CPK濃度升高。本品也不能完全排除產生上述症狀之可能性。在此類病例中，包括本品之所有抗精神病藥物治療者應停止。
3. 老年與腎或肝功能不全患者，建議起始劑量及隨後之增量皆應減半。
4. 帕金森氏病患服用本品時應小心，因為可能導致病情惡化。傳統抗精神分裂症藥物已確定曾降低癲癎發作閥值。雖然本品之試驗並未顯示此危險性，用於治療癲癎病人時仍應小心。
5. 由於可能增加體重，應告知病人避免飲食無度。
6. 本品可能會干擾需要警覺性之活動。因此，應警告病人在恢復個人敏感度以前不得駕駛或操作機械。
7. 服用本品可能皮膚會對光敏感，不宜暴曬陽光下。
藥品保存方式 : 藥品應置於攝氏 15 ~ 25 度乾燥處所；如發生變質或過期，不可再食用。 
 --- (光田綜合醫院)
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RISPERIDONE   利培酮 ( 理思必妥 )
商品名 :
台灣健保藥品 --- Anxilet 悠寧膜衣錠 , Apa-Risdol 鴻汶理思得膜衣錠, Apo-Risperidone 安保瑞思得內服液劑 , Blue-Up 易憂安膜衣錠, Perisdone 普利思妥膜衣錠, Respor 理斯本內服液, Ripedon 思定妥膜衣錠, Riper 理波膜衣錠, Risdal 利生妥膜衣錠 , Risdine 利思暢 內服液劑 , Risdon 樂思得 膜衣錠, Risdone 雷司動錠, Rispal 勵思膜衣錠, Risperdal 理思必妥膜衣錠, Risperdal Quicklet 理思必妥速溶錠, Riston 理思通膜衣錠 , Seridol 賽力多內服液劑, Serotone 思悅通內服液劑, Spiterin 思特寧膜衣錠.
美國 ---  RisperDAL; RisperDAL M-Tab
藥物作用 :
      Risperidone 為第二代『非典型』精神病藥物，主要用於治療精神分裂症之相關症狀，雙極性疾患之躁症發作。治療失智症病人具嚴重攻擊性，或精神分裂症類似症狀。 它也可與鋰鹽(Lithium) 或valproic acid合併使用以控制躁鬱症。除了產品標籤所核准精神分裂適應症外﹑非典型精神病藥物常被醫師廣泛的運用到治療焦慮症﹑強迫症等。
     非典型精神病藥物的作用機制與大多數精神藥物一般，仍然未知﹑但相信它們主要作用於腦部神經傳導物質多巴胺(Dopamine)或血清素(Serotonine) 的感受器官而產生療效。相較『傳統』的抗精神藥物，『非典型』抗精神病較不會引起明顯的錐體外徑副作用。『非典型』抗精神病藥除了可以改善精神分裂症的正性症狀如幻覺﹑妄想﹑行為怪異及語無倫次等，對於負性症狀如社交退縮﹑缺乏邏輯﹑情緒冷漠﹑興趣缺乏等也具有療效。
用法 :
      Risperidone 通常一天服用一至二次，空腹或與食物併用均可，此藥之普通藥片可以壓碎服用，但是長效型錠劑應該整顆吞服，不可咀嚼或壓碎服用。由於藥物具有鎮靜安眠的特性，如果一天服藥一次﹑最好安排在睡前使用。當開始服藥，尤其在前幾個星期的治療期間，醫生會依照個人的臨床症狀，使用較低劑量並逐步增加劑量以降低副作用的可能，待穩定後再保持每日維持劑量，病患應該依照醫師指示服用。在服用藥物之前，如果有不了解的部分，應該要求醫師或藥師做詳細的解釋。此藥的藥效通常需2至4週才會發生作用，病患應遵循醫師指示服藥﹑在未經醫師許可前，不可自行停藥。

