title: Modafinil/armodafinil in obstructive sleep apnoea: a systematic review and meta-analysis.
abstract: Modafinil is used internationally to treat residual sleepiness despite continuous positive airway pressure in obstructive sleep apnoea (res-OSA). In 2011, the European Medicines Agency removed the indication based on an unfavourable risk-benefit profile in two trials for efficacy and all accumulated safety data. We performed a meta-analysis of all randomised controlled trials of modafinil (or armodafinil) in res-OSA to quantify efficacy and safety.We systematically searched and assessed studies from major databases, conferences and trials registries to find randomised, placebo-controlled trials of modafinil/armodafinil for ≥2 weeks in adult res-OSA treating sleepiness.We analysed 10 of the 232 articles identified that met inclusion criteria (1466 patients). Modafinil/armodafinil improved the Epworth Sleepiness Scale score (2.2 points, 95% CI 1.5-2.9) and the Maintenance of Wakefulness Test over placebo (3 min, 95% CI 2.1-3.8 min). Modafinil/armodafinil tripled adverse events and doubled adverse events leading to withdrawal but did not increase serious adverse events (hospitalisations or death).Modafinil and armodafinil improve subjective and objective daytime sleepiness in res-OSA. We believe our analysis is a fairer analysis of the risk-benefit profile of this indication. Clinicians may want to use this data to balance the risks and benefits on a case-by-case basis with their patients.
authors: The NHMRC Centres of Research Excellence, CIRUS and NEUROSLEEP, Woolcock Institute of Medical Research, The University of Sydney, Sydney, Australia julia.chapman@sydney.edu.au.
authors: Julia L
authors: JL
authors: Chapman
authors: The NHMRC Centres of Research Excellence, CIRUS and NEUROSLEEP, Woolcock Institute of Medical Research, The University of Sydney, Sydney, Australia Adelaide Institute for Sleep Health, A Flinders Centre of Research Excellence, School of Medicine, Faculty of Medicine, Nursing and Health Sciences, Flinders University, Adelaide, Australia.
authors: Andrew
authors: A
authors: Vakulin
authors: Centre for Sleep and Vigilance Disorders, Dept of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Jan
authors: J
authors: Hedner
authors: The NHMRC Centres of Research Excellence, CIRUS and NEUROSLEEP, Woolcock Institute of Medical Research, The University of Sydney, Sydney, Australia Dept of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, Australia.
authors: Brendon J
authors: BJ
authors: Yee
authors: The NHMRC Centres of Research Excellence, CIRUS and NEUROSLEEP, Woolcock Institute of Medical Research, The University of Sydney, Sydney, Australia Sydney Nursing School, The University of Sydney, Sydney, Australia.
authors: Nathaniel S
authors: NS
authors: Marshall
mesh_terms: D000328:Adult; D001559:Benzhydryl Compounds / Q000008:administration & dosage*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage; D045422:Continuous Positive Airway Pressure; D006970:Disorders of Excessive Somnolence; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D016032:Randomized Controlled Trials as Topic; D020181:Sleep Apnea, Obstructive / Q000188:drug therapy*; D012894:Sleep Stages; D012893:Sleep Wake Disorders / Q000628:therapy; D016896:Treatment Outcome; D014851:Wakefulness; D064690:Wakefulness-Promoting Agents / Q000008:administration & dosage
chemical_list: D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D064690:Wakefulness-Promoting Agents; D000077408:Modafinil