0
Original Research: Sleep Disorders |

Depressive Symptoms Before and After Long-term CPAP Therapy in Patients With Sleep ApneaCPAP Therapy and Depression in Sleep Apnea FREE TO VIEW

Frédéric Gagnadoux, MD, PhD; Marc Le Vaillant, PhD; François Goupil, MD; Thierry Pigeanne, MD; Sylvaine Chollet, MD; Philippe Masson, MD; Acya Bizieux-Thaminy, MD; Marie-Pierre Humeau, MD; Nicole Meslier, MD on behalf of the IRSR Sleep Cohort Group*
Author and Funding Information

From the LUNAM Université (Prof Gagnadoux and Dr Meslier), Angers; Université d’Angers (Prof Gagnadoux and Dr Meslier), CHU Angers, Département de Pneumologie, Angers; CERMES (Dr Le Vaillant), CNRS UMR8211 - Inserm U988 - EHESS, Villejuif; Centre Hospitalier (Dr Goupil), Service de Pneumologie, Le Mans; Pôle santé des Olonnes (Dr Pigeanne), Unité de Pneumologie, Olonne sur Mer; Institut du Thorax (Dr Chollet), Pneumologie, Hôpital Laennec, Nantes; Centre Hospitalier (Dr Masson), Service de Pneumologie, Cholet; Centre Hospitalier (Dr Bizieux-Thaminy), Service de Pneumologie, La Roche sur Yon; Nouvelles Cliniques Nantaises (Dr Humeau), Pneumologie, Nantes, France.

Correspondence to: Frédéric Gagnadoux, MD, PhD, Université d’Angers, CHU Angers, Département de Pneumologie, 4 rue Larrey, 49033 Angers Cedex, France; e-mail: frgagnadoux@chu-angers.fr


A complete list of group members can be found in e-Appendix 1.

Funding/Support: The authors have reported to CHEST that no funding was received for this study.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;145(5):1025-1031. doi:10.1378/chest.13-2373
Text Size: A A A
Published online

Background:  The outcome of depressive symptoms under CPAP therapy for OSA-hypopnea syndrome (OSAHS) has been poorly evaluated. In this multicenter, prospective cohort study, we evaluated the prevalence and correlates of persistent depressive symptoms after long-term CPAP therapy for OSAHS.

Methods:  This study included 300 patients with OSAHS and depressive symptoms (13-item, self-rated Pichot depression scale [QD2A] ≥ 7) at diagnosis. The primary dependent variable was persistent depressive symptoms after ≥ 1 year of CPAP therapy. Multivariate regression analyses were performed to determine variables independently associated with the persistence of depressive symptoms.

Results:  After an average of 529 days (range, 365-1,569 days) of CPAP therapy, the mean (SD) QD2A score decreased from 9.2 (2.0) to 5.4 (4.0) (P < .0001), but 125 patients (41.7%) presented persistent depressive symptoms. The persistence of depressive symptoms was independently associated with persistent excessive daytime sleepiness (EDS) (OR, 2.72; 95% CI, 1.33-5.61), comorbid cardiovascular disease (OR, 1.76; 95% CI, 1.02-3.00), and female sex (OR, 1.53; 95% CI, 1.09-2.13). A positive linear trend was observed for the adjusted OR of persistent depressive symptoms with decreasing CPAP effect on the Epworth sleepiness scale (P < .0001).

Conclusions:  CPAP therapy does not resolve depressive symptoms in many patients with OSAHS. Persistent depressive symptoms are strongly associated with EDS. Active monitoring of depressive symptoms is needed in patients with OSAHS who are treated with CPAP. Interventional trials are required to evaluate the impact of antidepressants, cognitive behavioral therapy, or both on comorbid depression in patients with OSAHS.

Figures in this Article

OSA-hypopnea syndrome (OSAHS) is a highly prevalent disease characterized by recurrent episodes of partial or complete obstruction of the upper airways during sleep. Randomized controlled trials of CPAP therapy in OSAHS have demonstrated a benefit on daytime alertness, quality of life, and BP.1,2 Depression is one of the most common psychiatric illnesses in adults and is a major public health problem. According to the World Health Organization, depression was the fourth leading cause of disability in 2000 and is expected to be the second leading cause in 2020.3 In France, the lifetime prevalence of depression is estimated at 13% to 17% in men and 25% to 30% in women.4

High rates of depressive symptoms have been observed in people with OSAHS.5 In the general population, excessive daytime sleepiness (EDS) is more strongly associated with depression than with sleep-disordered breathing (SDB) severity.6 Any relationship between OSAHS and depression may be at least partially explained by overlapping symptoms including fatigue, loss of interest, decreased libido, and poor concentration.5 Depression shares common comorbid medical conditions with OSAHS, such as obesity, metabolic syndrome,7 and cardiovascular diseases (CVDs),8 that may contribute to the association. If a causal link exists between OSAHS and depression, then depressive symptoms would be expected to improve during CPAP therapy. However, limited data are available regarding the outcome of depressive symptoms in response to CPAP therapy.5 Overall, it appears that symptoms of depression may persist in at least some patients treated for OSAHS.5 This multicenter, prospective cohort study was designed to evaluate the outcome of depressive symptoms in patients with OSAHS who were treated with CPAP and to determine the prevalence and correlates of persistent depressive symptoms after long-term CPAP therapy.

Design and Study Population

This multicenter, prospective, observational cohort study was conducted on the Institut de Recherche en Santé Respiratoire des Pays de la Loire (IRSR) sleep cohort. Since May 15, 2007, consecutive patients aged ≥ 18 years in whom CPAP therapy is prescribed for OSAHS at seven centers from the west of France are eligible for inclusion in the IRSR sleep cohort. Patients with intellectual developmental disabilities, patients who were unable to fill in the questionnaires or to read and/or speak French, and patients with neuromuscular diseases are excluded from the IRSR sleep cohort.

