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| ORIGINAL ARTICLE |
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| Year : 2022 | Volume
: 10
| Issue : 2 | Page : 173-178 |
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Risk for obstructive sleep apnea in patients with bipolar disorder, prevalence from Kashmir
Rayees Ahmad Wani1, Shabir Ahmad Dar1, Naveed Nazir Shah2, Inaamul Haq3, Suraya Gani4
1 Department of Psychiatry, Government Medical College, Srinagar, Jammu and Kashmir, India
2 Department of Chest Medicine, Government Medical College, Srinagar, Jammu and Kashmir, India
3 Department of Social and Preventive Medicine, Government Medical College, Srinagar, Jammu and Kashmir, India
4 Department of Nursing, Government Medical College, Srinagar, Jammu and Kashmir, India
| Date of Submission | 09-Sep-2022 |
| Date of Decision | 10-Nov-2022 |
| Date of Acceptance | 10-Nov-2022 |
| Date of Web Publication | 15-Dec-2022 |
Correspondence Address:
Rayees Ahmad Wani
Departments of Psychiatry Government Medical College, Srinagar, Jammu and Kashmir
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/jhnps.jhnps_60_22
Background: An association exists between obstructive sleep apnea (OSA) and bipolar disorder (BD). The prevalence of OSA in BD has significantly increased during the past two decades. We aimed to assess the prevalence of risk for OSA in BD. Materials and Methods: This was a hospital-based, cross-sectional, case–control study. Out of 218 participants enrolled in the study, 109 had BD and 109 were recruited for comparison in the control group. All the participants were asked to complete the Berlin Questionnaire, a self-assessment tool to establish the risk for OSA. Results: About two-thirds of the patients with BD were found to be at risk for OSA as compared to the 19.27% of prevalence in the control group. Patients of BD at high risk for OSA were males, had significantly higher body mass index (BMI), with comorbid physical illnesses, and in those who were on a combination of valproate and lithium in comparison to valproate alone. Conclusion: Patients with BD had significantly higher BMI in comparison to controls. In comparison to controls, significant higher percentage of patients with BD had higher risk for OSA in comparison to healthy controls. Our finding of over half of patients being in the high-risk range should be sufficient to sensitize clinicians and raise awareness concerning OSA in BD.
Keywords: Bipolar disorders, obstructive sleep apnea, sleep
How to cite this article:
Wani RA, Dar SA, Shah NN, Haq I, Gani S. Risk for obstructive sleep apnea in patients with bipolar disorder, prevalence from Kashmir. J Head Neck Physicians Surg 2022;10:173-8 |
How to cite this URL:
Wani RA, Dar SA, Shah NN, Haq I, Gani S. Risk for obstructive sleep apnea in patients with bipolar disorder, prevalence from Kashmir. J Head Neck Physicians Surg [serial online] 2022 [cited 2023 Jun 4];10:173-8. Available from: https://www.jhnps.org/text.asp?2022/10/2/173/363929 |
| Introduction | |  |
In comparison to the general population, patients with bipolar disorder (BD) are at an increased risk of medical comorbidities such as diabetes mellitus, cardiovascular diseases, metabolic syndrome (Mets), and obstructive sleep apnea (OSA).[1],[2],[3],[4],[5]
Sleep disturbances are the core symptoms of BD[6],[7] with a great variability in sleep duration.[8]
In patients of BD, the decreased need for sleep predicts the onset of a manic or hypomanic episode, the following day,[9] whereas sleep extension occurs frequently in depressive episodes.[10],[11],[12]
The frequent disturbance in sleep–wake cycle tends to exacerbate or precipitate frequent mood episodes[13] and thereby acts as a risk factor for relapse of a mood episode.[14] It has been seen that sleep deprivation can trigger manic episodes in animal BD models too.[15],[16] The lack of sleep in patients with BD is a symptom for poor prognosis and also increasing the risk of suicide in patients with past suicidal attempts.[17] Sleep disturbances are quite common in patients with BD even during the symptom-free period of illness.[7]
From the above findings and depending on the rhythmic nature of BD, it can be said that the endogenous circadian system plays an important role in clinical presentation, etiology, and outcome in BD.[18],[19]
Part of the detrimental effect of these conditions on mood regulation may be ascribed to underlying sleep-related breathing problems. Patients who develop OSA as a result of cumulative risk factors may be overrepresented among those who present a history of chronic and treatment-resistant depressive symptoms.
