A randomized, placebo-controlled trial using a novel PAP delivery platform to treat patients with OSA and comorbid PTSD
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Positive airway pressure (PAP) adherence is poor in comorbid OSA/PTSD. SensAwake™ (SA) is a wake-sensing PAP algorithm that lowers pressure when wake is detected. We compared auto-PAP (aPAP) with and without SA for comorbid OSA/PTSD.
Prospective, randomized crossover study comparing aPAP to aPAP + SA. We enrolled patients with OSA/PTSD who were PAP naïve. Four weeks after randomization, the patients were crossed over to the alternate treatment group, with final follow-up at eight weeks. Sleep questionnaires (ESS, ISI, FSS, and FOSQ-10) were assessed at baseline and follow-up.
We enrolled 85 patients with OSA/PTSD. aPAP reduced AHI to < 5/h in both groups. Our primary endpoint, average hours of aPAP adherence (total) after 4 weeks, was significantly increased in the SA group in our intention-to-treat (ITT) analysis (ß = 1.13 (95% CI 0.16–2.1); p = 0.02), after adjustment for ESS differences at baseline. After adjustment for ESS, SA (ITT analysis) also showed significant improvement in percentage of nights used for ≥ 4 h (ß = 14.9 (95% CI 1.02–28.9); p = 0.04). There were trends toward an increase in percentage nights used total (ß = 17.4 (95% CI − 0.1 to 34.9); p = 0.05), average hours of aPAP adherence (nights used) (ß = 1.04 (95% CI − 0.07 to 2.1); p = 0.07), and regular use (OR = 7.5 (95% CI 0.9–64.7); p = 0.07) after adjustment for ESS at baseline. After adjustment for ESS and days to cross over, SA by actual assignment did not show any effect on adherence variables. The ESS, ISI, FSS, and FOSQ-10 all showed significant improvements with PAP, but there were no differences in the magnitude of improvement in any score between groups.
Adherence to aPAP may be improved with the addition of SA and deserves further study. SA is as effective as standard aPAP for normalizing the AHI and improving sleep-related symptoms.
Clinical trial registration
“Comparison Study Using APAP With and Without SensAwake in Patients With OSA and PTSD”.
KeywordsObstructive sleep apnea Post-traumatic stress disorder PTSD Continuous positive airway pressure CPAP CPAP adherence CPAP compliance
American Academy of Sleep Medicine
continuous positive airway pressure
auto-PAP (auto-adjustable continuous positive airway pressure)
Epworth Sleepiness Scale
Functional Outcomes of Sleep Questionnaire
Fatigue Severity Scale
Insomnia Severity Index
obstructive sleep apnea
positive airway pressure
pressure transducer airflow
post-traumatic stress disorder
SensAwake™ (SA; Fisher and Paykel Healthcare, Auckland, New Zealand)
Walter Reed National Military Medical Center, Bethesda, MD
All of the study authors contributed to the study and have reviewed the final manuscript. Dr. Holley conceived the research idea and performed statistical analysis and manuscript editing. Dr. Shaha contributed to data collection and analysis and assisted in the first draft of the manuscript. Mr. Terry contributed to patient recruitment, data collection, and data analysis. Dr. Costan-Toth contributed to data collection and data analysis. Dr. Slowik contributed to data collection and analysis. Dr. Robertson contributed to patient recruitment and data analysis. Dr. Williams contributed to patient recruitment and data collection. Ms. Golden contributed to patient recruitment, data collection, and analysis. Mr. Andrada contributed to data collection. Ms. Skeete contributed to patient recruitment and data collection. Ms. Sheikh contributed to patient recruitment and data collection. Mr. Butler contributed to data collection. Dr. Collen is the guarantor of the final article and is responsible for the integrity of the data and contents of this manuscript from study inception to publication of the final product.
This study was funded by Fisher-Paykel Healthcare (Grant #WR-GVA-FPH-10-32). This investigator-initiated project was conducted by using an unrestricted research grant and PAP machines provided by Fisher & Paykel Healthcare to the Geneva Foundation for the Advancement of Military Medicine. Fisher & Paykel Healthcare was involved with the study design, but not with patient enrollment, data collection and interpretation, manuscript preparation, or the decision to submit the manuscript for publication.
Compliance with ethical standards
Conflict of interest
None of the study authors have any relevant conflicts of interest to disclose.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
Statement and declarations
All authors have seen and approve the manuscript. This investigator-initiated project was conducted by using an unrestricted research grant and PAP machines provided by Fisher & Paykel Healthcare to the Geneva Foundation for the Advancement of Military Medicine. Fisher & Paykel Healthcare was involved with the study design, but not with patient enrollment, data collection and interpretation, manuscript preparation, or the decision to submit the manuscript for publication. The study authors have no other relevant disclosures.
