Can Latuda (lurasidone) worsen restless leg syndrome?

Lurasidone Can Worsen Restless Legs Syndrome

Yes, Latuda (lurasidone) can worsen restless legs syndrome (RLS) because it is a dopamine antagonist (antipsychotic) medication, and dopamine antagonists are known to exacerbate RLS symptoms. 1

Mechanism of Worsening

• Lurasidone is an antipsychotic that blocks dopamine receptors, and dopamine antagonism is a well-established mechanism for triggering or worsening RLS 1
• The FDA label for lurasidone (Latuda) specifically lists "restlessness" as an adverse reaction occurring in clinical trials at rates higher than placebo (4% vs <1%) 2
• Antipsychotics are specifically mentioned in guidelines as medications that can exacerbate RLS symptoms 1

Evidence from Guidelines

• The American Academy of Sleep Medicine guidelines identify "dopamine antagonists (antipsychotics)" as medications that can exacerbate RLS 3
• A variety of medications, including tricyclic antidepressants, SSRIs, lithium, and dopamine antagonists (antipsychotics) have been reported to exacerbate RLS 1
• Drug-induced RLS is most often associated with the effect of medications on various receptors and neurotransmitter systems, in particular, the dopamine system 4

Management Recommendations

• If a patient develops or experiences worsening of RLS while taking lurasidone, consider the following options:

1. Assess for iron deficiency - Check serum ferritin and transferrin saturation, as iron supplementation may help mitigate RLS symptoms if ferritin ≤75 ng/mL or transferrin saturation <20% 3

2. Consider medication alternatives if clinically appropriate:

   • Discuss with the prescribing psychiatrist whether an alternative antipsychotic with less dopamine antagonism might be suitable 1
   • If lurasidone must be continued, consider adding treatments for RLS:
     • Alpha-2-delta ligands (gabapentin, pregabalin) are first-line treatments for RLS 3
     • Iron supplementation if indicated by lab values 3

3. Timing adjustment - If possible, administer lurasidone earlier in the day rather than in the evening to minimize nighttime RLS symptoms 3

Risk Factors for Drug-Induced RLS

• Older age increases risk of drug-induced RLS 4
• Gastrointestinal diseases can increase risk 4
• Higher medication doses increase likelihood of RLS symptoms 4
• Concurrent use of multiple medications that can affect RLS (≥2 drugs) increases risk 4

Prevention and Monitoring

• Monitor for early signs of RLS when starting lurasidone, including:

  • Urge to move the legs accompanied by uncomfortable sensations 1
  • Symptoms that begin or worsen during periods of rest 1
  • Relief with movement 1
  • Symptoms that worsen in the evening or at night 1

• For patients already diagnosed with RLS, carefully weigh the risks and benefits of starting lurasidone, as it may significantly worsen their condition 1, 3

Remember that drug-induced RLS treatment primarily involves identifying and withdrawing the causative medication when possible, or decreasing its dosage if discontinuation is not an option 4.