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REM Sleep Behavior Disorder in MSA

Symptoms and Treatments

REM sleep behavior disorder (RBD), also referred to as REM sleep without atonia (RSWA), is a condition in which muscles fail to relax during REM sleep, instead, remaining active or contracted. RSWA is diagnosed via sleep study (polysomnogram) and is distinct from sleep walking, sleep terrors, and nocturnal panic disorder. Bed partners of patients with RSWA often describe that their partners display highly active and/or violent behavior during sleep, such as flailing limbs, dream enactment, and walking from or falling out of bed. Patients often recall their dreams, which correlate with their enactment behavior. However, rather than being aggressive in nature, patients usually report their dreams as being defensive, such as fending off an attack, as opposed to being the attacker. Though not all patients with RSWA experience dream enactment, when present, it raises the potential for injury to both themselves and their partners.

RBD is regarded as a potential early sign of MSA and other alpha-synuclein disorders. Risk for developing Parkinsonism after being diagnosed with RBD is 20% to 45% within 5 years and 45% to 55% within 12 years. MSA is the most common of the alpha-synucleinopathies to be associated with RBD, with 68% to 88% of MSA patients affected. Antidepressant use increases risk of developing RBD by 500%.


Non-Pharmacological Treatment Options


Safety First

Safety concerns dictate that the first order of treatment for patients with RBD is to injury-proof the bedroom as much as possible1. Remove guns, weapons, and loose objects that could be used as weapons. Pad sharp corners of furniture. Place the mattress and box spring directly on the floor or place a second mattress on the floor next to the bed or use bed rails around the bed to cushion or prevent falls from the bed.

Specialized Alarm System

To prevent injury during episodes of RBD, an alarm system that gently awakens the patient has been devised. The technique has been reported successful in patients with a history of sleep-related injury from RBD who were not responsive to medication2. This technique may also prove to be preferable to prolonged use of pharmaceuticals, which cause side effects, such as daytime drowsiness, cognitive impairment, falls, and worsening of sleep apnea.

The alarm technique is feasible due to the fact that during REM sleep, the brain processes sounds in a way that is similar to the waking state. As a result, RBD patients are easy to awaken and are often responsive to verbal communication while involved in dream enactment. The system uses either a pressure-sensing pad or a cord attached to the bed by a magnet connected to an alarm. The other end of the cord is clipped to the patient’s bed clothes. When triggered by movement that breaks the magnetic contact, such as the patient falling out or attempting to leave the bed, the alarm plays a pre-recorded, familiar voice speaking gently and reassuringly to the patient. Serious and minor sleep-related injuries were completely eliminated during the 36-month study period. Additionally, after the first few months, fewer interventions were necessary, indicating overall improvement in REM phases of sleep. Patients who used the alarm system also reported feeling less anxious about going to sleep.



Pharmacological Treatment Options

GABA-Enhancing Drugs

Clonazepam (Klonopin), a GABA-enhancing drug in the benzodiazepine family, reduces dream enactment in REM behavior disorder3, or RBD. Clonazepam increases total sleep time, decreases episodes of waking up during the night, and improves sleep quality6. However, clonazepam can worsen sleep apnea and should not be used in patients with sleep apnea that is not managed. Clonazepam and other benzodiazepine drugs also can cause daytime sleepiness3, impair gait3, and decrease activity of serotonin, which leads to mood problems such as depression4. About 30% of patients who take clonazepam for RBD stop taking the drug or use a lower, possibly less effective, dose4 because of these disruptive side effects. For RBD patients who are able to take clonazepam, long-term use of the drug has been shown to improve the quality of non-REM sleep, increase frequency of a certain type of healthy brain wave pattern, and decrease the number of times patients wake up throughout the night5.

One alternative to clonazepam is a drug called zopiclone, which was demonstrated to be effective for 73% of patients in one study and caused fewer side effects than clonazepam4. Zopiclone, which is also a benzodiazepine drug, has been used for MSA patients who experience sleep apnea together with RBD and cannot take clonazepam. Zopiclone is not commercially available in the US but is similar to ezopiclone (Lunesta) which is currently available.


A hormone the brain manufactures to control the body’s day/night cycle, melatonin has shown some success in treating RBD. Levels of the hormone, which is available as an over-the-counter supplement, normally increase at night to induce sleep. In one clinical trial, melatonin reduced episodes of REM sleep accompanied by muscle activity by 30%7. Benefits were sustained during the second phase of the study, meaning that those who received melatonin in the first phase showed continued improvement in spite of receiving a placebo during that phase. Melatonin did not change the pattern of eye movements or reduce certain types of muscle activity during REM sleep. However, it significantly improved the overall symptom picture in many patients and completely eliminated symptoms in some patients. Melatonin also has been shown to provide sufficient improvement without adverse side effects for some patients, while others may require a combination of both clonazepam and melatonin to obtain satisfactory results3.Though there is some concern that melatonin usage might worsen orthostatic hypotension, recent evidence points to melatonin’s safety with regard to blood pressure maintenance8.

A drug called ramelteon, trade name Rozerem, sensitizes brain cells to melatonin and has been shown effective in treatment of REM behavior disorder in MSA and Parkinson’s disease9. Ramelteon improves symptoms of dream enactment and also improves the proportion of REM sleep without muscle activity. It offers an alternative to clonazepam for patients who experience side effects or for whom clonazepam is ineffective9. Potential side effects of ramelteon include dizziness, sleepiness, body aches, movement or breathing difficulties, fever, and nausea10.

Dopamine-Promoting Drugs

For some RBD patients, increasing dopamine activity can be effective. In one study, a dopamine-promoting drug called pramipexole, trade name Mirapex, improved RBD symptoms in 62% of participants11. A synergistic effect also occurred in this study, as a group that received pramipexole and clonazepam in combination showed significantly greater muscle relaxation during REM sleep than with either of the drugs by themselves.

In another study, pramipexole reduced RBD symptoms by half in most participants. Patients also reported having fewer nightmares. Pramipexole’s benefits may be attributed to reduced eye movements during REM sleep. However, while pramipexole also reduced leg movements during non-REM sleep, it did not reduce leg-muscle activity during REM sleep, a defining characteristic of RBD. Potential side effects of pramipexole include sudden and extreme sleepiness, sweating, lightheadedness, fainting, hallucinations, chest pain, dark-colored urine, and irregular heart rate or rhythm13.


A central nervous system depressant called sodium oxybate, trade name Xyrem, has been used successfully in some RBD patients who do not respond well to other medications14. This drug also can reduce daytime sleepiness in patients with sleeping disorders. Side effects of sodium oxybate include hallucinations, confusion, shallow breathing, sleepwalking, and waking up during the night15. It also can cause depression, nausea, numbness or tingling, tremor, and blurred vision15. Because sodium oxybate takes effect within minutes, it must be taken while in bed and immediately before going to sleep15. Patients usually are prescribed two doses per night, requiring users to set an alarm to awaken for the second dose. Additionally, sodium oxybate is habit-forming and can cause severe withdrawal reactions if abruptly discontinued15.

Other Agents

Other agents that have been reported as helpful are imipramine (Tofranil), carbamazepine (Tegretol), triazolam (Halcion), quetiapine (Seroquel), and clozapine (Clozaril). 16.

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