Approval was obtained from the University of Angers ethics committee and from the Comité Consultative sur le Traitement de l’Information en matière de Recherche dans le domaine de la Santé (07.207bis). The database is anonymous and complies with the restrictive requirements of the Commission Nationale Informatique et Liberté, the French information technology and personal-data protection authority. All patients included in the IRSR sleep cohort have given their written informed consent.

Between May 15, 2007, and April 30, 2013, patients from the IRSR sleep cohort were eligible for the present study when CPAP therapy had been prescribed ≥ 365 days prior to inclusion and baseline evaluation reported the presence of depressive symptoms as defined by a 13-item, self-rated Pichot depression scale (QD2A) score911 ≥ 7 regardless of antidepressant medication use. Patients were excluded from the present study when (1) CPAP treatment was abandoned at < 365 days, and/or (2) CPAP use was not recorded in the database, and/or (3) QD2A or the Epworth sleepiness scale (ESS) was not completed at the follow-up visit.

Depression and EDS Questionnaires

Depressive symptoms and EDS were assessed prior to CPAP initiation and at each follow-up visit. Symptoms of depression were assessed with the QD2A score.911 This 13-item questionnaire was specifically designed for depression screening in community studies and has a high internal consistency (α = 0.91). Each of the following items presents a statement that the subjects must answer as true or false: (1) I cannot get rid of adverse thoughts that go through my head; (2) I have no energy; (3) I do not appreciate things I used to like as fully as before; (4) I feel disappointed and disgusted with myself; (5) I feel helpless or blocked by the slightest thing I need do; (6) Right now I feel unhappier than most people; (7) I have the blues; (8) I have to force myself to do every little thing I have to do; (9) I feel my mind is not as clear as usual; (10) I am unable to make up my mind as easily as usual; (11) Right now I feel sad; (12) I have trouble doing the things I used to do; and (13) I feel my life is empty. The score is established by the number of items marked as true and ranges between 0 and 13. The threshold for a positive indication of depression is a QD2A score ≥ 7. EDS was defined by an ESS > 10.12

Assessment of Comorbidities

Each patient enrolled in the IRSR sleep cohort completed surveys on medical history and underwent fasting assays of serum lipids, blood glucose, and glycated hemoglobin. BP was measured after ≥ 5 min of rest in the sitting position. The mean of three measurements was recorded. Hypertension was defined by systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg, or the presence of antihypertensive treatment. Patients were classified as having comorbid CVD if they reported one or more of the following CVDs: ischemic heart disease, cardiac arrhythmia, congestive heart failure, and stroke. Patients with fasting blood glucose levels > 126 mg/dL or glycated hemoglobin levels ≥ 6.5%, or those receiving antidiabetic treatment were considered to present with diabetes. The presence of metabolic syndrome was analyzed according to the National Cholesterol Education Program Adult Treatment Panel III clinical criteria.13

Sleep Recordings

OSAHS was diagnosed by overnight polysomnography (PSG) or overnight respiratory recording. Overnight PSG was performed with continuous recording of the following channels: EEG, electrooculogram, chin electromyogram, arterial oxygen saturation (finger oximetry), nasal-oral airflow (pressure cannula and tracheal sounds), ECG, chest and abdominal wall motion (piezoelectrodes), bilateral tibialis electromyogram, and body position. Overnight respiratory recordings were performed with continuous recording of arterial oxygen saturation, nasal-oral airflow, chest and abdominal wall motion, and body position. Respiratory events were scored manually using recommended criteria.14

CPAP Initiation and Follow-up

The decision to prescribe CPAP therapy was based on the following criteria: apnea-hypopnea index ≥ 30 or between 5 and 30 with EDS, and two or more OSAHS symptoms, including snoring, choking, or gasping during sleep; unrefreshing sleep; daytime fatigue; impaired concentration; and/or nocturia. According to the French recommendations for reimbursement of CPAP therapy, patients were seen in consultation by the sleep specialist during the first 5 months, at 12 months, and then at least annually. Daily CPAP use was recorded at each follow-up visit.

Statistical Analysis

All statistical analyses were performed with SAS software (SAS/STAT Package 2002-2003; SAS Institute Inc). The primary dependent variable of interest was the persistence of depressive symptoms as defined by a QD2A score ≥ 7 at the last CPAP therapy follow-up visit at least 365 days after treatment start. Patients with and without persistent depressive symptoms were compared using the χ2 test for categorical variables and two-sample t test for continuous variables. Variables with P value < .05 were then entered in a logistic procedure with backward stepwise regression analysis to determine variables independently associated with the persistence of depressive symptoms. Results were expressed as mean (SD) and adjusted OR (95% CI). A two-tailed probability value < .05 was considered significant.

