Abstract

Abstract Introduction Although commonly described in the blind population, diagnosis in sighted individuals can be difficult due to perceived rarity and underlying co-morbid conditions. Our objective was to identify the characteristics of N24 rhythm individuals, and responses to varied treatments. Methods Patients were identified to have non-24-hour sleep wake syndrome (N24) via history, sleep diaries or digital logs, paired melatonin profiling as well as actigraphy through retrospective chart review at the Beth Israel Deaconess Medical Center, Sleep Disorders Clinic. Results 37 patients were identified from 2007 to 2019 with N24 syndrome, BMI of 28, and 67% male. The mean age of onset was within the teenage years (16), and age at diagnosis of 35 years. Paired melatonin profiles (24-hour salivary melatonin, 3-hourly, separated by 7 days, in the subject’s own home) showed “movement”. Depression and anxiety were seen in 54% and 29% of the cohort respectively. 75% (28) of the patients had a treatment strategy involving light, and 54% (20) included melatonin. The combination of melatonin and light led to a clinical improvement in 41% of individuals under that regimen (17). Low dose lithium (8 subjects) enhanced melatonin/light responses. A strategy of combining the orexin antagonist suvorexant with melatonin or ramelteon (3 subjects) helped stabilize the circadian rhythm. Tasimelteon treatment has been initiated in 4 subjects. Conclusion These data suggest that while comorbid psychiatric conditions are prevalent, a significant proportion of the cohort did not have associated psychiatric disease. Patients reported onset of symptoms in the teenage years, however there was significant delay to diagnosis. Besides light/melatonin, orexin antagonism and low dose lithium may have benefits, but require more systematic assessments. Paired melatonin estimations could be considered as a definitive testing strategy. Support

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