eMedicine Specialties > Pulmonology > Sleep-Related Disorders

Obstructive Sleep Apnea: Treatment & Medication

Author: Ralph Downey III, PhD, DABSM, FAASM, Associate Professor of Medicine, Pediatrics, and Neurology, Loma University School of Medicine; Adjunct Associate Professor, Department of Psychology, University of California at Riverside; Chief, Sleep Medicine, Loma Linda University Medical Center and the Loma Linda University Children's Hospital
Coauthor(s): Philip M Gold, MD, Professor of Medicine, Chief of Pulmonary and Critical Care Medicine, Medical Director of Respiratory Care, Loma Linda University Medical Center; Himanshu Wickramasinghe, MD, MBBS, Attending Physician; Pulmonary, Critical Care, and Sleep Medicine; Henry Mayo Newhall Memorial Hospital, Valencia, California
Contributor Information and Disclosures

Updated: Jul 30, 2009

Treatment

Medical Care

Overview

Board-certified sleep specialists evaluate PSG results and make treatment recommendations for obstructive sleep apnea (OSA) patients.

Summary of treatments

From least invasive and effective to most invasive and effective, treatments can be summarized as follows:

  • All patients should be offered nasal CPAP therapy first.
  • In patients with mild-to-severe OSA who refuse or reject nasal CPAP therapy, BiPAP therapy should be tried next. If this therapy fails or is rejected, OA therapy should be considered.
  • OAs may be considered first-line therapy for patients with mild OSA, particularly if they are unwilling to try nasal CPAP therapy.
  • All interventions to improve tolerance of CPAP therapy should be attempted prior to deciding that treatment has failed in a particular patient (see Follow-Up).
  • Patients in whom noninvasive medical therapy (eg, positive airway pressure, OAs) fails should be offered surgical options. Patients should be made aware of the success rates for each surgical procedure. They should be informed that they might require more than 1 surgical procedure, some fairly extensive, to cure OSA. Refer patients only to centers that have personnel experienced in these special surgical techniques.
General and behavioral measures, such as weight loss and avoidance of alcohol use, sedative use, and being in the supine position, are elements of nonsurgical treatment. Mechanical measures include OA therapy or positive airway pressure with a CPAP or BiPAP device. Pharmacologic therapy is not part of treatment. No clinically useful drug therapy is currently available.

Nasal CPAP therapy

General considerations
Initially described in 1981, nasal CPAP is currently the treatment of choice for patients with OSA and UA resistance syndrome. Continuous positive pressure is applied to the UA with a nasal mask, nasal pillows, or oronasal mask. CPAP acts as a pneumatic splint to maintain UA patency during sleep, and it is effective in the treatment of SDB. 

The CPAP device consists of a blower unit that produces positive-pressure airflow. This airflow is usually applied at the nose and is then directed through the UA. CPAP increases the caliber of the airway in the retropalatal and retroglossal regions (see Media File 4). It increases the lateral dimensions of the UA and thins the lateral pharyngeal walls, which are thicker in patients with OSA than in people without OSA.

Top image is 3-dimensional surface renderings of ...

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.

[ CLOSE WINDOW ]
Top image is 3-dimensional surface renderings of ...

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.


Application of adequate levels of nasal CPAP during sleep almost always resolves obstructive apnea and/or hypopnea, oxyhemoglobin desaturation, and RERAs from sleep. It also results in adequate sleep continuity.

Effectiveness
CPAP therapy improves daytime hypersomnolence, daytime alertness, and neuropsychiatric functioning. CPAP improves right-sided heart function, left-sided heart function in patients with left ventricular dysfunction, and systemic and pulmonary hypertension. Patients have improved quality of life, and some studies report improved survival rates. The benefits parallel those observed after tracheostomy. CPAP is effective for treating mixed apneas and some central apneas.

