How do you differentiate and treat Restless Leg Syndrome (RLS) versus akathisia?

Differentiating and Treating Restless Leg Syndrome (RLS) versus Akathisia

The key to differentiating RLS from akathisia lies in the symptom pattern, timing, and triggers, with RLS typically worsening at night and being relieved by movement while akathisia involves whole-body restlessness without circadian pattern and is commonly medication-induced.

Key Diagnostic Differences

Restless Leg Syndrome (RLS)

• RLS is characterized by an urge to move the legs (sometimes arms) accompanied by uncomfortable or unpleasant sensations in the legs 1, 2
• Symptoms begin or worsen during periods of rest or inactivity 1, 2
• Movement partially or totally relieves symptoms for as long as the activity continues 1, 2
• Symptoms worsen or only occur in the evening or night (circadian pattern) 1, 2
• Often associated with periodic limb movements during sleep (PLMS) 3

Akathisia

• Presents as an urge to move the whole body rather than just the legs 4, 5
• Lacks the uncomfortable sensations/dysesthesias typical in RLS 5, 6
• No clear circadian pattern (not specifically worse at night) 5, 6
• Commonly induced by dopamine antagonists (antipsychotics) 5, 7
• Movement may not provide the same degree of relief as in RLS 6

Assessment Algorithm

1. Evaluate symptom location and quality:

   • RLS: Primarily legs, with uncomfortable sensations described as crawling, pulling, or itching 1
   • Akathisia: Generalized restlessness without specific sensory complaints 5

2. Determine timing pattern:

   • RLS: Clear evening/nighttime predominance 1
   • Akathisia: No specific circadian pattern 6

3. Assess medication history:

   • RLS exacerbators: Tricyclic antidepressants, SSRIs, lithium, dopamine antagonists 1
   • Akathisia triggers: Antipsychotics (particularly first-generation and some second-generation) 5, 7

4. Check for relief with movement:

   • RLS: Immediate relief with movement that continues as long as movement persists 1
   • Akathisia: May have partial relief but often with persistent discomfort 6

5. Laboratory assessment:

   • For suspected RLS: Check serum ferritin (values <50 ng/mL support RLS diagnosis) 1
   • For suspected akathisia: No specific laboratory test; clinical assessment based on medication exposure 5

Treatment Approaches

For RLS:

1. First-line treatments:

   • Iron supplementation (ferrous sulfate) for patients with low ferritin levels (<50 ng/mL) 1, 2
   • Gabapentin or pregabalin (particularly for patients with comorbid pain) 2

2. Second-line options:

   • Dipyridamole 1
   • Bilateral high-frequency peroneal nerve stimulation 1
   • Extended-release oxycodone or other opioids for refractory cases 1

3. Use with caution:

   • Dopaminergic agents (ropinirole, pramipexole, rotigotine) may be effective short-term but have high risk of augmentation with long-term use 1
   • Levodopa should be avoided for long-term use due to high augmentation risk 1

4. Treatments to avoid:

   • Cabergoline (strong recommendation against use) 1
   • Bupropion, carbamazepine, clonazepam, valproic acid 1

For Akathisia:

1. Primary approach:

   • Discontinue or reduce dose of causative agent (typically antipsychotic) if clinically feasible 5, 7
   • Consider switching to an antipsychotic with lower akathisia risk (e.g., quetiapine) 7

2. Pharmacologic interventions:

   • Beta-blockers (propranolol)
   • Anticholinergics (benztropine)
   • Low-dose benzodiazepines
   • 5-HT2A antagonists (mirtazapine)

Special Considerations

• End-stage renal disease with RLS:

  • Gabapentin is suggested as first-line treatment 1
  • IV iron sucrose for patients with ferritin <200 ng/mL and transferrin saturation <20% 1
  • Vitamin C supplementation may be beneficial 1

• Pediatric RLS:

  • Iron supplementation is recommended for children with appropriate iron parameters 1
  • Careful assessment needed as children may have difficulty describing symptoms 1

• Cognitive impairment with suspected RLS:

  • Look for observable signs: rubbing/kneading legs, groaning while holding lower extremities 1
  • Assess for excessive motor activity that worsens at night and improves with movement 1

Common Pitfalls to Avoid

• Misdiagnosing RLS as akathisia or vice versa - remember that RLS has a strong circadian pattern and specific sensory symptoms 5, 6
• Failing to check iron status in RLS patients - iron deficiency is a common treatable cause 1, 2
• Using dopaminergic agents as first-line for RLS - current guidelines suggest caution due to augmentation risk 1
• Overlooking medication causes of symptoms - many drugs can exacerbate or trigger both conditions 1, 7
• Treating symptoms without addressing underlying causes (e.g., iron deficiency, medication effects) 2