SEARCH

SEARCH BY CITATION

Keywords:

  • depression;
  • mood disorders;
  • obstructive sleep apnea syndrome;
  • risk factors;
  • screening

Abstract

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES

Aims:  Previous studies have reported that the incidence of obstructive sleep apnea syndrome (OSAS) in patients with depression is higher than in the general population. We examined the risk factors to predict OSAS in mood disorder patients with depressive symptoms.

Method:  We conducted polysomnography for patients who satisfied the following criteria: (i) diagnosis of major depressive disorder or bipolar disorder according to the Mini-International Neuropsychiatric Interview (MINI); (ii) a score of ≥10 on the Hamilton Rating Scale for Depression (HAM-D); (iii) fulfillment of either (a) or (b) below: (a) at least one of the following: severe snoring, witnessed apnea during sleep, excessive daytime sleepiness; (b) at least one of the following plus an oxygen desaturation index of 4% ≥5 times/h by pulse oximeter: mild snoring, sleep disturbance, headache, high blood pressure. The patients with apnea hypopnea index ≥5 were diagnosed with OSAS.

Results:  Of the 32 mood disorder patients who met the subject conditions, 59.4% had OSAS. The diagnosis rate with our criteria was significantly higher than the previously reported incidence of OSAS in patients with depression. There was no significant difference among diagnosis rates as to individual risk factors or the number of risk factors. A multiple regression test showed no significant association between apnea–hypopnea index and other clinical factors including depression severity.

Conclusion:  The present results showed that OSAS can be detected at a remarkably higher rate by considering appropriate OSAS risk factors in mood disorder patients, and suggested that there is a high rate of undetected and therefore untreated OSAS among mood disorder patients.

OBSTRUCTIVE SLEEP APNEA SYNDROME (OSAS) has attracted attention as a cause of various physical disorders, as well as traffic or industrial accidents and occupational difficulties due to excessive daytime sleepiness and cognitive dysfunction. Depression and OSAS have many common symptoms, including sleep disturbance, general fatigue, decreased volition and judgment ability, and other various physical manifestations. Earlier studies have reported that the incidence of OSAS complications in cases of depression is about 11–18%, higher than in the general population.1,2 From this, one may predict that there is much untreated OSAS among depression patients, and it would be reasonable to assume that some of these cases are treated as treatment-resistant depression.3 There are also a number of reports of OSAS treatment that improved comorbid depressive symptoms.4,5 By identifying and treating OSAS in depression patients, therefore, it may be possible to alleviate not only the various symptoms that accompany OSAS and the deterioration in quality of life, but also the depressive symptoms themselves.

Screening with the use of appropriate risk factors is needed for the easy detection of OSAS in the daily clinical setting. Reported risk factors for OSAS include sex, age, obesity, snoring and/or witnessed apnea during sleep, pharyngeal abnormalities, and cephalometric features.6–10 Some reports presented the usage of risk factors for OSAS prediction;6,8,11,12 however, there is lack of consensus, because the subjects of these previous studies were the general population. Additionally there has been no reported study on risk factors or screening for OSAS in mood disorder patients, as far as we know.

With the aim of identifying and treating OSAS in mood disorder patients presenting with depression, we conducted OSAS screening with known risk factors in these patients. And we examined whether the screening model in this study was useful and valid in the clinical setting of psychiatry, and which or how many risk factors would contribute most to OSAS screening.

METHODS

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES

Subjects

Among patients who were treated for mood disorder in the departments of psychiatry at Fujita Health University Hospital and Okehazama Hospital, those who had no previous diagnosis of OSAS and who met the following criteria were selected as candidates for inclusion with high risk for latent OSAS, between April 2007 and March 2008.

Selection criteria

  • 1
    Diagnosis of major depressive disorder or bipolar disorder (in a major depressive episode) through a structured Mini-International Neuropsychiatric Interview (MINI) based on the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV); excluding untreated patients or patients in the acute phase whose drug regimen is being adjusted.
  • 2
    A score of ≥10 on the Hamilton Rating Scale for Depression (HAM-D).
  • 3
    Fulfillment of either (a) or (b) below.
    • (a) 
      At least one of the following: severe snoring, witnessed apnea during sleep, or excessive daytime sleepiness.
    • (b) 
      At least one of the following: mild snoring, sleep disturbance (arousal during sleep, unrefreshing sleep or mild daytime sleepiness), headache, or high blood pressure. In addition, oxygen desaturation index of 4% (ODI 4%) of ≥5 times per h, measured by a pulse oximeter.

