Milton K. Erman, MD

Sleep apnea, a medical disorder with significant health and behavioraleffects, is of particular interest to psychiatrists for its capacityto mimic or exacerbate symptoms of psychiatric disturbances suchas depression, anxiety and panic disorder.

Apnea presents with cessation of breathing for at least 10 secondsduring sleep. Three types of apneas have been described. In obstructivesleep apnea (OSA), cessation of breathing (gas exchange) occursdespite persistent respiratory efforts. In central apnea, thereis no respiratory effort and thus no gas exchange. Mixed apneausually begins with absent effort and terminates with obstruction.

Although most patients with obstructive and mixed apnea complainof excessive sleepiness, some OSA patients report midnocturnalawakenings. These patients may awaken with a startle or senseof panic, and complain of anxiety and insomnia at night as wellas daytime sleepiness. Brief central apneas at sleep onset arefairly common and usually clinically unimportant. Sleep onsetmay be disrupted by central apnea, generating nonre-storativesleep and complaints of insomnia.

The majority of OSA patients are men age 50 and older. Virtuallyall report a history of loud, continuous snoring. Though theymay be unaware of pauses in breathing, spouses or family memberswill describe gasping, choking or snorting breakthroughs for airconcurrent with brief arousals. Although most such patients aremoderately obese, relatively few have a classic Pickwickian habitus,and some are at or below a normal weight for their height. Thinindividuals with significant apnea are likely to show upper airwayabnormalities. These include, e.g., hypertrophic tonsils and adenoids,a low-set palate or palatal webbing, a large uvula, a large tongueor a small mandible.

Obstructive sleep apnea (OSA) is a very common disorder. A recentreport by Young and colleagues generated a conservative estimateof 9 percent prevalence in working-age men and 4 percent in working-agewomen. In addition to sleepiness, OSA symptoms include restlesssleep, headache, intellectual deterioration, impotence and moodchanges, such as irritability, emotional lability and depression.Many obstructive apnea patients deny the severity of their symptoms.

Serious medical complications may develop in persistent apnea.Complications can include pulmonary and systemic hypertension,congestive heart failure and cardiac arrhythmias. The pathogenesisof this disorder probably relates both to disrupted nocturnalsleep and to brain and systemic anoxia. Even with severe disturbance,marked improvement and even complete cure may be attained withappropriate therapy.

Sleep position often influences OSA. Most patients snore moreloudly in the supine position; bed partners often "encourage"them to move to their side while asleep. 

Cartwright showed that some patients who have repetitive apneaswhile sleeping on their backs may breathe normally when they sleepon their side.

Polysomnography (PSG) is a diagnostic procedure for sleep apnea,performed in a sleep disorders center. Although PSG is expensive,it provides critical diagnostic information. Typical PSG monitoringfor sleep apnea would include recordings of electroencephalogram(EEG), electrocardiogram (EKG), eye movements or electrooculogram(EOG), body muscle tone (EMG) and body movement, respiratory effortfrom the chest and abdomen, airflow, snoring and blood oxygensaturation.

New diagnostic approaches have become available in recent years.Some use new technology; others have been developed in responseto economic pressures of the managed care environment. Technologynow allows patients to be recorded in a home or hospital settingwithout a technician in attendance, with remote monitoring capabilityvia modem. Other limited recording approaches include montageswithout EEG or other typical "scoring" channels, oruse of oximetry alone as a screening device.

Various medications have been explored as treatments for OSA.Acetazolamide (Diamox) has respiratory stimulant properties, butis apparently not effective in the treatment of OSA. Whyte andassociates showed that despite a reduction in apnea/hypopnea frequencywith acetazolamide, there was no symptomatic benefit, and paresthesiaswere common. Medroxyprogesterone (Amen and others) also has somerespiratory stimulant properties. Although it has been suggestedas a treatment for OSA, studies performed by Cook and colleaguessuggest that it provides little if any therapeutic benefit.

