Effect of viloxazine and trazodone in obstructive sleep apnoea: a randomised, placebo-controlled, cross-over study
- PMID: 40360261
- DOI: 10.1136/thorax-2024-222513
Effect of viloxazine and trazodone in obstructive sleep apnoea: a randomised, placebo-controlled, cross-over study
Abstract
Introduction: Combination of the noradrenergic atomoxetine with either the antimuscarinic aroxybutynin or trazodone has been shown to improve obstructive sleep apnoea (OSA) severity. However, atomoxetine may contribute to apnoea-cycling and reduced drug tolerability due to wake-promoting, especially in a subgroup (poor cytochrome 2D6 metabolisers leading to higher blood concentration of medication). We investigated the effect of a potentially more manageable noradrenergic, viloxazine, with and without trazodone, on OSA severity.
Methods: In this double-blind, placebo-controlled, cross-over study, 24 patients with OSA (18-75 years) were analysed and randomised to 500 mg viloxazine, 500/75 mg viloxazine-trazodone (vilo-trazo) or placebo; taken before bed for 2 weeks with 1-week washout between treatments. In-laboratory polysomnography was performed at the end of each cross-over period. Mixed-model analyses compared the effect of vilo-trazo versus placebo on AHI4 (apnoea-hypopnoea index with 4% desaturations; primary outcome) and hypoxic burden (secondary outcome). Additional outcomes examined the effects of vilo-trazo versus viloxazine on total sleep time (TST) and wake-after-sleep-onset (WASO). Safety endpoints (patient-reported outcomes, heart rate and adverse events) were also assessed.
Results: Vilo-trazo reduced AHI4 (mean difference (95% CI): 10.5 (6.6, 13.6) events/hour, p<0.001) and hypoxic burden (16.7 (9.6, 21.8) %min/hr, p<0.001) versus placebo. Compared with viloxazine, TST tended to be longer on vilo-trazo (22.3 (-1.4, 46.0) min, p<0.065), while WASO was unchanged. TST and WASO remained significantly reduced on vilo-trazo versus placebo. Both interventions worsened patient-reported outcomes, although to a lesser extent on vilo-trazo, and increased heart rate versus placebo. Commonly reported adverse events were insomnia, constipation, headache and xerostomia.
Conclusions: Viloxazine-trazodone reduced OSA severity. Potential deleterious effects of viloxazine on sleep quality appeared partly attenuated by trazodone.
Trial registration number: NCT05793684.
Keywords: Respiratory Measurement; Sleep; Sleep apnoea.
© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.
Conflict of interest statement
Competing interests: AAi (corresponding author) has served as a consultant for Apnimed Inc in the past. HP, LG and LT-M are employees at Apnimed. DV serves as a consultant for Inspire Medical Systems. AAi reports grant support from Somnifix and serves as a consultant for Somnifix, Respicardia, Eli Lily, Inspire, Cerebra and Apnimed. AAz and AW serves as a consultant for Apnimed, Nox, Inspire, Mosanna and Takeda. He has received grants from Prosumnus. He also has a financial interest in Apnimed Corp., a company developing pharmacological therapies and wearable oximetry devices for sleep apnoea. AW interests were reviewed and are managed by Brigham and Women’s Hospital and Partners HealthCare in accordance with their conflict-of-interest policies. SS received grants from Apnimed, Prosomnus and Dynaflex, and personal fees from Apnimed, Merck, Nox Medical, LinguaFlex, Lilly, Respicardia and Forepont. LM received Apnimed grant funding for this study.
References
Publication types
MeSH terms
Substances
Associated data
LinkOut - more resources
Full Text Sources
Medical
