The Laryngoscope C 2014 The American Laryngological, V

Rhinological and Otological Society, Inc.

TRIOLOGICAL SOCIETY CANDIDATE THESIS

Does Surgery for Obstructive Sleep Apnea Improve Depression and Sleepiness? Stacey L. Ishman, MD, MPH; James R. Benke, BS; Aliza P. Cohen, MA; Matthew J. Stephen, BS; Lisa E. Ishii, MD, MHS; Christine G. Gourin, MD, MPH Objectives/Hypothesis: To determine if surgical intervention for OSA (obstructive sleep apnea), particularly multilevel surgery, decreases depression and sleepiness. Study Design: Prospective cohort study. Methods: Chart and prospective outcome database review of patients who underwent surgery from August 2008 through November 2012. Patients were evaluated before and after surgery using the Epworth Sleepiness Scale (ESS), the Beck Depression Index (BDI), and overnight polysomnography. Results: Forty-four patients (12 females; 32 males) met inclusion criteria. Mean age of participants was 44.0 years (SD, 10.2); mean body mass index was 31.9 (SD, 9.3). The mean preoperative obstructive respiratory disturbance index (RDI) was 35.8 events/hour (SD, 21.9; range, 6.6–94.2), which decreased to 17.1 (SD, 19.5; range, 0.8–78.1; P < 0.0001). Mean ESS improved from 10.8 (SD, 4.7) to 6.3 (SD, 3.7; P 5 0.0001); whereas BDI scores improved from 8.4 (SD, 8.2) to 4.9 (SD, 6.0; P 5 0.0051). There were 22 (50.0%) patients with excessive daytime sleepiness and 12 (27.3%) patients with depression before surgery. Surgery was associated with resolution of sleepiness in 17 patients (77.3%) and depression in 9 patients (75.0%). In multivariable regression analysis, only change in ESS (P 5 0.003) and baseline BDI (P < 0.001) were associated with improvement in depression. RDI was not significant (P 5 0.15). Conclusions: Surgical treatment of OSA, especially multilevel surgery, resulted in significantly reduced depression, with resolution in 75% of patients. Similarly, surgery resulted in significantly reduced sleepiness, with resolution in 77% of patients. Reduction in sleepiness scores, but not OSA severity, was predictive of improvement in depression scores. Further evaluation with a larger sample size and a control group is warranted. Key Words: Epworth Sleepiness scale, obstructive sleep apnea, depression, sleepiness, Beck Depression Inventory, surgery. Level of Evidence: 4. Laryngoscope, 124:2829–2836, 2014

INTRODUCTION Obstructive sleep apnea (OSA) is a relatively common sleep-related breathing disorder known to have a negative impact on the health and psychological wellbeing of affected individuals.1 This disease is characterized by recurring partial or complete obstruction in breathing during sleep, and these events are often asso-

From the Department of Otolaryngology–Head and Neck Surgery, University of Cincinnati College of Medicine (S.L.I., A.P.C.); the Divisions of Pediatric Otolaryngology & Pulmonary Medicine, Cincinnati Children’s Hospital Medical Center (S.L.I.), , Cincinnati, Ohio; the Department of Otolaryngology–Head and Neck Surgery, Johns Hopkins Medical Institutions (J.R.B., L.E.I., C.G.G.), Baltimore; and the National Institutes of Health (M.J.S.), Bethesda, Maryland, U.S.A. Editor’s Note: This Manuscript was accepted for publication April 21, 2014. Preliminary data (first 12 patients) was presented at the Triological Society Annual Meeting, Chicago, Illinois, U.S.A., May 2011. Stacey L. Ishman, MD, MPH, is a contractor for First Line Medical. The authors have no other funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Stacey L. Ishman, MD, MPH, Surgical Director, Upper Airway Center Division of Pediatric Otolaryngology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, MLC 2018, Cincinnati, OH 45229. E-mail: [email protected] DOI: 10.1002/lary.24729

