Rescue Pharmacotherapy for OSA

Inclusion criteria

• Individuals who have failed MAD or HGNS therapy, defined as a residual AHI ≥ 15 events/hr on MAD or HGNS therapy.

Exclusion criteria

• Sleep disordered breathing or respiratory disorders other than obstructive sleep apnea:

central sleep apnea (>50% of respiratory events scored as central), chronic hypoventilation/hypoxemia (awake SaO2 < 92% by oximetry) due to chronic obstructive pulmonary disease or other respiratory conditions.

• Other sleep disorders: periodic limb movements (periodic limb movement index > 20/hr), narcolepsy, or parasomnias.
• Any unstable major medical condition.
• Medications expected to stimulate or depress respiration (including opioids, barbiturates, benzodiazepines, doxapram, almitrine, theophylline, 4-hydroxybutanoic acid).
• Use of SSRIs/SNRIs.
• Contraindications for atomoxetine, including:
• pheochromocytoma
• use of monoamine oxidase inhibitors
• benign prostatic hypertrophy, urinary retention
• untreated narrow angle glaucoma
• bipolar disorder, mania, psychosis
• clinically significant constipation, gastric retention
• pre-existing seizure disorders
• clinically-significant kidney disorders
• clinically-significant liver disorders
• clinically-significant cardiovascular conditions
• severe hypertension (SBP>180 mmHg or DBP>110 mmHg measured at baseline)
• cardiomyopathy (LVEF<50%) or heart failure
• advanced atherosclerosi
• history of cerebrovascular events
• history of cardiac arrhythmias e.g., atrial fibrillation, QT prolongation
• other serious cardiac conditions that would raise the consequences of an increase in blood pressure or heart rate
• myasthenia gravis
• pregnancy/breast-feeding
• Contraindications for eszopiclone, including:
• Hypersensitivity to eszopiclone
• Chronic Obstructive Pulmonary Disease (COPD)
• Pregnancy
• Breast feeding
• Liver disease
• Contraindications for acetazolamide, including:
• Hyperchloremic acidosis
• Hypokalemia
• Hyponatremia
• Adrenal insufficiency
• Impaired kidney function
• Hypersensitivity to acetazolamide or other sulfonamides.
• Marked liver disease or impairment of liver function, including cirrhosis.
• Contraindications for trazodone, including:
• suicidal ideation
• bipolar disorder, mania
• use of monoamine oxidase inhibitors
• coronary artery disease
• cardiac arrhythmias
• QT prolongation
• hepatic disease
• renal failure or impairment
• closed angle glaucoma
• priapism
• pregnancy/breast-feeding