Since the depressive phase of BD is often chronic and difficult to treat, and undiagnosed underlying medical conditions may greatly contribute to its unfavorable outcome, it is reasonable to speculate that sleep-disordered breathing may play a role in this clinical picture. Indeed, the presence of medical comorbidities that constitute risk factors for OSA has been associated with a worse outcome of BD.[20] For example, obesity has been linked to a higher number of lifetime depressive episodes and to a shorter time to relapse.[21] Abdominal obesity, particularly is associated with increased suicidality.[3]
Therefore, this study was taken to examine whether BD was associated with an increased risk of subsequent OSA using sex- and age-matched healthy voluntary controls.
| Materials and Methods | | |
Study design
This cross-sectional, case–control study was conducted at Department of Psychiatry ,which is an associated hospital of Govt. Medical College,Srinagar. The patients with BD currently in the euthymic phase of illness were recruited for the study. Euthymia for this study was defined as the Hamilton Depression Rating Scale (HDRS)[22] and the Young Mania Rating Scale (YMRS)[23] score of ≤7. This study was conducted over 18 months from mid-June 2020 to mid-December 2021 after seeking permission from the institutional ethics committee. The study was approved under institutional ethics committee approval number, GMCS/IEC-332-2020 dated March 13, 2020. The patients were selected through a purposive sampling technique after informed written consent.
Inclusion criteria that were adopted included (1) age of ≥18 years; (2) euthymia for at least 3 months before participation in the study; and (3) those who gave written informed consent.
Patients receiving treatments for any medical illness known to alter sleep patterns, substance use disorder, being hospitalized, being involved in shift work, those with recent history of transmeridian travel or a history of major life events were excluded from the study.
Age- and gender-matched voluntary healthy controls were recruited through adverts who gave written informed consent.
Demographic and clinical variables
Basic demographic data, clinical details, and treatment records were collected from the patients/relatives and medical records section. Height, weight, and neck circumferences were measured in all patients. The YMRS and HDRS scales were used for quantifying the severity of current manic or depressive symptoms.
Berlin Sleep Questionnaire[24] is a 10-item valid instrument which is used globally to determine the risk of OSA. In this instrument category, one risk is defined as persistent symptoms reported in response to two or more questions about snoring. Category 2 assesses persistent occurrences of drowsy driving, wake-time sleepiness, or both. Category 3 risk factors include factors such as high body mass index (BMI <30/m2) and high blood pressure (<140/90) or the use of antihypertensive medication. Individuals are classified as high risk for OSA if they meet high-risk criteria in two of the three categories. The positive predictive value of the instrument was found to be 0.88.[25]
The Epworth Sleepiness Scale[26] is an 8-item questionnaire which is widely used as a subjective measure of patient's day time sleepiness. Patients are asked to rate their likelihood of falling asleep in a variety of situations on a 4-point scale (0–3). Total scores range from 0 to 24. A total score of <10 indicates clinically significant day time sleepiness.
Statistical analysis
Data were analyzed using the Statistical Package for the Social Sciences, 16 versions (SPSS Inc., Chicago ).[27] The data were analyzed in the form of frequencies, percentages, mean, and standard deviation. Comparisons were done using the Chi-square test and t-test.
| Results | | |
A total of 218 participants were enrolled in the study, out of which 109 had BD and 109 were for comparison in the control group. Patients and controls were matched for age, gender, family type, and occupation. As shown in [Table 1], significantly higher proportions of those in the control group were educated beyond matric. Participants with BD had a mean age of onset of 32.90 ± 5.17 years, with a mean duration of illness of 18.78 ± 5.17 years, and the mean number of life time mood episodes was 8.78 ± 4.17. The mean YMRS score was 2.266 ± 1.05 and the mean HDRS score was 1.87 ± 0.61.
The mean years of schooling were 8.78 ± 3.90 years in cases in comparison to controls (10.10 ± 3.83). The mean height, weight, and waist circumference were significantly higher in cases than in controls. In terms of anthropometric measures, compared to the healthy controls, patients with BD had significantly higher BMI, as shown in [Table 2].