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ciated with intermittent oxygen desaturations and/or arousals from sleep. Prevalence studies indicate that up to 18% of adults have at least 15 disordered breathing events/hour2,3 and that symptomatic OSA is seen in 3% to 7% of men and in 2% to 5% of women.1,3 Epidemiologic studies reveal that untreated OSA results in a threefold increase in cardiovascular events4 and more than a twofold increase in motor vehicle accidents.5 OSA also contributes to the development of hypertension, congestive heart failure, diabetes, and stroke.5 Affected patients present with a wide array of symptoms, which may include snoring, decreased cognitive functioning, witnessed apneas, memory loss, morning headaches, depression, and excessive daytime sleepiness. In a review of 55 OSA studies, Saunamaki and Jehkonen6 found that authors reported a consistent association between OSA and depression. In studies that used the Beck Depression Inventory (BDI) as a depression screening instrument (n 5 7), 16% to 55% of patients screened positive for depression. These rates are consistently higher than those in both community-based populations (3%–5%)7 and the primary care setting (5%–10%).8 To date, two studies have evaluated the prevalence of depression in patients with OSA presenting to

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otolaryngology clinics.9,10 In a retrospective prevalence study, Chandra et al.9 reported a depression rate of 14% among patients presenting with a primary complaint of OSA. In a case-control study conducted by our group,10 we reported depression rates of 34% in the OSA cohort and 8% in controls (P < 0.001). Moreover, patients with high Epworth Sleepiness Scale (ESS) scores were most likely to have elevated depression scores.10 Associations between sleepiness and sleep-related conditions have been well-documented. Daytime sleepiness is often the primary reason that patients with insomnia, circadian rhythm disorders, and sleep-related breathing disorders present for treatment. Nonetheless, it is not always a reliable clinical indicator for identifying OSA.11 Sleepiness has, however, been found to be an independent risk factor associated with depression.12 The current guideline developed by the American Academy of Sleep Medicine (AASM) for the care of OSA in adults recommends the use of continuous positive airway pressure (CPAP) as the first-line management approach.13 The guideline recommends oral appliances, behavioral modification (e.g., weight loss), and surgical therapy for patients who are intolerant to CPAP, have surgically correctable obstructive anatomy, or who prefer non-CPAP management options. Several studies examining the effect of CPAP on depression have reported improvement in depression symptom scores after CPAP treatment.14–17 Two studies have measured the effect of oral appliance therapy on depression.18,19 The first study found a significant decrease in the BDI after therapy; however, it was equivalent to the improvement after a placebo condition.18 The second study found no improvement in overall BDI scores (P > 0.05), but a mild improvement in the somatic component (P < 0.05).19 Investigations of the impact of surgery on depression in adults with OSA consist of three single-modality studies in which patients underwent uvulopalatopharyngoplasty (UPPP) or radiofrequency ablation to the tongue base.20–22 All three studies suggest that depressive symptoms are improved with surgery. However, the impact of multilevel surgery on depression has not been investigated. In view of the cited improvement in depression with single-modality surgery,20–22 we felt that it was prudent to examine the impact of surgery on both depression and sleepiness and also to determine the impact of multilevel surgery on these debilitating OSA symptoms. We hypothesized that depression and sleepiness would be reduced after surgery.

MATERIALS AND METHODS Patient Population We reviewed the medical records and prospective outcomes database of consecutive OSA patients who underwent surgery from 2008 to 2012. All patients had presented to our otolaryngology sleep surgery clinic. Inclusion criteria included the preoperative and postoperative completion of the Epworth Sleepiness Scale (ESS), Beck Depression Inventory-II (BDI-II), and overnight polysomnography (PSG). Patients were excluded if they were younger than 18 years of age, using an oral appliance or CPAP, or undergoing solo adjunctive procedures (i.e., nasal surgery and pillar implant placement) that were not expected to significantly improve OSA without concurrent oro-

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pharyngeal or hypopharyngeal surgery. This protocol was approved by the Johns Hopkins Institutional Review Board.