注意事項 :
       禁忌症：對Risperidone 以及Paliperidone藥物或其賦形劑成分過敏者不該使用此藥。
     如果懷孕，對藥物過敏，經常飲用大量的酒，腎臟病﹑心絞痛﹑心跳不規則，乳癌患者﹑肝臟疾病，酒精成癮﹑藥物濫用﹑癲癇發作等，醫師需要針對這些情況謹慎用藥，因此在使用此藥前，應該先通知醫師。
       美藥管局(FDA)曾發出警訊指出﹑使用『非典型』精神病藥物可能會使老年癡呆症患者帶來嚴重不良反應。根據臨床結果顯示﹑患有老年癡呆的年長精神病患在使用『非典型』精神病藥物的死亡率(4.5%)較使用安慰劑的對照組(2.6%)高出約1.6倍。通報並指出雖然病患的死因不同﹑但大多與心臟疾病或細菌感染有關﹑死亡率的增加是否與精神藥物的使用或病患具有的某些特性有關﹑還無法進一步的確定。目前為止使用Risperidone治療患有老年癡呆的精神病患是不適當的。
       所有抗精神病藥物包括Risperidone可能發生極罕見﹑有潛在致死性的復合症狀群,稱為『抗精神病藥惡性症狀群(NMS)』此一副作用發生的機率極為低﹑但與藥物的劑量及使用時間長短無關﹑任何服藥期間都可能發生﹑但以最初用藥的三十天內發生機率最高。NMS主要症狀為心跳速率增快或失常﹑肌肉無力﹑肌肉痛﹑肌肉僵硬﹑血壓不穩﹑呼吸急促，冒汗﹑脉博不规律﹑發高燒﹑精神狀態改變﹑顫抖﹑橫紋肌溶解進而產生腎衰竭等。如果有以上症狀發生﹑應該立即通知醫師
       使用抗精神類藥物較需考慮的副作用是藥物所引起的錐體外徑症狀。雖然『非典型』抗精神病藥不同於『傳統』的抗精神藥物，比較不會引起錐體外徑副作用﹑但是病患在服藥期間仍需留意服藥後的反應﹑如有症狀發生﹑應該咨詢醫師的意見。常見錐體外徑症狀為無法控制地眨眼睛﹑手臂或雙腿有抖動的現象﹑舌頭經常往外突出﹑嘴巴歪斜﹑眼球上吊﹑頸向後仰，無法克制想起來走動的感覺。
       Risperidone可能使體內血糖濃度增高﹑導致糖尿病及其它併發症的發生。身體過於度肥胖及有糖尿病家族史的病患﹑發生的機率最大。病患在使用藥期間應該定期測量血糖﹑常運動及保持適當體重﹑並隨時留意糖尿病可能症狀如：容易饑餓和口渴﹑感覺疲勞  視力減弱﹑尿頻等。若出現高血糖症狀時應立即測量血糖值。假若在危急情況下﹑應該立即通知醫師。
       Risperidone只能用來控制病情，但不能治癒病症。經過一陣子服藥後，即使感覺病情穩定，仍需繼續服藥，更不可隨意停藥。突然停藥可能使病況轉壞或再次發作，同時也可能產生噁心，嘔吐，失眠或昏睡等戒斷症状。如有必要停藥時，醫師通常會逐漸減少藥量，然後再停。
       此藥會降低身體排汗及散熱的能力。因此，應該避免在陽光下及過熱的地方站立太久﹑以免中暑;同時，洗澡時也應該避免水溫太熱﹑散熱不良及血壓下降而造成暈倒。
       此藥可能會讓您覺得眩暈或嗜睡，除非已經適應了藥物的作用，當開車或操作危險機械時，應該格外小心謹慎。如果感覺眩暈，緩慢站立或坐起，應該會減少此一現象。酒精會增加藥物嗜睡的副作用，應當避免或限制酒量。