Here, excessive daytime sleepiness is defined as drowsiness that interferes with social activities even though the patient feels that he or she received sufficient sleep. Pulse oximetry was carried out using Pulsox 6 (Minolta, Tokyo, Japan), a continuous, non-invasive arterial oxygen saturation monitor that was attached to one of the patient's fingers. The number of times that arterial oxygen saturation decreased by ≥4% over one night was divided by the number of hours in bed to get the ODI 4%.

Assessment

Overnight polysomnography (PSG) was conducted according to the following procedure for patients who satisfied the above conditions. Patients with an apnea–hypopnea index (AHI) of ≥5 times per h were diagnosed as having OSAS that should be considered for treatment, according to the International Classification of Sleep Disorders 2nd edition (ICSD2). Hypnotics that have a muscle relaxant effect were discontinued before PSG, with the exception of short-acting ones. Also, benzodiazepines were discontinued in principle prior to examination, however, if the patients could not discontinue benzodiazepines because of symptoms such as anxiety, only the short-acting varieties were allowed to be continued. Other psychotropic drugs, including antidepressants and mood stabilizers, were continued.

Besides the HAM-D, we also conducted the Beck Depression Inventory (BDI), Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) for included subjects when they underwent PSG.

The study was approved by the ethics committees of Fujita Health University and Okehazama Hospital, and conducted after written explanations were given to all patients and their consent was obtained.

PSG

PSG was carried out following the procedure below, according to the clinical electroencephalography standards of the Japanese Society of Clinical Neurophysiology. Electroencephalogram (EEG), eye movement, chin electromyogram (EMG), expiration thermistor measurements, chest and abdominal expansion, electrocardiogram (ECG), arterial oxygen saturation, snoring, and leg EMG were recorded. Recordings from EEG electrodes were made at C3, C4, O1, and O2 according to the ten-twenty electrode system. A1 and A2 were placed at the bilateral mastoid processes as reference electrodes and connected to the contralateral cranial electrodes. For EMG, electrodes were attached 1 cm lateral and 1 cm superior to the lateral orbit margin of the left eye, and 1 cm lateral and 1 cm inferior to the lateral orbit margin of the right eye, with connections from two leads of these electrodes with the mastoid process A1 (single lead). For chin EMG, two electrodes were attached to the submental muscle, and for leg EMG two electrodes were attached to the tibialis anterior muscle and bipolar leads were used. ECG employed a CM5 lead. Measurements were made from 21.00 hours to 06.00 hours the following morning in an air-conditioned, sound insulated and dark room. The obtained signals were stored as digital data into a personal computer using one of two PSG systems, Alice 3 (Respironics, Murrysville, PA, USA) or Somnostar (Viasys, Conshohocken, PA, USA). The sleep stages and parameters were based on the criteria of Rechtschaffen and Kales, revised manually by trained technicians following automatic scoring by either PSG system. Apnea events were based on complete cessation or ≥50% reduction of air flow of 10 sec or longer, and hypopnea events were the air flow reductions accompanied by SaO2 reduction of ≥3% or an arousal response when the reductions were <50%. The apnea or hypopnea counts were also revised manually by trained technicians after automatic scoring, and the mean number of both events per h divided by the total sleep time was taken as the AHI.

Statistical analysis

The χ2-test was conducted to verify the increase in the OSAS diagnosis rate for all cases included in this study based on the previously reported OSAS complication rate in depression. The difference in OSAS diagnosis rate in patients with each risk factor, and the difference in OSAS diagnosis rate between patients with one risk factor and those with two or more risk factors, was compared using the χ2-test or Fisher's exact test. To test the relation between the other clinical factors and the severity of OSAS in the subject group, multiple regression analysis was conducted with AHI as the dependent variable and the clinical items (sex, age, psychiatric diagnosis, body mass index (BMI), ESS score, HAM-D score, BDI score, and PSQI score) as independent variables. Statistical calculations were conducted with JMP 5.0.1J computer software package (SAS Institute Japan, Tokyo, Japan). The significant level in the tests was set at P < 0.05.

RESULTS

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES

Thirty-two subjects (24 men and eight women) met the screening criteria and were included in the study. The mean age of these patients was 48.4 ± 11.8 years. The psychiatric diagnosis was major depressive disorder in 19 and bipolar affective disorder in 13. Their mean HAM-D score was 15.69 ± 3.94 for 17 items. The risk factors matched for screening were witnessed apnea during sleep in six subjects, severe snoring in 21, excessive daytime sleepiness in 15, and mild symptoms plus ODI 4% of five or more times per h by pulse oximeter in four (multiple factors applied to some patients).

