Abstract
Aim:
To evaluate the prevalence of risk for obstructive sleep apnea (OSA) among patients with bipolar disorder (BD).
Methodology:
Eighty-seven patients with BD and 50 matched controls were assessed by using the Berlin questionnaire.
Results:
One-fifth of the patients with BD was found to be at high risk for OSA, compared to the 6% prevalence in the control group. Patients in high risk for OSA were more often females, had significantly higher body mass index, high waist circumference, and comorbid physical illnesses. In terms of pharmacotherapy, there was association of use of antipsychotics with higher risk of OSA at the trend level (p=0.052).
Conclusion:
The prevalence of high risk for OSA is significantly higher among patients with BD and higher prevalence is related to obesity and comorbid physical illnesses.
Keywords: Bipolar disorder, obstructive sleep apnea obesity, prevalence
Bipolar disorder (BD) is one of the leading causes of disabilities among the mental disorders, accounting for 9.9 million disability adjusted life years (DALYs) in 2013, explaining overall 0.4% of total DALYs and 1.3% of total years lost due to disability.[1] Patients with BD have a higher prevalence of medical comorbidities such as diabetes mellitus, cardiovascular disorders, obesity, metabolic syndrome, and obstructive sleep apnea (OSA) when compared with the general population.[2,3,4,5,6,7]
Although a vast literature is available for insomnia, daytime sleepiness, circadian rhythm disturbances in patients with BD and how these contribute to poor quality of life, frequent relapses, and have adverse consequences for affective functioning,[8,9] relatively less is understood about OSA in patients with BD. A systematic review reported the prevalence of OSA to vary from 2.9% to 69%, with a median of 19.8% in clinical-based studies and a median of 6.9% in population-based studies. However, this review was limited to studies which assessed OSA using polysomnography (PSG).[10] A recent meta-analysis reported a pooled prevalence of OSA in patients with BD in the clinical settings to be 24.5%, and this prevalence figure is comparable to clinical studies in the general population.[7] However, it is important to note that most of these studies have been carried out in Western countries, which have a high prevalence of obesity, which can possibly influence the prevalence of OSA among patients with BD. There is a paucity of research in the Indian context with respect to the prevalence of risk for OSA among patients with BD. In this background, this study attempted to evaluate the prevalence of risk for OSA and its correlates among patients with BD.
METHODOLOGY
This cross-sectional study was carried out in the outpatient department of a tertiary care teaching hospital. To be included in the study, the patients with BD were required to be in clinical remission, i.e., Hamilton Depression Rating Scale (HDRS)[11] and Young's Mania Rating Scale Patients (YMRS)[12] score ≤7 and provided written informed consent.
Patients were excluded if they had comorbid psychiatric syndromes including intellectual disability and organic brain syndromes, sleep disorders before onset of BD, uncontrolled physical illnesses despite treatment, substance abuse or dependence (other than tobacco), on shift duties and irregular daytime work schedules, with recent (within 2 months prior to the study) international travel, pregnancy, childbirth, and bereavement.
Sociodemographic, clinical, and treatment details were obtained from the patients and their relatives, as well as the medical records. The severity of mood was assessed using YMRS and HDRS. Patients were asked to complete the Berlin Sleep Questionnaire Hindi version[13] and Epworth Sleepiness Scale (ESS).[14] Hypertension was defined as the systolic blood pressure (BP) of >140 mmHg or diastolic BP of 90 mmHg of OSA were compared or when the participants were on antihypertensive medications.
Berlin questionnaire
It is a screening instrument to ascertain the risk of having OSA and comprises of three categories of symptoms related to the risk of having OSA: Five questions are related to snoring and cessation of breathing in category 1, four questions are related to daytime sleepiness in category 2; there is a question about high BP and also a question about the body mass index (BMI) in category 3. Category 1/Category 2 is positive if the person scores 2 or more points for each category. Category 3 is positive if there is presence of hypertension (>140/90 mmHg or use of medication) or a BMI >30 kg/m2. Patients are classified as having a high risk for OSA if scores are positive on two or more categories. The Hindi version of the scale has a sensitivity of 89% and specificity of 58%. Positive predictive value of the instrument was 0.87, whereas the negative predictive value was 0.63.[13,15]
Epworth sleepiness scale
The ESS is an 8-item questionnaire which assesses daytime 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 score >10 indicates clinically “significant daytime sleepiness.”[14]
Statistical analysis
Data were analyzed using the Statistical Package for Social Sciences, Sixteenth version (SPSS-16). (SPSS Inc. Released 2007. SPSS for Windows, Version 16.0. Chicago, SPSS Inc.). The data were analyzed in the form of frequencies, percentage, mean, and standard deviation. Comparisons were done using the Chi-Square test and t-test.