Compliance

Compliance may be poor. Although an average of 20-40% of patients do not use the prescribed therapy, some sleep disorder centers have achieved greater than 90-95% compliance rates with CPAP therapy. In the authors' experience, regular, close, and personalized follow-up greatly enhances compliance.

Complications and adverse effects

Pressure- and airflow-related complications include a sensation of suffocation or claustrophobia, difficulty exhaling, inability to sleep, musculoskeletal chest discomfort, aerophagia, and sinus discomfort. Pneumothorax and/or pneumomediastinum (extremely rare), pneumoencephalos (isolated case report), and tympanic membrane rupture (rare) also can occur.

Mask-related problems include skin abrasions, rash, and conjunctivitis (due to air leaks). Nasal problems can include rhinorrhea, nasal congestion, epistaxis, and nasal and/or oral dryness. Other problems include noise and spousal intolerance.

Guidelines for use
Patients with severe SDB (RDI >20-30) should be treated irrespective of their symptoms because of the increased risk of cardiovascular morbidity. Patients with an RDI of 5-20 should be treated if they have symptoms or coexistent cardiovascular disease. Patients with UA resistance syndrome may need CPAP therapy.

CPAP is titrated after the diagnostic portion of a split-night protocol or on a separate night after a diagnostic PSG. Proper titration includes identifying the minimum CPAP level that abolishes obstructive apneas and/or hypopneas, oxyhemoglobin desaturation, RERAs, and snoring in all sleep stages and in all sleep positions. The pressure needed is typically 5-20 cm of water.

BiPAP therapy 

In contrast to CPAP, which delivers a constant pressure during both inspiration and expiration, BiPAP permits independent adjustment of the pressures delivered during inspiration and expiration. The ability to set independent inspiratory positive airway pressure and expiratory positive airway pressure levels lowers mean airway pressures compared with those of CPAP. In a given patient, the expiratory positive airway pressure level that must be applied is lower than the corresponding CPAP level required to maintain airway patency.
 
No studies have conclusively demonstrated improved compliance with BiPAP devices compared with CPAP devices. In patients who cannot tolerate CPAP, a trial of BiPAP is warranted. However, BiPAP is too expensive to be used as first-line therapy, and it has no distinct advantages over CPAP therapy.

OA therapy
OAs for repositioning the mandible were first developed for the treatment of mandibular retrusion (retrognathia). Robin described an appliance, called the Monobloc device, that was used in the treatment of retrognathia. This appliance also affected the patient's airway. Subsequent designs incorporated repositioning or advancement of the mandible.

The first-recognized appliance for the management of snoring- and sleep-related breathing disorders (SRBDs) was the tongue-retaining device (TRD). This was similar to an athletic mouth guard and incorporated a pliable bulb in the front that holds the tongue forward. This bulb prevented the tongue from collapsing back into the airway during sleep.

Later, mandibular repositioners became available. These were designed for mandibular advancement. Early devices were made in one piece and locked the mandible in one position. Newer designs have separate upper and lower parts that are attached to each other and that allow for adjustability and jaw mobility. These repositioners are adjusted to advance the jaw to 60-70% of the maximum protrusion of the jaw.
 
At present, 3 basic designs of OAs are used to treat SRBD: mandibular repositioners, TRDs, and palatal lifting devices. More than 40 OAs are available to manage SRBD and OSAS.
 
OAs are believed to be effective for the following reasons:

  • OAs enlarge the UA by moving (pulling) the tongue forward (ie, with a TRD) or by moving the mandible and soft palate anteriorly (ie, with a mandibular repositioner). They open or dilate the airway. Most recent studies have been performed with mandibular repositioners.
  • The biomechanical factors responsible for the effectiveness of OAs are not completely understood. Increased tone of UA musculature is thought to be the predominant influence on the caliber and volume of the airway. Key among these muscles is the palatoglossus muscle. When the jaw is opened, the palatoglossus muscle (with other muscles in the pharyngeal airway) influences the airway to improve its caliber and stability.
  • OAs thin the lateral pharyngeal walls by exerting traction. According to imaging studies, the size of the lateral pharyngeal fat pads and the thickness of the lateral pharyngeal muscular walls are greater in patients with apnea than in healthy subjects. For OA therapy to be successful, the lateral dimension of the airway is the critical factor.
A review of the literature by the American Sleep Disorders Association (ASDA) indicated the following findings26 :
  • Overall, 51% of patients studied achieved an RDI of less than 10 with OA therapy.
  • Of patients who had a pretreatment RDI of greater than 20, 39% continued to have an RDI above this level despite OA therapy. At least 1 randomized controlled trial demonstrated that OAs have better success rates in patients with mild OSA (81%) than in those with moderate (60%) or severe (25%) OSA.
  • Continuous adjustment or replacement, as needed, improves success rates with OAs in the long term.
  • No patient characteristics predicted success with OA therapy.
  • No particular OA had any advantages over the others studied.
  • Some patients have an increase in AHI with OA treatment. 
  • Endpoints assessed in the studies of OAs varied and included an RDI of less than 10, an RDI of less than 20, or a greater than 50% reduction in the AHI. This variation made the comparison of results difficult. Furthermore, many studies did not stratify patients by severity of OSA.
  • OAs were more likely to be successful in patients with low BMIs, at a young age, with a small neck circumference, with a short soft palate, or with a small oropharynx and in treating positional OSA, as based on retrospective data analysis.

Subsequent prospective controlled clinical trials to compare OA therapy with nasal CPAP therapy to treat OSA and snoring demonstrated the following results:

  • Treatment was successful in 55% of patients using an adjustable mandibular repositioner and in 48% of patients using a nonadjustable mandibular repositioner. Treatment success was defined as a posttreatment RDI of less or equal to 10, with symptomatic relief.
  • CPAP therapy was superior to mandibular repositioning in normalizing the RDI, reducing snoring, and improving oxygenation.
  • CPAP and adjustable mandibular repositioning equally improved daytime sleepiness.
  • Most patients preferred mandibular repositioning therapy to CPAP therapy.

Treatment success with mandibular repositioners (OAs in general) appears to be inversely related to the initial RDI. A growing body of evidence now suggests that the severity of OSA is predictive of the response to OAs. In one study, OAs were more effective than UPPP in the treatment of OSA. OAs may also be useful in managing OSA syndrome if surgery fails.

The use of OAs in clinical practice is limited because of the difficulty in predicting the therapeutic response of individual patients. Tsai et al27 used a remote-controlled device to titrate OA treatment during a single-night sleep study to predict the therapeutic response. In concept, this approach is similar to titrating nasal CPAP during a single-night sleep study. Raphaelson et al28 and Petelle et al29 first demonstrated the titration of mandibular advancement during a sleep study. Petelle et al demonstrated that determining the optimum level of mandibular advancement required for an individual patient during a single-night study is possible. Of note, Tsai et al did not report the same.

Apart from raising the possibility of predicting therapeutic responses in individual patients, this titration approach potentially provides an opportunity to determine the optimum therapeutic dose of mandibular advancement required during a single-night sleep study.

Further work is required in this area because it could greatly affect the use of OAs in SRBD. This research may yield the method required to identify patients who may respond to OAs and to determine the optimum level of advancement required for an individual patient.