       Risperidone可能會造成姿態性低血壓症，這是由於病人由平躺的姿勢突然改為直立時，由於血壓迅速降低且無法在短時間提升造成頭昏目眩，視力模糊，虛弱﹑甚至昏厥等不適症狀。這種現象通常在最初給藥的3-5天以及劑量調整期間最常發生，對於平常血壓過低的病人，剛開始服藥時應該特别小心，不過如果能夠緩慢地站立或坐起，應該會減少此一現象。
懷孕及哺乳
        美國藥管局(FDA)將此藥歸類為懷孕類別C級：動物生殖研究顯示對胚胎有不利影響，但缺乏孕婦對照研究確認藥物是否安全。盡管有潛在風險，但若藥物利益大於危險，仍可考慮使用。
        澳洲藥管局(TGA)懷孕用藥分級C級:    此藥品由於其藥理特性，曾經造成或懷疑有可能會引起胎兒不良影響但不會引起畸形。這些不良影響是可逆的，在停藥後應該可以恢復正常。
       動物研究顯示﹑暴露於Risperidone下有增加胎兒死亡率的可能。懷孕最後三個月使用藥物有可能使新生兒產生可逆的錐體外症候群或戒斷症狀。此症狀包括情緒激動﹑哺乳困難﹑肌張力亢進﹑張力減退﹑呼吸困難﹑嗜睡和顫抖等。新生兒的這些症狀可能會自行康復或需要住院治療。此藥對人類孕婦沒有足夠和良好對照的研究﹑如果懷孕就應該通知醫師。除了用藥的優點勝於對胎兒的危險性，並且經過醫師的許可外，孕婦應該避免服用此藥。
      婦女使用精神藥物期間如果發現懷孕。在醫師評估病情及許可前﹑不該自行停止服藥。
     Micromedex公司哺乳評級結論﹕ 對嬰兒的風險性還無法排除。
    (由於現有資料不足或專家結論不同情況下﹑無法充分證明哺乳期間使用藥物是否會增加嬰兒的風險。婦女若考慮使用母奶哺乳嬰兒﹑應該權衡藥物的優點或藥物對嬰兒潛在的風險性。)
      Risperidone 及其代謝後的產物會經由母乳排出。餵奶的母親在使用此藥時，應該停止餵食母乳，而改用其他的乳製品取代或在停藥後的12週後才可使用母乳餵食嬰孩。
副作用 :
     Risperidone最常見的副作用為：嗜睡（3％至49％;）﹑便秘（8％至21％）﹑食慾增加（4％至47％）﹑消化不良（2％至10％）﹑噁心（4％至16％）﹑頭暈（4％至16％）﹑口乾（4％至15％）。其它可能副作用包括：腹瀉﹑胃灼熱﹑唾液增加﹑體重增加﹑胃痛﹑焦慮﹑激動﹑躁動﹑多夢﹑失眠﹑性能力降低﹑視力問題﹑肌肉或關節疼痛﹑皮膚乾燥﹑排尿困難﹑胃部不適﹑頭痛等。這些副作用，通常在服用藥物一陣子後，應該會漸漸消失。如果這些副作用達到困擾你的程度，或者經過一段時間後，這些症狀還不能完全消除，就應該通知醫師。
     此藥較嚴重的副作用為: 心跳快速或不規則﹑ 皮膚或眼白泛黃﹑肌肉僵硬﹑舌頭不自主伸縮﹑吞咽或呼吸困難﹑身體扭曲呈現怪異姿勢眼球上吊不能向下望﹑眼痛或視覺改變﹑脖子僵硬﹑發燒﹑短暫﹑或不規則心悸﹑視力模糊﹑說話速度變慢或困難﹑嘴巴歪斜﹑ 頸向後仰﹑顛癇或抽搐等等。通常這些副作用發生的機率較低，但是如果發生時，應該盡快通知醫師。
     以上所列舉不包含所有可能副作用﹑詳細藥物資料﹑請
參閱原廠說明書或訊問醫師意見。
忘記用藥 :
      如果忘記服藥，應該在記得時，立即服用。但是，如果距離下次服藥的時間太近，就應該捨棄所遺忘的藥物，恢復到下次正常服藥的時間，千萬不可一次服用雙倍的劑量。

