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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.

SUBMITTER: Taranto-Montemurro L

PROVIDER: S-EPMC5437721 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Desipramine improves upper airway collapsibility and reduces OSA severity in patients with minimal muscle compensation.

Taranto-Montemurro Luigi L Sands Scott A SA Edwards Bradley A BA Azarbarzin Ali A Marques Melania M de Melo Camila C Eckert Danny J DJ White David P DP Wellman Andrew A

The European respiratory journal 20161006 5

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 treatm ...[more]

PMID: 27799387

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Project description:STUDY OBJECTIVES:Obstructive sleep apnea (OSA) results from the interaction of several physiological traits; specifically a compromised upper airway anatomy and muscle function, and two key non-anatomical deficits: elevated loop gain and a low arousal threshold. Although continuous positive airway pressure (CPAP) is an efficacious treatment, it is often poorly tolerated. An alternative approach could involve administering therapies targeting the non-anatomic causes. However, therapies (oxygen or hypnotics) targeting these traits in isolation typically improve, but rarely resolve OSA. Therefore, our aim was to determine how the combination of oxygen and eszopiclone alters the phenotypic traits and OSA severity and to assess the baseline phenotypic characteristics of responders/nonresponders to combination therapy. METHODS:In a single-blinded randomized crossover study, 20 OSA patients received combination therapy (3 mg eszopiclone and 40% oxygen) versus placebo/sham air, with 1 w between conditions. Under each condition, we assessed the effects on OSA severity (clinical polysomnography) and the phenotypic traits causing OSA using CPAP manipulations (research polysomnography). RESULTS:Combination therapy reduced the apnea-hypopnea index (51.9 ± 6.2 vs. 29.5 ± 5.3 events/h; P < 0.001), lowered both the ventilation associated with arousal (5.7 ± 0.3 vs. 5.2 ± 0.3 L/min; P = 0.05) and loop gain (3.3 ± 0.5 vs. 2.2 ± 0.3; P = 0.025). Responders to therapy (apnea-hypopnea index reduced by > 50% to below 15 events/h; n = 9/20) had less severe OSA (P = 0.001), a less collapsible upper airway (P = 0.01) and greater upper airway muscle effectiveness (P = 0.002). CONCLUSIONS:The combination of lowering loop gain and raising the arousal threshold is an effective therapy in patients whose anatomy is not severely compromised. Our work demonstrates that combining therapies that target multiple traits can resolve OSA in selected individuals. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov, ID: NCT01633827.

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Desipramine improves upper airway collapsibility and reduces OSA severity in patients with minimal muscle compensation.

Publications

Desipramine improves upper airway collapsibility and reduces OSA severity in patients with minimal muscle compensation.

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