Effects of continuous positive airway pressure on depression and anxiety symptoms in patients with obstructive sleep apnoea: results from the sleep apnoea cardiovascular Endpoint randomised trial and meta-analysis

doi:10.1016/j.eclinm.2019.05.012

. 2019 Jun 13:11:89-96.

doi: 10.1016/j.eclinm.2019.05.012. eCollection 2019 May-Jun.

Effects of continuous positive airway pressure on depression and anxiety symptoms in patients with obstructive sleep apnoea: results from the sleep apnoea cardiovascular Endpoint randomised trial and meta-analysis

Danni Zheng^{1

2}, Ying Xu^{2

3}, Shoujiang You⁴, Maree L Hackett^{2

5}, Richard J Woodman⁶, Qiang Li², Mark Woodward^{2

7

8}, Kelly A Loffler⁹, Anthony Rodgers², Luciano F Drager^{10

11}, Geraldo Lorenzi-Filho¹², Xia Wang², Wei Wei Quan¹³, Manjari Tripathi¹⁴, Olga Mediano^{15

16}, Qiong Ou¹⁷, Rui Chen¹⁸, Zhihong Liu¹⁹, Xilong Zhang²⁰, Yuanming Luo²¹, Nigel McArdle²², Sutapa Mukherjee^{9

22

23}, R Douglas McEvoy^{9

23}, Craig S Anderson^{2

24

25}

Affiliations

¹ Centre for Big Data Research in Health, University of New South Wales, Sydney, NSW, Australia.
² The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
³ Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
⁴ Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, PR China.
⁵ Faculty of Health and Wellbeing, The University of Central Lancashire, Preston, Lancashire, UK.
⁶ Flinders Centre for Epidemiology and Biostatistics, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia.
⁷ The George Institute for Global Health, University of Oxford, Oxford, Oxfordshire, UK.
⁸ Department of Epidemiology, Johns Hopkins University, Baltimore, MD, USA.
⁹ Adelaide Institute for Sleep Health, Flinders University, Adelaide, SA, Australia.
¹⁰ Hypertension Unit, Heart Institute (InCor), University of Sao Paulo Medical School, Sao Paulo, Brazil.
¹¹ Hypertension Unit, Renal Division, University of Sao Paulo Medical School, Sao Paulo, Brazil.
¹² Sleep Laboratory, Pulmonary Division, University of Sao Paulo Medical School, Sao Paulo, Brazil.
¹³ Department of Cardiology, Rui Jin Hospital and Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
¹⁴ Department of Neurology, All India Institute of Medical Sciences, Delhi, India.
¹⁵ Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
¹⁶ Respiratory Department, Hospital Universitario de Guadalajara, Universidad de Alcalá, Madrid, Spain.
¹⁷ Sleep Center, Respiratory and Critical Medical Department, Guangdong Institute of Geriatrics, Guangdong Academy of Medical Sciences, Guangdong Provincial People's Hospital, Guangzhou 510000, Guangdong PR, PR China.
¹⁸ The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, PR China.
¹⁹ Department of Cardiology, Fuwai Hospital, Beijing, PR China.
²⁰ The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
²¹ The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Guangzhou, PR China.
²² West Australian Sleep Disorders Research Institute, Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.
²³ Sleep Health Service, Respiratory and Sleep Services, Southern Adelaide Local Health Network, Flinders Medical Centre, Adelaide, SA, Australia.
²⁴ Neurology Department, Royal Prince Alfred Hospital, Sydney Health Partners, Sydney, NSW, Australia.
²⁵ The George Institute for Global Health China at Peking University Health Science Center, Beijing, PR China.

PMID: 31312807
PMCID: PMC6610775
DOI: 10.1016/j.eclinm.2019.05.012

Effects of continuous positive airway pressure on depression and anxiety symptoms in patients with obstructive sleep apnoea: results from the sleep apnoea cardiovascular Endpoint randomised trial and meta-analysis

Danni Zheng et al. EClinicalMedicine. 2019.

. 2019 Jun 13:11:89-96.

doi: 10.1016/j.eclinm.2019.05.012. eCollection 2019 May-Jun.