The 2005 AASM practice parameters for the treatment of snoring and OSA with OAs include the following recommendations:

  • The presence or absence of OSA must be determined before treatment with OAs is started in order to identify patients at risk because of complications of sleep apnea and to provide a baseline to establish the effectiveness of subsequent treatment.
  • For patients with OSA, the desired outcome of treatment includes resolution of the clinical signs and symptoms of OSA and normalization of the patient's AHI and oxyhemoglobin saturation.
  • Although OA therapy is not as effective as CPAP, OAs are indicated for use in patients with mild-to-moderate OSA who prefer OAs to CPAP, those whose condition does not respond to CPAP, those who are not appropriate candidates for CPAP, and those in whom attempted CPAP or behavioral measures (eg, weight loss, changing sleeping positions) fail.
  • Patients with severe OSA should receive an initial trial of nasal CPAP because CPAP is more effective than OA therapy. UA surgery may also supersede the use of OAs in patients for whom these operations are predicted to be highly effective in treating sleep apnea.
  • To ensure satisfactory therapeutic benefit from OAs, patients with OSA should undergo PSG or an attended cardiorespiratory (type 3) sleep study with the OA in place after final adjustment of fit is performed.

According to the guidelines listed above, the major role for OA therapy appears to be the treatment of patients with mild-to-moderate OSA who cannot tolerate CPAP (and BiPAP) therapy. These devices are relatively unlikely to benefit patients with severe OSA. Clinicians and patients prefer a titratable device, such as a mandibular repositioner, because it can be adjusted to improve both effectiveness and comfort.

Patients should receive a complete evaluation by a sleep disorders specialist and a dental professional, both of whom should be experienced in OA therapy; their close collaboration is required. Follow-up PSG after final adjustment of the device is recommended to ensure that OSA is treated adequately, particularly in patients with moderate-to-severe OSA. OA devices may resolve snoring without adequately treating OSA.

Complications and/or adverse effects include excessive salivation, dental misalignment with bite change, and tooth movement. Additionally, patients may experience temporomandibular joint pain and/or discomfort. The patient should not have notable discomfort or difficulty when opening the jaw upon awakening in the morning. Finally, patients may object to having an appliance in their mouth throughout the night.

The lack of long-term studies with OA may limit the clinician from choosing it as an option. Insurance payers may not pay for the use of OAs at this time. Check with individual insurance carriers.

Surgical Care

AASM recommendations for surgery

Nasal CPAP is the recommended initial therapy for patients with moderate-to-severe OSA (RDI >20, lowest oxyhemoglobin saturation <85%). Patients with symptomatic mild OSA also may prefer nasal CPAP therapy.

Surgery is indicated in patients who have a specific underlying abnormality that is causing the OSA.

Surgery may be indicated if noninvasive medical therapy (nasal CPAP or OA) fails or is rejected, if the patient desires such therapy, and if he or she is medically stable enough to undergo the procedure. If the patient has OSA that is moderately severe or severe (RDI >40 or lowest oxyhemoglobin saturation <80%), the patient requires perioperative airway protection with either nasal CPAP or a tracheostomy.

Surgery is indicated as initial therapy for patients with mild OSA (RDI <20, lowest oxyhemoglobin saturation >90%) if medical therapy is refused or rejected and if the patients are medically stable enough to undergo the procedure.

Obstruction

Three of 200 adults with OSA have a specific space-occupying lesion that causes an UA obstruction. Although surgical correction of such an abnormality (ie, tonsillectomy) can potentially cure OSA, most adult patients do not have such correctible lesions.

The level of obstruction in patients with SDB is classified into 3 types. Type I is obstruction in only the retropalatal region. Type II is obstruction in both the retropalatal and retrolingual regions. Type III is obstruction in only the retrolingual region.

Surgical procedures

Functional division of the pharynx into retropalatal and oropharyngeal (region posterior to the soft palate) and retrolingual and hypopharyngeal (region posterior to the vertical portion of the tongue) regions has been proposed.

Different surgical procedures have been proposed for patients with different levels of obstruction. UPPP may correct type I obstruction. Genioglossus advancement with hyoid myotomy (GAHM) may correct type III obstruction. Maxillomandibular advancement osteotomy (MMO) may correct obstruction at all levels.