In comparison to controls, higher percentage of patients with BD had higher risk for OSA in comparison to controls and the difference was statistically significant, as shown in [Table 2].
On comparing patients of BD and normal healthy controls, a significantly higher proportion of cases where having higher BMI, significantly higher proportion of them had BMI of ≥25, and had significantly higher prevalence of patients with comorbid physical illnesses as shown in [Table 3]. Significantly higher risk for sleep apnea was seen in those who were on a combination of valproate and lithium in comparison to valproate alone. When the patients of BD, at low and high risk of OSA were compared, it was seen that patients at high risk were significantly more often males, and having comorbid physical illnesses.
| Discussion | | |
OSA is a common chronic breathing disorder affecting 2%–4% of the adult population that involves the recurrent collapse of the upper airways leading to episodes of hypoxemia and arousal during sleep.[28],[29]
Daytime sleepiness, due to nocturnal sleep fragmentation, is a key symptom of OSA, being present in more than 80% of the patients. As the disorder progresses, sleepiness becomes increasingly dangerous, causing impaired performance at work and major work-related and road traffic accidents.[30],[31]
In the present study, about two-thirds of the patients with BD were found to be at risk for OSA, and this was significantly higher than that observed in the matched healthy control group. At least three possible explanations may be worth considering in regard to the link between BD and the risk of OSA. First, different types of sleep disturbances are described in all phases of BD, including remission.[32] Second, sympathetic hyperactivity and hyperarousal associated with sleep disturbances may lead to instability of the upper respiratory tract and may contribute to subsequent OSA.[33] Third, benzodiazepines prescribed for sleep problems lead to muscle relaxation, and in turn, lead to the collapse of the airways.[34]
Our results resonate with other authors who reported the prevalence of OSA to vary from 22% to 54.1% in clinical settings.[35],[36],[37] The studies, where authors have used polysomnography, have reported the prevalence of OSA to be 22%.[37],[38]
In the present study, cases of BD had significantly higher BMI in comparison to the healthy controls. Some of the previous studies, have also reported the mean BMI of the sample to range from 29.18 to 36.80 kg/m2[35],[36],[37] and thus coincides with our study results.
BMI is one of the important predictors of OSA.[39] Many patients with OSA can develop cognitive and neurobehavioral dysfunction, inability to concentrate, memory impairment, and mood changes such as irritability and depression which further impair performance at work with a remarkable effect on the quality of life.[40]
It is a well-established fact that OSA, if left untreated, is a major determinant of cardiovascular morbidity and mortality.[41],[42] The main cardiovascular disorders described include drug-resistant systemic hypertension (>50% of the patients), ischemic heart disease, cardiac arrhythmias, and stroke.[41]
Recently, sleep-related hypoxia has also been associated with a low-grade systemic inflammation, which in turn may contribute to initiate or accelerate the process of atherogenesis.[31] Therefore, OSA is often associated with the symptoms of Mets.[43]
Patients with BD have an unhealthy lifestyle exacerbated by mood symptoms and poorer access and quality of physical health care, which increases the likelihood of developing a Mets.[44],[45] In addition, an important metabolic impairment occurs in OSA independently from the body weight. Insulin resistance, type II diabetes, and altered serum lipid profile, widely described in patients with OSA, can represent a further risk of cardiovascular morbidity.[31],[46]
There is now little doubt that an increased mortality occurs in patients with untreated sleep apnea compared with healthy controls.[47],[48] First-line treatments for BD include lithium and valproic acid supplemented by the use of atypical antipsychotics, all of which are associated with myriad multisystem side effects, especially weight gain, that predispose patients to OSA among other potential complications.[49],[50] It has been also seen that serotonergic agonists positively regulate central respiratory drive and increase airway diameter. Therefore, inhibition of this serotonin pathway is suggested to worsen OSA by increasing upper airway resistance.
The main finding of this study was the discovery of a higher incidence of OSA in male patients with BD after adjustment for baseline demographics and comorbidities. The stratification analysis by sex also revealed that the risk trend with BD and subsequent OSA was mainly contributed by male BD patients and female BD patients weakened the overall association. There are a number of sex differences that could explain the above results.[51]
For example, the activity of the dilator muscles of the upper respiratory tract may be increased in women, making the closure of the upper airway less likely to occur during sleep. In addition, fat deposition in the upper respiratory tract (e.g., lateral parapharyngeal fat pads) is greater in men than in women.