Authors

Affiliations

¹ Centre for Big Data Research in Health, University of New South Wales, Sydney, NSW, Australia.
² The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
³ Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
⁴ Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, PR China.
⁵ Faculty of Health and Wellbeing, The University of Central Lancashire, Preston, Lancashire, UK.
⁶ Flinders Centre for Epidemiology and Biostatistics, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia.
⁷ The George Institute for Global Health, University of Oxford, Oxford, Oxfordshire, UK.
⁸ Department of Epidemiology, Johns Hopkins University, Baltimore, MD, USA.
⁹ Adelaide Institute for Sleep Health, Flinders University, Adelaide, SA, Australia.
¹⁰ Hypertension Unit, Heart Institute (InCor), University of Sao Paulo Medical School, Sao Paulo, Brazil.
¹¹ Hypertension Unit, Renal Division, University of Sao Paulo Medical School, Sao Paulo, Brazil.
¹² Sleep Laboratory, Pulmonary Division, University of Sao Paulo Medical School, Sao Paulo, Brazil.
¹³ Department of Cardiology, Rui Jin Hospital and Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
¹⁴ Department of Neurology, All India Institute of Medical Sciences, Delhi, India.
¹⁵ Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
¹⁶ Respiratory Department, Hospital Universitario de Guadalajara, Universidad de Alcalá, Madrid, Spain.
¹⁷ Sleep Center, Respiratory and Critical Medical Department, Guangdong Institute of Geriatrics, Guangdong Academy of Medical Sciences, Guangdong Provincial People's Hospital, Guangzhou 510000, Guangdong PR, PR China.
¹⁸ The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, PR China.
¹⁹ Department of Cardiology, Fuwai Hospital, Beijing, PR China.
²⁰ The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
²¹ The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Guangzhou, PR China.
²² West Australian Sleep Disorders Research Institute, Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.
²³ Sleep Health Service, Respiratory and Sleep Services, Southern Adelaide Local Health Network, Flinders Medical Centre, Adelaide, SA, Australia.
²⁴ Neurology Department, Royal Prince Alfred Hospital, Sydney Health Partners, Sydney, NSW, Australia.
²⁵ The George Institute for Global Health China at Peking University Health Science Center, Beijing, PR China.

PMID: 31312807
PMCID: PMC6610775
DOI: 10.1016/j.eclinm.2019.05.012

Abstract

Background: Whether continuous positive airway pressure (CPAP) treatment can improve depression or anxiety symptoms in obstructive sleep apnoea (OSA) patients remains uncertain.

Methods: Secondary analysis of the Sleep Apnea Cardiovascular Endpoints (SAVE) trial, combined with a systematic review of randomised evidence. The SAVE secondary analyses involved 2410 patients with co-existing moderate-severe OSA and established cardiovascular disease randomly allocated to CPAP treatment plus usual care or usual care alone and followed up for 3·7 (SD 1·6) years. We evaluated the effect of CPAP treatment on depression and anxiety caseness (scores ≥ 8 on the Hospital Anxiety and Depression Scale depression and anxiety subscales [HADS-D and HADS-A]) for OSA patients.

Findings: CPAP treatment was associated with reduced odds of depression caseness (adjusted odds ratio [OR] 0·80, 95% confidence interval [CI] 0·65-0·98, P = 0·031) compared to usual care in the SAVE trial and the treatment effect was greater in those with pre-existing depression symptoms. A systematic review of 20 randomised trials including 4255 participants confirmed a benefit of CPAP in reducing depression symptoms in OSA patients: the overall effect (standardised mean difference) was - 0·18 (95% CI - 0·24 to - 0·12). No effect of CPAP treatment on anxiety caseness was found both in patients of the SAVE study (adjusted OR 0·98, 95% CI 0·78-1·24, P = 0·89) and the systematic review.

Interpretation: CPAP reduces depression symptoms in patients with co-existing OSA and CVD independently of improvements in sleepiness.

Keywords: Anxiety; Cardiovascular diseases; Continuous positive airway pressure; Depression; Mood; OSA; Obstructive sleep apnoea.

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Figures

**Fig. 1**
Consort flow diagram CPAP denotes continuous positive airways pressure; OSA, obstructive sleep apnoea.

**Fig. 2**
Meta-analysis of the effect of CPAP for depression symptoms Pooled standardised mean difference (SMD) was calculated using a random effects model. Boxes are SMD and lines are 95% confidence interval (CI). The vertical solid line represents no difference between CPAP and control. Values to the left of the solid line favour CPAP benefit. Pooled SMDs and 95%CI are represented by the diamond shapes.

**Fig. 3**
Meta-analysis of the effect of CPAP for anxiety symptoms Pooled standardised mean difference (SMD) was calculated using a random effects model. Boxes are SMD and lines are 95% confidence interval (CI). The vertical solid line represents no difference between CPAP and control. Values to the left of the solid line favour CPAP benefit. Pooled SMD and 95%CI are represented by diamond shapes.