A flow diagram is presented in Figure 1. On April 30, 2013, 349 patients from the IRSR sleep cohort had been prescribed CPAP therapy for OSAHS ≥ 365 days prior to inclusion, and had a QD2A score ≥ 7 at baseline, indicating symptoms of depression. Forty-nine patients were excluded from the analysis due to one of the exclusion criteria. As shown in Table 1, the only significant difference between excluded and included patients was a slightly lower age in excluded patients. The final sample size was 300 patients with OSAHS diagnosed by PSG (n = 108) or overnight respiratory recording (n = 192). After an average of 529 (195) days (range, 365-1,569 days) of CPAP use (mean daily use, 5.5 [2.0] h), the QD2A score decreased from 9.2 (2.0) to 5.4 (4.0) (P < .0001) (mean change in Q2DA score, −3.8; 95% CI, −4.2 to −3.3). In this sample of 300 patients, 125 (41.7%) had a QD2A score ≥ 7 (mean, 9.7 [2.0]) after long-term CPAP use, indicating persistent depressive symptoms. The mean change in QD2A score after long-term CPAP therapy was −0.24 (95% CI, −0.7 to −0.2) in patients with persistent depressive symptoms vs −6.3 (95% CI, −6.7 to −5.9) in patients without persistent depressive symptoms. Eighty-nine patients received antidepressant therapy at baseline, of whom 41 (46%) were taken off the drugs during follow-up. The antidepressant therapy was discontinued during follow-up in 14 of 40 patients (35%) with persistent depressive symptoms and 27 of 49 patients (55%) without persistent depressive symptoms while using CPAP (P = .06). Conversely, 17 patients were put on antidepressant medication during follow-up, of whom 12 had persistent depressive symptoms while using CPAP and five had no persistent depressive symptoms. A comparison of patients with and without persistent depressive symptoms is presented in Table 2. The persistence of depressive symptoms was associated with higher age, higher prevalence of CVD, and a higher rate of persistent EDS on CPAP therapy. In contrast, no significant difference was observed between patients with and without persistent depressive symptoms in terms of sex, BMI, SDB severity, baseline ESS, alcohol and smoking habits, hypertension, diabetes, metabolic syndrome, use of antidepressant therapy at baseline, and CPAP adherence.

Figure Jump LinkFigure 1. Flow diagram of subjects during the study. IRSR = Institut de Recherche en Santé Respiratoire des Pays de la Loire; OSAHS = OSA-hypopnea syndrome; QD2A = 13-item, self-rated Pichot depression scale.Grahic Jump Location
Table Graphic Jump Location
Table 1 —Comparison of Patients Included in the Analysis and Patients Excluded Due to CPAP Withdrawal, Missing Adherence Data, or Unavailable ESS and/or QD2A Score During Follow-up

Data are expressed as mean (SD) or % unless otherwise indicated. AHI = apnea-hypopnea index; CVD = cardiovascular disease; ESS = Epworth Sleepiness Scale; QD2A = 13-item, self-rated Pichot depression scale.

a 

Alcohol consumption ≥ 20 g/d by women or ≥ 30 g/d by men.

Table Graphic Jump Location
Table 2 —Comparison of Patients With and Without Persistent Depressive Symptoms After Long-term CPAP Therapy

Data are expressed as mean (SD) or % unless otherwise indicated. EDS = excessive daytime sleepiness. See Table 1 legend for expansion of other abbreviations.

a 

Persistent EDS was defined by an ESS score > 10 at the last CPAP follow-up visit.

b 

Alcohol consumption of ≥ 20 g/d by women or ≥ 30 g/d by men.

A stepwise regression analysis was performed to determine variables independently associated with persistent depressive symptoms. The following four variables were entered in the model: age, sex, persistent EDS, and CVD. Although sex was not significantly different between patients with and without persistent depressive symptoms, it was considered clinically relevant to include this variable in the model, as women are about twice as likely as men to develop depression and the relationship between depression and CVD has been demonstrated to be strongly modified by sex.8 As shown in Table 3, three variables were associated with the persistence of depressive symptoms on multivariable analysis: persistent EDS (OR, 2.72; 95% CI, 1.33-5.61), comorbid CVD (OR, 1.76; 95% CI, 1.02-3.00), and female sex (OR, 1.53; 95% CI, 1.09-2.13). As shown in Figure 2, a significant positive linear trend was observed for the adjusted OR of persistent depressive symptoms with decreasing CPAP effect on ESS. The percentage of patients with persistent depressive symptoms increased from 29.9% in patients with the highest quartile of ESS reduction (> 7 points) to 56.5% in patients with the lowest quartile of ESS reduction (< 1 point).

Table Graphic Jump Location
Table 3 —Stepwise Regression Analysis of Variables Associated With Persistent Depressive Symptoms After Long-term CPAP Therapy

See Table 1 and 2 legends for expansion of abbreviations.

a 

P value is significant at < .05.

b 

Persistent EDS was defined by an ESS > 10 at the last CPAP follow-up visit.

Figure Jump LinkFigure 2. Adjusted ORs for persistent depressive symptoms according to quartiles of reduction of ESS after long-term CPAP therapy. ORs were adjusted for age, sex, and cardiovascular diseases. *Tested by the Cochrane-Armitage trend test. ESS = Epworth Sleepiness Scale; ref. = reference.Grahic Jump Location

This multicenter, prospective cohort study including 300 patients with OSAHS and symptoms of depression prior to treatment demonstrated a significant improvement of depression scores in response to CPAP therapy. However, almost 42% of patients displayed persistent depressive symptoms after ≥ 1 year of CPAP use. In multivariate analysis, the persistence of depressive symptoms was independently associated with persistent EDS, comorbid CVD, and female sex. In contrast, the persistence of depressive symptoms was not correlated with antidepressant therapy at baseline, metabolic disorders, SDB severity, alcohol consumption, smoking habits, or CPAP adherence.

Few studies have addressed the outcome of depressive symptoms during CPAP therapy for OSAHS. In several1517 but not all18 observational studies, CPAP therapy was associated with a reduction of depressive symptoms. In contrast, data from five randomized trials reporting the Hospital Anxiety and Depression Scale and that were pooled in a meta-analysis, showed no significant difference between CPAP use and placebo in terms of either anxiety or depression.1 Additional trials19,20 also failed to demonstrate a beneficial impact of CPAP therapy on mood symptoms in patients with OSAHS. However, most previous studies evaluating the outcome of depressive symptoms in patients with sleep apnea who were treated with CPAP included subjects with depression scores mainly in the nonclinical range, which may be associated with floor effects of any intervention.5 Furthermore, most trials measured the outcome of depressive symptoms after only 2 to 4 weeks of CPAP use, while the duration of the acute phase of antidepressant therapy may be 6 to 12 weeks or longer, depending on the individual patient’s response and the number of medication changes. The present study overcomes these methodologic limitations by including a large sample of patients with OSAHS and symptoms of depression at diagnosis and by providing outcome data after ≥ 1 year of CPAP therapy.