Riley-Powell-Stanford surgical protocol30,31

Because several sites of obstruction may be responsible, a systematic approach for selecting surgery has been developed. This is the Riley-Powell-Stanford surgical protocol designed in 1988. The protocol has 2 phases. Phase I consists of the UPPP and GAHM procedures, and phase II consists of the more complicated MMO procedure. Patients who are not adequately treated with phase I surgery are offered phase II surgery.

For phase I surgery, perform UPPP for patients with type I obstruction, GAHM for patients with type III obstruction, and simultaneous UPPP and GAHM for patients with type II obstruction. The overall success rate for phase I surgery is approximately 61%, although patients with severe OSA (RDI >60, lowest oxyhemoglobin saturation <70%) have a success rate of only 42%.

Phase II surgery consists of MMO, in which the jaw is advanced anteriorly. With the phased protocol, the success rate has been in excess of 90% for phase II surgery.

Postoperative care and outcomes

In some patients, tracheostomy or CPAP therapy is required in the perioperative period to ensure a safe airway.

The success of these surgical procedures depends on accurate identification of the site of obstruction in the UA. Modalities available for identifying the site of obstruction include lateral cephalometry, endoscopy, fluoroscopy, CT scanning, and MRI. The accuracy of these methods in identifying the sites of obstruction is not clear. Success rates for UPPP are only approximately 50% despite preselection of patients with type I obstruction.

Data regarding surgical therapy for OSA are mainly from case series. The phased protocol of Riley-Powell-Stanford holds promise for achieving cure in patients with OSA, but further data from controlled clinical trials are needed to decide its role in the overall management of OSA.

The success rates quoted are from select centers with surgeons highly skilled in these special procedures. These results cannot be extrapolated to the general population of patients with OSA. All patients undergoing surgery for treatment of OSA should undergo follow-up PSG.

Uvulopalatopharyngoplasty

UPPP is the most common surgical procedure performed for adults with OSA. Fujita and colleagues introduced this procedure to the United States in 1981. UPPP involves removal of the tonsils (if present), the uvula, the distal margin of the soft palate, and the redundant pharyngeal tissue, as well as reshaping of the soft tissues in the lateral pharyngeal walls. 

The surgical success rate is approximately 50% when surgical success is defined as both 50% reduction in RDI and/or apnea index, and a postoperative RDI of less than 20 (or apnea index <10). This rate is despite preselection of patients with type I obstruction by using imaging and endoscopic studies. This finding highlights the inadequacy of the methods available to identify sites of UA obstruction. The outcome of UPPP is difficult to predict.
 
Although the procedure usually is well tolerated and uneventful, complications can include the following:
  • Pain with swallowing and pain with speech, usually for 1-2 weeks postoperatively
  • Hemorrhage (2-4%)
  • Swallowing difficulties, particularly regurgitation of food 
  • Long-term pharyngeal discomfort
  • Disturbance in taste
  • Numbness of tongue
  • Nasopharyngeal stenosis

Silent apnea may result. UPPP may end snoring but have no notable effect on episodes of sleep-associated obstruction. Patients must undergo postoperative PSG to rule out persistent OSA.

AASM recommendations for UPPP state "The UPPP, with or without tonsillectomy, may be appropriate for patients with narrowing or collapse in the retropalatal region. Good preoperative evaluation does not guarantee surgical success; the effectiveness of the UPPP is variable, and the procedure should be considered when non-surgical treatment options, such as CPAP have been considered."

Two studies showed that UPPP may make OSA worse, as it did in 31% of the patient population studied. Previous UPPP reduces the maximal level of pressure that patients who require CPAP therapy can tolerate. It may also compromise subsequent CPAP therapy by promoting mouth leaking. Uvulopalatopharyngoglossoplasty (UPPPG) is a modified UPPP with limited resection of the base of the tongue in which both the retropalatal and retrolingual regions of the UA are enlarged. 