See this image and copyright information in PMC

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Full Text Sources

[1] Ohayon M.M. The effects of breathing-related sleep disorders on mood disturbances in the general population. J Clin Psychiatry. 2003;64:1195–1200. [quiz, 1274-6] - PubMed

Ohayon MM. The effects of breathing-related sleep disorders on mood disturbances in the general population. J Clin Psychiatry 2003; 64: 1195-200; quiz, 1274-6. - PubMed

[2] Ohayon M.M. The effects of breathing-related sleep disorders on mood disturbances in the general population. J Clin Psychiatry. 2003;64:1195–1200. [quiz, 1274-6] - PubMed

[3] Ohayon MM. The effects of breathing-related sleep disorders on mood disturbances in the general population. J Clin Psychiatry 2003; 64: 1195-200; quiz, 1274-6. - PubMed

[4] Sharafkhaneh A., Giray N., Richardson P., Young T., Hirshkowitz M. Association of psychiatric disorders and sleep apnea in a large cohort. Sleep. 2005;28:1405–1411. - PubMed

Sharafkhaneh A, Giray N, Richardson P, Young T, Hirshkowitz M. Association of psychiatric disorders and sleep apnea in a large cohort. Sleep 2005; 28: 1405–11. - PubMed

[5] Sharafkhaneh A., Giray N., Richardson P., Young T., Hirshkowitz M. Association of psychiatric disorders and sleep apnea in a large cohort. Sleep. 2005;28:1405–1411. - PubMed

[6] Sharafkhaneh A, Giray N, Richardson P, Young T, Hirshkowitz M. Association of psychiatric disorders and sleep apnea in a large cohort. Sleep 2005; 28: 1405–11. - PubMed

[7] Wheaton A.G., Perry G.S., Chapman D.P., Croft J.B. Sleep disordered breathing and depression among U.S. adults: National Health and Nutrition Examination Survey, 2005–2008. Sleep. 2012;35:461–467. - PMC - PubMed

Wheaton AG, Perry GS, Chapman DP, Croft JB. Sleep disordered breathing and depression among U.S. adults: National Health and Nutrition Examination Survey, 2005-2008. Sleep 2012; 35: 461–67. doi:10.5665/sleep.1724. - PMC - PubMed

[8] Wheaton A.G., Perry G.S., Chapman D.P., Croft J.B. Sleep disordered breathing and depression among U.S. adults: National Health and Nutrition Examination Survey, 2005–2008. Sleep. 2012;35:461–467. - PMC - PubMed

[9] Wheaton AG, Perry GS, Chapman DP, Croft JB. Sleep disordered breathing and depression among U.S. adults: National Health and Nutrition Examination Survey, 2005-2008. Sleep 2012; 35: 461–67. doi:10.5665/sleep.1724. - PMC - PubMed

[10] Harris M., Glozier N., Ratnavadivel R., Grunstein R.R. Obstructive sleep apnea and depression. Sleep Med Rev. 2009;13:437–444. - PubMed

Harris M, Glozier N, Ratnavadivel R, Grunstein RR. Obstructive sleep apnea and depression. Sleep Med Rev 2009; 13: 437–44. doi:10.1016/j.smrv.2009.04.001. - PubMed

[11] Harris M., Glozier N., Ratnavadivel R., Grunstein R.R. Obstructive sleep apnea and depression. Sleep Med Rev. 2009;13:437–444. - PubMed

[12] Harris M, Glozier N, Ratnavadivel R, Grunstein RR. Obstructive sleep apnea and depression. Sleep Med Rev 2009; 13: 437–44. doi:10.1016/j.smrv.2009.04.001. - PubMed

[13] Saunamäki T., Jehkonen M. Depression and anxiety in obstructive sleep apnea syndrome: a review. Acta Neurol Scand. 2007;116:277–288. - PubMed

Saunamäki T, Jehkonen M. Depression and anxiety in obstructive sleep apnea syndrome: a review. Acta Neurol Scand 2007; 116: 277–88. doi:10.1111/j.1600-0404.2007.00901.x. - PubMed

[14] Saunamäki T., Jehkonen M. Depression and anxiety in obstructive sleep apnea syndrome: a review. Acta Neurol Scand. 2007;116:277–288. - PubMed

[15] Saunamäki T, Jehkonen M. Depression and anxiety in obstructive sleep apnea syndrome: a review. Acta Neurol Scand 2007; 116: 277–88. doi:10.1111/j.1600-0404.2007.00901.x. - PubMed

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Effects of continuous positive airway pressure on depression and anxiety symptoms in patients with obstructive sleep apnoea: results from the sleep apnoea cardiovascular Endpoint randomised trial and meta-analysis

Affiliations

Effects of continuous positive airway pressure on depression and anxiety symptoms in patients with obstructive sleep apnoea: results from the sleep apnoea cardiovascular Endpoint randomised trial and meta-analysis

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