The combination of atomoxetine and oxybutynin for the treatment of obstructive sleep apnea in children with Down syndrome.

STUDY OBJECTIVES: Children with Down syndrome (DS) are at very high risk for obstructive sleep apnea (OSA). Current OSA treatments have limited effectiveness in this population. We evaluated the effectiveness of atomoxetine and oxybutynin (ato-oxy) to treat OSA in children with Down syndrome. METHODS: Children ages 6-7 years old with Down syndrome and OSA participated in a double-blind crossover clinical trial evaluating two dose regimens of ato-oxy. Participants received low-dose ato-oxy (0.5 mg/kg atomoxetine and 5 mg oxybutynin) and high-dose ato-oxy (1.2 mg/kg atomoxetine and 5 mg oxybutynin) for 1 month in random order. The primary study outcome was change in obstructive apnea-hypopnea index. Health-related quality of life as measured by the OSA-18 as well as changes in sleep architecture were secondary outcomes. RESULTS: Fifteen participants qualified for randomization and 11 participants had complete data at all points. Baseline obstructive apnea-hypopnea index was 7.4 ± 3.7 (mean ± standard deviation), obstructive apnea-hypopnea index with low-dose ato-oxy was 3.6 ± 3.3 (P = .001 vs baseline), and obstructive apnea-hypopnea index with high-dose ato-oxy was 3.9 ± 2.8 (P = .003 vs baseline). No significant sleep architecture differences were present with ato-oxy. No significant difference in OSA-18 score was present. OSA-18 total score was 51 ± 19 at baseline, 45 ± 17 (P = .09) at the end of 4 weeks of low-dose ato-oxy, and 45 ± 16 (P = .37) at the end of high-dose ato-oxy therapy. The most common adverse effects were irritability and fatigue, and these were generally mild. CONCLUSIONS: Ato-oxy is a promising treatment for OSA in children with Down syndrome. CLINICAL TRIAL REGISTRATION: Registry: Clinicaltrials.gov; Name: Medications for Obstructive Sleep Apnea In Children With Down Syndrome (MOSAIC); URL: https://clinicaltrials.gov/ct2/show/NCT04115878; Identifier: NCT04115878. CITATION: Combs D, Edgin J, Hsu C-H, et al. The combination of atomoxetine and oxybutynin for the treatment of obstructive sleep apnea in children with Down syndrome. J Clin Sleep Med. 2023;19(12):2065-2073.

The effects of time horizon and guided choices on explore-exploit decisions in rodents.

Humans and animals have to balance the need for exploring new options with exploiting known options that yield good outcomes. This tradeoff is known as the explore-exploit dilemma. To better understand the neural mechanisms underlying how humans and animals address the explore-exploit dilemma, a good animal behavioral model is critical. Most previous rodents explore-exploit studies used ethologically unrealistic operant boxes and reversal learning paradigms in which the decision to abandon a bad option is confounded by the need for exploring a novel option for information collection, making it difficult to separate different drives and heuristics for exploration. In this study, we investigated how rodents make explore-exploit decisions using a spatial navigation horizon task (Wilson et al., 2014) adapted to rats to address the above limitations. We compared the rats' performance to that of humans using identical measures. We showed that rats use prior information to effectively guide exploration. In addition, rats use information-driven directed exploration like humans, but the extent to which they explore has the opposite dependance on time horizon than humans. Moreover, we found that free choices and guided choices have different influences on exploration in rodents, a finding that has not yet been tested in humans. This study reveals that the explore-exploit spatial behavior of rats is more complex than previously thought. (PsycInfo Database Record (c) 2023 APA, all rights reserved).