Not All Sleepiness Is Sleep Apnea
Abstract & Commentary
By Barbara A. Phillips, MD, MSPH, Professor of Medicine, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington. Dr. Phillips is a retained consultant for Cephalon and Ventus, and serves on the speakers bureaus for Cephalon and Boehringer Ingelheim.
Synopsis: In patients with obstructive sleep apnea who are treated with CPAP, those who report persistent sleepiness are more likely to have history of depression, diabetes, and heart disease, and to have been sleepier prior to treatment.
Source: Koutsourelakis I, et al. Predictors of residual sleepiness in adequately treated obstructive sleep apnoea patients. Eur Respir J 2009;34:687-693.
This study comes from a clinical population of patients who were referred to a Greek hospital for suspected sleep apnea. From the patients who were diagnosed with sleep apnea, the investigators recruited those who had both a respiratory distress index (RDI) on baseline diagnostic full-night polysomnography of > 5 events/hour and excessive daytime sleepiness. Excessive daytime sleepiness was defined as having an Epworth Sleepiness Scale (ESS) score > 10, which is a fairly standard approach.1 Those who did not accept or comply with continuous positive airway pressure (CPAP), who used antihistamines or sleeping pills, or who had a coexisting sleep disorder (including shift work) were excluded. The final group of patients who were studied included 208 individuals who were followed for at least 6 months.
All of the patients had at least three assessments, including a baseline sleep study, an all-night CPAP titration, and a follow-up clinic visit. The clinic visit evaluation included documenting ischemic heart disease, hypertension, heart failure, cardiac arrhythmia, stroke, or chronic obstructive pulmonary disease. Depression was considered to be present in those patients who used any antidepressants prescribed by a psychiatrist and had a Center for Epidemiological Studies of Depression (CES-D)2 score > 16 before beginning antidepressant medication. In such cases, the patient's psychiatrist was contacted to request the CES-D score and confirm the diagnosis of depression, although sometimes one of the investigators took the CES-D score from patient recall. Alcohol use was defined as the ingestion of 2 or more alcoholic drinks and day, and current tobacco use was considered to be present if tobacco was used during the preceding month.
All subjects were treated with CPAP devices capable of objectively monitoring CPAP adherence, and all used the same kind of CPAP machine. All of the patients had follow-up appointments at least at 1 and 3 months in the outpatient clinic. A final evaluation assessed CPAP adherence and ESS score at least 6 months after the start of treatment. Good compliance was considered to be CPAP use for at least 4 hours/day. Patients who exhibited a normal ESS score (< 11) following CPAP treatment were defined as CPAP responders. The resulting cohort of 208 patients included 94 CPAP responders (45%) and 114 CPAP nonresponders (55%). Nonresponders (those who were still sleepy on CPAP) tended to be older and female. They had less severe sleep apnea and were sleepier to begin with at baseline. And they were much more likely to have diabetes, heart disease, or depression (see Table, below).
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CPAP responders exhibited a mean decrease in ESS score of 8.4 ± 2.7 after CPAP treatment, whereas CPAP nonresponders showed a mean decrease in ESS score of 2.4 ± 2.4 after CPAP treatment. Objective compliance was not significantly different between the two groups: 6.1 ± 1.0 hours/night for CPAP responders and 5.9 ± 0.9 hours/night for CPAP nonresponders. Depression offered nearly complete discrimination between responders and nonresponders, so it was not included in subsequent logistic regression analysis. Multivariate logistic regression analysis (without depression) revealed that the independent predictors of residual subjective sleepiness following CPAP therapy were the presence of diabetes or heart disease, a higher ESS score, and a lower RDI on baseline assessment. The authors concluded that it may be possible to predict which sleep apnea patients will continue to experience daytime sleepiness following adequate CPAP use.
Commentary
Sleepiness is a prevalent symptom in patients who are treated for obstructive sleep apnea (OSA), and may occur in up to half of those who are begun on continuous positive airway pressure treatment. Indeed, the alerting agent modafinil is FDA-approved for the treatment of residual sleepiness in patients who are effectively treated for OSA. However, the current study strongly suggests that other evaluation and therapeutic options might be more appropriate (especially since new evidence suggests that modafinil has the potential for abuse and dependence3).
This finding essentially reinforces work done with the Penn State Cohort. In this group of individuals drawn from the population at large (not those who had a diagnosis of sleep apnea), Bixler and colleagues found that depression was the most significant risk factor for excessive daytime sleepiness, followed by body mass index, age, typical sleep duration, diabetes, smoking, and finally sleep apnea.4 So, diabetes and depression pop up on the list of causes of sleepiness in the general population as well as in those who are being treated for sleep apnea.
Stradling has taken this idea one step further. In a study in the United Kingdom, he found no difference in the prevalence of sleepiness in a CPAP-treated group and a group of unselected controls, and concluded "post-CPAP sleepiness" may not be a specific clinical entity.5
What does this mean for us, in evaluating the common and distressing symptom of persistent sleepiness in patients who are treated for OSA with CPAP? First, remember that inadequate CPAP use or pressure can be a cause of persistent sleepiness in these patients. Indeed, Weaver et al have demonstrated that function and sleepiness, while improved with CPAP use of 4 hours/night (the minimal acceptable duration of use for many insurance companies), continue to improve as use increases to 7 hours/night.6 The current work, coupled with the reports of Bixler and others, suggest that patients who are using CPAP well but who are still sleepy should be thoroughly assessed for depression. It is also reasonable to remember that not all sleepiness or fatigue can be attributed to sleep apnea or to any sleep disorder; people who have chronic illness, especially heart disease and diabetes, also report fatigue. It may be that gentle reassurance may be the wisest approach for some fatigued individuals.
References
1. Johns MW. A new method for measuring daytime sleepiness: The Epworth sleepiness scale. Sleep 1991;14:540-545.
2. Shafer AB. Meta-analysis of the factor structures of four depression questionnaires: Beck, CES-D, Hamilton, and Zung. J Clin Psychol 2006;62: 123-146.
3. Volkow ND, et al. Effects of modafinil on dopa- mine and dopamine transporters in the male human brain: Clinical implications. JAMA 2009;301:1148-1154.
4. Bixler EO, et al. Excessive daytime sleepiness in a general population sample: The role of sleep apnea, age, obesity, diabetes, and depression. J Clin Endocrinol Metab 2005;90:4510-4515.
5. Stradling JR, et al. Post-CPAP sleepiness - a specific syndrome? J Sleep Res 2007;16:436-438.
6. Weaver T, et al. Relationship between hours of CPAP use and achieving normal levels of sleepiness and daily functioning. Sleep 2007;30:711-719.
In patients with obstructive sleep apnea who are treated with CPAP, those who report persistent sleepiness are more likely to have history of depression, diabetes, and heart disease, and to have been sleepier prior to treatment.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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