Quetiapine modestly improves sleep and breathing but impairs next day performance in people with OSA and difficulty maintaining sleep: A randomized controlled trial

Abstract Rationale Quetiapine is commonly prescribed “off-label” to people with insomnia symptoms. People with undiagnosed obstructive sleep apnea (OSA) frequently report insomnia symptoms, particularly difficulties maintaining sleep. In 2023, 10.7 million prescriptions were dispensed for quetiapine in the United States. Yet, there is limited information regarding the effects of quetiapine on sleep, breathing, and next-day performance in people with OSA. Objectives To determine the effects of 50 mg of quetiapine versus placebo on OSA severity and other polysomnographic parameters plus next day vigilance and driving simulator performance in people with OSA who also reported difficulty maintaining sleep. Methods We performed a double-blind, randomized, placebo-controlled, cross-over study (NCT05303935) in 15 people with OSA and difficulty maintaining sleep. Participants were studied overnight via polysomnography twice ∼1 week apart and received either 50 mg of quetiapine or placebo (order randomized) just prior to sleep. A 10-minute psychomotor vigilance task (PVT) and 30-minute driving simulator test were performed each morning. Results Compared to placebo, quetiapine reduced the apnea/hypopnea index (primary outcome) (Mean ± SD 27 ± 16 vs. 20 ± 12 events/h, P = .009), arousal index (32 ± 16 vs. 25 ± 9 arousals/h, P = .012), and increased sleep efficiency (80 ± 11 vs. 87 ± 9%, P .001) without worsening hypoxemia (mean overnight SpO2 94.7 ± 1.2 vs. 94.5 ± 1.5%, P = .38). However, next morning vigilance (median PVT reaction time 336 ± 48 vs. 382 ± 84 ms, P = .008) and driving simulator performance (steering deviation 72 ± 38 vs. 96 ± 53 cm, P .01) were significantly impaired with quetiapine. Conclusions Consistent with a hypnotic effect, a single night of low-dose quetiapine reduced OSA severity as measured via the apnea/hypopnea index and increased sleep efficiency without worsening overnight hypoxemia. However, there was evidence of next day impairment in vigilance and driving simulator performance. Clinical Trial Registration NCT05303935 Primary Source of Funding National Health and Medical Research Council of Australia (1196261).