Which medication, Lexapro (escitalopram), Wellbutrin (bupropion), or Risperidone, is most likely causing Restless Legs Syndrome (RLS) in this patient and what alternative treatment can be given?

Risperidone is Most Likely Causing Restless Legs Syndrome; Consider Switching to Pregabalin

Risperidone is the most likely culprit causing Restless Legs Syndrome (RLS) in this patient, and it should be discontinued and replaced with pregabalin as a first-line treatment for RLS. 1

Medication Culprit Analysis

1. Risperidone (Most Likely):

   • Antipsychotics that block dopaminergic systems are known to aggravate RLS 2
   • Case reports specifically document RLS induced by antipsychotics like olanzapine, with risperidone being in the same class 2
   • The dopamine-blocking properties of risperidone directly oppose the central dopaminergic function needed to prevent RLS

2. Escitalopram (Lexapro) (Possible):

   • SSRIs can induce or exacerbate RLS symptoms 3
   • Case reports document escitalopram specifically causing RLS that resolved upon discontinuation 3

3. Bupropion (Wellbutrin) (Unlikely):

   • Bupropion has been reported to actually improve RLS symptoms 4, 5
   • As a dopamine reuptake inhibitor, bupropion enhances dopaminergic activity, which typically helps RLS symptoms
   • Multiple case reports show bupropion resolving RLS within days of initiation 5

Management Approach

Step 1: Discontinue the Offending Agent

• Gradually taper and discontinue risperidone
• Consider alternative antipsychotic options with lower risk of RLS if antipsychotic treatment is still needed

Step 2: First-Line Treatment Options

• Pregabalin is recommended as a first-line treatment for RLS by the American Academy of Sleep Medicine with moderate certainty of evidence 1
• Benefits of pregabalin:
  • More favorable long-term safety profile
  • Lower risk of augmentation compared to dopaminergic agents
  • Effective for RLS symptoms

Step 3: Additional Considerations

• Check iron status: Measure serum ferritin and transferrin saturation
• If ferritin ≤75 ng/mL or transferrin saturation <20%, initiate iron supplementation 1
• Consider gabapentin as an alternative if the patient has comorbid kidney disease 1

Important Clinical Pearls

• Don't confuse RLS with akathisia: RLS typically occurs at rest/bedtime and is relieved by movement, while akathisia is a constant restlessness not necessarily relieved by movement
• Maintain bupropion: Since bupropion may actually help RLS symptoms, it should be maintained in the regimen
• Monitor for neuropathy: Assess for peripheral neuropathy which can exacerbate RLS and may require higher medication doses 6
• Non-pharmacological approaches: Recommend regular exercise and good sleep hygiene practices as adjunctive measures 1

Follow-up Plan

• Reassess RLS symptoms 1-2 weeks after medication changes
• If symptoms persist, consider adding or switching to alternative agents like gabapentin
• Periodically reassess iron status if supplementation was initiated

By addressing the most likely causative agent (risperidone) and implementing evidence-based treatment with pregabalin, RLS symptoms should improve significantly while maintaining treatment for the patient's underlying psychiatric conditions.