Genioglossus advancement with hyoid myotomy

The genioglossus muscle is repositioned anteriorly through an inferior mandibular osteotomy (genioglossus advancement). This maneuver places the pharyngeal muscles and the base of the tongue on tension and expands the airway. The hyoid is suspended to the superior edge of the larynx and fixed in this position, adding to the effect of genioglossus advancement.

Maxillomandibular advancement osteotomy

The midface, palate, and mandible are moved forward in this procedure, increasing the space behind the tongue and increasing tension on the genioglossus muscle. This surgery is more extensive than any of the others described. It is usually reserved for patients in whom other treatment modalities fail.

Tracheostomy

This procedure bypasses the UA and is the most effective surgical procedure for treatment of OSA; it is virtually 100% effective. Unfortunately, tracheostomy is a disfiguring procedure and decreases the patient's quality of life. Tracheostomy is now reserved for patients with severe OSA in whom other medical and surgical treatment modalities fail. Tracheostomy is also used for airway protection during UA reconstructive surgery.

Other surgical options

Laser-assisted uvulopalatoplasty is successful for reducing snoring in 90% of patients, but the success rate in patients with SDB is not clear. It may cause more scarring than UPPP, and it could potentially worsen apnea. Worsened OSA has been observed in the early postoperative period after laser-assisted uvulopalatoplasty. Laser-assisted uvulopalatoplasty is not recommended for the treatment of OSA until further data are available.

Laser midline glossectomy and lingualplasty are performed to enlarge the retrolingual region by using a laser to remove a portion of the posterior aspect of the tongue. The role of these procedures in the management of SDB has yet to be defined.

Nasal surgery includes septoplasty, turbinectomy, and polypectomy and may be useful as an adjunct to other procedures or to improve CPAP compliance. Nasal surgery by itself is rarely effective for the treatment of OSA. 

Radiofrequency volumetric tissue reduction of the soft palate (somnoplasty)

Recent interest has been generated in this new technique that Powell and associates pioneered.32 Radiofrequency energy is used to ablate the soft palate. The US Food and Drug Administration (FDA) has approved this procedure for the treatment of snoring and OSA.

A midline soft palate submucosal scar is created by using a needle electrode inserted near the border of the hard palate and directing it toward the uvula. Pulses of radiofrequency energy are delivered, resulting in tissue necrosis and needle-tract fibrosis over subsequent weeks to months.

A study of 22 patients33 with mild SDB demonstrated reduced volume of the palatal tissue and improved symptoms in all subjects. However, no data are available regarding improvement of RDI and oxyhemoglobin saturation. Follow-up over 12-18 months revealed that approximately 41% of patients who underwent radiofrequency volumetric reduction of the soft palate developed recurrent snoring. Evidence showed postsurgical improvement in the severity of esophageal pressure swings, indicating that this treatment may be useful in patients with UA resistance syndrome.

One study of radiofrequency volumetric reduction of the soft palate in 12 patients demonstrated success in treating snoring, but data regarding adequate treatment of SDB are lacking.34 Data from large controlled studies are required before this technique can be recommended for the treatment of SDB. Radiofrequency volumetric reduction appears to decrease morbidity compared with UPPP, laser-assisted uvulopalatoplasty, and lingualplasty.

Finally, animal studies of radiofrequency volumetric reduction of the tongue have shown volume reduction in tongue tissue after treatment. Results of human studies are pending.

Consultations

Patients should undergo complete evaluation by a sleep disorders specialist and a dental professional, both of whom should be experienced in OA therapy; their close collaboration is required.
 
