Depressive Symptoms Before and After Long-term CPAP Therapy in Patients With Sleep Apnea

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1 CHEST Originl Reserch Depressive Symptoms Before nd After Long-term CPAP Therpy in Ptients With Sleep Apne Frédéric Ggndoux, MD, PhD ; Mrc Le Villnt, PhD ; Frnçois Goupil, MD ; Thierry Pigenne, MD ; Sylvine Chollet, MD ; Philippe Msson, MD ; Acy Bizieux-Thminy, MD ; Mrie-Pierre Humeu, MD ; nd Nicole Meslier, MD ; on behlf of the IRSR Sleep Cohort Group* SLEEP DISORDERS Bckground: The outcome of depressive symptoms under CPAP therpy for OSA-hypopne syndrome (OSAHS) hs been poorly evluted. In this multicenter, prospective cohort study, we evluted the prevlence nd correltes of persistent depressive symptoms fter long-term CPAP therpy for OSAHS. Methods: This study included 300 ptients with OSAHS nd depressive symptoms (13-item, selfrted Pichot depression scle [QD2A] 7) t dignosis. The primry dependent vrible ws persistent depressive symptoms fter 1 yer of CPAP therpy. Multivrite regression nlyses were performed to determine vribles independently ssocited with the persistence of depressive symptoms. Results: After n verge of 529 dys (rnge, 365-1,569 dys) of CPAP therpy, the men (SD) QD2A score decresed from 9.2 (2.0) to 5.4 (4.0) ( P,.0001), but 125 ptients (41.7%) presented persistent depressive symptoms. The persistence of depressive symptoms ws independently ssocited with persistent excessive dytime sleepiness (EDS) (OR, 2.72; 95% CI, ), comorbid crdiovsculr disese (OR, 1.76; 95% CI, ), nd femle sex (OR, 1.53; 95% CI, ). A positive liner trend ws observed for the djusted OR of persistent depressive symptoms with decresing CPAP effect on the Epworth sleepiness scle ( P,.0001). Conclusions: CPAP therpy does not resolve depressive symptoms in mny ptients with OSAHS. Persistent depressive symptoms re strongly ssocited with EDS. Active monitoring of depressive symptoms is needed in ptients with OSAHS who re treted with CPAP. Interventionl trils re required to evlute the impct of ntidepressnts, cognitive behviorl therpy, or both on comorbid depression in ptients with OSAHS. CHEST 2014; 145(5): Abbrevitions: CVD 5 crdiovsculr disese; EDS 5 excessive dytime sleepiness; ESS 5 Epworth Sleepiness Scle; IRSR 5 Institut de Recherche en Snté Respirtoire des Pys de l Loire; OSAHS 5 OSA-hypopne syndrome; PSG 5 polysomnogrphy; QD2A 5 13-item, self-rted Pichot depression scle; SDB 5 sleep-disordered brething OSA-hypopne syndrome (OSAHS) is highly prevlent disese chrcterized by recurrent episodes of prtil or complete obstruction of the upper irwys during sleep. Rndomized controlled trils of CPAP therpy in OSAHS hve demonstrted benefit on dytime lertness, qulity of life, nd BP. 1,2 Depression is one of the most common psychitric illnesses in dults nd is mjor public helth problem. According to the World Helth Orgniztion, depression ws the fourth leding cuse of disbility in 2000 nd is expected to be the second leding cuse in In Frnce, the lifetime prevlence of depression is estimted t 13% to 17% in men nd 25% to 30% in women.4 High rtes of depressive symptoms hve been observed in people with OSAHS. 5 In the generl popultion, excessive dytime sleepiness (EDS) is more strongly ssocited with depression thn with sleep-disordered brething (SDB) severity. 6 Any reltionship between OSAHS nd depression my be t lest prtilly explined by overlpping symptoms including ftigue, loss of inter est, decresed libido, nd poor concentrtion. 5 Depression shres common comorbid medicl conditions with OSAHS, such s obesity, metbolic syndrome, 7 journl.publictions.chestnet.org CHEST / 145 / 5 / MAY