On PSG, 19 patients had OSAS of AHI ≥ 5 (AHI ≥ 10 in 15 patients, AHI ≥ 20 in 10 patients). In the group with AHI ≥ 5 (OSAS group), the risk factors matched for inclusion were witnessed apnea during sleep in five patients, severe snoring in 13, excessive daytime sleepiness in seven, and mild symptoms plus ODI 4% of ≥5 times/h by pulse oximeter in four (multiple factors applied to some patients). The OSAS group had 17 men and two women (Table 1). Setting the rate of complication with OSAS in mood disorder patients at 20%, which was higher than that from previous studies, the increase in the OSAS diagnosis rate was still statistically significant even when using the criterion of AHI ≥ 10 from the present results (P = 0.00005).

Table 1. Demographic data and risk factors of the subjects
 All patientsOSASNon-OSAS AHI < 5 P-value
AHI ≥ 5AHI ≥ 10AHI ≥ 20
  • Data are shown by mean ± standard deviation. P-value shows the result of multiple regression test.

  • BMI > 25 is not included in the screening major items.

  • AHI, apnea–hypopnea index; BD, bipolar disorder; BDI, Beck Depression Inventory; BMI, body mass index; EDS, excessive daytime sleepiness; ESS, Epworth Sleepiness Scale; HAM-D, Hamilton Rating Scale for Depression; MDD, major depressive disorder; ODI, oxygen desaturation index.; OSAS, obstructive sleep apnea syndrome; PSQI, Pittsburgh Sleep Quality Index.

n 3219151013 
Sex (M/F)24/817/213/28/27/60.753
Age48.4 ± 11.851.3 ± 12.253.1 ± 12.453.8 ± 13.444.2 ± 10.20.186
Diagnosis (MDD/BD)19/1310/98/75/59/40.503
BMI (kg/m2)27.2 ± 5.226.5 ± 5.326.2 ± 5.726.9 ± 6.728.1 ± 5.20.114
ESS (score)7.6 ± 5.26.7 ± 5.65.9 ± 5.06.4 ± 5.88.9 ± 4.40.255
HAM-D (score)15.7 ± 3.914.8 ± 3.614.4 ± 5.415.3 ± 4.317.0 ± 4.160.978
BDI (score)22.2 ± 10.921.7 ± 11.419.4 ± 9.718.6 ± 9.822.9 ± 10.40.114
PSQI (score)11.8 ± 4.311.4 ± 3.811.5 ± 3.911.8 ± 4.312.2 ± 5.10.079
Risk factorsApnea (n)65321
Snore (n)21131078
EDS (n)157548
ODI4% ≥ 5 (n)44310
BMI > 25 (n)2213969

The OSAS diagnosis rate for each risk factor in the patients included in the present study was as follows: OSAS was diagnosed in 83.3% (5/6) of patients with witnessed apnea during sleep, 61.9% (13/21) with severe snoring, and 46.7% (7/15) with excessive daytime sleepiness. Although no BMI inclusion criterion was considered in this screening, OSAS was diagnosed in 59.1% (13/22) of patients with BMI > 25. All patients with mild symptoms plus ODI 4% of ≥5 times/h by pulse oximeter (4/4) were diagnosed with OSAS. By sex, OSAS was diagnosed in 69.6% (16/23) of men and 28.6% (2/7) of women. After excluding witnessed apnea during sleep and ODI 4% because there were too few of these items for statistical analysis, no significant difference was seen in the percentage of OSAS diagnosis between the three risk factors BMI > 25, severe snoring, and excessive daytime sleepiness (P = 0.638). OSAS was diagnosed in 57.9% (11/19) of patients who fulfilled only one of the inclusion criteria of severe snoring, excessive daytime sleepiness, witnessed apnea, and ODI 4%, and in 61.5% (8/13) of patients who fulfilled two or more; no significant difference was seen in these rates of diagnosis (P = 0.836). Adding BMI > 25 as a risk factor, which was not one of the inclusion criteria, the rate of diagnosis became 62.5% (5/8) of patients who fulfill only one criteria, and 58.3% (14/24) of patients who fulfill two or more; also no significant difference was seen between these two diagnostic rates (P = 1.00; Fisher's exact test).

In the multiple regression analysis, no significant relation was seen between AHI and any of the other clinical characteristics (Table 1).

