1170 Iron and Modafinil Efficacy

Introduction Central diseases of hypersomnolence (CDH) are lifelong disorders characterized by excessive sleep and daytime sleepiness. Treatment options include modafinil, armodafinil, psychostimulants, pitolisant, clarithromycin, and gamma-hydroxy butyrate. Although the mechanism of action behind efficacy is poorly understood, modafinil is often the first-line therapy. Modafinil’s efficacy relies upon the integrity of brain dopamine (DA) signaling: it increases extracellular dopamine by inhibiting the dopamine transporter (DAT), and genetic deletion of the DAT renders modafinil Synaptic dopamine signaling is further highly dependent upon brain iron availability, leading us to consider whether systemic iron deficiency might impact the efficacy of common wake-promoting agents in CDH. Report of case(s) A 30-year-old woman diagnosed with Idiopathic Hypersomnia (IH) at the age of 22 self referred to our sleep center expressing concern over the loss of her modafinil’s wake-promoting benefits. Her PSG/MSLT had shown a sleep efficiency of 96%, a mean sleep latency of 4.6 minutes, and a single SOREMp on her 2nd nap of 5. She was prescribed modafinil (200mg QAM increased to BID over the past year), which provided symptomatic relief for nearly a decade. Her laboratory work revealed 5% transferrin saturation, low ferritin level ( 7 ng/ml), and normal CSF iron and orexin levels of 33 ng/ml and 261.8 pg/ml, respectively; therefore, she was started on oral iron supplements. At 2 weeks follow-up, serum transferrin saturation and ferritin levels increased to 23% and 17 ng/ml, respectively. Follow-up CSF orexin level was 266.6 pg/ml , and repeat assessments of CSF iron parameters are pending. After iron repletion, modafinil was restarted and titrated over one week to 200 mg in the morning and 100 mg in the afternoon. Subjective sleepiness improved, as evidenced by the patient regaining confidence in driving safely in excess of 70 minutes continuously. Iron deficiency negatively impacts sleep, vigilance, and motor programs in human infants and impairs synaptic dopamine signaling in animal studies. This could explain why the patient responded to Modafinil after iron was repleted. Conclusion Pre-anemic and anemic iron deficiency should be considered a potential readily treatable cause of modafinil’s lack of efficacy by way of effects upon wake-promoting brain dopamine circuits. Support (if any)