Protriptyline (Vivactil), a tricyclic antidepressant generallydescribed as a more "stimulating" agent than other tricyclics,has been used in the treatment of several sleep disorders includingnarcolepsy and OSA. Brownell and colleagues proposed rapid eyemovement (REM) sleep suppression to explain improvement in OSAseverity, but Stepanski and associates interpreted improvementin oxygenation, respiratory events and arousals as not being causedby REM suppression. 

Although mechanisms of protriptyline effects on sleep apnea arenot known, Bonora and others focused on its capacity to raiseskeletal muscle tone in sleep and, perhaps particularly in REM,preventing airway collapse and decreasing apnea severity. Sériesand Cormier demonstrated that protriptyline treatment producedimprovements in oxygen and carbon dioxide levels in patients withchronic obstructive pulmonary disease, suggesting a possible primaryrespiratory stimulant effect.

Nortriptyline (Pamelor) and desipramine (Norpramin) may providealternatives to protriptyline. Sunderrajan and colleagues describedeffects of nortriptyline treatment in a 61-year-old male withsevere renal disease. Treatment of depression with nortriptylineat a dose of 125 mg provoked severe hyperventilation. Medicationwas stopped and restarted with similar results. In patients intolerantof protriptyline side effects, we have used nortriptyline withreported improvement in snoring and OSA symptoms.

A study comparing fluoxetine (Prozac) with protriptyline in 12OSA patients was performed by Hanzel and colleagues. Both drugsdecreased the proportion of REM sleep time and decreased the numberof apneas in non-REM sleep. For the entire group, no sig-nificantimprovement was seen for either drug in oxygenation, desaturationevents or arousals. Wide variability was seen in response to eachmedication, but six of the 12 patients had a good response toone or both medications. Fluoxetine was better tolerated overall.

Sullivan's description of the use of nasal continuous positiveairway pressure (CPAP) ventilation for OSA established a "goldstandard" against which other treatments can now be measured.CPAP functions as a "pneumatic splint" to maintain apatent airway, preventing pharyngeal collapse despite the negativepressure of inspiration. The effects of even a single night'streatment may be remarkable. Advances in CPAP technology includeramp settings to allow gradual increases in pressure at the startof the night, systems to maintain appropriate pressure settingsdespite small leaks, BIPAP (bilevel CPAP), and alternate deliverymasks and apparatus. Although nasal CPAP is a mainstay of treatment,some patients are not able to adapt to it. In addition, as manyas 30 percent to 40 percent of patients provided CPAP cannot beconfirmed as using it on a regular basis in long-term follow-upstudies.

The first reported use of an oral prosthesis to open the mouthand advance the mandible was by Robin. In 1985, the use of sucha device in adults with OSA was reported by Soll and George. Threeyears earlier, Cartwright and Samelson described a tongue-retainingdevice (TRD) used to bring the tongue forward and away from theposterior pharyngeal walls. 

Menn and associates from our group have reported on our experiencewith 23 patients with OSA ranging from mild to severe. We treatedthem with an oral prosthesis, the mandibular repositioning device(MRD), and followed for a period of 27 to 36 months. Twenty reporteddramatic improvement in snoring (per bed partner report). Improveddaytime alertness was reported in 18 to 20 and was objectivelyconfirmed in nine of the 12 patients tested. Our experience confirmedthat the MRD provided acceptable treatment of mild to moderateOSA for a period of up to two years.

In general, use of alcohol and most other CNS depressants in thehours before bedtime should be avoided. For example, Mitler andcolleagues have shown that a 2 mL per kg dose of 100-proof alcohol(about 4.7 oz for a 70 kg individual) can double the number ofapneas seen in asymptomatic snorers. Sedatives presumably worsenapnea by promoting relaxation of the airway musculature and bydecreasing arousability. It is not clear that the benzodiazepineand imidazopyridine hypnotic agents significantly worsen apnea,but until proven otherwise these agents are best avoided by theapneic patient.

It is often erroneously assumed that all sleep apnea patientsare grossly obese. Although snoring and apnea usually worsen withweight gain, weight loss alone is rarely a viable treatment optionfor obstructive apnea. Many patients with significant sleep apneaare thin, within a normal weight range or only mildly overweight.In these "thin" patients, oropharyngeal or mandibular/maxillofacialabnormalities are likely to be present. Even for severely overweightpatients, weight loss substantial enough to reduce apnea severityis generally elusive. Many have been advised for years to reduceweight to decrease risks of hypertension, heart disease or otherdiseases, but have been unable to do so.