It has been demonstrated in population- and clinic-based studies that reduced daytime alertness is associated with higher depression scores in subjects with untreated OSAHS.6,21 EDS at OSAHS diagnosis is more strongly associated with depressive symptoms than with SDB severity.6 Data from a French Sleep Registry have shown that 18% of patients with sleep apnea who are treated with CPAP and who attend follow-up visits may exhibit persistent EDS despite regular CPAP use.22 Previous studies have reported an association between daytime sleepiness and persistent depression on CPAP therapy for OSAHS.23,24 In 17 patients with OSAHS and persistent major depressive disorder despite pharmacotherapy, Habukawa et al23 found significant correlations between the improvement rates of depression scores and ESS during CPAP use. In a cross-sectional study based on a postal survey with a 74% response rate,24 high depression scores were associated with EDS and nonadherence to CPAP therapy. In line with these previous reports, our multicenter, prospective cohort study demonstrated a strong independent association between persistent depressive symptoms and persistent EDS after long-term CPAP therapy. In contrast, no significant relationship was demonstrated between persistent depressive symptoms and CPAP adherence, whereas self-reported CPAP use < 3 nights/wk was associated with high anxiety and depression scores in a previous study.24 However, the self-reported nature of adherence data in this previous study may have resulted in misclassifications.24 Altogether, our findings and those from previous studies23,24 indicate that patients with persistent EDS despite regular CPAP use for OSAHS should be assessed for depression.

Depression is recognized as an independent risk factor for CVD.8,25 In the present study, we demonstrate that patients with comorbid CVD are at higher risk for persistent depressive symptoms under CPAP therapy after adjustment for age, sex, and persistent EDS. Although the underlying relationship is unclear, the association between OSAHS, CVD, and depression may be explained by common comorbid conditions such as obesity and metabolic syndrome7 and by common underlying biologic alterations. OSAHS is associated with increased circulating levels of proinflammatory cytokines that are not modified by CPAP use26 and may contribute to the pathogenesis of EDS,27 CVD,28 and depression.29 The serotonergic function, known to influence mood, is also thought to represent a biologic link between depression and CVD8 and to contribute to the reduced upper-airway dilator muscle activity during sleep.30

The bidirectional association between depression and CVD has been found to be strongly modified by sex.8 Sex also appeared to modify the relationship between OSAHS severity, obesity, and depression.31 In a large, clinic-based population, depression scores were significantly higher in women than in men for all age groups and for all levels of respiratory disturbance index, suggesting that men and women with OSAHS manifest depression differently.32 In line with these previous findings, our study demonstrates that women are at higher risk of persistent depressive symptoms after long-term CPAP therapy.

We acknowledge that the main weakness of the present study is its observational design, which does not allow any conclusion to be drawn regarding the causal pathway of the observed associations. In the absence of a placebo arm, it is impossible to establish a direct link between long-term CPAP therapy of OSAHS and the improvement of depression scores. However, depressive disorders require long-term treatment and it would have been unethical to expose patients with moderate to severe OSAHS, EDS, and frequent cardiometabolic-associated conditions to placebo treatment of > 1 year. Furthermore, rigorous observational cohort studies can complement data from randomized controlled trials by providing information on long-term treatment efficacy in patients encountered in day-to-day clinical practice.33 We also acknowledge that the QD2A depression scale is less commonly used than other depression scores such as the Hospital Anxiety and Depression scale or the Beck Depression Inventory. However, the QD2A presents several properties that make this tool interesting for mood assessment in a large cohort of French-speaking patients with a chronic medical illness. This is a short, easy-to-use, French-language questionnaire with high internal consistency (α = 0.91) and the ability to discriminate among subjects with depressive symptoms in the context of somatic disorders.9,10 It has been validated against several other depression scales, such as the Zung Self-rating Depression Scale.9,10 The QD2A has been widely used in France to assess mood in large community- or clinic-based cohorts of subjects with chronic medical illness such as hypertension34,35 or SDB.22,3638 Our finding that persistent depressive symptoms are strongly associated with EDS is highly consistent with previous data using more commonly used questionnaires such as the Beck Depression Inventory.23

A major finding of the present study is that CPAP therapy does not resolve depressive symptoms in a large proportion of patients with OSAHS. This finding emphasizes the importance of close follow-up of depressive symptoms once CPAP treatment is initiated in patients with OSAHS. Our study is also a reminder that depression needs to be specifically addressed as a likely comorbid condition in these patients. Depressive symptoms are common in chronic medical illnesses and may result in undue distress or greater impairment. Active treatment of depressive symptoms including psychologic and lifestyle interventions with or without antidepressant medication is recommended in patients with chronic physical health problems.39 A recent meta-analysis demonstrated that complex psychologic and/or lifestyle interventions that include an exercise component significantly improve symptoms of depression in people with COPD.40 In a randomized study including sedentary and overweight/obese adults with moderate to severe untreated OSAHS, 12 weeks of moderate-intensity exercise training resulted in significant improvements in depressive symptoms.41 As CPAP use does not appear to reliably treat comorbid depression in patients with OSAHS, further trials are needed to evaluate the impact of specific therapeutic strategies, including antidepressants and psychologic and/or lifestyle interventions. Such trials should also evaluate the impact of these strategies on a range of outcomes, including EDS and CPAP compliance.

CPAP therapy does not resolve depressive symptoms in many patients with OSAHS. Persistent depressive symptoms are strongly associated with EDS. Active monitoring of depressive symptoms is needed in patients with OSAHS who are treated with CPAP. Interventional trials are required to evaluate the impact of antidepressants, cognitive behavioral therapy, or both on comorbid depression in patients with OSAHS.