Since OSA has important effects on a patient's cognitive well-being, work performance, and quality of life and this condition can result in pulmonary hypertension, which can be further complicated by acute hypoxemic respiratory failure, cor pulmonale, and death, therefore, it becomes imperative that we screen for OSA in patients BD.
Significantly higher risk for sleep apnea was seen in those who were on combination of valproate and lithium in comparison to valproate alone which actually contradicts the fact that lithium and sodium valproate reduce melatonin light sensitivity and increased the activity period. It can be postulated that these effects on the circadian system can impact sleep regulation. Further research is required to better understand the relationships between these two processes in BD.
Limitations
- Given the cross-sectional design of the study, we could not ascertain whether the onset of apnea risk followed or preceded the onset of BD
- The present study was based on a validated self-report screening questionnaire and the patients who were screened to be at high risk were not subjected to PSG, which is the gold standard for diagnosing OSA
- Our findings are applicable to BD patients in Kashmir only and cannot be generalized
- Purposive sampling and single-center study may also bias the results.
| Conclusion | | |
Patients with BD had significantly higher BMI in comparison to controls. In comparison to controls, significant higher percentage of patients with BD had higher risk for OSA in comparison to healthy controls. Our finding of over half of patients being in the high-risk range should be sufficient to sensitize clinicians and raise awareness concerning OSA in BD. Future research should address whether lifestyle and biological factors specific to BD are responsible for the increased risk for OSA. Moreover, given the evidence that patients at risk for sleep-disordered breathing have increased mood symptoms and longitudinal studies that investigate the probable reciprocal interaction between mood and OSA are needed.
In summary, considering the substantial overlap between symptoms of OSA and symptoms of depression and the potentially harmful effects of sleep disruption in patients with mood disorders, a systematic screening to assess the prevalence and associated features of OSA in patients with BD is clearly warranted.
Acknowledgment
The authors are thankful to the participants who generously participated in the study.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Disclosure
This material has never been published and is not currently under evaluation in any other peer-reviewed publication.
Ethical approval
The permission was taken from the institutional ethics committee before starting the project. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent
Informed consent was obtained from all individual participants included in the study.
| References | | |
| 1. | Kupfer DJ. The increasing medical burden in bipolar disorder. JAMA 2005;293:2528-30.  |
| 2. | Fagiolini A, Frank E, Houck PR, Mallinger AG, Swartz HA, Buysse DJ, et al. Prevalence of obesity and weight change during treatment in patients with bipolar I disorder. J Clin Psychiatry 2002;63:528-33. |
| 3. | Fagiolini A, Frank E, Scott JA, Turkin S, Kupfer DJ. Metabolic syndrome in bipolar disorder: Findings from the bipolar disorder center for pennsylvanians. Bipolar Disord 2005;7:424-30. |
| 4. | Diaz FJ, James D, Botts S, Maw L, Susce MT, de Leon J. Tobacco smoking behaviors in bipolar disorder: A comparison of the general population, schizophrenia, and major depression. Bipolar Disord 2009;11:154-65. |
| 5. | Gonzalez-Pinto A, Gutierrez M, Ezcurra J, Aizpuru F, Mosquera F, Lopez P, et al. Tobacco smoking and bipolar disorder. J Clin Psychiatry 1998;59:225-8. |