Parkinson's Disease and Sleep
Source: National Sleep Foundation
       Parkinson's disease is a disorder of the central nervous system that causes a loss of cells in the part of the brain that controls movement. People with Parkinson’s disease experience a range of symptoms, including tremor (shaking), rigidity (stiffness), slowness of movement, and problems with balance and coordination. They may also have memory problems, depression, and sleep complaints. Parkinson's disease is both chronic and progressive, meaning that once it occurs it does not go away and symptoms generally get worse over time; the rate or speed of progression is different from person to person.
       Parkinson’s disease can be idiopathic, meaning that it occurs with no known cause. In this case it probably develops by some interaction between a person's genes and their environment. It can also be secondary, occurring as a result of another disease, exposure to certain drugs, or as a result of repeated head trauma. According to the Parkinson's Disease Foundation, between 15 and 25 percent of people with Parkinson's have a relative with the disease, suggesting that for some people it may be inherited. Age is also a risk factor, with older people being more likely to develop Parkinson’s disease than younger people, according to the National Institute of Neurological Disorders and Stroke at the National Institutes of Health. Exposure to toxins may also play a role but the nature of that role is not well understood.

       Sleep problems may be an early sign of Parkinson’s disease, even before motor symptoms have begun. Some of the common sleep problems for Parkinson’s patients include:
● Insomnia
● Excessive daytime sleepiness
● Nightmares
● Sleep attacks (a sudden involuntary episode of sleep)
● REM sleep behavior disorder (acting out dreams during sleep)
● Periodic leg movement disorder (PLMD)
● Restless legs syndrome (RLS)
● Sleep apnea
● Nocturia (frequent nighttime urination)

       A recent study by UCLA researchers found an association between Parkinson's disease and narcolepsy, a disorder caused by the brain's inability to regulate sleep/wake cycles normally. The study revealed that patients with Parkinson's disease and those with narcolepsy both display a loss of orexin/hypocretin (Hcrt) cells in the brain and that loss of Hcrt cells is correlated with severity of PD. However, there is no reason to believe that narcolepsy patients are at increased risk of developing Parkinson's disease. According to study author Jerry Siegel, PhD, professor of psychiatry and biobehavioral sciences at the Semel Institute for Neuroscience and Human Behavior at UCLA, the cause of the hypocretin cell loss in Parkinson's is likely to be quite different from the cause of this cell loss in narcolepsy.
       There may also be a connection between REM sleep behavior disorder (dream–enacting behaviors during sleep) and the subsequent development of Parkinson’s disease. In one study, researchers found that up to 75% of patients with REM behavior disorder went on to develop a Parkinsonian disorder, presumably Parkinson’s disease. In addition, people with Parkinson’s disease are at higher risk for restless legs syndrome (RLS) and periodic leg movement disorder, two conditions that may seriously disrupt sleep. However, there is no evidence that RLS or PLMD are risk factors for Parkinson’s disease.
       In addition to sleep problems, people with Parkinson's disease often experience sleepiness during the daytime. In fact, one study found daytime sleepiness in 76% of Parkinson’s patients. These sleep-related symptoms can have a major impact on quality of life for Parkinson’s patients and treatment for these problems should be integrated with their therapeutic regimens.
       Because of the mystery surrounding the origin of Parkinson’s disease, a great deal of research has been done on this problem. We know that the symptoms of Parkinson’s are primarily the result of the gradual loss of dopaminergic cells (neurons that release dopamine, a neurotransmitter that activates dopamine receptors) in the brain. Some Parkinson’s research has focused on the relationship between Parkinson’s and both the timing and duration of sleep. For example, a 12-year study by researchers at the National Institute of Environmental Health Sciences of the U.S. National Institutes of Health found that among nearly one million nurses, working the night shift was associated with a lower risk of Parkinson’s disease. They also found that long sleep (sleeping 9 hours or more) was associated with a higher risk.
       People with Parkinson’s disease have a shortened life expectancy and may find it difficult to maintain their quality of life. Striving to maintain healthy sleep habits can help Parkinson’s patients with both the physical and psychological symptoms of their disease.

SYMPTOMS:
       The hallmark symptoms of Parkinson's disease are tremor, rigidity, slow movements and problems maintaining balance. Other symptoms may include difficulty walking, talking, eating, or carrying out other simple tasks. Parkinson’s patients also suffer incontinence, constipation, and sexual dysfunction and are at higher risk for developing depression, anxiety, memory, and emotional problems.
       Because Parkinson's disease is associated with "sleep attacks," patients may be suddenly overcome with drowsiness and fall asleep – regardless of what they are doing. This is particularly dangerous for those patients who are still driving, operating equipment (even kitchen and lawn equipment or other tools) or caring for dependents.
       Not everyone with Parkinson's disease develops all or even most of the symptoms described above. The rate at which the disease progresses is also variable, with some people experiencing a rapid worsening of symptoms shortly after being diagnosed and others spending many years with only mild symptoms.