2 nd crdiovsculr diseses (CVDs), 8 tht my contribute to the ssocition. If cusl link exists between OSAHS nd depression, then depressive symptoms would be expected to improve during CPAP therpy. However, limited dt re vilble regrding the outcome of depressive symptoms in response to CPAP therpy. 5 Overll, it ppers tht symptoms of depression my persist in t lest some ptients treted for OSAHS. 5 This multicenter, prospective cohort study ws designed to evlute the outcome of depressive symptoms in ptients with OSAHS who were treted with CPAP nd to determine the prevlence nd correltes of persistent depressive symptoms fter longterm CPAP therpy. Design nd Study Popultion Mterils nd Methods This multicenter, prospective, observtionl cohort study ws conducted on the Institut de Recherche en Snté Respirtoire des Pys de l Loire (IRSR) sleep cohort. Since My 15, 2007, consecutive ptients ged 18 yers in whom CPAP therpy is prescribed for OSAHS t seven centers from the west of Frnce re eligible for inclusion in the IRSR sleep cohort. Ptients with intellectul developmentl disbilities, ptients who were unble to fill in the questionnires or to red nd/or spek French, nd ptients with neuromusculr diseses re excluded from the IRSR sleep cohort. Approvl ws obtined from the University of Angers ethics committee nd from the Comité Consulttive sur le Tritement de l Informtion en mtière de Recherche dns le domine de l Snté (07.207bis). The dtbse is nonymous nd complies with the restrictive requirements of the Commission Ntionle Informtique et Liberté, the French informtion technology nd personl-dt protection uthority. All ptients included in the IRSR sleep cohort hve given their written informed consent. Between My 15, 2007, nd April 30, 2013, ptients from the IRSR sleep cohort were eligible for the present study when CPAP therpy hd been prescribed 365 dys prior to inclusion nd Mnuscript received October 6, 2013; revision ccepted December 17, 2013; originlly published Online First Jnury 16, Affilitions: From the LUNAM Université (Prof Ggndoux nd Dr Meslier), Angers; Université d Angers (Prof Ggndoux nd Dr Meslier), CHU Angers, Déprtement de Pneumologie, Angers; CERMES (Dr Le Villnt), CNRS UMR Inserm U988 - EHESS, Villejuif; Centre Hospitlier (Dr Goupil), Service de Pneumologie, Le Mns; Pôle snté des Olonnes (Dr Pigenne), Unité de Pneumologie, Olonne sur Mer; Institut du Thorx (Dr Chollet), Pneumologie, Hôpitl Lennec, Nntes; Centre Hospitlier (Dr Msson), Service de Pneumologie, Cholet; Centre Hospitlier (Dr Bizieux-Thminy), Service de Pneumologie, L Roche sur Yon; Nouvelles Cliniques Nntises (Dr Humeu), Pneumologie, Nntes, Frnce. A complete list of group members cn be found in e-appendix 1. Funding/Support: The uthors hve reported to CHEST tht no funding ws received for this study. Correspondence to: Frédéric Ggndoux, MD, PhD, Université d Angers, CHU Angers, Déprtement de Pneumologie, 4 rue Lrrey, Angers Cedex, Frnce; e-mil: frggndoux@chungers.fr 2014 Americn College of Chest Physicins. Reproduction of this rticle is prohibited without written permission from the Americn College of Chest Physicins. See online for more detils. DOI: /chest bseline evlution reported the presence of depressive symptoms s defined by 13-item, self-rted Pichot depression scle (QD2A) score regrdless of ntidepressnt mediction use. Ptients were excluded from the present study when (1) CPAP tretment ws bndoned t, 365 dys, nd/or (2) CPAP use ws not recorded in the dtbse, nd/or (3) QD2A or the Epworth sleepiness scle (ESS) ws not completed t the follow-up visit. Depression nd EDS Questionnires Depressive symptoms nd EDS were ssessed prior to CPAP initition nd t ech follow-up visit. Symptoms of depression were ssessed with the QD2A score This 13-item questionnire ws specificlly designed for depression screening in community studies nd hs high internl consistency ( 50.91). Ech of the following items presents sttement tht the subjects must nswer s true or flse: (1) I cnnot get rid of dverse thoughts tht go through my hed; (2) I hve no energy; (3) I do not pprecite things I used to like s