| 6. | Geoffroy PA, Scott J, Boudebesse C, Lajnef M, Henry C, Leboyer M, et al. Sleep in patients with remitted bipolar disorders: A meta-analysis of actigraphy studies. Acta Psychiatr Scand 2015;131:89-99. |
| 7. | Ng TH, Chung KF, Ho FY, Yeung WF, Yung KP, Lam TH. Sleep-wake disturbance in interepisode bipolar disorder and high-risk individuals: A systematic review and meta-analysis. Sleep Med Rev 2015;20:46-58. |
| 8. | Franzen PL, Buysse DJ. Sleep disturbances and depression: Risk relationships for subsequent depression and therapeutic implications. Dialogues Clin Neurosci 2008;10:473-81. |
| 9. | Leibenluft E, Albert PS, Rosenthal NE, Wehr TA. Relationship between sleep and mood in patients with rapid-cycling bipolar disorder. Psychiatry Res 1996;63:161-8. |
| 10. | Murray G, Harvey A. Circadian rhythms and sleep in bipolar disorder. Bipolar Disord 2010;12:459-72. |
| 11. | Ritter PS, Höfler M, Wittchen HU, Lieb R, Bauer M, Pfennig A, et al. Disturbed sleep as risk factor for the subsequent onset of bipolar disorder – Data from a 10-year prospective-longitudinal study among adolescents and young adults. J Psychiatr Res 2015;68:76-82. |
| 12. | Wehr TA. Sleep loss: A preventable cause of mania and other excited states. J Clin Psychiatry 1989;50 Suppl: 8-16. |
| 13. | Hirata FC, Lima MC, de Bruin VM, Nóbrega PR, Wenceslau GP, de Bruin PF. Depression in medical school: The influence of morningness-eveningness. Chronobiol Int 2007;24:939-46. |
| 14. | Sylvia LG, Dupuy JM, Ostacher MJ, Cowperthwait CM, Hay AC, Sachs GS, et al. Sleep disturbance in euthymic bipolar patients. J Psychopharmacol 2012;26:1108-12. |
| 15. | Arent CO, Valvassori SS, Steckert AV, Resende WR, Dal-Pont GC, Lopes-Borges J, et al. The effects of n-acetylcysteine and/or deferoxamine on manic-like behavior and brain oxidative damage in mice submitted to the paradoxal sleep deprivation model of mania. J Psychiatr Res 2015;65:71-9. |
| 16. | Logan RW, McClung CA. Animal models of bipolar mania: The past, present and future. Neuroscience 2016;321:163-88. |
| 17. | Stange JP, Kleiman EM, Sylvia LG, Magalhães PV, Berk M, Nierenberg AA, et al. Specific mood symptoms confer risk for subsequent suicidal ideation in bipolar disorder with and without suicide attempt history: Multi-wave data from step-BD. Depress Anxiety 2016;33:464-72. |
| 18. | Lamont EW, James FO, Boivin DB, Cermakian N. From circadian clock gene expression to pathologies. Sleep Med 2007;8:547-56. |
| 19. | Wirz-Justice A. Biological rhythm disturbances in mood disorders. Int Clin Psychopharmacol 2006;21 Suppl 1:S11-5. |
| 20. | Thompson WK, Kupfer DJ, Fagiolini A, Scott JA, Frank E. Prevalence and clinical correlates of medical comorbidities in patients with bipolar I disorder: Analysis of acute-phase data from a randomized controlled trial. J Clin Psychiatry 2006;67:783-8. |
| 21. | Fagiolini A, Kupfer DJ, Houck PR, Novick DM, Frank E. Obesity as a correlate of outcome in patients with bipolar I disorder. Am J Psychiatry 2003;160:112-7. |
| 22. | Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56-62. |
| 23. | Young RC, Biggs JT, Ziegler VE, Meyer DA. A rating scale for mania: Reliability, validity and sensitivity. Br J Psychiatry 1978;133:429-35. |
| 24. | Gupta R, Ali R, Dhyani M, Das S, Pundir A. Hindi translation of Berlin questionnaire and its validation as a screening instrument for obstructive sleep apnea. J Neurosci Rural Pract 2016;7:244-9. [ PUBMED] [Full text] |
| 25. | Netzer NC, Stoohs RA, Netzer CM, Clark K, Strohl KP. Using the Berlin questionnaire to identify patients at risk for the sleep apnea syndrome. Ann Intern Med 1999;131:485-91. |
| 26. | Johns MW. A new method for measuring daytime sleepiness: The Epworth sleepiness scale. Sleep 1991;14:540-5. |
| 27. | IBM Corp. IBM SPSS Statistics for Windows. Version 23.0. Armonk, NY: IBM Corp; 2015. |
