DAAG summary of the updated 2026 Mayo Clinic guidance for Restless Legs Syndrome

The Mayo Clinic is one of the world's leading academic medical centres, internationally recognised for its clinical care, medical research and evidence-based guidance. Its publications are widely respected by healthcare professionals around the world. 

In May 2026, the Scientific and Medical Advisory Board of the Restless Legs Syndrome Foundation published an updated treatment algorithm for Restless Legs Syndrome (RLS) in Mayo Clinic Proceedings. 

Why this update matters

The updated algorithm reinforces an important shift in clinical practice that began with the 2021 guidance, placing even greater emphasis on:

  • first identifying and treating iron deficiency;

  • using gabapentinoids as the preferred first-line treatment;

  • reserving dopamine agonists for exceptional circumstances only;

  • recognising augmentation early;

  • regular monitoring for complications;

  • safer withdrawal from dopamine agonists; and

  • ensuring patients are fully informed before treatment begins.

The key changes

Iron replacement takes centre stage

The updated algorithm gives much greater prominence to identifying and treating iron deficiency. Compared with the 2021 guidance, intravenous (IV) iron is recommended for a wider range of patients, reflecting growing evidence that correcting iron deficiency can substantially improve RLS symptoms and, for some patients, reduce the need for medication altogether.

Gabapentinoids remain the preferred first-line treatment

The 2021 algorithm moved away from dopamine agonists as the routine first-line treatment for RLS. The 2026 update reinforces this recommendation. For most people requiring medication, gabapentinoids (including gabapentin, pregabalin and gabapentin enacarbil) remain the preferred first-line option.

Dopamine agonists should only be used in exceptional circumstances

The updated guidance makes clear that dopamine agonists should no longer be used routinely for treating RLS because of their recognised long-term risks. 

Instead, they should generally be reserved for carefully selected situations where other treatments are unsuitable, ineffective or cannot be tolerated, following a full discussion of the potential benefits and risks. The algorithm notes that this may include, for example, some patients receiving palliative or end-of-life care, where longer-term complications are less relevant.

Where dopamine agonists are prescribed, the guidance recommends using the lowest effective dose, avoiding dose escalation wherever possible, and reviewing treatment regularly.

Earlier recognition of augmentation

The updated algorithm places even greater emphasis on augmentation – the progressive worsening of RLS caused by dopamine agonist treatment. It estimated augmentation occurs in approximately 42–70% of patients treated with dopamine agonists for RLS over a 10-year period.

When a dopamine agonist appears to become less effective, clinicians are now advised to first suspect augmentation rather than simply increasing the dose. Dose escalation is discouraged because it frequently makes augmentation worse over time.

Greater emphasis on monitoring and patient safety

The updated guidance reinforces that patients taking dopamine agonists should be reviewed regularly for both augmentation and impulse control disorders. Rather than waiting until complications become severe, clinicians are encouraged to identify problems early, discuss treatment options with patients and take prompt action where appropriate. This represents a stronger emphasis on preventing harm through regular monitoring and ongoing review.

Safer withdrawal

The preferred approach for patients developing augmentation is to transition gradually to an alternative treatment, usually a gabapentinoid. The guidance specifically warns that dopamine agonists should never be stopped abruptly, highlighting the risks of severe rebound RLS, insomnia, mood changes and Dopamine Agonist Withdrawal Syndrome (DAWS). Instead, treatment should be reduced gradually under medical supervision.

Greater emphasis on informed consent

Shared decision-making is now central to the algorithm. Before starting a dopamine agonist, patients should be informed about the risks of augmentation, impulse control disorders, withdrawal symptoms and the possibility of temporary worsening during treatment changes. Ongoing review for these complications is also emphasised.

What should patients do?

If you are currently taking a dopamine agonist such as pramipexole, ropinirole or rotigotine, the updated guidance does not mean you should stop your medication.

However, it does suggest that your treatment should be reviewed if you are experiencing problems, require increasing doses, or have never discussed the long-term risks and alternative treatment options with your healthcare professional.

We recommend that patients:

  • Do not stop a dopamine agonist suddenly. Abrupt withdrawal can lead to severe rebound symptoms and Dopamine Agonist Withdrawal Syndrome (DAWS). Any reduction should be carefully planned and supervised by your healthcare professional.

  • Read the updated guidance so that you understand the latest recommendations and can take an active role in decisions about your treatment.

  • Share the updated guidance with your healthcare professional. While the 2021 algorithm significantly changed the recommended approach to treating RLS, not all clinicians adopted those recommendations immediately, and many may not yet be familiar with the updated 2026 guidance. Sharing the guidance ahead of your appointment may help support informed discussions about your treatment.

  • Ask whether your iron levels have been fully assessed, including ferritin and transferrin saturation, and whether iron replacement could benefit your symptoms.

  • Seek medical advice if your symptoms are starting earlier in the day, becoming more severe, spreading to other parts of your body, or you need increasing doses of medication, as these may be signs of augmentation.

  • Tell your healthcare professional if you have experienced impulsive or compulsive behaviours, such as gambling, excessive shopping, binge eating or hypersexuality, even if these symptoms have since improved.

  • Expect regular monitoring. If you remain on a dopamine agonist, you should be reviewed regularly for augmentation and impulse control disorders, with opportunities to discuss whether your treatment remains appropriate. 

  • Inform family members or those close to you about the potential side effects of dopamine agonists. They may notice changes in behaviour, such as impulsive or compulsive behaviours, before you do and can play an important role in helping you seek medical advice early.

DAAG’s response

Emma Sanderson-Nash, Co-founder of the Dopamine Agonist Action Group (DAAG), said:

“This is a significant and long-overdue step forward for patient safety for people living with Restless Legs Syndrome. The updated guidance closely reflects many of the changes DAAG has been calling for, including better informed consent, closer monitoring, earlier recognition of complications and safer withdrawal from dopamine agonists.

While this algorithm is specific to RLS, many of its underlying principles are relevant wherever dopamine agonists are prescribed. The challenge now is ensuring these recommendations are consistently translated into everyday clinical practice. Every patient prescribed a dopamine agonist should be fully informed of the risks, monitored appropriately throughout treatment, and supported safely if their medication needs to change. That is how we turn expert guidance into better outcomes for patients.”