fully s before; (4) I feel disppointed nd disgusted with myself; (5) I feel helpless or blocked by the slightest thing I need do; (6) Right now I feel unhppier thn most people; (7) I hve the blues; (8) I hve to force myself to do every little thing I hve to do; (9) I feel my mind is not s cler s usul; (10) I m unble to mke up my mind s esily s usul; (11) Right now I feel sd; (12) I hve trouble doing the things I used to do; nd (13) I feel my life is empty. The score is estblished by the number of items mrked s true nd rnges between 0 nd 13. The threshold for positive indiction of depression is QD2A score 7. EDS ws defined by n ESS Assessment of Comorbidities Ech ptient enrolled in the IRSR sleep cohort completed surveys on medicl history nd underwent fsting ssys of serum lipids, blood glucose, nd glycted hemoglobin. BP ws mesured fter 5 min of rest in the sitting position. The men of three mesurements ws recorded. Hypertension ws defined by systolic BP 140 mm Hg or distolic BP 90 mm Hg, or the presence of ntihypertensive tretment. Ptients were clssified s hving comorbid CVD if they reported one or more of the follow ing CVDs: ischemic hert disese, crdic rrhythmi, congestive hert filure, nd stroke. Ptients with fsting blood glucose levels. 126 mg/dl or glycted hemoglobin levels 6.5%, or those receiv ing ntidibetic tretment were considered to present with dibetes. The presence of metbolic syndrome ws nlyzed ccording to the Ntionl Cholesterol Eduction Progrm Adult Tretment Pnel III clinicl criteri. 13 Sleep Recordings OSAHS ws dignosed by overnight polysomnogrphy (PSG) or overnight respirtory recording. Overnight PSG ws performed with continuous recording of the following chnnels: EEG, electrooculogrm, chin electromyogrm, rteril oxygen sturtion (finger oximetry), nsl-orl irflow (pressure cnnul nd trchel sounds), ECG, chest nd bdominl wll motion (piezoelectrodes), bilterl tibilis electromyogrm, nd body position. Overnight respirtory recordings were performed with continuous recording of rteril oxygen sturtion, nsl-orl irflow, chest nd bdominl wll motion, nd body position. Respirtory events were scored mnully using recommended criteri. 14 CPAP Initition nd Follow-up The decision to prescribe CPAP therpy ws bsed on the following criteri: pne-hypopne index 30 or between 5 nd 30 with EDS, nd two or more OSAHS symptoms, including snoring, choking, or gsping during sleep; unrefreshing sleep; dytime ftigue; impired concentrtion; nd/or nocturi. According to the 1026 Originl Reserch

3 French recommendtions for reimbursement of CPAP therpy, ptients were seen in consulttion by the sleep specilist during the first 5 months, t 12 months, nd then t lest nnully. Dily CPAP use ws recorded t ech follow-up visit. Sttisticl Anlysis All sttisticl nlyses were performed with SAS softwre (SAS/STAT Pckge ; SAS Institute Inc). The primry dependent vrible of interest ws the persistence of depressive symptoms s defined by QD2A score 7 t the lst CPAP therpy follow-up visit t lest 365 dys fter tretment strt. Ptients with nd without persistent depressive symptoms were compred using the x 2 test for ctegoricl vribles nd two-smple t test for continuous vribles. Vribles with P vlue,.05 were then entered in logistic procedure with bckwrd stepwise regression nl ysis to determine vribles independently ssocited with the persistence of depressive symptoms. Results were expressed s men (SD) nd djusted OR (95% CI). A two-tiled probbility vlue,.05 ws considered significnt. Results A flow digrm is presented in Figure 1. On April 30, 2013, 349 ptients from the IRSR sleep cohort hd been prescribed CPAP therpy for OSAHS 365 dys prior to inclusion, nd hd QD2A score 7 t bseline, indicting symptoms of depression. Forty-nine ptients were excluded from the nlysis due to one of the exclusion criteri. As shown in Tble 1, the only significnt difference between excluded