- 10.Krakow B, Melendrez D, Warner TD, Clark JO, Sisley BN, Dorin R, Harper RM, Leahigh LK, Lee SA, Sklar D, Hollifield M (2006) Signs and symptoms of sleep-disordered breathing in trauma survivors: a matched comparison with classic sleep apnea patients. J Nerv Ment Dis 194(6):433–439PubMedCrossRefGoogle Scholar
- 16.Mysliwiec V, Matsangas P, Gill J, Baxter T, O'Reilly B, Collen JF, Roth BJ (2015) A comparative analysis of sleep disordered breathing in active duty service members with and without combat-related posttraumatic stress disorder. J Clin Sleep Med 11(12):1393–1401PubMedPubMedCentralCrossRefGoogle Scholar
- 18.Krakow B, Lowry C, Germain A, Gaddy L, Hollifield M, Koss M, Tandberg D, Johnston L, Melendrez D (2000) A retrospective study on improvements in nightmares and post-traumatic stress disorder following treatment for co-morbid sleep-disordered breathing. J Psychosom Res 49(5):291–298PubMedCrossRefGoogle Scholar
- 25.Bryan CJ, Gonzales J, Rudd MD, Bryan AO, Clemans TA, Ray-Sannerud B, Wertenberger E, Leeson B, Heron EA, Morrow CE et al (2015) Depression mediates the relation of insomnia severity with suicide risk in three clinical samples of U.S. military personnel. Depress Anxiety 32(9):647–655PubMedCrossRefGoogle Scholar
- 26.Hom MA, Lim IC, Stanley IH, Chiurliza B, Podlogar MC, Michaels MS, Buchman-Schmitt JM, Silva C, Ribeiro JD, Joiner TE Jr (2016) Insomnia brings soldiers into mental health treatment, predicts treatment engagement, and outperforms other suicide-related symptoms as a predictor of major depressive episodes. J Psychiatr Res 79:108–115PubMedCrossRefGoogle Scholar
- 33.Shemesh E, Rudnick A, Kaluski E, Milovanov O, Salah A, Alon D, Dinur I, Blatt A, Metzkor M, Golik A, Verd Z, Cotter G (2001) A prospective study of posttraumatic stress symptoms and nonadherence in survivors of a myocardial infarction (MI). Gen Hosp Psychiatry 23(4):215–222PubMedCrossRefGoogle Scholar
- 38.Rapoport DM, Norman RG, inventors; New York University, New York, NY, assigned. Positive airway pressure system and method for treatment of sleeping disorder in patient. US patent 6,988,994. January 24, 2006Google Scholar
- 40.Dungan GC 2nd, Marshall NS, Hoyos CM, Yee BJ, Grunstein RR (2011) A randomized crossover trial of the effect of a novel method of pressure control (SensAwake) in automatic continuous positive airway pressure therapy to treat sleep disordered breathing. J Clin Sleep Med 7(3):261–267PubMedPubMedCentralGoogle Scholar
- 42.Berry R, Brooks R, Gamaldo CE, et al (2015) for the American Academy of Sleep Medicine. The AASM manual for the scoring of sleep and associated events: rules, terminology and technical specifications, Version 2.2. In. www.aasmnet.org: AASM
- 43.The Report of an American Academy of Sleep Medicine Task Force (1999) Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. Sleep 22(5):667–689Google Scholar
- 45.Weathers F, Litz B, Herman D, Huska J, Keane T (1993) The PTSD Checklist (PCL): reliability, validity, and diagnostic utility. In: Paper presented at 9th Annual Meeting of the International Society for Traumatic Stress Studies 9th Annual Meeting. San Antonio, TXGoogle Scholar
- 46.Weathers F, Huska J, Keane T (1991) The PTSD checklist military version (PCL-M). National Center for PTSD, BostonGoogle Scholar
- 50.The PTSD Checklist (PCL): reliability, validity, and diagnostic utility. Frank W Weathers, Brett T Litz, Debra S Herman, Jennifer A Huska, and Terence M Keane. Paper presented at the Annual Meeting of International Society for Traumatic Stress Studies, San Antonio, TX, October 1993Google Scholar
- 52.PCL Scoring information for DSM-IV. https://www.ptsd.va.gov/professional/assessment/documents/PCL_Scoring_Information.pdf (Accessed 26 April 2019)
- 53.PCL Psychometric information for DSM-IV. https://www.ptsd.va.gov/professional/assessment/documents/PCL_Psychometric_Information.pdf (Accessed 26 April 2019)
- 54.Using the PTSD checklist for DSM-IV. https://www.ptsd.va.gov/professional/assessment/documents/PCL_handoutDSM4.pdf (Accessed 26 April 2019).
- 62.El-Solh AA, Homish GG, Ditursi G, Lazarus J, Rao N, Adamo D, Kufel T (2017) A randomized crossover trial evaluating continuous positive airway pressure versus mandibular advancement device on health outcomes in veterans with posttraumatic stress disorder. J Clin Sleep Med 13(11):1327–1335PubMedPubMedCentralCrossRefGoogle Scholar
- 64.Tamanna S, Parker JD, Lyons J, Ullah M (2014) The effect of continuous positive air pressure (CPAP) on nightmares in patients with posttraumatic stress disorder (PTSD) and obstructive sleep apnea (OSA). Journal of Clinical Sleep Medicine: JCSM: Official Publication of the American Academy of Sleep Medicine 10(6):631Google Scholar
- 65.Edwards BA, Eckert DJ, McSharry DG, Sands SA, Desai A, Kehlmann G, Bakker JP, Genta PR, Owens RL, White DP et al (2014) Clinical predictors of the respiratory arousal threshold in patients with obstructive sleep apnea. Am J Respir Crit Care Med 190(11):1293–1300PubMedPubMedCentralCrossRefGoogle Scholar