A paradigm shift in RLS treatment
For decades, dopamine agonists like pramipexole and ropinirole were the standard for treating moderate-to-severe Restless Leg Syndrome. However, long-term use led to a phenomenon called "augmentation," where symptoms worsened, appeared earlier in the day, or spread to other parts of the body. This discovery prompted the American Academy of Sleep Medicine (AASM) to release updated guidelines in early 2025, recommending against the long-term use of these drugs and promoting safer alternatives.
The new first-line medication options
Following the AASM's 2025 guidelines, the front-line pharmacological approach for RLS has shifted significantly. The new recommendations focus on drugs that manage neurological signals without the risk of augmentation.
- Alpha-2-delta ligands: This class of drugs, which includes gabapentin, gabapentin enacarbil (Horizant), and pregabalin (Lyrica), is now strongly recommended for first-line treatment. These medications work by calming the central nervous system and have proven effective without causing augmentation.
- Intravenous (IV) iron supplementation: Experts now strongly emphasize the evaluation of iron status in all RLS patients. Even with normal blood iron levels, low brain iron is a contributing factor for RLS. For patients with low ferritin levels, intravenous iron preparations, such as ferric carboxymaltose, are a strong recommendation because they replenish iron more rapidly and effectively than oral supplements.
- Low-dose opioids: For severe cases that do not respond to other treatments, cautious use of low-dose extended-release opioids may be considered. These are prescribed under strict medical supervision due to the risks associated with opioid use.
Device-based therapies for moderate-to-severe RLS
In addition to medication, innovative device-based therapies offer a non-pharmacological option for patients who cannot tolerate or do not respond to medication. These are particularly valuable for those with moderate-to-severe symptoms.
Tonic Motor Activation (TOMAC) System
One of the most notable advances is the Noctrix NTX100 Tonic Motor Activation (TOMAC) System, which received FDA De Novo approval in 2023.
- How it works: This is a prescription therapy involving a pair of wearable devices placed on the lower legs. Before bedtime, the devices deliver electrical impulses to the peroneal nerves, triggering sustained, gentle muscle contractions. This tonic muscle activation helps suppress the neurological signals that cause RLS symptoms.
- Clinical benefits: Clinical trials have shown the TOMAC system significantly reduces RLS symptoms and improves sleep quality, particularly for patients who are refractory to standard medications. Its non-pharmacological nature makes it a valuable alternative for those concerned about drug side effects.
Stellate ganglion block
Recent case reports published in early 2024 suggest that stellate ganglion block (SGB), a minimally invasive procedure, shows promise for treating RLS, particularly in patients with comorbidities like severe kidney disease. By blocking sympathetic nerves, SGB helps regulate autonomic nervous system and immune responses, which have been linked to RLS symptoms.
Comparative table of RLS treatments
| Treatment Type | Examples | Augmentation Risk | Best For | Considerations |
|---|---|---|---|---|
| Alpha-2-delta ligands | Gabapentin, Pregabalin, Gabapentin Enacarbil | Very low | First-line moderate-to-severe RLS | Side effects can include drowsiness, dizziness, and weight gain. |
| IV Iron Supplementation | Ferric Carboxymaltose | None | RLS with low brain iron (based on serum ferritin) | Requires medical supervision; more effective and rapid than oral iron. |
| Low-Dose Opioids | Extended-release oxycodone | Low, but risk exists | Severe RLS refractory to other treatments | Prescribed with extreme caution due to addiction risk. |
| Dopamine Agonists | Ropinirole, Pramipexole, Rotigotine | High | Not recommended for long-term use per new guidelines | Only for short-term, selective use (e.g., occasional long flights). |
| Tonic Motor Activation (TOMAC) | NTX100 System | None | Moderate-to-severe RLS, especially if refractory to drugs | Device-based, non-pharmacological, requires prescription. |
| Lifestyle Adjustments | Exercise, avoiding triggers, massage | None | Mild RLS, or as adjunct therapy | Requires consistent effort and may not be sufficient alone. |
| Stellate Ganglion Block | SGB Procedure | Not established | Specialized cases, potentially with comorbidities | Minimally invasive procedure, still under investigation for RLS. |
Lifestyle modifications and complementary approaches
Even with these new treatments, lifestyle adjustments remain a critical component of RLS management, particularly for mild symptoms or in conjunction with other therapies.
Key strategies include:
- Regular, moderate exercise: Activities like walking, swimming, or biking can help relieve symptoms. However, intense exercise close to bedtime should be avoided.
- Avoiding triggers: Substances like caffeine, alcohol, and nicotine can worsen symptoms. Certain medications, including some antidepressants and cold medicines with antihistamines, should also be reviewed with a physician.
- Establishing good sleep hygiene: Creating a cool, dark, and quiet bedroom environment and maintaining a regular sleep schedule can help improve sleep quality, which is often compromised by RLS.
- Physical interventions: Soaking in a warm bath, massaging the legs, or using heating pads or ice packs can provide temporary relief.
Conclusion
For those wondering what is the new treatment for restless leg syndrome, the landscape has shifted decisively away from the long-term reliance on dopamine agonists due to the risk of augmentation. The new guidelines prioritize safer, more sustainable options. First-line treatments now focus on alpha-2-delta ligands like gabapentin, along with careful iron status evaluation and supplementation. For refractory cases, cautious use of low-dose opioids may be considered. Exciting new developments also include FDA-approved device therapies like the TOMAC system, which offers a non-pharmacological path to relief by stimulating the peroneal nerves. Combined with long-standing recommendations for lifestyle modifications, these new treatments offer patients a more effective and safer future for managing RLS. To explore these options, consider discussing the updated guidelines and latest therapies with a sleep medicine specialist.