nd included ptients ws slightly lower ge in excluded ptients. The finl smple size ws 300 ptients with OSAHS dignosed by PSG (n 5 108) or overnight respirtory recording (n 5 192). After n verge of 529 (195) dys (rnge, 365-1,569 dys) of CPAP use (men dily use, 5.5 [2.0] h), the QD2A score decresed from 9.2 (2.0) to 5.4 (4.0) ( P,.0001) (men chnge in Q2DA score, 23.8; 95% CI, to 2 3.3). In this smple of 300 ptients, 125 (41.7%) hd QD2A score 7 (men, 9.7 [2.0]) fter long-term CPAP use, indicting persistent depressive symptoms. The men chnge in QD2A score fter long-term CPAP therpy ws (95% CI, Figure 1. Flow digrm of subjects during the study. IRSR 5 Institut de Recherche en Snté Respirtoire des Pys de l Loire; OSAHS 5 OSA-hypopne syndrome; QD2A 5 13-item, self-rted Pichot depression scle. Tble 1 Comprison of Ptients Included in the Anlysis nd Ptients Excluded Due to CPAP Withdrwl, Missing Adherence Dt, or Unvilble ESS nd/or QD2A Score During Follow-up Vribles Excluded Included P Vlue Ptients, No Age, y 58.0 (12.6) 61.7 (11.3).0374 Femle ptients BMI, kg/m (6.9) 32.7 (6.4).0802 AHI 45.1 (21.3) 44.7 (21.0).8952 ESS score t bseline 11.3 (5.0) 11.6 (4.4).6431 QD2A score t bseline 9.3 (1.9) 9.2 (2.0).7266 Hypertension CVD Dibetes Metbolic syndrome Antidepressnt therpy t bseline Current smoker Alcohol consumer Dt re expressed s men ( SD) or % unless otherwise indicted. AHI 5 pne-hypopne index; CVD 5 crdiovsculr disese; ESS 5 Epworth Sleepiness Scle; QD2A 513-item, self-rted Pichot depression scle. Alcohol consumption 20 g/d by women or 30 g/d by men. to 2 0.2) in ptients with persistent depressive symptoms vs (95% CI, to 2 5.9) in ptients without persistent depressive symptoms. Eighty-nine ptients received ntidepressnt therpy t bseline, of whom 41 (46%) were tken off the drugs during follow-up. The ntidepressnt therpy ws discontinued during follow-up in 14 of 40 ptients (35%) with persistent depressive symptoms nd 27 of 49 ptients (55%) without persistent depressive symptoms while using CPAP ( P 5.06). Conversely, 17 ptients were put on ntidepressnt mediction during follow-up, of whom 12 hd persistent depressive symptoms while using CPAP nd five hd no persistent depressive symptoms. A comprison of ptients with nd without persistent depressive symptoms is presented in Tble 2. The persistence of depressive symptoms ws ssocited with higher ge, higher prevlence of CVD, nd higher rte of persistent EDS on CPAP therpy. In contrst, no significnt difference ws observed between ptients with nd without persistent depressive symptoms in terms of sex, BMI, SDB severity, bseline ESS, lcohol nd smoking hbits, hypertension, dibetes, metbolic syndrome, use of ntidepressnt therpy t bseline, nd CPAP dherence. A stepwise regression nlysis ws performed to determine vribles independently ssocited with persistent depressive symptoms. The following four vribles were entered in the model: ge, sex, persistent EDS, nd CVD. Although sex ws not significntly different between ptients with nd without persistent depressive symptoms, it ws considered cliniclly relevnt to include this vrible in the model, s journl.publictions.chestnet.org CHEST / 145 / 5 / MAY

4 Tble 2 Comprison of Ptients With nd Without Persistent Depressive Symptoms After Long-term CPAP Therpy Vribles Ptients With Persistent Depressive Symptoms Ptients Without Persistent Depressive Symptoms P Vlue Ptients, No Age, y 63.7 (11.9) 60.3 (10.7).0101 Femle ptients BMI, kg/m (6.0) 32.3 (6.7).2442 AHI 45.1 (21.0) 44.4 (21.3) % oxygen desturtion index 36.9 (22.6) 35.7 (26.0).7107 ESS score t bseline 11.3 (4.5) 11.9 (4.4).2889 ESS score with CPAP use 8.6 (4.5) 6.6 (3.7).0001 Persistent EDS Hypertension CVD Dibetes Metbolic syndrome CPAP use, 4 h/night Antidepressnt therpy t bseline Current smoker Alcohol consumer b Dt re expressed s men ( SD) or % unless otherwise indicted. EDS 5 excessive dytime sleepiness. See Tble 1 legend for expnsion of other bbrevitions. Persistent EDS ws defined by n ESS score. 