RESULTS
The present study included 87 patients of BD and 50 healthy controls. There was no significant difference between the two groups, in terms of demographic variables, except that, significantly higher proportion of those in the control group were educated beyond matric. In terms of anthropometric measures, compared to the healthy control group, patients of BD had significantly higher BMI [Table 1].
Table 1.
Demographic, clinical and anthropometric profiles of study groups
| Remitted (n=87) | Controls (n=50) | χ2/t-test/Mann-Whitney | |
|---|---|---|---|
| Age (years), mean (SD) [range] | 41.53 (13.22) [18-64] | 37.68 (12.09) [19-63] | T=0.43 (0.670) |
| Gender, n (%) | |||
| Male | 58 (66.7) | 34 (68) | χ2=0.03 (0.873) |
| Female | 29 (33.3) | 16 (32) | |
| Marital status, n (%) | |||
| Single | 16 (18.4) | 13 (26) | χ2=1.10 (0.294) |
| Married | 58 (81.6) | 37 (74) | |
| Years of schooling, mean (SD) [range] | 11.19 (3.62) [0-18] | 12.66 (4.68) [0-22] | T=0.62 (0.538) |
| Education status, n (%) | |||
| Matric and below | 34 (39.1) | 10 (20) | χ2=5.30 (0.021)* |
| Above matric | 53 (60.9) | 40 (80) | |
| Occupation, n (%) | |||
| Unemployed | 26 (29.9) | 18 (36) | χ2=0.54 (0.461) |
| Employed | 61 (70.1) | 32 (64) | |
| Income in rupees per months, mean (SD) [range] | 15,465.52 (20,753.93) [0-100,000] | 20,560.00 (22,187.66) [0-100,000] | U=545.50 (0.59) |
| Family type, n (%) | |||
| Nuclear | 33 (37.9) | 18 (36) | χ2=0.05 (0.822) |
| Nonnuclear | 54 (62.1) | 32 (64) | |
| Locality, n (%) | |||
| Urban | 35 (40.2) | 26 (52) | χ2=1.78 (0.182) |
| Rural | 52 (59.8) | 24 (48) | |
| Comorbid physical illnessa, n (%) | |||
| None | 72 (82.8) | 44 (88) | χ2=0.67 (0.412) |
| Yes | 15 (17.2) | 6 (12) | |
| Height (cm), mean (SD) [range] | 164.49 (7.32) [148.3-182] | 166.71 (6.55) [148.2-180] | T=1.774 (0.078) |
| Weight (kg), mean (SD) [range] | 71.91 (9.45) [50-99] | 70.11 (11.99) [52-113.6] | T=0.97 (0.333) |
| WC (cm), mean (SD) [range] | 94.51 (10.30) [71-119] | 92.14 (9.52) [77-119] | T=1.33 (0.185) |
| BMI (kg/m2), mean (SD) [range] | 26.66 (3.86) [19.36-42.74] | 25.13 (3.41) [20.32-39.07] | T=2.34 (0.021)* |
| BMI (kg/m2), n (%) | |||
| ≥25 | 53 (60.9) | 20 (40) | χ2=5.58 (0.018) |
| <25 | 34 (39.1) | 30 (60) | |
| Number of pack of cigarettes per years, mean (SD) [range] | 4.28 (9.62) [0-30] | 2.3 (6.72) [0-30] | T=486.00 (0.09) |
| Prevalence of OSA, n (%) | |||
| Low risk | 70 (80.45) | 47 (94) | χ2=4.67 (0.031)* |
| High risk | 17 (19.55) | 3 (6) | |
| Total ESS score, mean (SD) [range] | 5.33 (4.83) [0-13] | 3.58 (3.85) [0-12] | U=1640 (0.015) |
*P≤0.05; aDiabetes mellitus; hypertension; hypothyroidism. BMI - Body mass index; SD - Standard deviation; OSA - Obstructive sleep apnea; ESS - Epworth Sleepiness Scale; WC - Waist circumference
Compared to the healthy controls, significantly higher proportions of patients with BD were considered to be at high risk for OSA [Table 1].
Demographic, clinical, and anthropometric variables associated with high risk of obstructive sleep apnea
When the patients of BD, at low and high risk were of OSA were compared, it was seen that patients at high risk were significantly more often females, had higher BMI, higher proportion of them had BMI ≥25, were shorter in height, were heavier in weight, had higher waist circumference, and had higher prevalence of comorbid physical illnesses [Table 2].
Table 2.
