Treatment of Obstructive Sleep Apnea may be an Important Adjunct to Therapy of Posttraumatic Stress Disorder not to be Overlooked (2010)

THE ALMOST INEVITABLE EXPERIENCES OF LIFE-THREATENING TRAUMATA AND THE UBIQUITOUS CONFLICTS THAT PROMOTE THESE EVENTS HAVE left countless survivors with persisting cognitive, autonomic, and behavioral sequelae. Known in previous generations as battle fatigue, acute stress reaction, thousand-yard stare, soldiers heart syndrome, irritable heart, Da Costa Syndrome, shell shock, and many other designations, it was rediscovered and renamed posttraumatic stress disorder (PTSD) after its description by Friedman in 1980 as the Post-Vietnam Syndrome.1 It is estimated that as many as 15% to 30% of Vietnam combat veterans developed this disorder2 and that it affects 11% to 17% of recent Iraq and Afghanistan combat veterans.3 Current DSM IV diagnostic criteria include (A) exposure or witness to a seriously traumatic event with intense emotional response; (B) recurrent re-experiencing of the event in various ways; (C) persistent avoidance of stimuli associated with the trauma and numbing of general responsiveness; and (D) persistent autonomic, cognitive, and/or behavioral hyperarousal.4 Criterion B includes nightmares that have been designated the “hallmark symptom” of PTSD,5 and criterion D includes insomnia and other parasomnias. The nightmares typically include vivid trauma-related content. They are not exclusively REM-sleep related and emerge from all stages of sleep.

Patients typically describe insomnia and parasomnias such as loud somniloquy, and arousals resembling sleep terrors or panic. Some describe motor activation during sleep like sleepwalking or even dream enactment suggestive of REM sleep behavior disorder. Polysomnographic studies have not demonstrated consistent findings to implicate a fundamental sleep disorder of PTSD, but studies of sleep microstructure and brain imaging may offer more insight.6–8 There have been reports of increased incidence of obstructive sleep apnea (OSA) in patients with PTSD, and comorbidity is not unexpected, given the already high prevalence of OSA.9

In the paper by El-Solh and colleagues10 in this issue of SLEEP, the authors report on adherence to therapy with various modalities of positive airway pressure (PAP) in a consecutive retrospective case series of OSA in veterans with and without PTSD. Using the Computerized Patient Record System at a Veterans Affairs Healthcare System, the authors abstracted cases from a continuous 4.5-year period to compare 142 veterans with OSA and PTSD with 147 having OSA without PTSD that were matched for age, race, gender, BMI, and OSA severity indices. These individuals were seen for initial follow-up at 30 days following prescription of PAP, reflecting a loss to follow-up of only 6 PTSD subjects and one control. Adherence to PAP was defined by > 4 hours use per night for 70% of nights. Using this definition, 82 of 142 patients (57.7%) with PTSD and 43 of 147 control cases (29.3%) were non-adherent.10

In the PTSD group, non-adherence to PAP was associated with post-treatment endorsement of nightmares (P = 0.002) and PAP adherence with pre-treatment Epworth Sleepiness Scale score (P = 0.01). Nightmares were endorsed at follow-up visit by 28% of adherent and 56% of non-adherent patients, as compared with 73% of all PTSD patients prior to treatment. Adherent patients endorsed pre-treatment ESS scores greater by 2 points, compared with non-adherent patients (14.4 ± 5.3 vs 12.3 ± 5.9). This small difference suggests a relationship between symptomatic sleepiness and motivation for therapy, but is not enough to indicate much clinical significance. Though depression and substance abuse were more frequently documented in the PTSD patients, they did not distinguish adherent from non-adherent cases; neither did age, BMI, marital status, employment, substance abuse, severity of OSA, pulmonary function (FEV1), PAP modality, mask type, or pressure. Opiate medication was prescribed for more non-adherent patients (26% vs 13%) but this did not reach statistical significance. There was no significant difference for any of the common complaints about PAP use such as mask discomfort, air hunger, high pressure, claustrophobia, leaks, nasal dryness, or epistaxis.

El-Solh et al. suggest that persistent nightmares could influence treatment adherence by frequent awakenings. Indeed, this could inhibit replacement of the mask in the setting of post-awakening anxiety. It may also indicate a bidirectional relationship, with nightmare-related anxiety leading to reduced mask use and PAP or OSA-related increases in nightmare propensity. Their retrospective study does not permit evaluation of post-treatment total sleep time, sleep efficiency, or patient interview data to clarify these possible relationships. Also, the absence of quantitative PTSD assessment does not allow for comparison of PTSD severity between adherent and non-adherent patients. The authors correctly note that their chart review does not permit evaluation of initial response to PAP titration, social support system, referral source, or understanding of risk.10

The high lack of adherence to PAP in these cases of OSA in patients with PTSD poses major challenges as well as opportunities in view of the cardiovascular, metabolic, and hypersomnia risks that endanger these non-adherent patients. Furthermore, the fragmentation of their sleep can predispose them to additional morbidity such as continuing nightmares and other parasomnias that can add risk of injury. Interestingly, it has been reported that dream recall is reduced in the presence of OSA.11 However, posttraumatic nightmares might be promoted by apnea-induced arousals. It is well documented that nightmares, sleepwalking, and sleep terrors can be precipitated by sleep fragmentation such as with OSA, and diminish with PAP therapy.12,13 This would be similar for “pseudo-REM-sleep behavior disorder,”14 in which OSA-induced arousals from REM and NREM sleep result in recurrent spells of aggressive and violent dream enactment behaviors that resolve with PAP therapy, as documented by spousal report and by repeat PSG monitoring (that again confirms normal presence of REM-atonia).

Though polysomnographic studies of sleep in PTSD have shown little clinically significant sleep pathology, patients endorse many symptoms that tend not to appear in the safe, supervised environment of the sleep laboratory.6 The ubiquity of sleep symptoms, however, implicates some fundamental aberration of sleep in this disorder, and there are reports suggesting that sleep-focused treatment alleviates PTSD.15 It is reasonable, therefore, to anticipate that treatment of OSA in these individuals may improve both disorders. Hence, the finding of El-Solh et al.10 raises the question of how the fundamental PTSD symptom of the nightmare may be both facilitated by OSA and also interfere with its therapy. Any means of diminishing nightmares could possibly promote more effective treatment of OSA as well as improve PTSD. Clearly, the provocative findings of El-Solh et al. beg for prospective studies to further elucidate these important and complex issues. For instance, the possibility that imagery rehearsal therapy or pharmacotherapy with prazosin might reduce nightmares and enhance CPAP adherence must be tested.15 Might alternative therapy for OSA such as mandibular advancement appliances improve comorbid PTSD? What is the lower limit of sleep disordered breathing severity that would be additive or complicate symptoms of PTSD? What is the possibility that use of CPAP, known to cause REM rebound with increased REM density,16 might increase nightmare intensity and discourage use of CPAP? The finding of El-Solh et al.10 stimulates us to think about the fundamental relationship between PTSD and sleep as well as the practical issue of how to enhance nocturnal sleep and daytime wakefulness, as well as mitigate PTSD symptoms and cardiovascular and metabolic risks in these individuals.