10 t the lst CPAP follow-up visit. b Alcohol consumption of 20 g/d by women or 30 g/d by men. women re bout twice s likely s men to develop depression nd the reltionship between depression nd CVD hs been demonstrted to be strongly modified by sex. 8 As shown in Tble 3, three vribles were ssocited with the persistence of depressive symptoms on multivrible nlysis: persistent EDS (OR, 2.72; 95% CI, ), comorbid CVD (OR, 1.76; 95% CI, ), nd femle sex (OR, 1.53; 95% CI, ). As shown in Figure 2, significnt positive liner trend ws observed for the djusted OR of persistent depressive symptoms with decresing CPAP effect on ESS. The percentge of ptients with persistent depressive symptoms incresed from 29.9% in ptients with the highest qurtile of ESS reduction (. 7 points) to 56.5% in ptients with the lowest qurtile of ESS reduction (, 1 point). Discussion This multicenter, prospective cohort study includ ing 300 ptients with OSAHS nd symptoms of depression prior to tretment demonstrted significnt improvement of depression scores in response to CPAP therpy. However, lmost 42% of ptients displyed persistent depressive symptoms fter 1 yer of CPAP use. In multivrite nlysis, the persistence of depressive symptoms ws independently ssocited with persistent EDS, comorbid CVD, nd femle sex. In contrst, the persistence of depressive symptoms ws not correlted with ntidepressnt therpy t bseline, metbolic disorders, SDB severity, lcohol consumption, smoking hbits, or CPAP dherence. Few studies hve ddressed the outcome of depressive symptoms during CPAP therpy for OSAHS. In severl but not ll 18 observtionl studies, CPAP therpy ws ssocited with reduction of depressive symptoms. In contrst, dt from five rndomized trils reporting the Hospitl Anxiety nd Depression Scle nd tht were pooled in met-nlysis, showed no significnt difference between CPAP use nd plcebo in terms of either nxiety or depression. 1 Additionl trils19,20 lso filed to demonstrte beneficil impct Tble 3 Stepwise Regression Anlysis of Vribles Associted With Persistent Depressive Symptoms After Long-term CPAP Therpy Vribles b (SE) OR (95% CI) P Vlue Age (0.0144) 1.02 ( ).1794 Sex (reference 5 mle) (0.1692) 1.53 ( ).0119 CVD (reference 5 none) (0.2729) 1.76 ( ).0387 Persistent EDS b (reference 5 none) (0.3679) 2.72 ( ).0064 See Tble 1 nd 2 legends for expnsion of bbrevitions. P vlue is significnt t,.05. b Persistent EDS ws defined by n ESS. 10 t the lst CPAP follow-up visit Originl Reserch

5 Figure 2. Adjusted ORs for persistent depressive symptoms ccording to qurtiles of reduction of ESS fter long-term CPAP therpy. ORs were djusted for ge, sex, nd crdiovsculr diseses. *Tested by the Cochrne-Armitge trend test. ESS 5 Epworth Sleepiness Scle; ref. 5 reference. of CPAP therpy on mood symptoms in ptients with OSAHS. However, most previous studies evluting the outcome of depressive symptoms in ptients with sleep pne who were treted with CPAP included subjects with depression scores minly in the nonclinicl rnge, which my be ssocited with floor effects of ny intervention. 5 Furthermore, most trils mesured the outcome of depressive symptoms fter only 2 to 4 weeks of CPAP use, while the durtion of the cute phse of ntidepressnt therpy my be 6 to 12 weeks or longer, depending on the individul ptient s response nd the number of mediction chnges. The present study overcomes these methodologic limittions by including lrge smple of ptients with OSAHS nd symptoms of depression t dignosis nd by providing outcome dt fter 1 yer of CPAP therpy. It hs been demonstrted in popultion- nd clinicbsed studies tht reduced dytime lertness is ssocited with higher depression scores in subjects with untreted OSAHS. 6,21 EDS t OSAHS dignosis is more strongly ssocited with depressive symptoms thn with SDB severity. 