What is the recommended approach for quitting methadone (opioid agonist) in a patient with Restless Legs Syndrome (RLS) who is currently taking a low dose of 5 to 10 mg?

Discontinuing Low-Dose Methadone for RLS: A Straightforward Approach

For patients taking methadone 5-10 mg daily for RLS who need to discontinue, gradual tapering by reducing the dose by 10-20% every 1-2 weeks is recommended, with the understanding that at these low doses, withdrawal symptoms are typically minimal and discontinuation is generally well-tolerated. 1, 2

Why Low-Dose Methadone Discontinuation is Different

The concern about quitting methadone stems primarily from high-dose opioid maintenance therapy (typically 80-120 mg/day for addiction treatment), not the low doses used for RLS. 1 At 5-10 mg daily—doses used specifically for refractory RLS—the physical dependence profile is substantially different from addiction treatment doses. 2, 3

• Patients with RLS on methadone 5-20 mg daily show minimal dose escalation over time, with long-term studies demonstrating stable dosing over 2-10 years without significant tolerance development. 3, 4
• The risk of severe withdrawal is considerably lower at these doses compared to maintenance therapy doses that are 8-16 times higher. 1, 5

Recommended Tapering Protocol

Reduce the daily dose by 1-2 mg every 1-2 weeks until discontinuation is complete. 1 For example:

• If currently taking 10 mg daily: reduce to 8 mg for 1-2 weeks, then 6 mg for 1-2 weeks, then 4 mg for 1-2 weeks, then 2 mg for 1-2 weeks, then stop. 1
• If currently taking 5 mg daily: reduce to 3-4 mg for 1-2 weeks, then 2 mg for 1-2 weeks, then stop. 1

The FDA label recommends that dose reductions should be less than 10% of the established dose with 10-14 day intervals between reductions, though this guidance is primarily for higher maintenance doses. 1 At RLS doses of 5-10 mg, a 1-2 mg reduction represents 10-40% of the total dose, which is generally well-tolerated. 1, 5

Expected Withdrawal Symptoms (Typically Mild)

At these low doses, withdrawal symptoms are usually minimal and may include:

• Mild restlessness or anxiety (not to be confused with RLS symptom recurrence). 1
• Mild muscle aches or flu-like symptoms that resolve within days. 1
• Return of RLS symptoms, which is not withdrawal but rather loss of therapeutic effect. 2, 5

The key distinction: RLS symptom recurrence is expected and represents the underlying condition re-emerging, not opioid withdrawal. 2, 5

Critical Pitfall to Avoid

Do not confuse RLS symptom recurrence with opioid withdrawal. 2, 5 When methadone is discontinued, the RLS symptoms that necessitated treatment will likely return, often within days. 5 This is the natural course of untreated RLS, not a withdrawal syndrome requiring continued opioid therapy. 2

Managing RLS After Methadone Discontinuation

Before discontinuing methadone, ensure alternative RLS management is in place:

• Check iron status (ferritin and transferrin saturation) and supplement if ferritin ≤75 ng/mL or transferrin saturation <20%. 6, 2
• Initiate first-line therapy with gabapentinoids (gabapentin 1800-2400 mg/day divided, gabapentin enacarbil 600-1200 mg/day, or pregabalin 150-450 mg/day) before or during methadone taper. 6, 2
• Discontinue any medications that worsen RLS, including serotonergic antidepressants, dopamine antagonists, and antihistamines. 6, 2

Why Methadone Was Likely Prescribed

Methadone at 5-10 mg daily is typically reserved for refractory RLS—cases that failed dopamine agonists (due to augmentation or inadequate efficacy) and alpha-2-delta ligands. 3, 5 The evidence supporting low-dose opioids for refractory RLS is strong, with studies showing 75-100% symptom reduction without augmentation over years of treatment. 4, 5

However, current guidelines now recommend gabapentinoids as first-line therapy, making methadone a second- or third-line option. 6, 2 If methadone was started without adequate trials of gabapentinoids and iron supplementation, transitioning to these evidence-based first-line therapies during the taper is appropriate. 6, 2

Monitoring During Discontinuation

• Assess for withdrawal symptoms (mild restlessness, anxiety, muscle aches) versus RLS symptom recurrence (urge to move legs with uncomfortable sensations, worse at rest and in evening). 1, 2
• If withdrawal symptoms are problematic, slow the taper further or hold at current dose for an additional week before continuing. 1
• If RLS symptoms become intolerable, ensure gabapentinoid therapy is optimized and iron status is adequate before considering resuming low-dose opioid therapy. 6, 2

Special Consideration: Hospitalized Patients

If discontinuation occurs in a hospital setting, the FDA label suggests that daily reductions of 20% of the total daily dose may be tolerated, meaning a patient on 10 mg could reduce by 2 mg daily. 1 However, this accelerated approach is typically unnecessary for outpatient discontinuation and may increase discomfort. 1