Author contributions: Prof Gagnadoux had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Prof Gagnadoux: contributed to data research, discussion, writing the manuscript, and reviewing and editing the manuscript and served as principal author.

Dr Le Vaillant: contributed to data research, discussion, writing the manuscript, and reviewing and editing the manuscript.

Dr Goupil: contributed to data research, discussion, and reviewing and editing the manuscript.

Dr Pigeanne: contributed to data research, discussion, and reviewing and editing the manuscript.

Dr Chollet: contributed to data research, discussion, and reviewing and editing the manuscript.

Dr Masson: contributed to data research, discussion, and reviewing and editing the manuscript.

Dr Bizieux-Thaminy: contributed to data research, discussion, and reviewing and editing the manuscript.

Dr Humeau: contributed to data research, discussion, and reviewing and editing the manuscript.

Dr Meslier: contributed to data research, discussion, writing the manuscript, and reviewing and editing the manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Additional information: The e-Appendix can be found in the “Supplemental Materials” area of the online article.

CVD

cardiovascular disease

EDS

excessive daytime sleepiness

ESS

Epworth Sleepiness Scale

IRSR

Institut de Recherche en Santé Respiratoire des Pays de la Loire

OSAHS

OSA-hypopnea syndrome

PSG

polysomnography

QD2A

13-item, self-rated Pichot depression scale

SDB

sleep-disordered breathing

McDaid C, Griffin S, Weatherly H, et al. Continuous positive airway pressure devices for the treatment of obstructive sleep apnoea-hypopnoea syndrome: a systematic review and economic analysis. Health Technol Assess. 2009;13(4):1-119,143-274.
 
Bazzano LA, Khan Z, Reynolds K, He J. Effect of nocturnal nasal continuous positive airway pressure on blood pressure in obstructive sleep apnea. Hypertension. 2007;50(2):417-423. [CrossRef] [PubMed]
 
Le Port A, Gueguen A, Kesse-Guyot E, et al. Association between dietary patterns and depressive symptoms over time: a 10-year follow-up study of the GAZEL cohort. PLoS ONE. 2012;7(12):e51593. [CrossRef] [PubMed]
 
Lépine JP, Gasquet I, Kovess V, et al. Prevalence and comorbidity of psychiatric disorders in the French general population [in French]. Encephale. 2005;31(2):182-194. [CrossRef] [PubMed]
 
Harris M, Glozier N, Ratnavadivel R, Grunstein RR. Obstructive sleep apnea and depression. Sleep Med Rev. 2009;13(6):437-444. [CrossRef] [PubMed]
 
Bixler EO, Vgontzas AN, Lin HM, Calhoun SL, Vela-Bueno A, Kales A. Excessive daytime sleepiness in a general population sample: the role of sleep apnea, age, obesity, diabetes, and depression. J Clin Endocrinol Metab. 2005;90(8):4510-4515. [CrossRef] [PubMed]
 
Pan A, Keum N, Okereke OI, et al. Bidirectional association between depression and metabolic syndrome: a systematic review and meta-analysis of epidemiological studies. Diabetes Care. 2012;35(5):1171-1180. [CrossRef] [PubMed]
 
Mulle JG, Vaccarino V. Cardiovascular disease, psychosocial factors, and genetics: the case of depression. Prog Cardiovasc Dis. 2013;55(6):557-562. [CrossRef] [PubMed]
 
Pichot P, Boyer P, Pull CB, Rein W, Simon M, Thibault A. A questionnaire for self-evaluation of depressive symptomatology, the QD2 Questionnaire: I. Construction, factorial structure and metrological properties [in French]. Rev Psychol Appl. 1984;34(3):229-250.
 
Pichot P, Boyer P, Pull CB, Rein W, Simon M, Thibault A. A questionnaire for self-evaluation of depressive symptomatology, the QD2 Questionnaire: II. Abridged version, QD2A [in French]. Rev Psychol Appl. 1984;34(4):323-340.
 
de Bonis M, Lebeaux MO, de Boeck P, Simon M, Pichot P. Measuring the severity of depression through a self-report inventory. A comparison of logistic, factorial and implicit models. J Affect Disord. 1991;22(1-2):55-64. [CrossRef] [PubMed]
 
Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14(6):540-545. [PubMed]
 
Barceló A, Piérola J, de la Peña M, et al. Free fatty acids and the metabolic syndrome in patients with obstructive sleep apnoea. Eur Respir J. 2011;37(6):1418-1423. [CrossRef] [PubMed]
 
Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep. 1999;22(5):667-689. [PubMed]
 
Schwartz DJ, Kohler WC, Karatinos G. Symptoms of depression in individuals with obstructive sleep apnea may be amenable to treatment with continuous positive airway pressure. Chest. 2005;128(3):1304-1309. [CrossRef] [PubMed]
 
Kawahara S, Akashiba T, Akahoshi T, Horie T. Nasal CPAP improves the quality of life and lessens the depressive symptoms in patients with obstructive sleep apnea syndrome. Intern Med. 2005;44(5):422-427. [CrossRef] [PubMed]
 
Diamanti C, Manali E, Ginieri-Coccossis M, et al. Depression, physical activity, energy consumption, and quality of life in OSA patients before and after CPAP treatment. Sleep Breath. 2013;17(4):1159-1168. [CrossRef] [PubMed]
 
Muñoz A, Mayoralas LR, Barbé F, Pericás J, Agusti AG. Long-term effects of CPAP on daytime functioning in patients with sleep apnoea syndrome. Eur Respir J. 2000;15(4):676-681. [CrossRef] [PubMed]
 
