RLS and PLMD: Part I

In previous posts we touched on how limb movement disorders are linked to air swallowing in PAP users and why leg jerks are often diagnosed in error when they are actually a disguised form of a subtle breathing event (aka UARS, RERAs, or flow limitations), which was not adequately titrated away during a PAP therapy polysomnogram.

Now, we will spend sufficient time to directly target limb movement disorders, because they are clearly disruptive to sleep among those who suffer from them independently, that is, in addition to suffering from sleep apnea, some patients experience co-occurring leg movements, awake (restless legs syndrome, RLS) or asleep (periodic limb movement disorder, PLMD). Our focus will be on learning to recognize independent limb movement disorders and how to treat them.

By definition, RLS generally occurs when you are lying or sitting and notice antsy feelings in your legs that make you want to move them. Movement then relieves the sensation. RLS usually occurs in the evening or right at bedtime. In some cases, RLS might trigger insomnia. PLMs are the actual leg motions or jerks that tend to occur rhythmically in your sleep in cycles lasting every 30 to 90 seconds, and these kicks may be dramatic enough to awaken the person sleeping with you or subtle enough to go completely unnoticed. In some cases leg jerks show obvious arousal activity in the brain, which indicates they are causing sleep fragmentation. In other cases, the arousal activity is not so obvious or even present on the sleep study. Some years ago, one study showed that even without brain arousal activity, leg jerks were linked to significant increases in blood pressure readings, thereby indicating a type of arousal affecting the autonomic nervous system, which could not be detected on a regular sleep study.

People with RLS have a very high probability of suffering as well from PLMD; whereas people who suffer from PLMD have a much lower probability of experiencing RLS. The biggest question to be answered about either RLS or PLMD is whether or not they are operating as independent disorders? In the majority of cases, these leg movement problems are really part of another sleep disorder, usually sleep-disordered breathing, and when SDB is treated, either RLS or PLMD or both will disappear, a very common occurrence among patients seeking care at a sleep center. I have repeated this point, because it is much more likely than not that sleep apnea is the real problem, and you would never want to miss out on the opportunity to treat this condition first to find out whether RLS/PLMD disappears. In fact, there are numerous patients who have suffered from RLS or PLMD for years due entirely to sleep apnea, and not one of their doctors or therapists recognized the problems or advised them on how to treat them. The same holds true for independent RLS/PLMD, but as you will read below such patients might receive a partial or indirect treatment.

One of the important and devastating “coincidences” about RLS/PLMD is they often appear in mental health patients, in part, because RLS in particular has been strongly associated with various mental disorders or symptoms, for example, anxiety and depression. Some research even points to the potential for RLS to aggravate suicidal thinking. Unfortunately, among patients with co-occurring leg movement issues and mental health disorders, it may prove extremely common for the RLS or PLMD to go unrecognized for years or decades. Making matters worse, the patients themselves may suffer some sort of deficit in their own capacity to recognize these symptoms. For example, I have met many patients who suffer from what is termed general anxiety disorder (GAD) who also clearly have leg jerks while they are asleep. These leg jerks (PLMD) can obviously be monitored on the sleep study. But, these same patients show a great deal of difficulty in sorting out whether or not they experience RLS, because they are so used to focusing on the feelings of anxiety.   I have only seen a few cases in which the individual finally realized that in addition to GAD, he or she also suffered from the RLS phenomenon.

I remain highly suspicious that many mental health patients suffer from RLS but do not appreciate the problem due to this difficulty in observing symptoms in their own bodies. In fact, this same deficit, so to speak, probably accounts for some of their mental illness. Compounding this problem is that many psychotropic medications, particularly in the antidepressant class, cause or aggravate either RLS or PLMD or both. One noteworthy finding on the sleep study seems to be the presence of very frequent leg jerks, cycling one or more times in less than 30 seconds, which emerges commonly in patients on antidepressants. Anxiolytic drugs to decrease anxiety also compound the problem, because the drug may have some slight beneficial impact on either RLS or PLMD, but these medications almost never lead to substantial improvements. More likely, anxiolytics, hypnotics and tranquilizers simply make it that much more difficult for individuals to notice whether or not they have any leg movement problems.

Along these lines, it is probably quite common for patients with mental health problems who are currently using a drug like a sleeping pill to in fact really be in need of a medication for RLS or PLMD. In these cases, we suspect the RLS/PLMD led to the insomnia and some of the mental health symptoms, but the prescribing physician or psychologist did not correctly piece this puzzle together and wrote the sedative prescription before having the patient complete a thorough sleep evaluation.