DISCUSSION

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES

Of the 32 mood disorder patients who met the subject conditions in the present study, 59.4% had OSAS. It has been reported that the prevalence of OSAS complications in depression patients is higher than that in healthy people. Kayukawa and Okada conducted PSG in 119 depression patients, and found that 11.8% had OSAS when the diagnostic criterion was AHI of ≥10.1 It was also reported, from a cross-sectional study using telephone surveys of 18 980 subjects in England and four other European countries, that complications with sleep-related breathing disorders including OSAS were present in 18% of depression patients diagnosed according to DSM-IV.2 In the screening conducted in the present study we were able to identify OSAS in 46.9% of subjects even using the criteria of AHI ≥ 10, which is remarkably and significantly greater than even a high estimate of a 20% complication rate with OSAS in mood disorder patients, based on the above previous reports. Therefore, we may consider that the screening criteria with the risk factors we employed in this study was an effective method of detecting OSAS in up to about half of mood disorder cases in a psychiatric clinical setting. Factors other than these risk factors that may have contributed to raising the diagnosis rate are the inclusion of patients with bipolar disorder, and having ≥10 points on HAM-D as inclusion criteria. It is thought that a high proportion of bipolar disorder patients are overweight, and the possibility cannot be ruled out that the complication rate of OSAS is higher than in major depressive disorder patients. However, in our results there was no significant difference even though the OSAS diagnosis rate for bipolar disorder was slightly higher than that for monopolar major depressive disorder in this study (data not shown). Additionally, in subgroups of both major depressive disorder and bipolar disorder the OSAS diagnosis rate was significantly higher than 20% based on the criterion of AHI ≥ 10 (data not shown). Therefore, it is difficult to conclude that including bipolar disorder patients by itself led to a higher rate of OSAS diagnosis. In addition, one may consider that there would be more complications with OSAS in patient groups with high HAM-D scores, because of the possibility that the HAM-D score increases with the occurrence of arousals during sleep or other sleep disturbance in OSAS patients, or the possibility that depression itself is exacerbated by OSAS. However, in our results no significant correlation was seen between the HAM-D score and the AHI or OSAS diagnosis (described below), and so it seems unlikely that having a score of ≥10 on the HAM-D would greatly increase the diagnosis rate of OSAS. We have no direct verification of this, however, as we do not have data for the HAM-D of <10.

From the above, one may conclude that establishing the risk factors used in the present screening was effective in significantly raising the diagnosis rate. For the past several years we have had a special sleep clinic in the psychiatry department, and patients strongly suspected of OSAS have already undergone PSG and been treated before this study began. We conducted this screening excluding the patients already diagnosed with OSAS. Screening with the present risk factors revealed latent OSAS for which treatment may be required in about half of patients, which suggests that it may be worthwhile to conduct similar screening for OSAS in other psychiatric clinical settings as well.

Previous studies have indicated that risk factors for OSAS include sex, age, snoring, witnessed apnea during sleep, obesity, pharyngeal abnormalities, and cephalometric features.6–10 We selected risk factors from among these with the purpose of thorough and effective screening in daily clinical practice in the psychiatric department. Excessive daytime sleepiness is a main symptom of OSAS, and it has been shown to be closely related to OSAS.13 Because it is used conventionally in daily clinical practice as a subjective symptom that does not require observation by others, we adopted it as the major item in the present screening. The indicators of severe snoring and witnessed apnea during sleep have been given as risk factors for OSAS in previous reports, which claim that they are the main symptoms of OSAS.8,10 Therefore, they were also adopted as the major items for screening. However, checking these items depends greatly on a patient's individual sleeping environment, particularly whether or not the patient has a bed partner, and so it would be very difficult to conduct screening with these items alone. Obesity, meanwhile, has been reported to have little usefulness as a risk factor for OSAS in the Asian population including the Japanese,14,15 and it was not included in the major screening items in this study. It has been noted that cephalometric features can replace obesity as a risk factor in the Japanese population,7,9 but cephalograms were not conducted as they are inconvenient for screening in the psychiatry clinic. Sex and age have been given as risk factors for OSAS,6,8,10,12 but OSAS cannot be suspected because of these factors alone and so they were not included as the major items in the present screening.

When these items were included in the screening, the OSAS diagnosis rate, in the order from the highest, was 83.3% (5/6) with witnessed apnea during sleep, 61.9% (13/21) with severe snoring, and 46.7% (7/15) with excessive daytime sleepiness. Although BMI > 25 was not included in the inclusion criteria, the diagnosis rate with it was 59.1% (13/22). No significant differences were seen between these diagnosis rates. Therefore, no evidence was discovered for arguing that the weight of the items should be changed for a more effective screening. However, there were only a small number of patients with witnessed apnea during sleep, so they were excluded from the statistical testing. It is possible that with more cases the diagnosis rate would be higher than with the other risk factors. Recent studies reported less predictive value of excessive daytime sleepiness for OSAS,8,16 and nonspecific daytime sleepiness from such as psychotropic drugs or the underlying disease itself may be stronger in mood disorder patients than in the general population. Although the diagnosis rate with excessive daytime sleepiness was lower than with other present risk factors, the difference was not significant: even so, the possibility cannot be ruled out that with a greater number of cases it would be significantly lower.