Surgical Treatment Appropriate surgical treatment was determined by physical examination findings, awake flexible nasopharyngoscopy/ laryngoscopy, and PSG results. Additionally, patients underwent drug-induced sleep endoscopy immediately prior to surgery to confirm the appropriateness of the surgical plan. Nasal surgery included septoplasty, nasal valve repair, inferior turbinate reduction with radiofrequency, and submucous resection of the inferior turbinates. Oropharyngeal surgery included tonsillectomy and UPPP, including z-palatoplasty. Hypopharyngeal surgery included genioglossal advancement, hyoid suspension, partial midline glossectomy, lingual tonsillectomy, and tongue suspension suture placement.

Overnight Polysomnography Standard overnight 16-channel PSG was performed in the sleep laboratory, as previously reported.10 Results were interpreted by board-certified sleep medicine physicians.

Measurement of OSA Severity The primary parameter used to measure OSA severity was the obstructive respiratory disturbance index (RDI). The RDI is calculated by taking the number or respiratory events (apneas, hypopneas, and respiratory event related arousals (RERAs), subtracting central apneas and central hypopneas, and dividing by the total sleep time. Apneas, hypopneas, and RERAs were scored in accordance with the AASM specifications.23 OSA severity was defined according to the criteria established by the AASM.13 Postoperative PSG was ordered for all patients 3 months after surgery. There are two sleep laboratories at Johns Hopkins that score flow limitation of at least 50% with arousals as either hypopneas or RERAs—the obstructive RDI rather than the obstructive AHI to standardize the results between sites.

Evaluating Sleepiness The ESS is an eight-item questionnaire used extensively to measure daytime sleepiness.24 A scale of 0 (never doze or sleep) to 3 (high chance of dozing or sleeping) is used for each question, with a range of total scores from 0 to 24. Excessive daytime sleepiness (EDS) was defined as a score > 10 as is standard for this instrument.

Evaluating Depression The BDI-II is a widely used 21-item self-rating scale for measuring depression. It is known to have high internal consistency, high content validity, and validity in differentiating between depressed and nondepressed patients.25,26 The BDI-II has also been shown to be sensitive to change in depressive symptoms.25–27

Statistical Analysis We used descriptive statistics to examine the distribution of demographic and clinical characteristics. Mean BDI, RDI, and ESS scores did not follow a normal (Gaussian) distribution. Therefore, the Wilcoxon sign rank test (nonparametric) was used to compare mean BDI, RDI, and ESS scores in patients before and after surgery. Spearman correlation analysis was

Ishman et al.: Does Surgery Improve Depression and Sleepiness?

TABLE I. Baseline Demographic and Clinical Characteristics of Patients Undergoing Surgery for Obstructive Sleep Apnea. Patient Variable

Age (mean/median) (years)

Mean

44.0/41.7 (SD 10.2, 21–67)

Sex Female

12 (27.3%)

Male

32 (72.7%)

Race Black

8 (18.2%)

White

31 (70.5%)

Hispanic/Other BMI (mean/median)(kg/m2)

5 (11.4%) 31.9/30.2 (SD 8.9, 19.2–68.0)

RDI (mean/median)(events/hour)

35.8/30.8 (SD 21.9, 6.6–94.2)1

OSA severity Mild (5–15 events/hour)

4 (9.1%)

Moderate (15–29 events/hour) Severe (>30 events/hour) Epworth Score (mean/median)

15 (34.1%) 25 (56.8%) 10.8/11.3 (SD 4.7, 2–24)

Sleepy by Epworth Score BDI (mean/median) Depressed by BDI

22 (50.0%)

Depression

8.4/5.5 (SD 8.2, 0–32) 12 (27.3%)

BDI 5 Beck Depression Inventory; BMI 5 body mass index; OSA 5 obstructive sleep apnea; RDI 5 obstructive respiratory disturbance index; SD 5 standard deviation.

