title: Desipramine improves upper airway collapsibility and reduces OSA severity in patients with minimal muscle compensation.
abstract: We recently demonstrated that desipramine reduces the sleep-related loss of upper airway dilator muscle activity and reduces pharyngeal collapsibility in healthy humans without obstructive sleep apnoea (OSA). The aim of the present physiological study was to determine the effects of desipramine on upper airway collapsibility and apnoea-hypopnea index (AHI) in OSA patients.A placebo-controlled, double-blind, randomised crossover trial in 14 OSA patients was performed. Participants received treatment or placebo in randomised order before sleep. Pharyngeal collapsibility (critical collapsing pressure of the upper airway (Pcrit)) and ventilation under both passive (V'0,passive) and active (V'0,active) upper airway muscle conditions were evaluated with continuous positive airway pressure (CPAP) manipulation. AHI was quantified off CPAP.Desipramine reduced active Pcrit(median (interquartile range) -5.2 (4.3) cmH2O on desipramine versus -1.9 (2.7) cmH2O on placebo; p=0.049) but not passive Pcrit(-2.2 (3.4) versus -0.7 (2.1) cmH2O; p=0.135). A greater reduction in AHI occurred in those with minimal muscle compensation (defined as V'0,active-V'0,passive) on placebo (r=0.71, p=0.009). The reduction in AHI was driven by the improvement in muscle compensation (r=0.72, p=0.009).In OSA patients, noradrenergic stimulation with desipramine improves pharyngeal collapsibility and may be an effective treatment in patients with minimal upper airway muscle compensation.
authors: Division of Sleep and Circadian Disorders, Depts of Medicine and Neurology, Brigham & Women's Hospital & Harvard Medical School, Boston, MA, USA taranto.luigi@gmail.com.
authors: Luigi
authors: L
authors: Taranto-Montemurro
authors: Division of Sleep and Circadian Disorders, Depts of Medicine and Neurology, Brigham & Women's Hospital & Harvard Medical School, Boston, MA, USA.|Dept of Allergy, Immunology and Respiratory Medicine and Central Clinical School, The Alfred and Monash University, Melbourne, Australia.
authors: Scott A
authors: SA
authors: Sands
authors: Division of Sleep and Circadian Disorders, Depts of Medicine and Neurology, Brigham & Women's Hospital & Harvard Medical School, Boston, MA, USA.|Sleep and Circadian Medicine Laboratory, Department of Physiology, Monash University, Melbourne, Australia.|School of Psychological Sciences and Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Melbourne, Australia.
authors: Bradley A
authors: BA
authors: Edwards
authors: Division of Sleep and Circadian Disorders, Depts of Medicine and Neurology, Brigham & Women's Hospital & Harvard Medical School, Boston, MA, USA.
authors: Ali
authors: A
authors: Azarbarzin
authors: Division of Sleep and Circadian Disorders, Depts of Medicine and Neurology, Brigham & Women's Hospital & Harvard Medical School, Boston, MA, USA.
authors: Melania
authors: M
authors: Marques
authors: Division of Sleep and Circadian Disorders, Depts of Medicine and Neurology, Brigham & Women's Hospital & Harvard Medical School, Boston, MA, USA.
authors: Camila
authors: C
authors: de Melo
authors: Neuroscience Research Australia (NeuRA) and the University of New South Wales, Randwick, Australia.
authors: Danny J
authors: DJ
authors: Eckert
authors: Division of Sleep and Circadian Disorders, Depts of Medicine and Neurology, Brigham & Women's Hospital & Harvard Medical School, Boston, MA, USA.
authors: David P
authors: DP
authors: White
authors: Division of Sleep and Circadian Disorders, Depts of Medicine and Neurology, Brigham & Women's Hospital & Harvard Medical School, Boston, MA, USA.
authors: Andrew
authors: A
authors: Wellman
mesh_terms: D059331:Adrenergic Neurons / Q000378:metabolism; D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000886:Anthropometry; D045422:Continuous Positive Airway Pressure; D018592:Cross-Over Studies; D003891:Desipramine / Q000627:therapeutic use*; D004311:Double-Blind Method; D004576:Electromyography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000187:drug effects* / Q000503:physiopathology; D010349:Patient Compliance; D012890:Sleep; D020181:Sleep Apnea, Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D016683:Supine Position
chemical_list: D018759:Adrenergic Uptake Inhibitors; D003891:Desipramine