A number of surgical approaches have been tried in treatment ofOSA. Septoplasty and tracheostomy have both been used but havefallen from favor, although for different reasons. Nasal surgeryrarely alleviates snoring and is of less help for OSA. Althoughtracheostomy is effective in immediately reversing even very severesleep apnea, it is now rarely used even when no effective alternativesare immediately available. It can be of great benefit to patientswho are intolerant of or refuse to use nasal CPAP.

Uvulopalatopharyngoplasty (UPPP) surgery to remove tissue fromthe soft palate and oral mucosa, developed to treat snoring, hasbeen used in OSA. Although it may provide relief for simple snoringand perhaps for mild apnea, it does not improve survival ratesfor patients with significant sleep apnea and has been performedwith decreasing frequency as a treatment for OSA in recent years.

Laser-assisted uvuloplasty (LAUP) is a modified version of UPPP.It may reduce snoring with fewer side effects than the "scalpel"UPPP. It is not yet clear that LAUP is superior to the traditionalUPPP treatment   for sleep apnea. Further studies are needed to determine whether it is an acceptable      alternative.

Other surgical procedures utilized in OSA include mandibular-maxillaryadvancement, combined with UPPP and other techniques. These proceduresare usually reserved for young patients with anatomic abnormalitiesor patients with significant sleep apnea intolerant of or unwillingto use nasal CPAP.

Obstructive sleep apnea is a remarkably common medical disorder.Laboratory or other objective evaluation is usually needed todetermine whether simple snoring or frank obstructive apnea ispresent, and to characterize the severity of the apnea. Greatstrides have been made in the development of medical and surgicaltherapies, so that a broad range of options is available. Thereis now improved likelihood of successful outcome provided by individualizedtreatment approaches with efficacy to reduce the long-term healthrisks associated with this disorder.

 Bonora M, St. John W, Bledsoe T. Differential elevation byprotriptyline and depression by diazepam of upper airway respiratorymotor activity. 

 Brownell L, West P, Sweatman P, et al. Protriptyline in obstructivesleep apnea: A double blind trial. 

 Cartwright R. Effect of Sleep position on sleep apnea severity.

 Cartwright R, Samelson C. The effects of a nonsurgical treatmentfor obstructive sleep apnea: The tongue retaining device. 

 Cook W, Benich J, Wooten S. Indices of severity of obstructivesleep apnea do not change during medroxyprogesterone acetate therapy.

 Hanzel DA, Proia NG, Hudgel DW. Response of obstructive sleepapnea to fluoxetine and protriptyline. 

 Menn S, Berger J, Morgan T, et al. Efficacy of a jaw advancementdevice in the treatment of sleep apnea: Nighttime and daytimepolysomnography. 

 Mitler M, Dawson A, Henriksen S, et al. Bedtime ethanol increasesresistance of upper airways and produces sleep apneas in asymptomaticsnorers. 

 Robin P. Glossosis due to atresia and hypotrophy of the mandible.

 Séries F, Cormier Y. Effects of protriptyline on diurnaland nocturnal oxygenation in patients with chronic obstructivepulmonary disease. 

 Soll B, George P. Treatment of obstructive sleep apnea witha nocturnal airway patency appliance. 

 Stepanski E, Conway W, Young D, et al. A double-blind trialof protriptyline in the treatment of obstructive sleep apnea.

 Sullivan C, Issa F, Berthon-Jones M, Eves L. Reversal of obstructivesleep apnea by continuous positive airway pressure applied throughthe nares. 

 Sunderrajan S, Brooks CS, Sunderrajan EV. Nortriptyline-inducedsevere hyperventilation. 

 Whyte K, Gould G, Airlie M, et al. Role of protriptyline andacetazolamide in the sleep apnea/hypopnea syndrome. 

 Young T, Palta M, Dempsey J, et al. The occurrence of sleep-disorderedbreathing among middle-aged adults. 

Milton K. Erman, MD

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