| 28. | Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 1993;328:1230-5. |
| 29. | Malhotra A, White DP. Obstructive sleep apnoea. Lancet 2002;360:237-45. |
| 30. | Guilleminault C, Quo SD. Sleep-disordered breathing. A view at the beginning of the new Millennium. Dent Clin North Am 2001;45:643-56. |
| 31. | Jordan AS, McSharry DG, Malhotra A. Adult obstructive sleep apnoea. Lancet 2014;383:736-47. |
| 32. | Bradley AJ, Webb-Mitchell R, Hazu A, Slater N, Middleton B, Gallagher P, et al. Sleep and circadian rhythm disturbance in bipolar disorder. Psychol Med 2017;47:1678-89. |
| 33. | Sériès F, Roy N, Marc I. Effects of sleep deprivation and sleep fragmentation on upper airway collapsibility in normal subjects. Am J Respir Crit Care Med 1994;150:481-5. |
| 34. | Gupta MA, Simpson FC. Obstructive sleep apnea and psychiatric disorders: A systematic review. J Clin Sleep Med 2015;11:165-75. |
| 35. | Geoffroy PA, Micoulaud Franchi JA, Maruani J, Philip P, Boudebesse C, Benizri C, et al. Clinical characteristics of obstructive sleep apnea in bipolar disorders. J Affect Disord 2019;245:1-7. |
| 36. | Soreca I, Levenson J, Lotz M, Frank E, Kupfer DJ. Sleep apnea risk and clinical correlates in patients with bipolar disorder. Bipolar Disord 2012;14:672-6. |
| 37. | Kelly T, Douglas L, Denmark L, Brasuell G, Lieberman DZ. The high prevalence of obstructive sleep apnea among patients with bipolar disorders. J Affect Disord 2013;151:54-8. |
| 38. | Mieczkowski BP, Oduguwa A, Kowatch RA, Splaingard M. Risk factors for sleep apnea in children with bipolar disorder. J Affect Disord 2014;167:20-4. |
| 39. | Varadharajan N, Grover S. Prevalence of risk for obstructive sleep apnea in patients with bipolar disorder. Ind Psychiatry J 2021;30:285-90. [Full text] |
| 40. | Vaessen TJ, Overeem S, Sitskoorn MM. Cognitive complaints in obstructive sleep apnea. Sleep Med Rev 2015;19:51-8. |
| 41. | Bradley TD, Floras JS. Obstructive sleep apnoea and its cardiovascular consequences. Lancet 2009;373:82-93. |
| 42. | Young T, Finn L, Peppard PE, Szklo-Coxe M, Austin D, Nieto FJ, et al. Sleep disordered breathing and mortality: Eighteen-year follow-up of the Wisconsin sleep cohort. Sleep 2008;31:1071-8. |
| 43. | Vgontzas AN, Bixler EO, Chrousos GP. Sleep apnea is a manifestation of the metabolic syndrome. Sleep Med Rev 2005;9:211-24. |
| 44. | Kilbourne AM, Rofey DL, McCarthy JF, Post EP, Welsh D, Blow FC. Nutrition and exercise behavior among patients with bipolar disorder. Bipolar Disord 2007;9:443-52. |
| 45. | Mitchell AJ, Malone D, Doebbeling CC. Quality of medical care for people with and without comorbid mental illness and substance misuse: Systematic review of comparative studies. Br J Psychiatry 2009;194:491-9. |
| 46. | Sharma SK, Agrawal S, Damodaran D, Sreenivas V, Kadhiravan T, Lakshmy R, et al. CPAP for the metabolic syndrome in patients with obstructive sleep apnea. N Engl J Med 2011;365:2277-86. |
| 47. | Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: An observational study. Lancet 2005;365:1046-53. |
| 48. | Kendzerska T, Gershon AS, Hawker G, Leung RS, Tomlinson G. Obstructive sleep apnea and risk of cardiovascular events and all-cause mortality: A decade-long historical cohort study. PLoS Med 2014;11:e1001599. |
| 49. | Chengappa KN, Suppes T, Berk M. Treatment of bipolar mania with atypical antipsychotics. Expert Rev Neurother 2004;4:S17-25. |
| 50. | Moonga SS, Mischoulon D, Winkelman JW, Stern TA. Obstructive sleep apnea as a complication of bipolar disorder and its treatment: A review and approach to management. Prim Care Companion CNS Disord 2017;19:17f02194. |
| 51. | Schwab J. Sex differences and sleep apnoea. Thorax 1999;54:284-5. |
[Table 1], [Table 2], [Table 3]
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