Medication Summary

Pharmacologic therapy is generally not a part of the primary treatment recommendations. Acetazolamide, medroxyprogesterone, fluoxetine, and protriptyline have been used to treat obstructive sleep apnea (OSA); however, these medications are not recommended. Modafinil is approved by the US Food and Drug Administration (FDA) for use in patients who have residual daytime sleepiness despite optimal use of CPAP. The most improvement has been seen in patients who have taken modafinil at doses of 200-400 mg/d. Armodafinil, the R-enantiomer of modafinil, is also now FDA approved for use in these patients.

Solriamfetol, a dopamine/norepinephrine reuptake inhibitor (DNRI), was approved in 2019 and is indicated to improve wakefulness in patients with excessive daytime sleepiness who have OSA.

The American Academy of Sleep Medicine (AASM), in a practice parameter and review of medical therapies for OSA,^{[153, 218]}listed the use of protriptyline as a guideline (patient care strategy based on level 2 or 3 evidence).^[218]The use of modafinil was recommended for the treatment of residual sleepiness in persons with OSA and was considered a standard treatment (generally accepted patient care strategy with level 1 or excellent level 2 evidence).

The parameters state as standards that selective serotonin reuptake inhibitors, methylxanthines, and estrogen replacement therapy should not be considered for the treatment of OSA.

Class Summary

Central nervous system (CNS) stimulants may be used to promote daytime wakefulness in sleep apnea patients who have residual daytime sleepiness despite optimal use of continuous positive airway pressure (CPAP). They treat fatigue without interfering with normal sleep architecture. Modafinil and armodafinil are indicated for OSA.

Modafinil (Provigil)

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The mechanism of action of modafinil in wakefulness is unknown. It has wake-promoting actions similar to sympathomimetic agents. It is indicated as adjunctive treatment to standard therapy for OSA/hypopnea syndrome to improve wakefulness in patients with excessive sleepiness.

Armodafinil (Nuvigil)

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Armodafinil is the R-enantiomer of modafinil (mixture of R- and S-enantiomers). It elicits wake-promoting actions similar to sympathomimetic agents, although its pharmacologic profile is not identical to those of sympathomimetic amines. In vitro, armodafinil binds dopamine transporters and inhibits dopamine reuptake. It is not a direct- or indirect-acting dopamine receptor agonist. It is indicated to improve wakefulness in individuals with excessive sleepiness associated with narcolepsy, OSA, or shift-work sleep disorder.

Class Summary

The mechanism of action by which solriamfetol improves wakefulness in patients with excessive daytime sleepiness associated with narcolepsy is unclear, but is thought to be mediated through its inhibition of dopamine/norepinephrine reuptake.

Solriamfetol (Sunosi)

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Solriamfetol is a dopamine/norepinephrine reuptake inhibitor (DNRI). It is indicated to improve wakefulness in adults with excessive daytime sleepiness associated with OSA.

Questions

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SLEEP 2017. 31st Annual Meeting of the Associated Professional Sleep Societies. Presented June 5, 2017. Abstract 0448:
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Media Gallery