6 Dt from French Sleep Registry hve shown tht 18% of ptients with sleep pne who re treted with CPAP nd who ttend follow-up visits my exhibit persistent EDS despite regulr CPAP use. 22 Previous studies hve reported n ssocition between dytime sleepiness nd persistent depression on CPAP therpy for OSAHS. 23,24 In 17 ptients with OSAHS nd persistent mjor depressive disorder despite phrmcotherpy, Hbukw et l 23 found significnt correltions between the improvement rtes of depression scores nd ESS during CPAP use. In cross-sectionl study bsed on postl survey with 74% response rte, 24 high depression scores were ssocited with EDS nd nondherence to CPAP therpy. In line with these previous reports, our multicenter, prospective cohort study demonstrted strong independent ssocition between persistent depressive symptoms nd persistent EDS fter long-term CPAP therpy. In contrst, no significnt reltionship ws demonstrted between persistent depressive symptoms nd CPAP dherence, wheres self-reported CPAP use, 3 nights/wk ws ssocited with high nxiety nd depression scores in previous study. 24 However, the self-reported nture of dherence dt in this previous study my hve resulted in misclssifictions. 24 Altogether, our findings nd those from previous studies 23,24 indicte tht ptients with persistent EDS despite regulr CPAP use for OSAHS should be ssessed for depression. Depression is recognized s n independent risk fctor for CVD. 8,25 In the present study, we demonstrte tht ptients with comorbid CVD re t higher risk for persistent depressive symptoms under CPAP therpy fter djustment for ge, sex, nd persistent EDS. Although the underlying reltionship is uncler, the ssocition between OSAHS, CVD, nd depression my be explined by common comorbid conditions such s obesity nd metbolic syndrome 7 nd by com mon underlying biologic ltertions. OSAHS is ssocited with incresed circulting levels of proinflmmtory cytokines tht re not modified by CPAP use 26 nd my contribute to the pthogenesis of EDS, 27 CVD, 28 nd depression. 29 The serotonergic function, known to influence mood, is lso thought to represent biologic link between depression nd CVD 8 nd to contribute to the reduced upper-irwy diltor muscle ctivity during sleep. 30 The bidirectionl ssocition between depression nd CVD hs been found to be strongly modified by sex. 8 Sex lso ppered to modify the reltionship between OSAHS severity, obesity, nd depression. 31 In lrge, clinic-bsed popultion, depression scores were significntly higher in women thn in men for ll ge groups nd for ll levels of respirtory disturbnce index, suggesting tht men nd women with OSAHS mnifest depression differently. 32 In line with these previous findings, our study demonstrtes tht women re t higher risk of persistent depressive symptoms fter long-term CPAP therpy. We cknowledge tht the min wekness of the present study is its observtionl design, which does not llow ny conclusion to be drwn regrding the cusl pthwy of the observed ssocitions. In the bsence of plcebo rm, it is impossible to estblish direct link between long-term CPAP therpy of OSAHS nd the improvement of depression scores. However, depressive disorders require long-term tretment nd it would hve been unethicl to expose ptients with moderte to severe OSAHS, EDS, nd frequent crdiometbolicssocited conditions to plcebo tretment of. 1 yer. Furthermore, rigorous observtionl cohort studies cn complement dt from rndomized controlled trils by providing informtion on long-term tretment efficcy in ptients encountered in dy-to-dy clinicl journl.publictions.chestnet.org CHEST / 145 / 5 / MAY