As you can imagine, this scenario could lead to someone receiving the wrong diagnosis for years, and it would not be unusual for such an individual to use whatever means available to attempt to solve the problem beyond a medical professional’s assistance. Drinking alcoholic beverages in the evening or near bedtime is arguably one of the most common self-medicating steps taken by undiagnosed RLS patients. Smoking marijuana or using OTC sleep aids are additional steps, albeit one interesting footnote (pun intended) is that Benadryl—a common ingredient in many OTC sleep aids—may actually worsen leg movements while you sleep. Eventually, as the severity of the limb movement disorders intensifies while the actual diagnosis eludes healthcare providers and patients, prescription medications for sleep (but not for RLS/PLMD) emerge as the therapy of last resort.

Turning to the good news, usually only one drug is needed to treat either or both RLS or PLMD. In rare cases, a patient may use two medications or alternate drugs. The oldest treatment is the Carbidopa- Levodopa combination called Sinemet, which has been around for decades and was originally used in Parkinson’s patients. It works through dopamine pathways and is taken at bedtime, and in some cases another dosage can be taken in the middle of the night. In the last 20 years, though, a controlled release version is available to take at bedtime and thus avoid the middle of the night dosage.

The starting dosage at the lowest level could be designated at 10/100, but most people can start at 25/100. Thus, a patient might increase to 50/200 (2 pills) and then may also take another 25/100 in the middle of the night. The controlled release pill’s dosage is usually 50/200 but there is also a 25/100 version as well. The above dosages are described as the maximum, but occasionally someone may tweak the dosage by adding in another 10/100 pill; however, as will be described below, larger dosages of dopamine drugs are associated with an odd side-effect called “augmentation syndrome” where the RLS or PLMD actually worsens.

Sinemet has a common side-effect (as many as 15% of patients or more) of nausea or vomiting. Interestingly, these symptoms often disappear in the first week or two, but who really wants to experience these gastrointestinal side-effects for that period of time? Then again, Sinemet would be the least expensive medication to use for RLS/PLMD. Other side effects include increased risk for depression among individuals with a past history or family history of depression. More severe side-effects include neurologic symptoms such as further movement symptoms such as tardive dyskinesia.

Newer dopaminergic agents include Pramipexole (Mirapex) and Ropinirole (Requip) and Rotigotine (Neupro), which have excellent safety profiles. You must start with the lowest dose for about a week and assess whether or not side-effects emerge. If not, then the dosages can be increased every 3 to 7 days, mostly depending on your own comfort level in gradually increasing the number of pills. This pattern of gradual increases may reduce or prevent side effects.

Mirapex starts out with a dosage of 0.125 mg, and the majority of patients seem to do very well in the 1 to 4 pill range or 0.125 mg to 0.500 mg. Yet, a sizeable proportion of cases must increase the dosage into the 5 to 8 pill range, that is, all the way up to 1.00 mg, although the stated maximum dosage for Mirapex is 0.75. Many patients go up to 1.00 mg without side effects, but then the question should arise as to whether another medication should be used instead? Requip is unique in that it is taken 1 to 3 hours before bedtime and starts at the dosage of 0.25 mg and usually can be increased up to the 1.00 mg. There is some confusion about the maximum dosage in that originally 1.00 mg was said to be the maximum, but it is not uncommon to encounter patients treated by psychiatrists who are taking as much as 4 mg of Requip per day. The dopaminergic drug Mirapex has an older history wherein it was used in the treatment of depression, which may account for how dosages go higher for some of these drugs in the hands of prescribing psychiatrists. The Neupro patch lasts 24 hours and is dosed from 1 to 3 mg.

Online or through other resources you will find many side-effects reported for these dopaminergic agents, but remember to take in to account that many of the symptoms described occur more frequently or occur more intensely at the noticeably higher dosages used in Parkinson’s patients —as much as twice to ten times higher. Thus, at the lower dosages used to treat RLS/PLMD, the side-effects may not apply.

A major caution for dopamine drugs is the paradoxical side effect of worsening RLS either by provoking the symptoms earlier in the day or intensifying restless legs sensations. They may also worsen leg jerks. The only treatment for this augmentation condition is stop the medication entirely, although many people will see improvement if they taper down the dosage. This side-effect can develop into an emergency, because the patient may become mentally unstable when round the clock RLS symptoms pervade one’s life. This augmentation effect usually indicates the drug may never be used again, which also means that any other member of the dopaminergic class can trigger the same exacerbation of symptoms. Obviously, any patient could get into trouble if he or she logically chooses to raise the dosage of the medication when leg symptoms worsen. Then, the person takes more meds but does not realize when the leg movements worsen again, the meds are the real problem. Therefore, it is always important to communicate with your prescribing doctor about changes in med dosages and changes in symptoms.

Next, we will review some of the other prescription medications for RLS/PLMD and then delve into other approaches such as supplements of vitamins and minerals as well as consider recent work on pneumatic compression devices. Tune in next week. 


Barry Krakow MD

Author

Dr Krakow’s 27 years of sleep research have focused on the complex relationship between physiological and psychological sleep disorders. Dr Krakow currently operates private sleep medical center, Maimonides Sleep Arts & Sciences, Ltd., and serves as Classic SleepCare’s paid Medical Director.



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