Sleep-related disordered breathing continuum ranging from simple snoring to obstructive sleep apnea (OSA). Upper airway resistance syndrome (UARS) occupies an intermediate position between these extremes. Note areas of overlap among the conditions.
In this polysomnogram summary graph, obstructive sleep apnea (OSA) severity and the degree of oxygen desaturation (SpO2%) worsen in rapid eye movement (REM) sleep (the black underlined sections) compared with non-REM sleep. This is often the case in OSA patients, especially in OSA patients with comorbid lung disease.
MRI rendering of a patient without obstructive sleep apnea (OSA) (left panel) and a patient with OSA (right panel).
Top image is 3-dimensional surface renderings of the upper airway demonstrating the effect of progressive increases in continuous positive airway pressure (CPAP) from 0-15 cm of water on upper-airway volume in a patient with upper airway narrowing. CPAP significantly increases airway volume in the retropalatal (RP) and retroglossal (RG) regions. Bottom image is soft tissue images in the same patient in the RP region at analogous levels of CPAP. With increasing CPAP, the upper airway progressively enlarges, particularly in the lateral dimension. Note the progressive thinning of the lateral pharyngeal walls as the level of CPAP increases. Little movement occurs in the parapharyngeal fat pads, the white structures lateral to the airway. The first image in each series depicts the baseline upper airway narrowing present in this patient.
Potential relationship between obstructive sleep apnea-hypopnea syndrome (OSAHS) and the metabolic syndrome. OSAHS has been associated with 3 of the 5 major clinical abnormalities associated with the metabolic syndrome, which is hypertension, insulin resistance, and proinflammatory/oxidative stress. OSAHS may be contributing to and/or modulating the severity of these metabolic abnormalities.
The Mallampati Classification is illustrated. The airway class is based on this visual heuristic.
Tonsil grades.
Obstructive sleep apnea. Note the absence of flow (red arrow) despite paradoxical respiratory effort (green arrow).
Central sleep apnea (thick areas). Note the absence of both flow and respiratory effort (green double arrows).
Comparison of a central apnea (box) and obstructive apnea (circle).
Mixed sleep apnea. Note that the apnea (orange arrow) begins as a central apnea (effort absent; red double arrow) and ends as an obstructive apnea (effort present; green double arrow). Note the arousal (blue arrow) that terminates the apnea and the desaturation (purple arrow) that follows.
A 2-minute recording of sleep showing 4 hypopneas (thick arrows) and associated oxygen desaturations (red arrows). This recording illustrates the recurrent nature of the sleep-disordered breathing observed in many patients.
Effect of nasal continuous positive airway pressure (CPAP) on oxygen saturation in sleep apnea. The upper portion of this figure shows the raw oxygen saturation trace from 1 night of a sleep study. Below the raw trace are vertical lines that indicate the presence of either an apnea or hypopnea. Before CPAP, frequent respiratory events with significant desaturations occurred. During the night, CPAP was applied, resulting in the elimination of the apnea and hypopneas and normalization of the oxygen trace.
Examples of good (upper panel) and poor (lower panel) compliance. In the upper panel, the patient is using continuous positive airway pressure (CPAP) most nights and generally for more than 4 hours (solid black line). In the lower panel, the patient is using CPAP infrequently and, when used, is wearing the CPAP device for less than 4 hours.
Approach to a patient with excessive daytime sleepiness after treatment with nasal continuous positive airway pressure.

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Author

Himanshu Wickramasinghe, MD, MBBS Attending Physician, Pulmonary, Critical Care, and Sleep Medicine, Henry Mayo Newhall Memorial Hospital

Himanshu Wickramasinghe, MD, MBBS is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

Coauthor(s)

James A Rowley, MD Professor, Fellowship Program Director, Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Wayne State University School of Medicine

James A Rowley, MD is a member of the following medical societies: American Academy of Sleep Medicine, American College of Chest Physicians, American College of Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Daniel R Ouellette, MD, FCCP Associate Professor of Medicine, Wayne State University School of Medicine; Medical Director, Pulmonary Medicine General Practice Unit (F2), Senior Staff and Attending Physician, Division of Pulmonary and Critical Care Medicine, Henry Ford Hospital

Daniel R Ouellette, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society, Society of Critical Care Medicine

Disclosure: Received research grant from: Sanofi Pharmaceutical.

Chief Editor

Zab Mosenifar, MD, FACP, FCCP Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine, Professor and Executive Vice Chairman, Department of Medicine, Medical Director, Women's Guild Lung Institute, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD, FACP, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society

Disclosure: Nothing to disclose.

Additional Contributors

Ralph Downey, III, PhD Staff Sleep Specialist, Cleveland Clinic Foundation; Associate Clinical Professor of Medicine, Loma Linda University School of Medicine

Ralph Downey, III, PhD is a member of the following medical societies: American Academy of Sleep Medicine

Disclosure: Nothing to disclose.

Sat Sharma, MD, FRCPC Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba Faculty of Medicine; Site Director, Respiratory Medicine, St Boniface General Hospital, Canada

Sat Sharma, MD, FRCPC is a member of the following medical societies: American Academy of Sleep Medicine, American College of Chest Physicians, American College of Physicians-American Society of Internal Medicine, American Thoracic Society, Canadian Medical Association, Royal College of Physicians and Surgeons of Canada, Royal Society of Medicine, Society of Critical Care Medicine, World Medical Association

Disclosure: Nothing to disclose.