Haensel A, Norman D, Natarajan L, Bardwell WA, Ancoli-Israel S, Dimsdale JE. Effect of a 2 week CPAP treatment on mood states in patients with obstructive sleep apnea: a double-blind trial. Sleep Breath. 2007;11(4):239-244. [CrossRef] [PubMed]
 
Lee IS, Bardwell W, Ancoli-Israel S, Loredo JS, Dimsdale JE. Effect of three weeks of continuous positive airway pressure treatment on mood in patients with obstructive sleep apnoea: a randomized placebo-controlled study. Sleep Med. 2012;13(2):161-166. [CrossRef] [PubMed]
 
Sforza E, de Saint Hilaire Z, Pelissolo A, Rochat T, Ibanez V. Personality, anxiety and mood traits in patients with sleep-related breathing disorders: effect of reduced daytime alertness. Sleep Med. 2002;3(2):139-145. [CrossRef] [PubMed]
 
Gasa M, Tamisier R, Launois SH, et al; Scientific Council of the Sleep Registry of the French Federation of Pneumology-FFP. Residual sleepiness in sleep apnea patients treated by continuous positive airway pressure. J Sleep Res. 2013;22(4):389-397. [CrossRef] [PubMed]
 
Habukawa M, Uchimura N, Kakuma T, et al. Effect of CPAP treatment on residual depressive symptoms in patients with major depression and coexisting sleep apnea: contribution of daytime sleepiness to residual depressive symptoms. Sleep Med. 2010;11(6):552-557. [CrossRef] [PubMed]
 
Kjelsberg FN, Ruud EA, Stavem K. Predictors of symptoms of anxiety and depression in obstructive sleep apnea. Sleep Med. 2005;6(4):341-346. [CrossRef] [PubMed]
 
Hippisley-Cox J, Fielding K, Pringle M. Depression as a risk factor for ischaemic heart disease in men: population based case-control study. BMJ. 1998;316(7146):1714-1719. [CrossRef] [PubMed]
 
Kohler M, Ayers L, Pepperell JC, et al. Effects of continuous positive airway pressure on systemic inflammation in patients with moderate to severe obstructive sleep apnoea: a randomised controlled trial. Thorax. 2009;64(1):67-73. [CrossRef] [PubMed]
 
Vgontzas AN, Zoumakis E, Lin HM, Bixler EO, Trakada G, Chrousos GP. Marked decrease in sleepiness in patients with sleep apnea by etanercept, a tumor necrosis factor-alpha antagonist. J Clin Endocrinol Metab. 2004;89(9):4409-4413. [CrossRef] [PubMed]
 
Libby P. Inflammation in atherosclerosis. Arterioscler Thromb Vasc Biol. 2012;32(9):2045-2051. [CrossRef] [PubMed]
 
Irwin MR, Miller AH. Depressive disorders and immunity: 20 years of progress and discovery. Brain Behav Immun. 2007;21(4):374-383. [CrossRef] [PubMed]
 
Fenik P, Veasey SC. Pharmacological characterization of serotonergic receptor activity in the hypoglossal nucleus. Am J Respir Crit Care Med. 2003;167(4):563-569. [CrossRef] [PubMed]
 
Aloia MS, Arnedt JT, Smith L, Skrekas J, Stanchina M, Millman RP. Examining the construct of depression in obstructive sleep apnea syndrome. Sleep Med. 2005;6(2):115-121. [CrossRef] [PubMed]
 
Pillar G, Lavie P. Psychiatric symptoms in sleep apnea syndrome: effects of gender and respiratory disturbance index. Chest. 1998;114(3):697-703. [CrossRef] [PubMed]
 
Silverman SL. From randomized controlled trials to observational studies. Am J Med. 2009;122(2):114-120. [CrossRef] [PubMed]
 
Wiernik E, Pannier B, Czernichow S, et al. Occupational status moderates the association between current perceived stress and high blood pressure: evidence from the IPC cohort study. Hypertension. 2013;61(3):571-577. [CrossRef] [PubMed]
 
Lemogne C, Thomas F, Consoli SM, Pannier B, Jégo B, Danchin N. Heart rate and completed suicide: evidence from the IPC cohort study. Psychosom Med. 2011;73(9):731-736. [CrossRef] [PubMed]
 
Gagnadoux F, Le Vaillant M, Paris A, et al; IRSR Sleep Cohort Group. Adherence to positive airway pressure in non-sleepy patients with obstructive sleep apnoea. Eur Respir J. 2013;42(3):863-866. [CrossRef] [PubMed]
 
Priou P, Le Vaillant M, Meslier N, et al; IRSR Sleep Cohort Group. Independent association between obstructive sleep apnea severity and glycated hemoglobin in adults without diabetes. Diabetes Care. 2012;35(9):1902-1906. [CrossRef] [PubMed]
 
Nguyên XL, Rakotonanahary D, Chaskalovic J, Fleury B. Insomnia related to sleep apnoea: effect of long-term auto-adjusting positive airway pressure treatment. Eur Respir J. 2013;41(3):593-600. [CrossRef] [PubMed]
 
Depression in adults with a chronic physical health problem: treatment and management. NICE clinical guideline 91. National Institute for Health and Clinical Excellence website. http://www.nice.org.uk/nicemedia/live/12327/45909/45909.pdf. Accessed January 28, 2013.
 