6 prctice. 33 We lso cknowledge tht the QD2A depression scle is less commonly used thn other depression scores such s the Hospitl Anxiety nd Depression scle or the Beck Depression Inventory. However, the QD2A presents severl properties tht mke this tool interesting for mood ssessment in lrge cohort of French-speking ptients with chronic medicl illness. This is short, esy-to-use, French-lnguge questionnire with high internl consistency ( ) nd the bility to discriminte mong subjects with depressive symptoms in the context of somtic disorders. 9,10 I t hs been vlidted ginst severl other depression scles, such s the Zung Self-rting Depression Scle. 9,10 The QD2A hs been widely used in Frnce to ssess mood in lrge community- or clinic-bsed cohorts of subjects with chronic medicl illness such s hypertension 34,35 or SDB. 22,36-38 Our finding tht persistent depressive symptoms re strongly ssocited with EDS is highly consistent with previous dt using more commonly used questionnires such s the Beck Depression Inventory. 23 A mjor finding of the present study is tht CPAP therpy does not resolve depressive symptoms in lrge proportion of ptients with OSAHS. This finding emph sizes the importnce of close follow-up of depressive symptoms once CPAP tretment is initited in ptients with OSAHS. Our study is lso reminder tht depression needs to be specificlly ddressed s likely comorbid condition in these ptients. Depressive symptoms re common in chronic medicl illnesses nd my result in undue distress or greter impirment. Active tretment of depressive symptoms including psychologic nd lifestyle interventions with or without ntidepressnt mediction is recommended in ptients with chronic physicl helth problems. 39 A recent met-nlysis demonstrted tht complex psychologic nd/or lifestyle interventions tht include n exercise component significntly improve symptoms of depression in people with COPD. 40 I n rndomized study including sedentry nd overweight/obese dults with moderte to severe untreted OSAHS, 12 weeks of moderte-intensity exercise trining resulted in significnt improvements in depressive symptoms. 41 As CPAP use does not pper to relibly tret comorbid depression in ptients with OSAHS, further trils re needed to evlute the impct of specific therpeutic strtegies, including ntidepressnts nd psychologic nd/or lifestyle interventions. Such trils should lso evlute the impct of these strtegies on rnge of outcomes, including EDS nd CPAP complince. Conclusions CPAP therpy does not resolve depressive symptoms in mny ptients with OSAHS. Persistent depres- sive symptoms re strongly ssocited with EDS. Active monitoring of depressive symptoms is needed in ptients with OSAHS who re treted with CPAP. Interventionl trils re required to evlute the impct of ntidepressnts, cognitive behviorl therpy, or both on comorbid depression in ptients with OSAHS. Acknowledgments Author contributions: Prof Ggndoux hd full ccess to ll of the dt in the study nd tkes responsibility for the integrity of the dt nd the ccurcy of the dt nlysis. Prof Ggndoux: contributed to dt reserch, discussion, writing the mnuscript, nd reviewing nd editing the mnuscript nd served s principl uthor. Dr Le Villnt: contributed to dt reserch, discussion, writing the mnuscript, nd reviewing Dr Goupil: contributed to dt reserch, discussion, nd reviewing Dr Pigenne: contributed to dt reserch, discussion, nd reviewing Dr Chollet: contributed to dt reserch, discussion, nd reviewing Dr Msson: contributed to dt reserch, discussion, nd reviewing Dr Bizieux-Thminy: contributed to dt reserch, discussion, nd reviewing Dr Humeu: contributed to dt reserch, discussion, nd reviewing Dr Meslier: contributed to dt reserch, discussion, writing the mnuscript, nd reviewing Finncil/nonfinncil disclosures : The uthors hve reported to CHEST tht no potentil conflicts of interest exist with ny compnies/orgniztions whose products or services my be discussed in this rticle. Additionl informtion: The e-appendix cn be found in the Supplementl Mterils re of the online rticle. References 1. McDid C, Griffin S, Wetherly H, et l. 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