Is there an association between Restless Legs Syndrome (RLS) and nicotine use?

Association Between Restless Legs Syndrome (RLS) and Nicotine Use

Smoking cessation is recommended for patients with Restless Legs Syndrome (RLS) as nicotine use may exacerbate RLS symptoms. 1

Evidence on Nicotine and RLS

The Management of Restless Legs Syndrome guidelines specifically recommend smoking cessation as part of non-pharmacological interventions for RLS. According to the American Geriatrics Society, smoking cessation, along with moderate exercise, alcohol avoidance, and caffeine reduction, should be implemented before or alongside pharmacological treatment for RLS 1.

While the evidence directly linking nicotine use to RLS development or severity is not extensively detailed in the available guidelines, smoking cessation is consistently included among lifestyle modifications recommended for RLS management.

Pathophysiological Considerations

Several mechanisms may explain why nicotine could potentially worsen RLS symptoms:

1. Vascular effects: Nicotine causes vasoconstriction, which may compromise peripheral circulation and potentially exacerbate RLS symptoms.

2. Sleep disruption: Nicotine is a stimulant that can interfere with normal sleep architecture, potentially worsening the sleep disturbances already experienced by RLS patients.

3. Dopaminergic system effects: RLS has been linked to dysfunction in dopaminergic pathways, and nicotine affects dopamine release and metabolism, potentially interfering with the same neurological systems involved in RLS.

Management Approach for RLS

Non-Pharmacological Interventions (First Line)

• Smoking cessation
• Regular aerobic and resistance exercise
• Alcohol avoidance
• Caffeine reduction or elimination
• Discontinuation of potentially exacerbating medications 1

Evaluation for Secondary Causes

• Check ferritin levels (values <50 ng/mL consistent with RLS; supplementation recommended for levels <75 ng/mL)
• Complete blood count
• Basic metabolic panel
• Liver function tests
• Thyroid function tests
• HbA1c and urine albumin:creatinine ratio 1

Pharmacological Management (When Needed)

1. First-line: Alpha-2-delta ligands (pregabalin or gabapentin) for moderate to severe RLS 1
2. Short-term use only: Dopamine agonists (ropinirole, pramipexole, or rotigotine patch) due to risk of augmentation 1, 2
3. For severe cases: Opioids may be considered for treatment-resistant cases 1

Clinical Pearls and Pitfalls

• Augmentation risk: Long-term use of dopamine agonists carries a high risk (30-80% of patients) of augmentation—a paradoxical worsening of symptoms 1, 2
• Iron status: Always check ferritin levels in RLS patients, as iron deficiency is a major treatable cause 1
• Medication timing: For pharmacological treatments, timing is crucial—medications should typically be administered 1-3 hours before bedtime 1
• Regular monitoring: Follow-up is essential to assess symptom control and adjust treatment, particularly to watch for augmentation with dopaminergic agents 1

Special Populations

For patients with chronic kidney disease or end-stage renal disease (ESRD) with RLS:

• Gabapentin is recommended as first-line treatment
• IV iron sucrose for ESRD patients with ferritin <200 ng/mL and transferrin saturation <20%
• Consider vitamin C supplementation 1

While the guidelines specifically recommend smoking cessation for RLS management, they do not provide detailed evidence on the direct mechanisms linking nicotine use to RLS severity or incidence. However, the consistent inclusion of smoking cessation in RLS management protocols suggests clinical experience has found this intervention beneficial.