ODI measured with a pulse oximeter has been reported to correlate with AHI to a certain extent, and there have also been several reports on methods to predict OSAS using pulse oximetry. However, there is a lack of agreement in the findings on the utility of this method. For example, one study supported the usefulness of pulse oximetry showing that the extent of the decline in SpO2 and ODI were sufficiently comparable to PSG;17 however, other studies showed that the device succeeded to affirm the diagnosis of severe OSAS but overlooked mild or moderate OSAS.18,19 There is also a report on the difficulty of diagnosis by evaluation with pulse oximetry alone.20 In the present study pulse oximetry was conducted for patients who did not have the above major risk factors but had at least one of the conditions of mild snoring or mild sleep disturbance (arousal during sleep, unrefreshing sleep or mild daytime sleepiness), headache, high blood pressure; so it was not performed in all cases. All of the present patients who exhibited ODI 4% ≥5 times per h were diagnosed with OSAS, but as it was only seen in four included cases its efficacy cannot be compared with other risk factors. While it is possible that screening with pulse oximetry would detect a greater number of OSAS cases, regardless of the presence or absence of other risk factors and symptoms for OSAS, it would be virtually impossible to conduct pulse oximetry in almost all mood disorder patients in an actual clinical psychiatric practice. Conversely, it may be that the diagnostic efficiency could be raised by conducting pulse oximetry and excluding patients with an ODI below a certain level among candidates who already have other major risk factors. However, considering an increase in false negatives among patients with comparatively mild OSAS in the light of the device's measurement principles and the above reported results, it does not suit the purpose of screening, which is to reduce the number overlooked. Therefore, the present screening method, in which pulse oximetry was used in cases with weak symptoms of suspected OSAS other than the major risk factors, is thought to have a certain validity.

Whether the presence of multiple risk factors is more efficient for OSAS prediction than a single risk factor is of interest. Some studies have presented a predictive model for OSAS with combined risk factors;6,8,11,12 however, they still lack consensus and the models are still inconvenient for daily clinical practice. Unexpectedly, our present results showed no significant difference in the diagnosis rate between cases with only one of the three major risk factors for inclusion and cases with more than one. Therefore, the presence of only one of these risk factors in screening is thought to have a uniform validity in strongly suspecting OSAS. Nor was there a significant difference between cases with one or multiple risk factors when the factor of BMI was included as a risk factor among the present cases, however no patients were included in the present study because of high BMI only, and so we cannot comment on the value of BMI alone as a major risk factor.

In a multiple regression analysis with the other clinical items as the independent variables and AHI as the dependent variable, no items showed a significant relation with AHI. This finding argues against the possibility that other specific factors contributed strongly to a diagnosis of OSAS in the cases included in the present study. It is worth noting that no correlation was seen between AHI and depressive severity according to BDI or HAM-D in the present subjects. Opinions are divided on the role of OSAS in depression,21–26 but the present results did not strongly support such a role.

One limitation in the present study was the small number of subjects. As mentioned above, the possibility cannot be ruled out that with a greater number of subjects some significant differences would be revealed among risk factors in their level of contribution to diagnosis. In this study we evaluated OSAS only in a group with risk factors; therefore, we cannot evaluate the sensitivity and specificity of this screening model. Pulse oximetry was conducted in only a small part of the patients, as noted above, and cephalograms were not obtained, so we could not evaluate these potential risk factors: However, to verify a screening model for ‘real world’ psychiatric clinical settings, it would seem to be meaningful that the evaluation was made using a rather practical form.

In summary, the present results showed that OSAS can be detected at a higher rate by considering appropriate OSAS risk factors in mood disorder patients, and suggested that there is a high rate of undetected and therefore untreated OSAS among mood disorder patients. Therapists involved in treating mood disorders should not overlook OSAS and at the same time need to be cautious in using drugs with a muscle relaxant effect such as benzodiazepines. They also need to pay attention to obesity, which can exacerbate OSAS. In the future we will need to conduct investigations with greater numbers of patients and verify whether or not improvements in depressive symptoms can be expected with treatment of detected OSAS.

ACKNOWLEDGMENTS

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES

The authors would like to express their sincere appreciation to Ms. Fujita (technician) and everyone else in the sleep and breathing laboratory for their cooperation in this study.

REFERENCES

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES