- Email: [email protected]
OSA Syndrome and Posttraumatic Stress Disorder
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Original Research Sleep Disorders
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OSA Syndrome and Posttraumatic Stress Disorder Clinical Outcomes and Impact of Positive Airway Pressure Therapy Christopher J. Lettieri, MD; Scott G. Williams, MD; and Jacob F. Collen, MD
BACKGROUND: We sought to determine the impact of OSA syndrome (OSAS) on symptoms and quality of life (QoL) among patients with posttraumatic stress disorder (PTSD). In addition, we assessed adherence and response to positive airway pressure (PAP) therapy in this population.
This was a case-controlled observational cohort study at the Sleep Disorders Center of an academic military medical center. Two hundred consecutive patients with PTSD underwent sleep evaluations. Patients with PTSD with and without OSAS were compared with 50 consecutive age-matched patients with OSAS without PTSD and 50 age-matched normal control subjects. Polysomnographic data, sleep-related symptoms and QoL measures, and objective PAP usage were obtained.
METHODS:
Among patients with PTSD, more than one-half (56.6%) received a diagnosis of OSAS. Patients with PTSD and OSAS had lower QoL and more somnolence compared with the other groups. Patients with PTSD demonstrated significantly lower adherence and response to PAP therapy. Resolution of sleepiness occurred in 82% of patients with OSAS alone, compared with 62.5% of PAP-adherent and 21.4% of nonadherent patients with PTSD and OSAS (P < .001). Similarly, posttreatment Functional Outcomes of Sleep Questionnaire $ 17.9 was achieved in 72% of patients with OSAS, compared with only 56.3% of patients with PTSD and OSA who were PAP adherent and 26.2% who were nonadherent (P < .03). RESULTS:
CONCLUSIONS: In patients with PTSD, comorbid OSAS is associated with worsened symptoms, QoL, and adherence and response to PAP. Given the negative impact on outcomes, the possibility of OSAS should be considered carefully in patients with PTSD. Close follow-up is needed to optimize PAP adherence and efficacy in this at-risk population.
CHEST 2016; 149(2):483-490
continuous positive airway pressure; CPAP adherence; obstructive sleep apnea; posttraumatic stress disorder; quality of life
KEY WORDS:
AHI = apnea-hypopnea index; ESS = Epworth Sleepiness Scale; FOSQ = Functional Outcomes of Sleep Questionnaire; OSAS = OSA syndrome; PAP = positive airway pressure; PTSD = posttraumatic stress disorder; QoL = quality of life; STOP-Bang = snoring, tiredness, observed apnea, BP, BMI, age, neck circumference, and gender; TBI = traumatic brain injury AFFILIATIONS: From the Department of Medicine (Drs Lettieri, Williams, and Collen), Uniformed Services University, Bethesda, MD; the Department of Pulmonary, Critical Care, and Sleep Medicine (Dr Lettieri), Walter Reed National Military Medical Center, Bethesda, MD; the Department of Pulmonary, Critical Care, and Sleep Medicine (Dr Williams), Womack Army Medical Center, Fort Bragg, NC; and ABBREVIATIONS:
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the Department of Pulmonary, Critical Care, and Sleep Medicine (Dr Collen), Brooke Army Medical Center, Fort Sam Houston, TX. FUNDING/SUPPORT: The authors have reported to CHEST that no funding was received for this study. CORRESPONDENCE TO: Jacob F. Collen, MD, Pulmonary, Critical Care and Sleep Medicine, San Antonio Military Medical Center, (Brooke Army Medical Center), 3551 Roger Brooke Dr, Fort Sam Houston, TX 78234; e-mail: [email protected] Published by Elsevier Inc. under license from the American College of Chest Physicians. DOI: http://dx.doi.org/10.1378/chest.15-0693
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Sleep complaints are common among patients with posttraumatic stress disorder (PTSD) and portend worsened clinical outcomes.1,2 OSA syndrome (OSAS) is particularly prevalent in PTSD.3-11 OSAS can independently diminish quality of life (QoL),12,13 and the adverse impact of sleep-disordered breathing on QoL in patients with PTSD has been demonstrated previously.5,7 Just as the presence of sleep disorders may complicate recovery in those with PTSD, resolution of sleep disruption can enhance the treatment response in affective disorders.14 Unfortunately, patients with PTSD and OSAS demonstrate low rates of positive airway pressure (PAP) adherence.15,16 Although several studies have evaluated the impact of OSAS in patients with PTSD, these have focused on
smaller, nonmilitary populations or on older veteran populations. The impact of both OSAS and PTSD on sleep-related QoL, daytime sleepiness and fatigue, PAP use, and the response to PAP therapy have not been evaluated systematically in the same population. We sought to evaluate the impact of comorbid OSAS on sleep-related symptoms and QoL among active duty military patients with PTSD. We further aimed to assess the effect of PTSD on adherence and response to PAP therapy. Given that the population represented in this study will filter out of the military health-care system and into the Veterans Affairs Healthcare System and the broader community for years to come, this study is of critical importance to physicians who care for patients who may have PTSD and OSAS.
Materials and Methods
Measured Variables
Study Design
We recorded the age, sex, and, BMI for each individual. Relevant comorbid diagnoses and symptoms were also recorded. For patients with PTSD, we recorded the number of psychoactive medications they were prescribed and their sleep-related symptoms. The degree of subjective sleepiness was assessed using the Epworth Sleepiness Scale (ESS)21, which grades daytime sleepiness with a point system from 0-24 points (point totals less than or equal to 10 are considered normal and higher scores indicate increased daytime sleepiness). The degree of fatigue or subjective tiredness was evaluated with the Stanford Fatigue Visual Numeric Scale which scores the degree of fatigue from 0 (“no fatigue”) to 10 points (“severe fatigue”).22 Sleeprelated QoL scores were assessed using the Functional Outcomes of Sleep Questionnaire (FOSQ) (e-Appendix 1).23 The total score for the FOSQ can range from 5-20 points with values less than 17.9 considered abnormal.24
We conducted an observational cohort study of 200 consecutive active duty service members receiving outpatient care for combat-related PTSD at Walter Reed Army Medical Center between 2008 and 2012. All patients were $ 18 years of age, were currently serving in the US Armed Forces, and had been given a diagnosis of PTSD following combat deployments to Iraq and/or Afghanistan. We excluded patients with preexisting PTSD and those with diagnosed sleep disorders prior to their most recent deployment. Otherwise, no records were excluded from this analysis. All available patients with PTSD following deployment were referred to our Sleep Disorders Center to undergo a comprehensive screening evaluation for sleep disorders. The study was approved by the institutional review board at Walter Reed Army Medical Center (IRB No. 355213). The diagnosis of PTSD was based on a clinical encounter with a doctorallevel behavioral health provider using the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) criteria and the PTSD Checklist Military Version,17,18 which is a subjective questionnaire that includes 17 questions (1-5 points each) addressing the 17 DSM-IV criteria for PTSD. A cutoff score of 50 points was used to assess for the presence of PTSD (17-85 points possible).18 All patients underwent a comprehensive sleep medicine evaluation within 6 months of combat deployment, including a level 1 attended, overnight polysomnography. All polysomnograms were scored and interpreted by the study investigators in accordance with guidelines published by the American Academy of Sleep Medicine.19 We compared our cohort with two separate, age and sex-matched control groups. The first group was composed of 50 consecutive matched patients with a diagnosis of OSAS but who had not deployed and did not have PTSD. The second group was composed of 50 healthy matched control subjects without prior deployment, PTSD, or clinically suspected sleep-disordered breathing. All normal subjects were administered the snoring, tiredness, observed apnea, BP, BMI, age, neck circumference, and gender (STOP-Bang) questionnaire, which has been validated as a screening tool for OSA.20 All included individuals had fewer than two STOP criteria and fewer than three STOP-Bang criteria (low pretest probability for OSA) and no clinical suspicion for sleep-disordered breathing.
484 Original Research
From polysomnographic studies, we recorded sleep efficiency (%), sleep latency (minutes), percentage of total sleep time spent in stage N3 sleep, percentage of total sleep time spent in stage R sleep, apnea-hypopnea index (AHI), total arousal index, and oxygen saturation nadir. The presence of OSAS and insomnia were determined for each patient. The diagnosis of OSAS was based on an AHI $ 5 events/h plus clinical symptoms of sleep-disordered breathing in accordance with American Academy of Sleep Medicine criteria.25 We defined insomnia as a subjective sleep latency of $ 30 min, early-morning awakenings, nonrestorative sleep, and/or subjective sleep fragmentation (nocturnal awakenings) occurring over the majority of nights for > 1 month, associated with daytime impairment.17 Those with a diagnosis of OSAS were prescribed PAP for long-term therapy. Prior to initiating treatment, all individuals received formal mask fitting and participated in a comprehensive educational program intended to familiarize them with OSAS, its clinical effects, and the available treatment options. All patients underwent a clinical evaluation after 1 month of therapy to assess PAP use and the clinical response to therapy, including an assessment of QoL (FOSQ), ESS, and fatigue scores. Objective PAP use was measured using the Respironics Encore Anywhere program (Philips Respironics) and included the percentage of nights used and the mean number of hours it was used per night.
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Outcomes The primary outcomes were the impact of comorbid OSAS on sleeprelated symptoms and QoL measures. Specifically, we compared the difference in baseline measures of the FOSQ, ESS, and Stanford fatigue visual numeric scale among patients with PTSD, PTSD and OSAS, OSAS, and normal control subjects. Secondary outcomes included the impact of PTSD on PAP adherence and response to PAP therapy based on changes in the above measures of sleepiness and QoL. We compared absolute PAP usage and rates of regular use between patients with OSAS with and without PTSD. Individuals using PAP for > 4 h per night on > 70% of nights were considered
Results Our study population consisted of 200 consecutive adult patients with PTSD. The cohort was composed predominantly of men (91.3%) with a mean age of 35.9 10.5 years and BMI of 28.7 4.5 kg/m2. Demographics were similar between those with PTSD and the two control groups. Subjective sleep complaints (daytime sleepiness and poor-quality sleep) were nearly universal (96.9%) in those with PTSD. The majority (94.4%) was prescribed psychoactive medication. The overall mean number of psychoactive medications was 3.4 1.5 per patient, and there was not a significant difference between those patients with and without OSA
TABLE 1
] Demographic and Clinical Variables Among Patients With PTSD
Variable Male sex Age, y BMI, kg/m2 Subjective sleep complaints Epworth Sleepiness Scale score (points, 0-24)a Epworth Sleepiness Scale score > 10 points Fatigue scale score (points, 0-10)b Functional Outcomes of Sleep Questionnaire score (5-20)
Patients 91.3 28.7 4.5 96.9 10.6 5.7 49.7
Data are presented as the mean 1 SD. Comparisons between categorical variables were performed using the c2 and Fisher exact tests, and differences between means using the independent samples t test and analysis of variance followed by the Tukey post hoc test. P values < .05 were considered statistically significant. Data were analyzed using the Statistical Package for Social Sciences 22.0 (IBM Corporation).
(3.2 1.4 vs 3.6 1.6, P ¼ .21). Mild traumatic brain injury (TBI) was present in 58% of the PTSD cohort (Table 1). There was not a history of TBI among the OSA-only and normal control groups. OSAS was diagnosed in 56.6% of those with PTSD, with a mean AHI of 23.1 22.7 events/h (PTSD þ OSA subgroup). The mean AHI was 1.8 1.6 events/h among those with PTSD only, and 26.9 27.4 events/h in the OSA control group. Within the PTSD cohort, those with OSAS were older and had a higher BMI. Otherwise, there were no significant differences between patients with PTSD with and without OSAS. Sleep quality was poor in the majority of the study population. Specifically, a reduced sleep efficiency was seen in 41.2% of patients, and 31.2% had a prolonged sleep latency during polysomnography. The majority experienced sleep fragmentation, with a mean total arousal index of 19.7 13.8 arousals/h. Altered sleep
TABLE 2
] Results of Polysomnography (n ¼ 200)
Variable Sleep efficiency, % Sleep efficiency < 80%, Sleep latency, min
7.1 1.7 17.8 2.8
Sleep latency > 60 min Stage N3 sleep, % Stage N3 sleep < 20%
53.1
Depression
85.7
Anxiety
40.0
Mild traumatic brain injury
58.0
Portion of cohort prescribed psychoactive medications
94.4 3.4 1.5
Data are given as % or mean SD. PTSD ¼ posttraumatic stress disorder. a The Epworth Sleepiness Scale ranges from 0-24 points. Scores that are less than or equal to 10 points are considered normal and scores greater than 10 points are indicative of excessive daytime sleepiness. b Fatigue Visual Numeric Scale: 0 points ¼ no fatigue, 10 points ¼ severe fatigue.
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Statistical Analysis
35.9 10.5
Insomnia
Psychoactive agents per subject, No.
to be using it regularly.26 We defined a resolution of sleepiness as a final ESS value of # 10, and a clinically significant improvement in QoL as an FOSQ $ 17.9.23,24
Stage REM sleep, % Stage REM sleep < 25%
Value 84.5 12.4 41.2 30.5 33.7 31.2 13.5 11.2 60.0 13.2 8.9 55.0
Total arousal index, events/h
19.7 13.8
Apnea-hypopnea index (entire cohort), events/h
16.2 21.2
Apnea-hypopnea index of those with OSA syndrome, events/h
23.1 22.7
Presence of OSA syndrome (entire cohort) O2 saturation nadir, %
56.6 86.4 6.0
Data are given as % or mean SD. O2 ¼ oxygen; REM ¼ rapid eye movement.
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architecture was also common, and a decrease in the percentage of both stages N3 and R sleep was observed in 55% and 60% of the cohort, respectively (Table 2). Although both OSAS and PTSD were associated with increased sleepiness and lower QoL indexes compared with those of normal control subjects, the presence of both led to further reductions in these measured variables than either condition independently. Daytime somnolence was common in the overall cohort, with a mean ESS value of 10.6 5.7, and 49.7% had an ESS > 10. ESS values were higher among those with PTSD and OSAS compared with those with PTSD alone and normal subjects (12.5 5.7 vs 9.5 5.2, P ¼ .002 and 12.5 5.7 vs 4.5 3.7, P < .001, respectively). Patients with PTSD and OSAS and OSAS alone had similar ESS values (12.5 5.7 vs 12.9 5.3, P ¼ .72). Fatigue was common among our cohort, with a mean Stanford fatigue visual numeric score of 7.1 1.7. Patients with PTSD (with or without OSA) experienced significantly greater fatigue compared with those with OSAS alone or with normal control subjects (Table 3). A reduced QoL, as measured by the FOSQ, was common among those with either PTSD or OSAS. However, both the absolute FOSQ score and the percentage of those with a score $ 17.9 at baseline were significantly lower in patients with both PTSD and OSAS compared with either condition alone. The proportion of those with a baseline FOSQ < 17.9 was 6.9% among normal control subjects, 24.0% in those with OSAS alone, 43.2% in those with PTSD alone, and 59.5% in those with PTSD and OSAS (Table 3). TABLE 3
All patients with OSAS were reassessed 4 weeks after initiation of PAP therapy to evaluate both adherence and the response to therapy. Patients with PTSD demonstrated significantly lower PAP adherence. Among those with PTSD and OSAS, there was not a significant difference between PAP-adherent and nonadherent patients regarding the rate of insomnia (61.5% vs 40.0%, P ¼ .24). Those with OSAS alone used PAP on 77.9% 22% of nights, for 5.8 0.9 h/night. In comparison, patients with PTSD and OSAS only used PAP on 53.3% 35.6% of nights (P < .001), for an average of 3.4 2.8 h/night (P < .001). Regular use of PAP was similarly reduced and was observed in 30.2% of those with PTSD and OSAS compared with 55.1% in those with OSAS alone (P ¼ .02) (Table 4). Patients with PTSD and OSAS also experienced a reduced treatment response compared with those with OSAS alone. Resolution of sleepiness (ESS # 10) occurred in 85.7% of PAP-adherent and 54.5% of PAP-nonadherent patients with OSA alone, compared with 72.1% of PAP-adherent and 21.4% of nonadherent patients with PTSD and OSAS (P < .001). In addition, a posttreatment FOSQ $ 17.9 occurred in 68.4% of PAP-adherent and 40.9% of PAP-nonadherent patients with OSAS alone, compared with only 56.3% of PAP-adherent and 26.2% of nonadherent patients with PTSD and OSAS (P < .03) (Fig 1).
Discussion We found that patients with PTSD and comorbid OSAS had worsened somnolence, fatigue, and sleep-related
] Comparison of Clinical and Demographic Variables Between Those With PTSD and OSAS, Those With PTSD Alone, Those With OSAS Alone, and Normal Subjects (Control Group)
Variable
PTSD and OSAS (n ¼ 113)
PTSD Alone (n ¼ 87)
OSAS Alone (n ¼ 50)
Age, y
39.5 10.6
31.3 8.7
41.5 7.6
P value BMI, kg/m2 P value ESS P value Fatigue scale P value FOSQ P value FOSQ < 17.9, % P value
. 29.6 4.8 . 12.5 5.7 . 6.9 1.7 . 14.7 3.0 . 59.5 .
< .001 27.6 3.9
.24 30.5 2.3
.003 9.5 5.2
.22 12.9 5.3
.002 7.3 1.8
.72 5.9 2.6
.38 18.0 3.0
.02
Normal (n ¼ 50) 41.4 7.6 .24 28.2 1.5 .06 4.5 3.7 < .001 2.8 2.4 < .001
18.7 1.9
19.4 1.1
< .001
< .001
.001 43.2
24.0 < .001
.15
6.9 < .001
Data are presented as mean SD unless indicated otherwise. ESS ¼ Epworth Sleepiness Scale; FOSQ ¼ Functional Outcomes of Sleep Questionnaire; OSAS ¼ OSA syndrome. See Table 1 legend for expansion of other abbreviations.
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TABLE 4
] Comparison of PAP Adherence PTSD and OSAS (n ¼ 113)
OSAS Alone (n ¼ 50)
Apnea-hypopnea index, events/h
23.1 22.7
26.9 27.4
PAP days used, %
53.3 35.6
77.9 22
Variable
P Value .41 < .001
Average use per night, h
2.6 2.6
5.8 0.9
< .001
Average use per night when PAP was used, h
3.4 2.8
4.6 1.7
.01
30.2
55.1
.02
Regular use
Data are presented as mean SD or %. PAP ¼ positive airway pressure. See Table 1 and 3 legends for expansion of other abbreviations.
QoL compared with those with either condition alone and normal subjects. Patients with PTSD and OSAS exhibited significantly worse PAP adherence, which has been documented previously.15,16 Notably, patients with PTSD and OSAS experienced a diminished response to PAP therapy and were less likely to have a resolution of symptoms than were those with OSAS only. Previous studies have documented high rates of OSAS among those with PTSD in both civilian5,8,10,27,28 and military populations.29-31 We recently evaluated 130 consecutive service members with combat-related PTSD at our institution, and 67.3% of those who underwent polysomnography for suspected sleep-disordered breathing had OSA (53.8% of cohort).31 In the current study, polysomnography was obtained in all patients regardless of a clinical suspicion for sleep-disordered breathing, and the prevalence of OSAS among individuals with PTSD was nearly identical. Not only is OSAS common in patients with PTSD, it leads to greater impairments in QoL, sleep-related symptoms, and poor daytime function.5,7,8,27 The impact of sleep-disordered breathing in patients with PTSD is
OSA: PAP Adherent PTSD + OSA: PAP Adherent OSA: PAP Nonadherent PTSD + OSA: PAP Nonadherent
80
P < .001a
70 60
68.4%
40.9%
26.2%
10
56.3%
20
21.4%
30
54.5%
40
P < .03a 72.1%
50
85.7%
Percentage of Patients
90
0 ESS < 10
FOSQ > 17.9
aANOVA
Figure 1 – Resolution of sleep-related symptoms following 1 mo of CPAP therapy. ANOVA ¼ analysis of variance; ESS ¼ Epworth Sleepiness Scale; FOSQ ¼ Functional Outcomes of Sleep Questionnaire; PAP ¼ positive airway pressure; PTSD ¼ posttraumatic stress disorder.
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not unexpected. Both conditions are associated with poor sleep quality, fatigue, and a decreased sense of wellbeing. In our population, we found that either PTSD or OSAS was associated with worsened symptoms of sleepiness, fatigue, and sleep-related QoL in comparison with normal subjects. The presence of both OSAS and PTSD led to greater impairments than either condition alone. Given the prevalence of OSAS in patients with PTSD and its adverse impact on symptoms and adherence, early identification may improve outcomes. Unfortunately, assessment tools that depend on subjective and overlapping symptoms may be of limited use in identifying specific sleep disorders in this population. Elevated fatigue scores in patients with PTSD (regardless of underlying sleep-disordered breathing) are likely driven by concomitant fragmented sleep, hyperarousal, and insomnia, which are common in these individuals. Similarly, subjective reports of daytime sleepiness and ESS values are highly variable even among patients with OSAS alone.32-34 This may account for the areas in which statistically significant differences were lacking in our cohort. The FOSQ was developed and validated originally as an instrument for evaluating the impact of OSAS on QoL and the efficacy of PAP therapy and has also become a valuable tool in assessing QoL related to other sleep disorders.23,26,35-37 Although previous smaller studies have addressed the FOSQ in patients with PTSD and comorbid sleep-disordered breathing,5,27 the current study is the first to systematically evaluate this in a large population of recent combat veterans compared with control subjects. Based on our results, the addition of sleep-related QoL measures to the commonly used measures of daytime symptoms may assist in longitudinally measuring the response to therapy in this population. Among patients with PTSD and OSAS, both daytime somnolence and QoL were improved with PAP therapy.
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Compared with patients who had poor adherence, those who used PAP regularly were more than three times as likely to resolve daytime sleepiness (ESS # 10) and more than twice as likely to have a normal QoL (FOSQ $ 17.9). Although we did not measure other PTSD-specific outcomes, prior investigations have found that treatment of comorbid OSAS improves PTSDrelated symptoms, including nightmares.6,28,38 Although treatment of OSAS improves outcomes in patients with PTSD, the response to therapy is blunted compared with the response of patients with OSAS without PTSD. In our study, patients with PTSD who used PAP regularly had more residual sleepiness and lower QoL scores compared with patients with PTSD and sleep apnea. There are several potential reasons for worsened symptoms despite PAP therapy in this population, including differences in perception based on their underlying illness, polypharmacy with psychoactive medications (which have the potential for sleep fragmentation), comorbid insomnia, and pharmacotherapy-refractory insomnia, all of which are common in service members with combat-related PTSD and sleep disorders.29,30,39,40 Given the diminished therapeutic response and the inherent barriers to successful therapy, PTSD represents an independent barrier to the effective treatment of OSAS and should prompt multipronged and individualized care. Ongoing studies are evaluating newer approaches that incorporate the biopsychosocial model, which uses holistic strategies to improve PAP adherence. Treatment may include sharing peer success stories, group education, cognitive behavioral therapy, and motivational enhancement. These strategies account for variability in patients’ ability and in their motivation for change, which are extremely relevant to the challenge of introducing PAP therapy to patients with PTSD.41-44 Currently, there are no studies that directly assess these methods in patients with PTSD and OSA. In addition, conservative lifestyle modifications, such as structured exercise programs, can improve disease severity, sleep-related symptoms, and daytime function in OSA, irrespective of weight loss.45,46 Finally, there are prospective clinical trials in progress evaluating the impact of PAP on sleep-related symptoms and QoL and comparing outcomes with PAP with mandibular advancement devices in PTSD-OSA.47,48 Limitations
Our study has several limitations. We included a cohort composed predominantly of men with recent military
488 Original Research
deployments and combat-related PTSD. As such, our findings may not reflect what is seen in other populations. As an observational study incorporating patients evaluated at a single sleep disorders center, our findings may be limited by selection bias. However, we included consecutive patients, and the population of interest (PTSD) was evaluated in our clinic based on a policy of screening following deployment, rather than a specific referral based on symptoms or clinical suspicion for a sleep disorder. Mild TBI was found in more than one-half of the patients with PTSD. The connection between TBI and OSA is well documented,49 and is also found frequently in active duty service members.39 The impact of TBI on our results is difficult to comment on in an observational study. A significant percentage of the patients in this study had comorbid insomnia, which may have impacted our results. It has been established previously that comorbid insomnia limits CPAP adherence,50,51 and pharmacotherapy refractory insomnia is a probable comorbidity in service members with sleep disorders.29,40 Additionally, we did not assess non-sleep-related symptoms, and it is unknown how the presence of OSAS affected other measures of interest in patients with PTSD (in particular, nightmares and nightmare frequency), or how these were impacted by PAP therapy. Based on chart review, the majority of patients in our study cohort had a diagnosis of depression, limiting our ability to make meaningful conclusions about the impact of PAP use in an observational study. Finally, we measured PAP use only during the first month of therapy and did not assess the long-term impact of PTSD on adherence or outcomes. However, it has been established previously that longterm PAP use can be predicted in the first few weeks of therapy.52-57
Conclusions Combat veterans with sleep complaints and PTSD represent a challenging population for sleep physicians. Given the adverse impact that comorbid OSAS and PTSD have on symptoms, QoL, adherence, and response to therapy, our results highlight the need for a high index of suspicion and a comprehensive approach to identifying and treating sleep-disordered breathing in these patients. Although PAP can significantly improve QoL in this population, the benefits are limited by poor dherence in an already compromised population. These results further advocate for a careful and individualized approach to therapy among patients with PTSD.
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Acknowledgments Author contributions: C. J. L had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis, including and especially any adverse effects. C. J. L. contributed to the study design; C. J. L., S. G. W., and J. F. C. contributed to the protocol development; C. J. L. and J. F. C. contributed to the data collection; C. J. L., S. G. W., and J. F. C. contributed to the data analysis; C. J. L., S. G. W., and J. F. C. contributed to the writing of the manuscript; and C. J. L. contributed to manuscript revision. Financial/nonfinancial disclosures: None declared. Other contributions: The views expressed herein are those of the authors and do not reflect the official policy or position of Walter Reed National Military Medical Center, Womack Army Medical Center, Brooke Army Medical Center, the US Army Medical Department, the US Army Office of the Surgeon General, the Department of the Army and Department of Defense, or the US Government. Additional information: The e-Appendix can be found in the Supplemental Materials section of the online article.
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apnea patients. J Nerv Ment Dis. 2006;194(6):433-439. 9. Mellman TA, Kulick-Bell R, Ashlock LE, Nolan B. Sleep events among veterans with combat-related posttraumatic stress disorder. Am J Psychiatry. 1995;152(1): 110-115. 10. Sharafkhaneh A, Giray N, Richardson P, Young T, Hirshkowitz M. Association of psychiatric disorders and sleep apnea in a large cohort. Sleep. 2005;28(11):1405-1411. 11. Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med. 2002;165(9):1217-1239. 12. Reimer MA, Flemons WW. Quality of life in sleep disorders. Sleep Med Rev. 2003;7(4):335-349. 13. Moyer CA, Sonnad SS, Garetz SL, Helman JI, Chervin RD. Quality of life in obstructive sleep apnea: a systematic review of the literature. Sleep Med. 2001;2(6):477-491. 14. Margolies SO, Rybarczyk B, Vrana SR, Leszczyszyn DJ, Lynch J. Efficacy of a cognitive-behavioral treatment for insomnia and nightmares in Afghanistan and Iraq veterans with PTSD. J Clin Psychol. 2013;69(10):1026-1042. 15. Collen JF, Lettieri CJ, Hoffman M. The impact of posttraumatic stress disorder on CPAP adherence in patients with obstructive sleep apnea. J Clin Sleep Med. 2012;8(6):667-672. 16. El-Solh AA, Ayyar L, Akinnusi M, Relia S, Akinnusi O. Positive airway pressure adherence in veterans with posttraumatic stress disorder. Sleep. 2010;33(11): 1495-1500. 17. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed, Text Rev. Washington, DC: American Psychiatric Association; 2000. 18. Weathers FW, Litz BT, Herman DS, Huska JA, Keane TM. The PTSD Checklist (PCL): reliability, validity, and diagnostic utility. Paper presented at: Annual Meeting of the International Society for Traumatic Stress Studies; October 1993; San Antonio, TX. 19. Iber C, Ancoli-Israel S, Chesson A, Quan S; for the American Academy of Sleep Medicine. The AASM Manual for Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications. 1st ed. Westchester, IL: American Academy of Sleep Medicine; 2007. 20. Chung F, Yegneswaran B, Liao P, et al. STOP questionnaire: a tool to screen patients for obstructive sleep apnea. Anesthesiology. 2008;108(5):812-821. 21. Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14(6):540-545. 22. Stanford fatigue visual numeric scale. Stanford Patient Education Research Center website. http://patienteducation. stanford.edu/research/vnsfatigue.html. Accessed July 14, 2015.
23. Weaver TE, Laizner AM, Evans LK, et al. An instrument to measure functional status outcomes for disorders of excessive sleepiness. Sleep. 1997;20(10):835-843. 24. Weaver TE, Maislin G, Dinges DF, et al. Relationship between hours of CPAP use and achieving normal levels of sleepiness and daily functioning. Sleep. 2007;30(6): 711-719. 25. American Academy of Sleep Medicine. International Classification of Sleep Disorders: Diagnostic and Coding Manual. 2nd ed. Westchester, IL: American Academy of Sleep Medicine; 2005. 26. Kribbs NB, Pack AI, Kline LR, et al. Objective measurement of patterns of nasal CPAP use by patients with obstructive sleep apnea. Am Rev Respir Dis. 1993;147(4):887-895. 27. Krakow B, Melendrez D, Pedersen B, et al. Complex insomnia: insomnia and sleepdisordered breathing in a consecutive series of crime victims with nightmares and PTSD. Biol Psychiatry. 2001;49(11): 948-953. 28. Youakim JM, Doghramji K, Schutte SL. Posttraumatic stress disorder and obstructive sleep apnea syndrome. Psychosomatics. 1998;39(2):168-171. 29. Mysliwiec V, Gill J, Lee H, et al. Sleep disorders in US military personnel: a high rate of comorbid insomnia and obstructive sleep apnea. Chest. 2013;144(2):549-557. 30. Mysliwiec V, McGraw L, Pierce R, Smith P, Trapp B, Roth BJ. Sleep disorders and associated medical comorbidities in active duty military personnel. Sleep. 2013;36(2):167-174. 31. Williams SG, Collen J, Orr N, Holley AB, Lettieri CJ. Sleep disorders in combatrelated PTSD. Sleep Breath. 2015;19(1): 175-182. 32. Chervin RD, Aldrich MS. The Epworth Sleepiness Scale may not reflect objective measures of sleepiness or sleep apnea. Neurology. 1999;52(1):125-131. 33. Nguyen AT, Baltzan MA, Small D, Wolkove N, Guillon S, Palayew M. Clinical reproducibility of the Epworth Sleepiness Scale. J Clin Sleep Med. 2006;2(2):170-174. 34. Damiani MF, Quaranta VN, Falcone VA, et al. The Epworth Sleepiness Scale: conventional self vs physician administration. Chest. 2013;143(6): 1569-1575. 35. Weaver TE. Outcome measurement in sleep medicine practice and research. Part 1: assessment of symptoms, subjective and objective daytime sleepiness, health-related quality of life and functional status. Sleep Med Rev. 2001;5(2):103-128. 36. Weaver TE, Mancini C, Maislin G, et al. Continuous positive airway pressure treatment of sleepy patients with milder obstructive sleep apnea: results of the CPAP Apnea Trial North American Program (CATNAP) randomized clinical trial. Am J Respir Crit Care Med. 2012;186(7):677-683.
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37. Antic NA, Catcheside P, Buchan C, et al. The effect of CPAP in normalizing daytime sleepiness, quality of life, and neurocognitive function in patients with moderate to severe OSA. Sleep. 2011;34(1):111-119. 38. Tamanna S, Parker JD, Lyons J, Ullah MI. The effect of continuous positive air pressure (CPAP) on nightmares in patients with posttraumatic stress disorder (PTSD) and obstructive sleep apnea (OSA). J Clin Sleep Med. 2014;10(6):631-636. 39. Collen J, Orr N, Lettieri CJ, Carter K, Holley AB. Sleep disturbances among soldiers with combat-related traumatic brain injury. Chest. 2012;142(3):622-630. 40. Mysliwiec V, Roth B. Pharmacotherapy refractory insomnia in soldiers with traumatic brain injury. Chest. 2013;143(2): 582-583. 41. Aloia MS, Arnedt JT, Strand M, Millman RP, Borrelli B. Motivational enhancement to improve adherence to positive airway pressure in patients with obstructive sleep apnea: a randomized controlled trial. Sleep. 2013;36(11):1655-1662.
44. Dickerson SS, Obeidat R, Dean G, et al. Development and usability testing of a self-management intervention to support individuals with obstructive sleep apnea in accommodating to CPAP treatment. Heart Lung. 2013;42(5):346-352.
51. Wickwire EM, Smith MT, Birnbaum S, Collop NA. Sleep maintenance insomnia complaints predict poor CPAP adherence: a clinical case series. Sleep Med. 2010;11(8):772-776.
45. Kline CE, Crowley EP, Ewing GB, et al. The effect of exercise training on obstructive sleep apnea and sleep quality: a randomized controlled trial. Sleep. 2011;34(12):1631-1640.
52. Stepnowsky CJ Jr, Marler MR, AncoliIsrael S. Determinants of nasal CPAP compliance. Sleep Med. 2002;3(3):239-247. 53. Weaver TE, Grunstein RR. Adherence to continuous positive airway pressure therapy: the challenge to effective treatment. Proc Am Thorac Soc. 2008;5(2):173-178.
46. Kline CE, Ewing GB, Burch JB, et al. Exercise training improves selected aspects of daytime functioning in adults with obstructive sleep apnea. J Clin Sleep Med. 2012;8(4):357-365.
54. Aloia MS, Arnedt JT, Stanchina M, Millman RP. How early in treatment is PAP adherence established? Revisiting night-to-night variability. Behav Sleep Med. 2007;5(3):229-240.
47. Effects of CPAP therapy on PTSD symptoms. NCT02019914. ClinicalTrials. gov. Bethesda, MD: National Institutes of Health; 2013. http://www.clinicaltrials. gov/ct/show/NCT02019914. Updated September 3, 2014.
42. Bartlett D, Wong K, Richards D, et al. Increasing adherence to obstructive sleep apnea treatment with a group social cognitive therapy treatment intervention: a randomized trial. Sleep. 2013;36(11): 1647-1654.
48. A randomized cross over trial of two treatments for obstructive sleep apnea in veterans with post-traumatic stress disorder. NCT01569022. ClinicalTrials. gov. Bethesda, MD: National Institutes of Health; 2012. http://www.clinicaltrials. gov/ct/show/NCT01569022. Updated May 4, 2015.
43. Crawford MR, Espie CA, Bartlett DJ, Grunstein RR. Integrating psychology and medicine in CPAP adherence–new
49. Castriotta RJ, Murthy JN. Sleep disorders in patients with traumatic brain injury: a review. CNS Drugs. 2011;25(3):175-185.
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50. Wickwire EM, Collop NA. Insomnia and sleep-related breathing disorders. Chest. 2010;137(6):1449-1463.
concepts? Sleep Med Rev. 2014;18(2): 123-139.
55. Budhiraja R, Parthasarathy S, Drake CL, et al. Early CPAP use identifies subsequent adherence to CPAP therapy. Sleep. 2007;30(3):320-324. 56. Lewis KE, Seale L, Bartle IE, Watkins AJ, Ebden P. Early predictors of CPAP use for the treatment of obstructive sleep apnea. Sleep. 2004;27(1):134-138. 57. Pépin JL, Krieger J, Rodenstein D, et al. Effective compliance during the first 3 months of continuous positive airway pressure. A European prospective study of 121 patients. Am J Respir Crit Care Med. 1999;160(4):1124-1129.
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Original Research Sleep Disorders
]
OSA Syndrome and Posttraumatic Stress Disorder Clinical Outcomes and Impact of Positive Airway Pressure Therapy Christopher J. Lettieri, MD; Scott G. Williams, MD; and Jacob F. Collen, MD
BACKGROUND: We sought to determine the impact of OSA syndrome (OSAS) on symptoms and quality of life (QoL) among patients with posttraumatic stress disorder (PTSD). In addition, we assessed adherence and response to positive airway pressure (PAP) therapy in this population.
This was a case-controlled observational cohort study at the Sleep Disorders Center of an academic military medical center. Two hundred consecutive patients with PTSD underwent sleep evaluations. Patients with PTSD with and without OSAS were compared with 50 consecutive age-matched patients with OSAS without PTSD and 50 age-matched normal control subjects. Polysomnographic data, sleep-related symptoms and QoL measures, and objective PAP usage were obtained.
METHODS:
Among patients with PTSD, more than one-half (56.6%) received a diagnosis of OSAS. Patients with PTSD and OSAS had lower QoL and more somnolence compared with the other groups. Patients with PTSD demonstrated significantly lower adherence and response to PAP therapy. Resolution of sleepiness occurred in 82% of patients with OSAS alone, compared with 62.5% of PAP-adherent and 21.4% of nonadherent patients with PTSD and OSAS (P < .001). Similarly, posttreatment Functional Outcomes of Sleep Questionnaire $ 17.9 was achieved in 72% of patients with OSAS, compared with only 56.3% of patients with PTSD and OSA who were PAP adherent and 26.2% who were nonadherent (P < .03). RESULTS:
CONCLUSIONS: In patients with PTSD, comorbid OSAS is associated with worsened symptoms, QoL, and adherence and response to PAP. Given the negative impact on outcomes, the possibility of OSAS should be considered carefully in patients with PTSD. Close follow-up is needed to optimize PAP adherence and efficacy in this at-risk population.
CHEST 2016; 149(2):483-490
continuous positive airway pressure; CPAP adherence; obstructive sleep apnea; posttraumatic stress disorder; quality of life
KEY WORDS:
AHI = apnea-hypopnea index; ESS = Epworth Sleepiness Scale; FOSQ = Functional Outcomes of Sleep Questionnaire; OSAS = OSA syndrome; PAP = positive airway pressure; PTSD = posttraumatic stress disorder; QoL = quality of life; STOP-Bang = snoring, tiredness, observed apnea, BP, BMI, age, neck circumference, and gender; TBI = traumatic brain injury AFFILIATIONS: From the Department of Medicine (Drs Lettieri, Williams, and Collen), Uniformed Services University, Bethesda, MD; the Department of Pulmonary, Critical Care, and Sleep Medicine (Dr Lettieri), Walter Reed National Military Medical Center, Bethesda, MD; the Department of Pulmonary, Critical Care, and Sleep Medicine (Dr Williams), Womack Army Medical Center, Fort Bragg, NC; and ABBREVIATIONS:
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the Department of Pulmonary, Critical Care, and Sleep Medicine (Dr Collen), Brooke Army Medical Center, Fort Sam Houston, TX. FUNDING/SUPPORT: The authors have reported to CHEST that no funding was received for this study. CORRESPONDENCE TO: Jacob F. Collen, MD, Pulmonary, Critical Care and Sleep Medicine, San Antonio Military Medical Center, (Brooke Army Medical Center), 3551 Roger Brooke Dr, Fort Sam Houston, TX 78234; e-mail: [email protected] Published by Elsevier Inc. under license from the American College of Chest Physicians. DOI: http://dx.doi.org/10.1378/chest.15-0693
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Sleep complaints are common among patients with posttraumatic stress disorder (PTSD) and portend worsened clinical outcomes.1,2 OSA syndrome (OSAS) is particularly prevalent in PTSD.3-11 OSAS can independently diminish quality of life (QoL),12,13 and the adverse impact of sleep-disordered breathing on QoL in patients with PTSD has been demonstrated previously.5,7 Just as the presence of sleep disorders may complicate recovery in those with PTSD, resolution of sleep disruption can enhance the treatment response in affective disorders.14 Unfortunately, patients with PTSD and OSAS demonstrate low rates of positive airway pressure (PAP) adherence.15,16 Although several studies have evaluated the impact of OSAS in patients with PTSD, these have focused on
smaller, nonmilitary populations or on older veteran populations. The impact of both OSAS and PTSD on sleep-related QoL, daytime sleepiness and fatigue, PAP use, and the response to PAP therapy have not been evaluated systematically in the same population. We sought to evaluate the impact of comorbid OSAS on sleep-related symptoms and QoL among active duty military patients with PTSD. We further aimed to assess the effect of PTSD on adherence and response to PAP therapy. Given that the population represented in this study will filter out of the military health-care system and into the Veterans Affairs Healthcare System and the broader community for years to come, this study is of critical importance to physicians who care for patients who may have PTSD and OSAS.
Materials and Methods
Measured Variables
Study Design
We recorded the age, sex, and, BMI for each individual. Relevant comorbid diagnoses and symptoms were also recorded. For patients with PTSD, we recorded the number of psychoactive medications they were prescribed and their sleep-related symptoms. The degree of subjective sleepiness was assessed using the Epworth Sleepiness Scale (ESS)21, which grades daytime sleepiness with a point system from 0-24 points (point totals less than or equal to 10 are considered normal and higher scores indicate increased daytime sleepiness). The degree of fatigue or subjective tiredness was evaluated with the Stanford Fatigue Visual Numeric Scale which scores the degree of fatigue from 0 (“no fatigue”) to 10 points (“severe fatigue”).22 Sleeprelated QoL scores were assessed using the Functional Outcomes of Sleep Questionnaire (FOSQ) (e-Appendix 1).23 The total score for the FOSQ can range from 5-20 points with values less than 17.9 considered abnormal.24
We conducted an observational cohort study of 200 consecutive active duty service members receiving outpatient care for combat-related PTSD at Walter Reed Army Medical Center between 2008 and 2012. All patients were $ 18 years of age, were currently serving in the US Armed Forces, and had been given a diagnosis of PTSD following combat deployments to Iraq and/or Afghanistan. We excluded patients with preexisting PTSD and those with diagnosed sleep disorders prior to their most recent deployment. Otherwise, no records were excluded from this analysis. All available patients with PTSD following deployment were referred to our Sleep Disorders Center to undergo a comprehensive screening evaluation for sleep disorders. The study was approved by the institutional review board at Walter Reed Army Medical Center (IRB No. 355213). The diagnosis of PTSD was based on a clinical encounter with a doctorallevel behavioral health provider using the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) criteria and the PTSD Checklist Military Version,17,18 which is a subjective questionnaire that includes 17 questions (1-5 points each) addressing the 17 DSM-IV criteria for PTSD. A cutoff score of 50 points was used to assess for the presence of PTSD (17-85 points possible).18 All patients underwent a comprehensive sleep medicine evaluation within 6 months of combat deployment, including a level 1 attended, overnight polysomnography. All polysomnograms were scored and interpreted by the study investigators in accordance with guidelines published by the American Academy of Sleep Medicine.19 We compared our cohort with two separate, age and sex-matched control groups. The first group was composed of 50 consecutive matched patients with a diagnosis of OSAS but who had not deployed and did not have PTSD. The second group was composed of 50 healthy matched control subjects without prior deployment, PTSD, or clinically suspected sleep-disordered breathing. All normal subjects were administered the snoring, tiredness, observed apnea, BP, BMI, age, neck circumference, and gender (STOP-Bang) questionnaire, which has been validated as a screening tool for OSA.20 All included individuals had fewer than two STOP criteria and fewer than three STOP-Bang criteria (low pretest probability for OSA) and no clinical suspicion for sleep-disordered breathing.
484 Original Research
From polysomnographic studies, we recorded sleep efficiency (%), sleep latency (minutes), percentage of total sleep time spent in stage N3 sleep, percentage of total sleep time spent in stage R sleep, apnea-hypopnea index (AHI), total arousal index, and oxygen saturation nadir. The presence of OSAS and insomnia were determined for each patient. The diagnosis of OSAS was based on an AHI $ 5 events/h plus clinical symptoms of sleep-disordered breathing in accordance with American Academy of Sleep Medicine criteria.25 We defined insomnia as a subjective sleep latency of $ 30 min, early-morning awakenings, nonrestorative sleep, and/or subjective sleep fragmentation (nocturnal awakenings) occurring over the majority of nights for > 1 month, associated with daytime impairment.17 Those with a diagnosis of OSAS were prescribed PAP for long-term therapy. Prior to initiating treatment, all individuals received formal mask fitting and participated in a comprehensive educational program intended to familiarize them with OSAS, its clinical effects, and the available treatment options. All patients underwent a clinical evaluation after 1 month of therapy to assess PAP use and the clinical response to therapy, including an assessment of QoL (FOSQ), ESS, and fatigue scores. Objective PAP use was measured using the Respironics Encore Anywhere program (Philips Respironics) and included the percentage of nights used and the mean number of hours it was used per night.
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Outcomes The primary outcomes were the impact of comorbid OSAS on sleeprelated symptoms and QoL measures. Specifically, we compared the difference in baseline measures of the FOSQ, ESS, and Stanford fatigue visual numeric scale among patients with PTSD, PTSD and OSAS, OSAS, and normal control subjects. Secondary outcomes included the impact of PTSD on PAP adherence and response to PAP therapy based on changes in the above measures of sleepiness and QoL. We compared absolute PAP usage and rates of regular use between patients with OSAS with and without PTSD. Individuals using PAP for > 4 h per night on > 70% of nights were considered
Results Our study population consisted of 200 consecutive adult patients with PTSD. The cohort was composed predominantly of men (91.3%) with a mean age of 35.9 10.5 years and BMI of 28.7 4.5 kg/m2. Demographics were similar between those with PTSD and the two control groups. Subjective sleep complaints (daytime sleepiness and poor-quality sleep) were nearly universal (96.9%) in those with PTSD. The majority (94.4%) was prescribed psychoactive medication. The overall mean number of psychoactive medications was 3.4 1.5 per patient, and there was not a significant difference between those patients with and without OSA
TABLE 1
] Demographic and Clinical Variables Among Patients With PTSD
Variable Male sex Age, y BMI, kg/m2 Subjective sleep complaints Epworth Sleepiness Scale score (points, 0-24)a Epworth Sleepiness Scale score > 10 points Fatigue scale score (points, 0-10)b Functional Outcomes of Sleep Questionnaire score (5-20)
Patients 91.3 28.7 4.5 96.9 10.6 5.7 49.7
Data are presented as the mean 1 SD. Comparisons between categorical variables were performed using the c2 and Fisher exact tests, and differences between means using the independent samples t test and analysis of variance followed by the Tukey post hoc test. P values < .05 were considered statistically significant. Data were analyzed using the Statistical Package for Social Sciences 22.0 (IBM Corporation).
(3.2 1.4 vs 3.6 1.6, P ¼ .21). Mild traumatic brain injury (TBI) was present in 58% of the PTSD cohort (Table 1). There was not a history of TBI among the OSA-only and normal control groups. OSAS was diagnosed in 56.6% of those with PTSD, with a mean AHI of 23.1 22.7 events/h (PTSD þ OSA subgroup). The mean AHI was 1.8 1.6 events/h among those with PTSD only, and 26.9 27.4 events/h in the OSA control group. Within the PTSD cohort, those with OSAS were older and had a higher BMI. Otherwise, there were no significant differences between patients with PTSD with and without OSAS. Sleep quality was poor in the majority of the study population. Specifically, a reduced sleep efficiency was seen in 41.2% of patients, and 31.2% had a prolonged sleep latency during polysomnography. The majority experienced sleep fragmentation, with a mean total arousal index of 19.7 13.8 arousals/h. Altered sleep
TABLE 2
] Results of Polysomnography (n ¼ 200)
Variable Sleep efficiency, % Sleep efficiency < 80%, Sleep latency, min
7.1 1.7 17.8 2.8
Sleep latency > 60 min Stage N3 sleep, % Stage N3 sleep < 20%
53.1
Depression
85.7
Anxiety
40.0
Mild traumatic brain injury
58.0
Portion of cohort prescribed psychoactive medications
94.4 3.4 1.5
Data are given as % or mean SD. PTSD ¼ posttraumatic stress disorder. a The Epworth Sleepiness Scale ranges from 0-24 points. Scores that are less than or equal to 10 points are considered normal and scores greater than 10 points are indicative of excessive daytime sleepiness. b Fatigue Visual Numeric Scale: 0 points ¼ no fatigue, 10 points ¼ severe fatigue.
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Statistical Analysis
35.9 10.5
Insomnia
Psychoactive agents per subject, No.
to be using it regularly.26 We defined a resolution of sleepiness as a final ESS value of # 10, and a clinically significant improvement in QoL as an FOSQ $ 17.9.23,24
Stage REM sleep, % Stage REM sleep < 25%
Value 84.5 12.4 41.2 30.5 33.7 31.2 13.5 11.2 60.0 13.2 8.9 55.0
Total arousal index, events/h
19.7 13.8
Apnea-hypopnea index (entire cohort), events/h
16.2 21.2
Apnea-hypopnea index of those with OSA syndrome, events/h
23.1 22.7
Presence of OSA syndrome (entire cohort) O2 saturation nadir, %
56.6 86.4 6.0
Data are given as % or mean SD. O2 ¼ oxygen; REM ¼ rapid eye movement.
485
architecture was also common, and a decrease in the percentage of both stages N3 and R sleep was observed in 55% and 60% of the cohort, respectively (Table 2). Although both OSAS and PTSD were associated with increased sleepiness and lower QoL indexes compared with those of normal control subjects, the presence of both led to further reductions in these measured variables than either condition independently. Daytime somnolence was common in the overall cohort, with a mean ESS value of 10.6 5.7, and 49.7% had an ESS > 10. ESS values were higher among those with PTSD and OSAS compared with those with PTSD alone and normal subjects (12.5 5.7 vs 9.5 5.2, P ¼ .002 and 12.5 5.7 vs 4.5 3.7, P < .001, respectively). Patients with PTSD and OSAS and OSAS alone had similar ESS values (12.5 5.7 vs 12.9 5.3, P ¼ .72). Fatigue was common among our cohort, with a mean Stanford fatigue visual numeric score of 7.1 1.7. Patients with PTSD (with or without OSA) experienced significantly greater fatigue compared with those with OSAS alone or with normal control subjects (Table 3). A reduced QoL, as measured by the FOSQ, was common among those with either PTSD or OSAS. However, both the absolute FOSQ score and the percentage of those with a score $ 17.9 at baseline were significantly lower in patients with both PTSD and OSAS compared with either condition alone. The proportion of those with a baseline FOSQ < 17.9 was 6.9% among normal control subjects, 24.0% in those with OSAS alone, 43.2% in those with PTSD alone, and 59.5% in those with PTSD and OSAS (Table 3). TABLE 3
All patients with OSAS were reassessed 4 weeks after initiation of PAP therapy to evaluate both adherence and the response to therapy. Patients with PTSD demonstrated significantly lower PAP adherence. Among those with PTSD and OSAS, there was not a significant difference between PAP-adherent and nonadherent patients regarding the rate of insomnia (61.5% vs 40.0%, P ¼ .24). Those with OSAS alone used PAP on 77.9% 22% of nights, for 5.8 0.9 h/night. In comparison, patients with PTSD and OSAS only used PAP on 53.3% 35.6% of nights (P < .001), for an average of 3.4 2.8 h/night (P < .001). Regular use of PAP was similarly reduced and was observed in 30.2% of those with PTSD and OSAS compared with 55.1% in those with OSAS alone (P ¼ .02) (Table 4). Patients with PTSD and OSAS also experienced a reduced treatment response compared with those with OSAS alone. Resolution of sleepiness (ESS # 10) occurred in 85.7% of PAP-adherent and 54.5% of PAP-nonadherent patients with OSA alone, compared with 72.1% of PAP-adherent and 21.4% of nonadherent patients with PTSD and OSAS (P < .001). In addition, a posttreatment FOSQ $ 17.9 occurred in 68.4% of PAP-adherent and 40.9% of PAP-nonadherent patients with OSAS alone, compared with only 56.3% of PAP-adherent and 26.2% of nonadherent patients with PTSD and OSAS (P < .03) (Fig 1).
Discussion We found that patients with PTSD and comorbid OSAS had worsened somnolence, fatigue, and sleep-related
] Comparison of Clinical and Demographic Variables Between Those With PTSD and OSAS, Those With PTSD Alone, Those With OSAS Alone, and Normal Subjects (Control Group)
Variable
PTSD and OSAS (n ¼ 113)
PTSD Alone (n ¼ 87)
OSAS Alone (n ¼ 50)
Age, y
39.5 10.6
31.3 8.7
41.5 7.6
P value BMI, kg/m2 P value ESS P value Fatigue scale P value FOSQ P value FOSQ < 17.9, % P value
. 29.6 4.8 . 12.5 5.7 . 6.9 1.7 . 14.7 3.0 . 59.5 .
< .001 27.6 3.9
.24 30.5 2.3
.003 9.5 5.2
.22 12.9 5.3
.002 7.3 1.8
.72 5.9 2.6
.38 18.0 3.0
.02
Normal (n ¼ 50) 41.4 7.6 .24 28.2 1.5 .06 4.5 3.7 < .001 2.8 2.4 < .001
18.7 1.9
19.4 1.1
< .001
< .001
.001 43.2
24.0 < .001
.15
6.9 < .001
Data are presented as mean SD unless indicated otherwise. ESS ¼ Epworth Sleepiness Scale; FOSQ ¼ Functional Outcomes of Sleep Questionnaire; OSAS ¼ OSA syndrome. See Table 1 legend for expansion of other abbreviations.
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TABLE 4
] Comparison of PAP Adherence PTSD and OSAS (n ¼ 113)
OSAS Alone (n ¼ 50)
Apnea-hypopnea index, events/h
23.1 22.7
26.9 27.4
PAP days used, %
53.3 35.6
77.9 22
Variable
P Value .41 < .001
Average use per night, h
2.6 2.6
5.8 0.9
< .001
Average use per night when PAP was used, h
3.4 2.8
4.6 1.7
.01
30.2
55.1
.02
Regular use
Data are presented as mean SD or %. PAP ¼ positive airway pressure. See Table 1 and 3 legends for expansion of other abbreviations.
QoL compared with those with either condition alone and normal subjects. Patients with PTSD and OSAS exhibited significantly worse PAP adherence, which has been documented previously.15,16 Notably, patients with PTSD and OSAS experienced a diminished response to PAP therapy and were less likely to have a resolution of symptoms than were those with OSAS only. Previous studies have documented high rates of OSAS among those with PTSD in both civilian5,8,10,27,28 and military populations.29-31 We recently evaluated 130 consecutive service members with combat-related PTSD at our institution, and 67.3% of those who underwent polysomnography for suspected sleep-disordered breathing had OSA (53.8% of cohort).31 In the current study, polysomnography was obtained in all patients regardless of a clinical suspicion for sleep-disordered breathing, and the prevalence of OSAS among individuals with PTSD was nearly identical. Not only is OSAS common in patients with PTSD, it leads to greater impairments in QoL, sleep-related symptoms, and poor daytime function.5,7,8,27 The impact of sleep-disordered breathing in patients with PTSD is
OSA: PAP Adherent PTSD + OSA: PAP Adherent OSA: PAP Nonadherent PTSD + OSA: PAP Nonadherent
80
P < .001a
70 60
68.4%
40.9%
26.2%
10
56.3%
20
21.4%
30
54.5%
40
P < .03a 72.1%
50
85.7%
Percentage of Patients
90
0 ESS < 10
FOSQ > 17.9
aANOVA
Figure 1 – Resolution of sleep-related symptoms following 1 mo of CPAP therapy. ANOVA ¼ analysis of variance; ESS ¼ Epworth Sleepiness Scale; FOSQ ¼ Functional Outcomes of Sleep Questionnaire; PAP ¼ positive airway pressure; PTSD ¼ posttraumatic stress disorder.
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not unexpected. Both conditions are associated with poor sleep quality, fatigue, and a decreased sense of wellbeing. In our population, we found that either PTSD or OSAS was associated with worsened symptoms of sleepiness, fatigue, and sleep-related QoL in comparison with normal subjects. The presence of both OSAS and PTSD led to greater impairments than either condition alone. Given the prevalence of OSAS in patients with PTSD and its adverse impact on symptoms and adherence, early identification may improve outcomes. Unfortunately, assessment tools that depend on subjective and overlapping symptoms may be of limited use in identifying specific sleep disorders in this population. Elevated fatigue scores in patients with PTSD (regardless of underlying sleep-disordered breathing) are likely driven by concomitant fragmented sleep, hyperarousal, and insomnia, which are common in these individuals. Similarly, subjective reports of daytime sleepiness and ESS values are highly variable even among patients with OSAS alone.32-34 This may account for the areas in which statistically significant differences were lacking in our cohort. The FOSQ was developed and validated originally as an instrument for evaluating the impact of OSAS on QoL and the efficacy of PAP therapy and has also become a valuable tool in assessing QoL related to other sleep disorders.23,26,35-37 Although previous smaller studies have addressed the FOSQ in patients with PTSD and comorbid sleep-disordered breathing,5,27 the current study is the first to systematically evaluate this in a large population of recent combat veterans compared with control subjects. Based on our results, the addition of sleep-related QoL measures to the commonly used measures of daytime symptoms may assist in longitudinally measuring the response to therapy in this population. Among patients with PTSD and OSAS, both daytime somnolence and QoL were improved with PAP therapy.
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Compared with patients who had poor adherence, those who used PAP regularly were more than three times as likely to resolve daytime sleepiness (ESS # 10) and more than twice as likely to have a normal QoL (FOSQ $ 17.9). Although we did not measure other PTSD-specific outcomes, prior investigations have found that treatment of comorbid OSAS improves PTSDrelated symptoms, including nightmares.6,28,38 Although treatment of OSAS improves outcomes in patients with PTSD, the response to therapy is blunted compared with the response of patients with OSAS without PTSD. In our study, patients with PTSD who used PAP regularly had more residual sleepiness and lower QoL scores compared with patients with PTSD and sleep apnea. There are several potential reasons for worsened symptoms despite PAP therapy in this population, including differences in perception based on their underlying illness, polypharmacy with psychoactive medications (which have the potential for sleep fragmentation), comorbid insomnia, and pharmacotherapy-refractory insomnia, all of which are common in service members with combat-related PTSD and sleep disorders.29,30,39,40 Given the diminished therapeutic response and the inherent barriers to successful therapy, PTSD represents an independent barrier to the effective treatment of OSAS and should prompt multipronged and individualized care. Ongoing studies are evaluating newer approaches that incorporate the biopsychosocial model, which uses holistic strategies to improve PAP adherence. Treatment may include sharing peer success stories, group education, cognitive behavioral therapy, and motivational enhancement. These strategies account for variability in patients’ ability and in their motivation for change, which are extremely relevant to the challenge of introducing PAP therapy to patients with PTSD.41-44 Currently, there are no studies that directly assess these methods in patients with PTSD and OSA. In addition, conservative lifestyle modifications, such as structured exercise programs, can improve disease severity, sleep-related symptoms, and daytime function in OSA, irrespective of weight loss.45,46 Finally, there are prospective clinical trials in progress evaluating the impact of PAP on sleep-related symptoms and QoL and comparing outcomes with PAP with mandibular advancement devices in PTSD-OSA.47,48 Limitations
Our study has several limitations. We included a cohort composed predominantly of men with recent military
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deployments and combat-related PTSD. As such, our findings may not reflect what is seen in other populations. As an observational study incorporating patients evaluated at a single sleep disorders center, our findings may be limited by selection bias. However, we included consecutive patients, and the population of interest (PTSD) was evaluated in our clinic based on a policy of screening following deployment, rather than a specific referral based on symptoms or clinical suspicion for a sleep disorder. Mild TBI was found in more than one-half of the patients with PTSD. The connection between TBI and OSA is well documented,49 and is also found frequently in active duty service members.39 The impact of TBI on our results is difficult to comment on in an observational study. A significant percentage of the patients in this study had comorbid insomnia, which may have impacted our results. It has been established previously that comorbid insomnia limits CPAP adherence,50,51 and pharmacotherapy refractory insomnia is a probable comorbidity in service members with sleep disorders.29,40 Additionally, we did not assess non-sleep-related symptoms, and it is unknown how the presence of OSAS affected other measures of interest in patients with PTSD (in particular, nightmares and nightmare frequency), or how these were impacted by PAP therapy. Based on chart review, the majority of patients in our study cohort had a diagnosis of depression, limiting our ability to make meaningful conclusions about the impact of PAP use in an observational study. Finally, we measured PAP use only during the first month of therapy and did not assess the long-term impact of PTSD on adherence or outcomes. However, it has been established previously that longterm PAP use can be predicted in the first few weeks of therapy.52-57
Conclusions Combat veterans with sleep complaints and PTSD represent a challenging population for sleep physicians. Given the adverse impact that comorbid OSAS and PTSD have on symptoms, QoL, adherence, and response to therapy, our results highlight the need for a high index of suspicion and a comprehensive approach to identifying and treating sleep-disordered breathing in these patients. Although PAP can significantly improve QoL in this population, the benefits are limited by poor dherence in an already compromised population. These results further advocate for a careful and individualized approach to therapy among patients with PTSD.
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Acknowledgments Author contributions: C. J. L had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis, including and especially any adverse effects. C. J. L. contributed to the study design; C. J. L., S. G. W., and J. F. C. contributed to the protocol development; C. J. L. and J. F. C. contributed to the data collection; C. J. L., S. G. W., and J. F. C. contributed to the data analysis; C. J. L., S. G. W., and J. F. C. contributed to the writing of the manuscript; and C. J. L. contributed to manuscript revision. Financial/nonfinancial disclosures: None declared. Other contributions: The views expressed herein are those of the authors and do not reflect the official policy or position of Walter Reed National Military Medical Center, Womack Army Medical Center, Brooke Army Medical Center, the US Army Medical Department, the US Army Office of the Surgeon General, the Department of the Army and Department of Defense, or the US Government. Additional information: The e-Appendix can be found in the Supplemental Materials section of the online article.
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