Proton Pump Inhibitor-Associated Restless Legs Syndrome

Proton pump inhibitors (PPIs) are among the most commonly prescribed medications worldwide and are generally well tolerated. Although gastrointestinal adverse effects are well recognized, sleep-related adverse effects are considered uncommon and remain underrecognized. We present the case of a 41-year-old man who developed restless legs syndrome resulting in significant sleep disturbance shortly after initiation of pantoprazole therapy for nonsteroidal anti-inflammatory drug (NSAID)-induced duodenal ulcer bleeding. Despite empiric oral iron supplementation for suspected iron deficiency following acute gastrointestinal blood loss, his symptoms persisted throughout the eight-week course of therapy and resolved within several days after discontinuation of pantoprazole. Although iron deficiency represented an important alternative explanation, the close temporal relationship with pantoprazole therapy, lack of response to iron supplementation, and rapid symptom resolution following drug discontinuation suggest a probable medication-associated adverse effect. This case highlights an uncommon but potentially reversible adverse drug reaction and reinforces the importance of considering PPIs in the differential diagnosis of new-onset restless legs syndrome or sleep disturbances after initiation of therapy.