Comparison of demographic, clinical and anthropometric variables of patients at high and low risk of obstructive sleep apnea
| Low risk (n=70) | High risk (n=17) | χ2/t-test/Mann-Whitney | |
|---|---|---|---|
| Age (years), mean (SD) [range] | 41.83 (13.37) [18-64] | 40.29 (12.92) [20-64] | T=0.43 (0.670) |
| Gender, n (%) | |||
| Male | 51 (72.9) | 7 (41.2) | χ2=6.18 (0.013)* |
| Female | 19 (27.1) | 10 (58.8) | |
| Marital status, n (%) | |||
| Single | 12 (17.1) | 4 (23.5) | χ2=0.37 (0.552) |
| Married | 58 (82.9) | 13 (76.5) | |
| Years of schooling, mean (SD) [range] | 11.31 (3.47) [0-18] | 10.70 (4.28) [0-18] | T=0.62 (0.538) |
| Education status, n (%) | |||
| Matric and below | 27 (38.6) | 7 (41.2) | χ2=0.04 (0.843) |
| Above matric | 43 (61.4) | 10 (58.8) | |
| Occupation, n (%) | |||
| Unemployed | 19 (27.1) | 7 (41.2) | χ2=1.29 (0.257) |
| Employed | 51 (72.9) | 10 (58.8) | |
| Income in rupees per month, mean (SD) [range] | 16,521.43 (22,120.62) [0-100,000] | 11117.65 (13,415.86) [0-50,000] | U=545.50 (0.59) |
| Family type, n (%) | |||
| Nuclear | 25 (35.7) | 8 (47.1) | χ2=0.75 (0.387) |
| Nonnuclear | 45 (64.3) | 9 (52.9) | |
| Locality, n (%) | |||
| Urban | 28 (40) | 10 (58.8) | χ2=0.008 (0.929) |
| Rural | 42 (60) | 7 (41.2) | |
| Height (cm), mean (SD) [range] | 165.47 (7.04) [152-182] | 160.46 (7.29) [148.3-176] | T=2.61 (0.011)** |
| Height for males, mean (SD) [range] | 167.71 (6.03) [154-182] | 165.71 (165.71) [153-176] | T=0.798 (0.428) |
| Height for females, mean (SD) [range] | 159.46 (6.07) [152-173] | 156.78 (4.60) [148.3-164] | T=1.22 (0.232) |
| Weight (kg), mean (SD) [range] | 70.26 (8.61) [50-92] | 78.71 (9.99) [60-99] | T=3.51 (0.001)*** |
| Weight for females, mean (SD) [range] | 66.92 (8.35) [50-82] | 76.8 (8.12) [66-94] | T=3.06 (0.005)** |
| Weight for males, mean (SD) [range] | 71.51 (8.45) [54-92] | 81.43 (12.34) [60-99] | T=2.75 (0.008)** |
| WC (cm), mean (SD) [range] | 102.24 (12.32) [82-119] | 92.64 (8.87) [71-113] | T=3.69 (<0.001)*** |
| WC for males, mean (SD) [range] | 93.29 (8.49) [71-113] | 98.43 (13.59) [82-119] | T=1.39 (0.171) |
| WC for females, mean (SD) [range] | 90.87 (9.84) [78-110] | 104.90 (11.30) [89-118] | T=3.47 (0.002)** |
| BMI (kg/m2), mean (SD) [range] | 25.97 (2.98) [17.93-32.26] | 30.68 (4.45) [22.58-42.74] | T=5.57 (<0.001)*** |
| BMI (kg/m2), n (%) | |||
| ≥25 | 37 (52.9) | 1 (8.6) | χ2=9.781 (0.002)** |
| <25 | 33 (47.1) | 16 (91.4) | |
| Number of pack of cigarettes per years, mean (SD) [range] | 6.29 (15.62) [0-66] | 0.09 (0.36) [0-1.50] | U=486.00 (0.09) |
| Age of onset (years), mean (SD) [range] | 29.18 (9.53) [17-58] | 29.00 (8.96) [17-58] | T=0.07 (0.942) |
| Duration of illness, mean (SD) [range] | 12.46 (8.80) [1-38] | 11.41 (7.85) [1-34] | T=0.45 (0.655) |
| Total number of episodes, mean (SD) [range] | 9.14 (8.38) [2-40] | 11.82 (8.50) [2-34] | T=1.18 (0.242) |
| YMRS scores, mean (SD) [range] | 1.34 (1.70) [0-5] | 0.41 (0.71) [0-2] | U=565.50 (0.678) |
| HDRS scores, mean (SD) [range] | 1.94 (1.70) [0-6] | 2.53 (1.66) [0-5] | U=455.5 (0.278) |
| Comorbid physical illness, n (%) | |||
| Present | 9 (12.9) | 6 (35.3) | 3.38 (0.04)* yates |
| Absent | 61 (87.1) | 11 (64.7) | |
| Mood stabilizers, n (%) | |||
| None | 6 (8.6) | - | |
| Lithium | 47 (67.1) | 11 (64.7) | |
| Valproate | 17 (24.3) | 5 (29.4) | |
| Lamotrigine | - | 1 (5.9) | |
| Chlorpromazine equivalent dose, mean (SD) [range] | 173.81 (181.52) [0-600] | 270.59 (261.11) [0-800] | U=467.00 (0.153) |
| Olanzapine, n (%) | 27 (38.6) | 6 (35.3) | |
| Quetiapine, n (%) | 9 (12.9) | 5 (29.4) | |
| Risperidone, n (%) | 1 (1.4) | 0 | |
| Aripiprazole, n (%) | 2 (2.9) | 1 (5.9) | |
| None, n (%) | 31 (44.3) | 5 (29.4) | 3.78 (0.052)* |
| Imipramine equivalent, mean (SD) [range] | 37.77 (60.80) [0-265.89] | 33.25 (56.11) [0-152.44] | U=565.50 (0.706) |
| Diazepam equivalent dose, mean (SD) [range] | 8.43 (12.90) [0-80] | 4.70 (8.00) [0-20] | U=488.50 (0.207) |
| Total ESS score, mean (SD) [range] | 5.06 (4.81) [0-13] | 6.47 (4.91) [0-13] | U=466.5 (0.243) |
*P≤0.05; **P≤0.01; ***P≤0.001. BMI - Body mass index; YMRS - Young’s Mania Rating Scale; HDRS - Hamilton Depression Rating Scale; ESS - Epworth Sleepiness Scale; SD - Standard deviation; WC - Waist circumference
DISCUSSION
