Does fluoxetine (selective serotonin reuptake inhibitor) worsen restless leg syndrome?

Fluoxetine and Restless Leg Syndrome

Yes, fluoxetine can worsen restless leg syndrome (RLS) symptoms through its serotonergic mechanism of action, which may interfere with dopaminergic pathways involved in RLS pathophysiology. 1, 2

Mechanism of Worsening

• Serotonergic medications, including selective serotonin reuptake inhibitors (SSRIs) like fluoxetine, are specifically identified as medications that can exacerbate RLS symptoms 3
• Fluoxetine appears to increase periodic limb movements that may not disrupt sleep but could still contribute to RLS symptomatology 1
• The American Academy of Sleep Medicine recommends addressing potential exacerbating factors, including serotonergic medications, when managing RLS 3

Evidence from Research

• Systematic reviews indicate that SSRIs like fluoxetine can cause or worsen RLS symptoms and increase periodic limb movements in some patients 1
• Approximately 5-10% of patients taking SSRIs like fluoxetine may experience new-onset or worsening of RLS symptoms 2
• Case reports have specifically linked fluoxetine to RLS, with symptoms typically emerging within days of starting therapy 4

Management Recommendations

• For patients with existing RLS who require antidepressant therapy, consider alternatives to fluoxetine when possible 3, 5
• Bupropion may be a better choice as it has been reported to potentially reduce RLS symptoms, at least in the short term 1
• However, the American Academy of Sleep Medicine suggests against the use of bupropion for treating RLS itself (conditional recommendation, moderate certainty of evidence) 3

First-Line Treatment Options for RLS

• Alpha-2-delta ligands (gabapentin, gabapentin enacarbil, or pregabalin) are strongly recommended as first-line pharmacological treatment for RLS 3, 5
• Check serum iron studies, including ferritin and transferrin saturation, in all patients with RLS 3
• Consider iron supplementation if serum ferritin ≤75 ng/mL or transferrin saturation <20% 3, 5

Monitoring and Follow-up

• If a patient develops or experiences worsening of RLS while taking fluoxetine, consider switching to an antidepressant less likely to exacerbate RLS 5
• Monitor for early signs of RLS when starting fluoxetine, including urge to move the legs accompanied by uncomfortable sensations, symptoms that begin or worsen during periods of rest, relief with movement, and symptoms that worsen in the evening or at night 5

Cautions and Contraindications

• Avoid dopaminergic agents like levodopa, pramipexole, ropinirole, and rotigotine as first-line therapy due to risk of augmentation with long-term use 3
• The American Academy of Sleep Medicine specifically recommends against the standard use of these agents due to concerns about augmentation 3

Remember that the relationship between fluoxetine and RLS is dose-dependent, so if fluoxetine must be continued, using the lowest effective dose may help minimize RLS symptoms 2.