Interestingly, Antic et al report that compared with physician-directed care, simplified nurse-led care was less costly and did not produce inferior care for the management of moderate-to-severe OSA.35

Diet

Because obesity is a major predictive factor for OSA, weight reduction reduces the risk of OSA. The best data suggest that a 10% reduction in weight leads to a 26% reduction in RDI. Benefits of weight reduction in patients with SDB include the following:

  • Decreased RDI
  • Lowered blood pressure
  • Improved pulmonary function and arterial blood gas values
  • Improved sleep structure and snoring
  • Possible reduction of optimum CPAP pressure required 
Weight gain is one of the most important determinants of relapse of OSA after surgical treatment. Although accomplishing and maintaining weight reduction are difficult, the results are extremely beneficial when patients can do so. The treatment approach to SDB is not complete if weight reduction is not addressed in patients who are obese.

Activity

Patients should restrict their body positions during sleep. SDB is worse in the supine position, and some patients have apnea only in this position. Preventing the patient from assuming the supine position by using devices such as a snore ball (eg, a tennis ball sewed onto the back of the patient's pajamas) or a gravity-activated position monitor may be useful. However, these devices are cumbersome and appear to benefit only those patients with mild OSA. Patients with marked obesity may benefit from sleeping in an upright position. Additionally, the FDA has approved a specially designed pillow (PillowPositive) for the treatment of snoring and mild OSA, which maintains the patient's head and neck position during sleep to optimize UA patency.

Patients should avoid smoking. Smoking increases the risk of snoring and apnea. Smoking cessation appears to decrease the risk. Individuals who smoke are also more likely than those who do not smoke to report problems with going to sleep, maintaining sleep, and daytime somnolence.

Patients should avoid drinking alcohol and using other sedatives known to make apnea worse. Finally, patients should avoid sleep deprivation.

Medication

Although acetazolamide, medroxyprogesterone, fluoxetine, and protriptyline have been used to treat obstructive sleep apnea (OSA), none of these medications is recommended. Modafinil is an FDA-approved medication 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.

CNS stimulants

May be used to promote daytime wakefulness in sleep apnea patients who have residual daytime sleepiness despite optimal use of CPAP. Modafinil and armodafinil are indicated for OSA.


Modafinil (Provigil)

Mechanism of action in wakefulness unknown. Has wake-promoting actions similar to sympathomimetic agents. Indicated as adjunctive treatment to standard therapy for obstructive sleep apnea-hypopnea syndrome.

Adult

200 mg PO in morning or prn; may increase to 400 mg/d if needed

Pediatric

<16 years: Not established

May decrease levels of cyclosporine or steroidal contraceptives, and, to a lesser degree, theophylline; may increase drug concentration levels of diazepam, propranolol, and phenytoin

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Monitor patients closely for signs of misuse or abuse, especially those with a history of drug or stimulant abuse such as with methylphenidate, amphetamine, or cocaine; leukopenia has been reported in pediatric patients


Armodafinil (Nuvigil)

R-enantiomer of modafinil (mixture of R- and S-enantiomers). Elicits wake-promoting actions similar to sympathomimetic agents, although pharmacologic profile is not identical to sympathomimetic amines. In vitro, binds dopamine transporter and inhibits dopamine reuptake. Not a direct- or indirect-acting dopamine receptor agonist. Indicated to improve wakefulness in individuals with excessive sleepiness associated with narcolepsy, obstructive sleep apnea-hypopnea syndrome, or shift-work sleep disorder.

Adult

150 mg PO qam; may increase dose, not to exceed 250 mg/d

Pediatric

<17 years: Not established
>17 years: Administer as in adults

Weakly induces CYP1A2 and CYP3A; may decrease levels of drugs metabolized by CYP1A2 (eg, theophylline) and CYP3A (eg, cyclosporine, midazolam, triazolam, steroidal contraceptives); may inhibit CYP2C19 activity, thereby increasing serum levels of CYP2C19 substrates (eg, omeprazole, phenytoin, propranolol)

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in hepatic impairment and decrease dose with severe hepatic impairment; serious rash, including Stevens-Johnson syndrome, has been reported; other serious hypersensitivity reactions include angioedema, anaphylactoid reactions, and multiorgan hypersensitivity reactions; psychiatric adverse events (eg, mania, delusions, hallucinations, suicidal ideation) have been reported with modafinil; may increase blood pressure; monitor patients closely for signs of misuse or abuse, especially those with a history of drug or stimulant abuse (eg, methylphenidate, amphetamine, or cocaine)