This study aimed to evaluate the prevalence of risk for OSA among patients with BD and evaluate the factors associated with high risk for OSA.
In the present study, about one-fifth of the patients were found to be at high risk for OSA, and this was significantly higher than that observed in a matched healthy control group. Studies from the different parts of the world which have evaluated the risk using self-rated questionnaires in clinic based settings have reported prevalence to vary from 22% to 54.1%,[16,17,18] whereas studies which have additionally used PSG to ascertain OSA, have reported prevalence of about 22%.[18,19] The findings of the present study are close to the lower end of the reported rates in the literature. This could be possibly due to the relatively lower BMI in our sample, compared to some of the previous studies, which have reported mean BMI of the study sample to range from 29.18 to 36.80 kg/m2,[16,17,18] which is one of the important predictor of OSA.
In terms of risk factors, the present study suggests that female gender, higher BMI, higher body weight, higher waist circumference, and presence of comorbid physical illnesses are associated with high risk of OSA. Previous studies which have evaluated the factors associated with high risk of OSA have come up with inconsistent association with gender, with some reporting higher prevalence of high risk among females,[16,17,18,20,21] whereas others have reported higher prevalence among males.[22] The association of high risk for OSA with higher BMI is a well-known fact, with majority of the literature supporting the same.[23,24,25,26] This association suggests that clinicians managing patients with BD should routinely measure anthropometric measures in their patients and encourage them to lose weight by following dietary restrictions and regular physical exercises.
In the present study, continuation of an antipsychotic during the remission phase was associated with high risk of OSA. This association can be understood in light of the fact that atypical antipsychotics are associated with significant weight gain. Previous studies have also reported similar associations.[27,28,29] Over the years, various treatment guidelines have started recommending atypical antipsychotics as pharmaco-prophylactic agents in the management of BD.[30,31,32] However, these recommendations are based on the efficacy of the various antipsychotics, without considering the long term negative effect of the same on other outcomes. Association of ongoing antipsychotics (at the trend level) with higher risk of OSA suggests that a caution must be practiced while using antipsychotics in the maintenance phase in patients with BD and the same should be based on weighing all the pros and cons of the same.
Available data suggest association of higher residual depressive symptoms to be an important predictor for OSA.[21] However, the present study do not support the same.
Limitations
Our study had certain limitations. First, it was based on the convenient sample of patients attending our outpatient services. The present study was based on a screening instrument and the patients who were screened to be at high risk were not subjected to PSG, which is the gold standard for diagnosing OSA. As it was cross-sectional study, it is difficult to ascertain whether OSA predisposed to BD by altering sleep or vice versa, given the bidirectional relationship between OSA and depression. Although Berlin questionnaire is an effective tool among other screening tools in the clinical settings in which the benefit of high sensitivity outweighs the disadvantage of low specificity, it is inferior to the gold standard diagnostic strategy, i.e., PSG. The study group and the control group were not matched for BMI and obesity. Future studies must attempt to overcome these limitations.
CONCLUSION
The present study suggests that about one-fifth of the patients with BD are at high risk for OSA, which is significantly higher than that seen in the healthy control group. In terms of risk factors, female gender, higher BMI, higher body weight, higher waist circumference, and presence of comorbid physical illnesses and continuation of antipsychotics in the maintenance phase are associated with high risk of OSA.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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