Medication For Parkinson’s And Restless Leg Syndrome

Parkinson’s Drug Could Treat Restless Leg Syndrome Study Suggests

Date:

Medical College of Georgia

Summary:

A drug prescribed for Parkinson’s disease may also treat restless leg syndrome without the adverse side effects of current therapies, researchers say.

A drug prescribed for Parkinson’s disease may also treat restless leg syndrome without the adverse side effects of current therapies, Medical College of Georgia researchers say.

Rasagaline works by prolonging the effect of dopamine, a chemical that transmits signals between nerve cells in the brain. The cause of RLS is unknown, but research suggests a dopamine imbalance. Parkinson’s is caused by a dopamine insufficiency.

“The hope is that Rasagaline, because it prolongs the effect of existing dopamine, instead of producing more, will not come with adverse side effects,” said Dr. Shyamal Mehta, an MCG neurologist and neuroscientist. “We are trying to evaluate its safety and efficacy in treating RLS at this point. When it has been used to treat Parkinson’s, it’s been well-tolerated with few side effects.”

Current RLS therapies include a group drugs that work by activating existing dopamine receptors, prompting the brain to make more dopamine. The problem, Mehta said, is that those drugs usually come with adverse effects, because dopamine increases feelings of euphoria.

Some reports also suggest decreased efficacy after extended use, as well as symptoms beginning earlier in the day.

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Can Restless Legs Syndrome Develop Into Something More Serious

Most people with restless legs syndrome have the idiopathic form, meaning theres no known cause. For them, there is no risk of RLS developing into something more serious, like Parkinsons disease.

Restless legs syndrome can get worse in people with other medical conditions if they dont get those conditions treated.

Dopamine Agonists May Cause Compulsive Behaviours

There have been several reports of pathological gambling by people taking pramipexole for restless legs syndrome.24,25 The risk may be lower than in Parkinson’s disease where higher doses of dopamine agonists are used. Other compulsive behaviours that occur rarely with dopamine agonists prescribed for Parkinson’s disease include hypersexuality and binge eating.26

Inform patients and carers that there is a small risk but that the consequences can be serious, and to seek medical advice if concerned.6

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Pramipexole Is Modestly Effective

In one 12-week double-blind trial in people with moderate to severe restless legs syndrome, the treating physicians rated 66% of participants receiving pramipexole as ‘much’ or ‘very much’ improved, compared with 40% of participants receiving placebo.13 Other placebo-controlled trials reported similar results.14

While trials consistently found improvements in patient-reported sleep quality, daytime sleepiness was not improved significantly.13,15,16

The Link Between Rls And Parkinsons: Dopamine Agonists

Although the cause of RLS remains unknown, we know that RLS runs in families in about one-half of the cases, and that some families have an abnormality on chromosome 12. Because RLS is well treated by medications that also treat Parkinsons disease, it is likely that some aspect of brain dopamine function is altered in RLS. However, unlike in Parkinsons disease, in which the deficit in substantia nigra dopamine-producing cells can be proven in many ways, no such abnormality has been shown in RLS. For example, studies show that there is no major deficit on PET or other imaging studies of the brain, as is there is in PD. The spinal fluid is normal in RLS, but shows low dopamine in PD.

Lastly, RLS does not progress to cause other major symptoms such as tremor, gait disorder, or loss of taste or smell, and does not progress to PD. In fact, one of the leading possibilities as the cause of RLS and for which there is good scientific evidence and much research is a form of iron-transport abnormality in the brain. In effect, RLS patients may have low levels of iron in brain nerve cellsjust the opposite of some portions of the brain in PD.

Dr. Poceta is a Consultant in Neurology and Sleep Disorders in the Division of Neurology, Scripps Clinic, La Jolla, and the Scripps Clinic Sleep Center. His current interests include organized medicine and Internet medicine.

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Restless Legs Syndrome And Parkinsons: Causes Symptoms And Treatment

For many people living with Parkinsons, poor sleep is one of the most burdensome symptoms they experience. Parkinsons can negatively impact sleep quality in a number of ways, causing everything from insomnia to nighttime sweating to sleep fragmentation. One common sleep disturbance experienced by people with Parkinsons is REM Sleep Behavior Disorder , and the connections between RBD and Parkinsons continue to be widely studied. Though less common, another sleep disorder experienced by many people with Parkinsons is Restless Legs Syndrome . In this article, well explore the causes and symptoms of RLS and treatment options to help you manage the symptom if its one you experience.

Restless Legs Syndrome Medication

• Author: Ali M Bozorg, MD Chief Editor: Selim R Benbadis, MD

Medications used in the treatment of restless legs syndrome include the following:

• Dopaminergic agents

• Alpha2 -adrenergic agonists

A network meta-analysis of 10,674 participants found that, compared with placebo, only levodopa is inefficient to relieve symptoms of RLS. The researchers recommend gabapentin, gabapentin enacarbil, and pregabalin as first-line treatement. Oxycodone-naloxone could be considered in patients with severe or very severe RLS who failed in treatment with other drugs.

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Tips For Coping With Restless Legs Syndrome

Learning to recognize and avoid your personal triggers can help you manage RLS over time.