Coventry PA, Bower P, Keyworth C, et al. The effect of complex interventions on depression and anxiety in chronic obstructive pulmonary disease: systematic review and meta-analysis. PLoS ONE. 2013;8(4):e60532. [CrossRef] [PubMed]
 
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. [PubMed]
 

Figures

Figure Jump LinkFigure 1. Flow diagram of subjects during the study. IRSR = Institut de Recherche en Santé Respiratoire des Pays de la Loire; OSAHS = OSA-hypopnea syndrome; QD2A = 13-item, self-rated Pichot depression scale.Grahic Jump Location
Figure Jump LinkFigure 2. Adjusted ORs for persistent depressive symptoms according to quartiles of reduction of ESS after long-term CPAP therapy. ORs were adjusted for age, sex, and cardiovascular diseases. *Tested by the Cochrane-Armitage trend test. ESS = Epworth Sleepiness Scale; ref. = reference.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 —Comparison of Patients Included in the Analysis and Patients Excluded Due to CPAP Withdrawal, Missing Adherence Data, or Unavailable ESS and/or QD2A Score During Follow-up

Data are expressed as mean (SD) or % unless otherwise indicated. AHI = apnea-hypopnea index; CVD = cardiovascular disease; ESS = Epworth Sleepiness Scale; QD2A = 13-item, self-rated Pichot depression scale.

a 

Alcohol consumption ≥ 20 g/d by women or ≥ 30 g/d by men.

Table Graphic Jump Location
Table 2 —Comparison of Patients With and Without Persistent Depressive Symptoms After Long-term CPAP Therapy

Data are expressed as mean (SD) or % unless otherwise indicated. EDS = excessive daytime sleepiness. See Table 1 legend for expansion of other abbreviations.

a 

Persistent EDS was defined by an ESS score > 10 at the last CPAP follow-up visit.

b 

Alcohol consumption of ≥ 20 g/d by women or ≥ 30 g/d by men.

Table Graphic Jump Location
Table 3 —Stepwise Regression Analysis of Variables Associated With Persistent Depressive Symptoms After Long-term CPAP Therapy

See Table 1 and 2 legends for expansion of abbreviations.

a 

P value is significant at < .05.

b 

Persistent EDS was defined by an ESS > 10 at the last CPAP follow-up visit.

References

McDaid C, Griffin S, Weatherly H, et al. Continuous positive airway pressure devices for the treatment of obstructive sleep apnoea-hypopnoea syndrome: a systematic review and economic analysis. Health Technol Assess. 2009;13(4):1-119,143-274.
 
Bazzano LA, Khan Z, Reynolds K, He J. Effect of nocturnal nasal continuous positive airway pressure on blood pressure in obstructive sleep apnea. Hypertension. 2007;50(2):417-423. [CrossRef] [PubMed]
 
Le Port A, Gueguen A, Kesse-Guyot E, et al. Association between dietary patterns and depressive symptoms over time: a 10-year follow-up study of the GAZEL cohort. PLoS ONE. 2012;7(12):e51593. [CrossRef] [PubMed]
 
Lépine JP, Gasquet I, Kovess V, et al. Prevalence and comorbidity of psychiatric disorders in the French general population [in French]. Encephale. 2005;31(2):182-194. [CrossRef] [PubMed]
 
Harris M, Glozier N, Ratnavadivel R, Grunstein RR. Obstructive sleep apnea and depression. Sleep Med Rev. 2009;13(6):437-444. [CrossRef] [PubMed]
 
Bixler EO, Vgontzas AN, Lin HM, Calhoun SL, Vela-Bueno A, Kales A. Excessive daytime sleepiness in a general population sample: the role of sleep apnea, age, obesity, diabetes, and depression. J Clin Endocrinol Metab. 2005;90(8):4510-4515. [CrossRef] [PubMed]
 
Pan A, Keum N, Okereke OI, et al. Bidirectional association between depression and metabolic syndrome: a systematic review and meta-analysis of epidemiological studies. Diabetes Care. 2012;35(5):1171-1180. [CrossRef] [PubMed]
 
Mulle JG, Vaccarino V. Cardiovascular disease, psychosocial factors, and genetics: the case of depression. Prog Cardiovasc Dis. 2013;55(6):557-562. [CrossRef] [PubMed]
 
Pichot P, Boyer P, Pull CB, Rein W, Simon M, Thibault A. A questionnaire for self-evaluation of depressive symptomatology, the QD2 Questionnaire: I. Construction, factorial structure and metrological properties [in French]. Rev Psychol Appl. 1984;34(3):229-250.
 
Pichot P, Boyer P, Pull CB, Rein W, Simon M, Thibault A. A questionnaire for self-evaluation of depressive symptomatology, the QD2 Questionnaire: II. Abridged version, QD2A [in French]. Rev Psychol Appl. 1984;34(4):323-340.
 
de Bonis M, Lebeaux MO, de Boeck P, Simon M, Pichot P. Measuring the severity of depression through a self-report inventory. A comparison of logistic, factorial and implicit models. J Affect Disord. 1991;22(1-2):55-64. [CrossRef] [PubMed]
 
Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14(6):540-545. [PubMed]
 
Barceló A, Piérola J, de la Peña M, et al. Free fatty acids and the metabolic syndrome in patients with obstructive sleep apnoea. Eur Respir J. 2011;37(6):1418-1423. [CrossRef] [PubMed]
 
Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep. 1999;22(5):667-689. [PubMed]
 
Schwartz DJ, Kohler WC, Karatinos G. Symptoms of depression in individuals with obstructive sleep apnea may be amenable to treatment with continuous positive airway pressure. Chest. 2005;128(3):1304-1309. [CrossRef] [PubMed]
 
Kawahara S, Akashiba T, Akahoshi T, Horie T. Nasal CPAP improves the quality of life and lessens the depressive symptoms in patients with obstructive sleep apnea syndrome. Intern Med. 2005;44(5):422-427. [CrossRef] [PubMed]
 
Diamanti C, Manali E, Ginieri-Coccossis M, et al. Depression, physical activity, energy consumption, and quality of life in OSA patients before and after CPAP treatment. Sleep Breath. 2013;17(4):1159-1168. [CrossRef] [PubMed]
 
Muñoz A, Mayoralas LR, Barbé F, Pericás J, Agusti AG. Long-term effects of CPAP on daytime functioning in patients with sleep apnoea syndrome. Eur Respir J. 2000;15(4):676-681. [CrossRef] [PubMed]
 
