Restless Legs Syndrome Foundation Blog

1. Start on www.rls.org/login and click on “Forgotten Username/Password” to request a password reset email. Be sure to check your "junk" folder for the email.
2. Before clicking on the link in the email be sure that you are NOT logged in to www.rls.org (home page says “Member Login” indicating that you are not logged in).

3. Create a NEW password (not used before) and write it down where you can locate it for future use. New password requirements include:
   • Minimum of 12 characters
   • One Upper Case Letter
   • One Lower Case Letter
   • One Number
   • One Special Character (Examples: @,#,$, or !)
   • Note: Password cannot include your Username or “RLS”.
4. Click on the link in the email and enter the NEW password you have created, repeat the new password in the second box, Click Submit.

5. When you receive the message: “Password updated successfully!” click on Member Login at the top of the website and enter your Username and NEW password (if your browser auto populates your password, delete it and manually enter your NEW password).
6. Click Login
7. You should see “WELCOME TO THE MEMBERS ONLY PORTAL” on your screen and “Welcome! You are now logged in.” at the top of the page.

8. As long as you see “Welcome! You are now logged in.” at the top of your screen you are logged in and have access to all materials in the Member Portal. If there is no activity after approximately 10 minutes you will be automatically logged out and the message at the top of your page will then say Member Login again.

The drug ecopipam shows promise for bringing relief to RLS patients who develop augmentation, a common side effect of dopamine medications.

Stefan Clemens, PhD, HdR, a professor of physiology at East Carolina University, is a member of the RLS Foundation’s Scientific and Medical Advisory Board, and chair of the Foundation’s Research Grant Committee. Regarding the worsening of RLS symptoms known as augmentation, Clemens developed the hypothesis, “Augmentation may be a consequence of increased D1-receptor activation in the nervous system” and that “identifying a new pharmacological target that specifically tackles the long-term side effects of standard dopaminergic treatments in RLS may keep the treatments effective for a longer time or avoid augmentation altogether.”

In other words, a dopamine-1 (D1)-receptor antagonist medication might be a new way to treat RLS and the symptoms of augmentation.

This new concept was first presented by Clemens and his group at the 2015 meeting of the International Restless Legs Syndrome Study Group. In 2016, a small pilot study funded by the RLS Foundation and performed by William Ondo, MD, suggested a positive clinical outcome when patients with RLS augmentation took ecopipam, a D1- receptor antagonist drug.

Clemens obtained a US patent for ecopipam to treat RLS augmentation, and East Carolina University has entered into a licensing agreement with Emalex Biosciences to study this first-in-class medication.

Many regular readers of NightWalkers know the basic facts about RLS treatments and the risks of augmentation, but a bit of history is useful to understand the importance of the new approach. For the 7% to 8% of the adult US population affected by RLS, some 3% need regular daily medication to control their symptoms. The Food and Drug Administration (FDA) has approved three dopaminergic drugs (pramipexole, ropinirole and rotigotine patch) for the treatment of RLS, and for decades these medications were considered first-line therapies for RLS.

Unfortunately, recent research has shown that of the patients on dopaminergic drugs, 7-8% per year develop augmentation so that by 10 years, almost 80% will be augmented and will experience a worsening of their symptoms caused by the drugs themselves. Augmentation typically includes an earlier onset of symptoms, an increase in intensity, a shorter period of rest or inactivity before symptoms start, and the involvement of other body parts (arms, torso or face). There are no FDA-approved medications for the treatment of RLS augmentation.

New clinical guidelines published in 2021 in the Mayo Clinic Proceedings no longer recommend dopaminergic drugs, but rather name iron and alpha-2 delta-ligands, such as gabapentin, first–line treatments for RLS. When a patient’s RLS becomes unresponsive to first- or second–line therapies due to augmentation or other side effects, it is considered refractory (resistant to treatment), and a low-total-daily-dose opioid therapy is the only option currently available. That is why new approaches and new drug therapies are urgently needed.

According to Clemens, ecopipam works by selectively blocking the dopamine D1-receptor subtype, whereas other dopaminergic medications that are used to treat RLS activate other dopamine receptor classes, in particular D3 and D2 subtypes. D3 and D2 receptors mediate inhibitory actions in the nervous system, meaning that they reduce excitability and thus reduce RLS symptoms. Over time, however, those effects wane and the nervous system responds with an upregulation of the D1-receptor subtype, the target of this new drug. In contrast to D3 and D2 receptor-mediated actions, the D1- receptor subtype mediates excitatory action in the nervous system, thus increasing its excitability and increasing the severity of the symptoms. The new drug, ecopipam, is thought to reduce the activation of the D1 receptor and in turn decrease the severity of augmentation symptoms.

The RLS Foundation’s executive director, Karla Dzienkowski says, “RLS augmentation is an untoward side effect of dopaminergic therapy. The potential for a new treatment for this side effect gives hope for the future for those living with the daily impacts of RLS augmentation. It could be a game changer.”

Planning Travel with RLS

Travel with RLS is possible with advanced planning to help manage unwanted symptoms during travel by plane, bus, train or car. These tips will help you to create a plan that employs several strategies to manage symptoms.

1. Make a List of Strategies that help you to cope with symptoms. Travel presents its own unique challenges for individuals with RLS. When a bout of RLS strikes, it is easier to have a list of helpful coping strategies to select from, rather than trying to remember them when symptoms are bothersome. Keep a running list of helpful things in your phone notes.
2. Get a Good Nights Sleep. A good night of sleep prior to travel will help to prevent or curb a worsening of RLS symptoms.
3. Bring Along Mental Alerting Activities such as Sudoku, crossword puzzles, needlework, video/digital games such as chess or solitaire to help to quell RLS symptoms during periods of inactivity.
   
4. Practice Mild to Moderate Physical Activity involving the limbs such as walking, yoga or stretching before, between travel connections and at the end of your journey to help in the management of symptoms during travel.
5. Book Travel Times during the early morning hours when RLS symptoms are generally least troublesome.
6. Make Seat Selection. Book or request an aisle seat so you can stretch your legs, stand or get up and walk if needed.
7. Download a Special Accommodations Card. If you don’t have access to our Member Portal you can call us and request an RLS Foundation Special Accommodations Card to present to travel personnel.
8. Know and Avoid Your RLS triggers. Avoid your RLS triggers during travel. Commonly reported triggers are alcohol, tobacco, nicotine, sugar, food, food dyes and salt. Refer to the RLS Medical Alert Card for a list of common medications that may worsen RLS, which includes most antidepressants, antipsychotics, antinausea medications and first-generation antihistamines.
9. Try Nonpharmacological Approaches to Help Manage Symptoms. Leg massage, compression stockings, foot hammock, snacks that can be eaten one at a time (cereal, popcorn, raisins) or calming teas are strategies to quell RLS during travel.
10. Don't Forget Medications. Speak to your RLS provider to discuss medication strategies (timing, dosage) or possible use of the short acting dopamine medication Sinemet to manage breakthrough symptoms during the day of travel (Note: Sinemet can be used up to three times per week as a rescue medication). Tramadol or other opioids may be very helpful to calm RLS symptoms during long flights.

Sleeping away from home presents problems for those with RLS. When you are out of your regular environment it can be difficult to stay on your usual exercise and medication schedule, but try to stick to your normal routine as much as possible. Know your iron levels and continue with iron supplementation as prescribed by your doctor. Don’t let RLS keep you from enjoying travel, plan your RLS strategies as you plan your trip. Bon Voyage!