Effective techniques for minimizing RLS symptoms vary from person to person. Many people find relief from keeping active throughout the day and using acupuncture, massage, stretching, or relaxation techniques at night. During the day, you may be able to ward off RLS symptoms by keeping your mind busy even when you are sitting still with activities like reading or chatting to a friend.

Though RLS is not life-threatening, the frustration of not being able to sleep well can take a toll on mental health. Cognitive behavioral therapy, support groups, or reaching out to family and friends may provide additional emotional resources for coping with RLS.

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What Are The Possible Side Effects Of Carbidopa/levodopa

Some of the most common side effects of carbidopa/levodopa therapy include:1

• Nausea, vomiting
• Daytime sleepiness

Long-term use of carbidopa/levodopa can cause a serious side effect known as augmentation.

These are not all the possible side effects of carbidopa/levodopa. Talk to your doctor about what to expect or if you experience any changes that concern you during treatment with carbidopa/levodopa.

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Interrupted Sleep: Exploring Links Between Parkinsons Disease And Restless Leg Syndrome

Restless Legs Syndrome and Parkinsons disease have interesting dopamine connections. Some Parkinsons pain may actually be restless legs or arms. Could changes in RLS treatment over the past few years be relevant to getting a good nights sleep with PD?

To those unfamiliar with the condition, the terminology Restless Legs makes it difficult to accept as the serious condition that it is. Whenever I hear the term Restless Legs Syndrome, my brain thinks ants in my pants. I picture myself back in elementary school, being forced to sit at a desk, when Id rather be running around outside. That is far from being an accurate description of this medical condition.

The USA National Institutes of Health describes RLS as follows:

I know the feeling all too well. Sitting anywhere for more than an hour or so where I cant stretch/straighten out my legs leads to extreme pain that can usually be walked off with just a few minutes of movement. Gymnasium bleachers are the worst for me. I used to prefer bulkhead rows on airplanes, but now they can be painful because I cannot stretch my legs into the space under the seat in front of me. Movie theaters generally arent a problem, as the old theaters have been replaced by megaplexes that are focused more on comfy recliner seats. By contrast, traditional theatre can be torturealthough an aisle seat usually provides me with enough wiggle room to endure until intermission.

What causes RLS?

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Cautions With Other Medicines

There are some medicines that do not mix well with ropinirole.

Tell your doctor, specialist nurse or pharmacist if you’re taking any of these medicines before starting ropinirole:

• anti-sickness medicines, such as metoclopramide or prochlorperazine
• antidepressants or antipsychotic medicines, such as fluvoxamine, amisulpride, risperidone or haloperiodol
• hormone replacement therapy or contraceptives that contain high levels of oestrogen
• medicines that can lower your blood pressure blood pressure medicines, tablets that make you pee more , or erectile dysfunction medicines such as sildenafil or tadalafil
• warfarin, to prevent blood clots

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Primary Or Idiopathic Rls

Idiopathic means that the cause is unknown.

It is the most common type and has the following characteristics:

• It usually begins before the age of 40.
• It can start as early as childhood.
• It may have a genetic cause.
• Once primary RLS starts, it tends to be lifelong.

Symptoms may be sporadic, or gradually worsen and become more prevalent over time.

In mild cases, the person may have no symptoms for a long time.

What Should I Do If I Forget A Dose

If you are taking regular pramipexole tablets to treat Parkinson’s disease, take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

If you are taking regular pramipexole tablets to treat restless legs syndrome, skip the missed dose. Take your regular dose 2 to 3 hours before your next bedtime. Do not double the next dose to make up for the missed dose.

If you are taking the extended-release pramipexole tablets and you miss a dose, take the missed dose as soon as you remember it. However, if more than 12 hours passed since your missed dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

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Problems With The Common Pathophysiology Theory

Symptoms of RLS in PD are milder than in patients with idiopathic disease and may be difficult to differentiate from other sensory and motor symptoms in PD, in particular akathisia affecting the lower extremities . RLS symptoms may also be a manifestation of wearing-off phenomenon, a levodopa related complication of PD .

Prolonged dopaminergic therapy in RLS patients, in particular with levodopa use, may result in a phenomenon known as augmentation in which the severity of symptoms increases, onset of symptoms begin earlier in the day and more rapidly, and spread of distribution to other body parts occurs. In contrast, PD patients develop dyskinesias and motor fluctuations after treatment with dopaminergic agents. These complications are not seen in RLS patients.

Hypofunction of the endogenous opioid system has been postulated to be a mechanism related to the pathogenesis of RLS. Exposure to the iron chelator desferoxamine in cell cultures of rat substantia nigra resulted in DNA fragmentation while pre- administration of enkephalin significantly protected the cells from damage by iron deficiency .

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Who Suffers From Restless Legs Syndrome

RLS is not common in young people. Instead, it is most often seen in middle-aged and older adults. The condition may have a genetic basis, so parents and children in the same families often have it. When this is the case, the age of onset is sometimes younger. RLS is more common in patients who have chronic kidney disease, iron deficiency, Parkinsons disease, diabetes, or peripheral neuropathy, and in those who are pregnant. RLS may also occur in patients withdrawing from sedatives or in those using caffeine, calcium channel blockers for high blood pressure, or lithium for bipolar disorder.