Haensel A, Norman D, Natarajan L, Bardwell WA, Ancoli-Israel S, Dimsdale JE. Effect of a 2 week CPAP treatment on mood states in patients with obstructive sleep apnea: a double-blind trial. Sleep Breath. 2007;11(4):239-244. [CrossRef] [PubMed]
 
Lee IS, Bardwell W, Ancoli-Israel S, Loredo JS, Dimsdale JE. Effect of three weeks of continuous positive airway pressure treatment on mood in patients with obstructive sleep apnoea: a randomized placebo-controlled study. Sleep Med. 2012;13(2):161-166. [CrossRef] [PubMed]
 
Sforza E, de Saint Hilaire Z, Pelissolo A, Rochat T, Ibanez V. Personality, anxiety and mood traits in patients with sleep-related breathing disorders: effect of reduced daytime alertness. Sleep Med. 2002;3(2):139-145. [CrossRef] [PubMed]
 
Gasa M, Tamisier R, Launois SH, et al; Scientific Council of the Sleep Registry of the French Federation of Pneumology-FFP. Residual sleepiness in sleep apnea patients treated by continuous positive airway pressure. J Sleep Res. 2013;22(4):389-397. [CrossRef] [PubMed]
 
Habukawa M, Uchimura N, Kakuma T, et al. Effect of CPAP treatment on residual depressive symptoms in patients with major depression and coexisting sleep apnea: contribution of daytime sleepiness to residual depressive symptoms. Sleep Med. 2010;11(6):552-557. [CrossRef] [PubMed]
 
Kjelsberg FN, Ruud EA, Stavem K. Predictors of symptoms of anxiety and depression in obstructive sleep apnea. Sleep Med. 2005;6(4):341-346. [CrossRef] [PubMed]
 
Hippisley-Cox J, Fielding K, Pringle M. Depression as a risk factor for ischaemic heart disease in men: population based case-control study. BMJ. 1998;316(7146):1714-1719. [CrossRef] [PubMed]
 
Kohler M, Ayers L, Pepperell JC, et al. Effects of continuous positive airway pressure on systemic inflammation in patients with moderate to severe obstructive sleep apnoea: a randomised controlled trial. Thorax. 2009;64(1):67-73. [CrossRef] [PubMed]
 
Vgontzas AN, Zoumakis E, Lin HM, Bixler EO, Trakada G, Chrousos GP. Marked decrease in sleepiness in patients with sleep apnea by etanercept, a tumor necrosis factor-alpha antagonist. J Clin Endocrinol Metab. 2004;89(9):4409-4413. [CrossRef] [PubMed]
 
Libby P. Inflammation in atherosclerosis. Arterioscler Thromb Vasc Biol. 2012;32(9):2045-2051. [CrossRef] [PubMed]
 
Irwin MR, Miller AH. Depressive disorders and immunity: 20 years of progress and discovery. Brain Behav Immun. 2007;21(4):374-383. [CrossRef] [PubMed]
 
Fenik P, Veasey SC. Pharmacological characterization of serotonergic receptor activity in the hypoglossal nucleus. Am J Respir Crit Care Med. 2003;167(4):563-569. [CrossRef] [PubMed]
 
Aloia MS, Arnedt JT, Smith L, Skrekas J, Stanchina M, Millman RP. Examining the construct of depression in obstructive sleep apnea syndrome. Sleep Med. 2005;6(2):115-121. [CrossRef] [PubMed]
 
Pillar G, Lavie P. Psychiatric symptoms in sleep apnea syndrome: effects of gender and respiratory disturbance index. Chest. 1998;114(3):697-703. [CrossRef] [PubMed]
 
Silverman SL. From randomized controlled trials to observational studies. Am J Med. 2009;122(2):114-120. [CrossRef] [PubMed]
 
Wiernik E, Pannier B, Czernichow S, et al. Occupational status moderates the association between current perceived stress and high blood pressure: evidence from the IPC cohort study. Hypertension. 2013;61(3):571-577. [CrossRef] [PubMed]
 
Lemogne C, Thomas F, Consoli SM, Pannier B, Jégo B, Danchin N. Heart rate and completed suicide: evidence from the IPC cohort study. Psychosom Med. 2011;73(9):731-736. [CrossRef] [PubMed]
 
Gagnadoux F, Le Vaillant M, Paris A, et al; IRSR Sleep Cohort Group. Adherence to positive airway pressure in non-sleepy patients with obstructive sleep apnoea. Eur Respir J. 2013;42(3):863-866. [CrossRef] [PubMed]
 
Priou P, Le Vaillant M, Meslier N, et al; IRSR Sleep Cohort Group. Independent association between obstructive sleep apnea severity and glycated hemoglobin in adults without diabetes. Diabetes Care. 2012;35(9):1902-1906. [CrossRef] [PubMed]
 
Nguyên XL, Rakotonanahary D, Chaskalovic J, Fleury B. Insomnia related to sleep apnoea: effect of long-term auto-adjusting positive airway pressure treatment. Eur Respir J. 2013;41(3):593-600. [CrossRef] [PubMed]
 
Depression in adults with a chronic physical health problem: treatment and management. NICE clinical guideline 91. National Institute for Health and Clinical Excellence website. http://www.nice.org.uk/nicemedia/live/12327/45909/45909.pdf. Accessed January 28, 2013.
 
Coventry PA, Bower P, Keyworth C, et al. The effect of complex interventions on depression and anxiety in chronic obstructive pulmonary disease: systematic review and meta-analysis. PLoS ONE. 2013;8(4):e60532. [CrossRef] [PubMed]
 
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. [PubMed]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).
Supporting Data

Online Supplement

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
Guidelines
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543