used to evaluate correlations between the BDI, RDI and ESS scores. The Fisher exact test was used to look at binary differences by gender in baseline depression and sleepiness and depression resolution and sleepiness. Single and multivariable linear regression modeling with backward and forward model selection was performed to show the relationship between depression scores, OSA disease severity, and sleepiness. The final prediction model for change in BDI included baseline BDI, baseline ESS, change in ESS, and change in RDI while controlling for age, race, and sex. Similarly, the final model for change in ESS included baseline ESS, change in RDI, and change in BDI also controlled for age, race, and sex. The inclusion of body mass index (BMI) and baseline RDI did not improve the model for change in BDI or ESS; therefore, they were excluded from the model. Significance was considered as a P value of < 0.05. Data was analyzed using Stata 12 (Stata Corporation, College Station, TX) and GraphPad Prism 5.0 (GraphPad Software, San Diego, CA).

RESULTS Demographics and Clinical Characteristics Forty-four patients (12 females; 32 males) met our inclusion criteria. These patients had a mean age of 44.0 years (range 21.0–67.3, SD 10.2) and a mean BMI of 31.9 (range 19.2–68.0, SD 8.9). Forty (90.9%) of these patients had severe (56.8%) or moderate (34.1%) OSA, while 4 (9.1%) patients had mild disease. Demographic and clinical characteristics of this cohort prior to surgery are summarized in Table I. Single-level surgery was performed in 11 (25%) patients. The remaining 33 patients underwent either 2level surgery (n 5 22, 50%) or 3-level surgery (n 5 11, Laryngoscope 124: December 2014

25%) (Table II). Of the 11 patients who underwent single-level surgery, seven patients had tonsillectomy, one patient had UPPP with tonsillectomy, and three patients had hypopharyngeal surgery alone. Overall, oropharyngeal surgery was performed in 41 (93.2%) patients, and surgery to the tongue or hypopharynx was performed in 31 (70.5%) patients. Nasal surgery was performed in conjunction with palatal or tongue-base surgery in 16 (36.4%) patients. Overall, the mean preoperative RDI decreased from 35.8 events/hour (SD, 21.9) to 17.1 (SD 19.5; P < 0.0001) (Table III), with 36 (81.8%) patients showing improvement after surgery (Fig. 1). Change in RDI was 15.5 events/hour (SD 24.45) for those who underwent singlelevel surgery and 19.81 events/hour (SD 19.29) for those who underwent multilevel surgery (P 5 0.33). There was no difference in the proportion (18%) of patients who showed no improvement or worsening of RDI after single-level or multilevel surgery (2/11 vs. 6/33, respectively).

Mean depression scores decreased from 8.4 (SD 8.2) to 4.9 (SD 6.0; P 5 0.0051) (Fig. 2). Twelve (27.3%) patients screened positive for depression at baseline; surgery relieved depression in 9 (75.0%) of these patients. Three additional patients who screened negative for depression prior to surgery were positive for depression postoperatively. These patients completed the BDI-II at 29 days, 33 days, and 186 days after surgery. The mean time from surgery to BDI-II completion was 115 days (SD 114). Subgroup analysis of depression by gender showed that five (41.7%) of the 12 women and seven (21.9%) of the 32 men screened positive for depression at baseline (P 5 0.26). Depression resolved postoperatively in three (60%) of the five women and six (86%) of the seven men (P 5 0.52). In a multiple logistic regression model including age, race, BMI, and baseline ESS, the change in RDI (P 5 0.011) and the change in ESS (P 5 0.005) in men were associated with the change in BDI score; these relationships were not significant in women (P 5 0.14, P 5 0.09, respectively). Change in BDI was associated with baseline BDI for both women and men (P 5 0.012, P

Does surgery for obstructive sleep apnea improve depression and sleepiness?

To determine if surgical intervention for OSA (obstructive sleep apnea), particularly multilevel surgery, decreases depression and sleepiness...
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