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What Should I Know About Storage And Disposal Of This Medication

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture . Store the regular tablets away from light.

It is important to keep all medication out of sight and reach of children as many containers are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location â one that is up and away and out of their sight and reach.

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA’s Safe Disposal of Medicines website for more information if you do not have access to a take-back program.

Restless Legs Syndrome Is An Idiopathic Sensorimotor Disorder

Restless legs syndrome consists of a pattern of symptoms involving an urge to move the legs because of unpleasant sensations. Symptoms are worse or only present at rest, worse or only present in the evening or night-time, and are relieved by movement . The diagnosis covers a spectrum from mild and harmless to severe and distressing. As the pathology is unknown and no objective test exists, diagnosis is based on patient report of symptoms, according to consensus criteria.

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What Are The Symptoms Of Rls

Symptoms usually start in the evening just as you sit down to relax, and may progressively worsen throughout the night. Both legs are usually affected although one may be worse than the other. In more severe cases, the arms and lower trunk may also be affected. RLS affects more than twice as many women as men.

Four out of five people with RLS have PLMS as well. These twitchy movements can be so violent that they often jerk the person awake, making for an exhausting night and very little sleep!

How Are Parkinsons Tremors Treated

Tremor can be unpredictable. Some experts say itâs the toughest symptom to treat with medication. Your doctor may prescribe medication for your tremors:

• Levodopa/carbidopa combination medicines . This treatment is a type of medication called a dopamine agonist. Itâs usually the first treatment for Parkinsonâs.

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Pramipexole Can Cause Somnolence And Sleep Attacks

Somnolence was a common drug-related adverse effect in restless legs trials.6 Sudden onset of sleep during daily activities in some cases without awareness or warning signs has been reported in people with Parkinson’s disease receiving pramipexole21, as have a few cases during clinical trials for restless legs syndrome.6,16,17,22

Advise patients not to drive or perform other dangerous tasks until they are used to the effects of pramipexole.

Patients who have a sleep attack should refrain from driving and other dangerous activities until they receive medical advice . Consider dose reduction or discontinue pramipexole in these cases.6

Reason For Pbs Listing

The Pharmaceutical Benefits Advisory Committee recommended listing pramipexole for severe primary restless legs syndrome on the basis that it was no worse than levodopa with benserazide in effectiveness and safety for the same cost. The comparison was based on 1 unpublished randomised controlled trial.1

In response to an earlier submission, the PBAC rejected the claim that pramipexole was superior overall to levodopa with benserazide, noting that pramipexole was associated with higher rates of nausea and other gastrointestinal adverse events, while levodopa with benserazide was associated with more nervous system adverse events.2

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Eat Organic Whenever Possible

More research needs to be done on this subject, but many experts now believe pesticides can increase the risk of Parkinsons disease. Researchers have found high levels of pesticides inside the brains of people with Parkinsons, and those chemicals can suppress the production of dopamine. Products that are certified organic arent supposed to contain any chemical pesticides or herbicides.

• Not swinging your arms while walking
• Multiple steps required to turn around when walking, possibly tripping up the feet
• One foot turning inward or outward a bit, causing tripping
• One arm could also be bent inward

The turning of the arm or foot, called dystonia, is often one of the first signs we see, so were always on the lookout for it, Dr. Joseph says.

Fourth Type Of Leg Pain Is Radicular Pain

In this case, the pain is caused by compression of nerves in lumbar area which results in weakness, numbness and tingling, and loss of reflexes from buttocks to foot in a distribution of a nerve. It can be acute or chronic, and can be worse with standing and sitting, or better with laying down. Of note: in my experience many patients including myself have these symptoms not because of physically herniated disc but rather by the stretching of a nerve in the canal as it exists due to severe musculoskeletal rigidity and abnormal posturing.

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Iron And Its Relation To The Dopamine System

Iron is an important cofactor in several DA metabolisms and can also produce neurotoxic species.

Usually iron accumulates in the normal aging brain, in particular in the putamen, globus pallidus, red nucleus, and substantia nigra . Elemental iron plays a critical role in oxidative metabolism and it also serves as a cofactor in the synthesis of neurotransmitters .

In PD, neurodegeneration occurs mainly in SNc , while other iron-rich areas remain unaffected. In early stages of the disease the identification through the use of transcranial ultrasonography of a hyperechogenicity of the SNc correlates positively with the increase of iron and ferritin evaluated in post-mortem analysis , allowing an early identification of patients at risk for PD .

The increase in neuronal iron may be secondary to an increase in influx, facilitated by transferrin receptor-2/divalent metal transporter-1 endocytosis or the diffusion of ferric citrate , an increase in efflux, due to alteration of the activity of ceruloplasmin, or a dysregulation of iron homeostasis, mediated mainly by the iron storage protein ferritin .

Some studies have shown reduced ferritin concentrations in the SN from Parkinson’s disease brain, suggesting an alteration of this storage mechanism and a consequent increase in the level of free and potentially harmful iron .