More on Obstructive Sleep Apnea

Overview: Obstructive Sleep Apnea
Differential Diagnoses & Workup: Obstructive Sleep Apnea
Treatment & Medication: Obstructive Sleep Apnea
Follow-up: Obstructive Sleep Apnea
Multimedia: Obstructive Sleep Apnea
References
Further Reading
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Keywords

obstructive sleep apnea, OSA, sleep apnea, apnea, sleep disorder, snoring, sleep-related disorder, sleep disordered breathing, SDB, central apnea, obstructive apnea, mixed apnea, hypopnea, upper airway resistance syndrome, UARS, nasal continuous positive airway pressure, nasal CPAP, CPAP, apnea index, AI respiratory disturbance index, RDI, apnea-hypopnea index, AH, PSG, polysomnography, pickwickian syndrome, excessive daytime sleepiness, EDS, uvulopalatopharyngoplasty, UPPP, respiratory event–related arousal, RERA, oral appliance, OA, bilevel positive airway pressure, BiPAP, sleep-related breathing disorder, SRBD

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Contributor Information and Disclosures

Author

Ralph Downey III, PhD, DABSM, FAASM, Associate Professor of Medicine, Pediatrics, and Neurology, Loma University School of Medicine; Adjunct Associate Professor, Department of Psychology, University of California at Riverside; Chief, Sleep Medicine, Loma Linda University Medical Center and the Loma Linda University Children's Hospital
Ralph Downey III, PhD, DABSM, FAASM is a member of the following medical societies: American Academy of Sleep Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Philip M Gold, MD, Professor of Medicine, Chief of Pulmonary and Critical Care Medicine, Medical Director of Respiratory Care, Loma Linda University Medical Center
Philip M Gold, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Clinical Research, American Heart Association, American Lung Association, American Medical Association, American Thoracic Society, Association of Subspecialty Professors, California Medical Association, California Thoracic Society, Society of Critical Care Medicine, and Undersea and Hyperbaric Medical Society
Disclosure: Glaxo-Smith-Kline Honoraria Speaking and teaching; Covidien Honoraria Speaking and teaching; Boeringer-Ingleheim Honoraria Speaking and teaching

Himanshu Wickramasinghe, MD, MBBS, Attending Physician; Pulmonary, Critical Care, and Sleep Medicine; Henry Mayo Newhall Memorial Hospital, Valencia, California
Himanshu Wickramasinghe, MD, MBBS is a member of the following medical societies: American College of Chest Physicians and American Thoracic Society
Disclosure: Nothing to disclose.

Medical Editor

Sat Sharma, MD, FRCPC, Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba; Site Director, Respiratory Medicine, St Boniface General Hospital
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, and World Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Daniel R Ouellette, MD, FCCP, Associate Professor of Medicine, Wayne State University School of Medicine; Consulting Staff, Pulmonary Disease and Critical Care Medicine Service, Henry Ford Health System
Daniel R Ouellette, MD, FCCP is a member of the following medical societies: American College of Chest Physicians and American Thoracic Society
Disclosure: Boehringer Ingleheim Honoraria Speaking and teaching; Pfizer Honoraria Speaking and teaching

CME Editor

Timothy D Rice, MD, Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, Saint Louis University School of Medicine
Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians
Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD, Director, Division of Pulmonary and Critical Care Medicine, Director, Women's Guild Pulmonary Disease Institute, Executive Vice Chair, Department of Medicine, Cedars Sinai Medical Center; Professor of Medicine, David Geffen School of Medicine at UCLA
Zab Mosenifar, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, and American Thoracic Society
Disclosure: Nothing to disclose.

 
 
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