TREATMENT:
       With Parkinson’s disease, there is a gradual loss of dopaminergic cells in the brain. There is no treatment for slowing or reversing this process, but there are drugs used to treat the symptoms that result. These drug therapies can dramatically improve quality of life for Parkinson's patients. Here are some of the most common types:
● Dopaminergic agents – a class of drugs made from the neurotransmitter dopamine; these are the most effective therapies for Parkinson's patients, improving all of the motor symptoms. Some dopaminergic medications may cause sleepiness.
● COMT inhibitors – block an enzyme that breaks down dopamine; decreases "off time" in Parkinson's patients, which is a period of impaired movement.
● MAO-B inhibitors – prolong the action of dopamine in the brain to improve symptoms; may cause insomnia.
● Anti-cholinergics – restore the balance between acetylcholine and dopamine, thus improving tremor and rigidity.
● Amantadine – an antiviral drug that improves tremor, rigidity, and movement control.

       Following diagnosis and the start of treatment, Parkinson's patients may experience a reduction of symptoms. This is called a "honeymoon." After a few years, the honeymoon ends and symptoms intensify, especially the motor symptoms.
       People with Parkinson’s disease often have excessive daytime sleepiness. They also fall into REM sleep more quickly than the average person, according to their brain activity. These are both symptoms of narcolepsy and although there is no evidence that narcolepsy is a risk factor for Parkinson’s disease or vice versa, sleep-related symptoms in patients with Parkinson’s may be successfully treated with drugs that are used for narcolepsy, including stimulants for daytime sleepiness and sleeping medication for nighttime sleep. Bothersome dream-enacting behaviors often respond favorably to clonazepam, a sedative medication.
       As Parkinson’s disease progresses and symptoms get worse, sleep problems may become more serious. For example, pain and uncontrollable movements may cause severe insomnia. Nighttime symptoms may be improved by taking Parkinson’s medication later in the day or by taking hypnotic sleep aides.
       Insomnia may also be caused by certain medications used to treat Parkinson’s symptoms. In that case, taking medication earlier in the day may improve sleep. Keep in mind that any change in medication – including the addition of sleep aides or the timing of administration - should be prescribed by a physician. Sleep aides you can buy without a prescription usually contain diphenhydramine, an anti-histamine, which blocks absorption of dopamine.
       Daytime sleepiness may also increase as Parkinson’s disease progresses. Using stimulant or alerting medications during the day may prevent sleep attacks and help patients avoid excessive napping, which may contribute to insomnia. In addition to drug therapies, behavioral techniques should be used for sleep and sleepiness problems in Parkinson’s patients.

COPING:
       Coping with Parkinson’s disease isn’t easy and will depend on the type and severity of the symptoms. However, there are certain things you can do to minimize symptoms, including taking medication as prescribed and getting healthy sleep. Here are some sleep tips for Parkinson’s patients:
● Keep a regular sleep schedule, going to bed and getting up at the same time each day.
● Take sedating medication late enough in the day so that you don’t get an increase in symptoms as you are trying to sleep.
● Use satin sheets and pajamas to help with getting in and out of bed.
● Minimize beverages before bedtime to help avoid nocturia (frequent nighttime urination).
● Get exercise and exposure to light early in the day.

       If the Parkinson’s disease is not advanced then behavioral therapies may be useful to try. Behavioral techniques may include changing attitudes about sleep, learning new sleep habits, and sticking to a regular sleep schedule.
       Parkinson’s patients are encouraged to spend time outdoors and to exercise each day, preferably in the morning or shortly after waking. Light therapy may also help normalize the sleep/wake cycles of Parkinson’s patients, especially those who may be unable to spend time outdoors.
       In general, the quality of life for patients with Parkinson’s disease may be optimized with support and recognizing the opportunities to make lifestyle adjustments. That is why support groups for patients, family members and caregivers can be important. They introduce the participants to caring and supportive individuals and you can learn what decisions others have made and what works best. This can help avoid getting "stuck" at one stage and can help to take advantage of a useful idea. Support groups may be in your local community or you may be able to participate in information exchanges online. Visit the National Parkinson Foundation support group information page to find support resources in your area.
 --- (Reviewed by David Rye, MD, PhD, and Mark Mahowald, MD.)