OSA AS A CAUSE OF DEPRESSION

Oya İTİL Dokuz Eylül Medical Faculty Dept.of Pulmonary Medicine İZMİR

OSAS

OSAS is a syndrome characterized by repetitive upper airway obstructions and frequent oxygen desaturations during sleep.

Major Symptoms Cardiopulmonary Symptoms

Snoring Sensation of obstruction during sleep

Witnessed apnea Atypical chest pain

Excessive daytime sleepiness Nocturnal arythmia

Neuropsychiatric symptoms Other symptoms

Morning headache Mouth dryness

Insufficient and fragmentated sleep Nocturnal sweatining

Insomnia Nocturnal cough

Decrease in the ability of making a decision

Nocturia , enuresis

Weakness in memory Decrease in libido , impotance

Changes in personality Hear loss

Problem in adaptation to environment Gastro-oesphageal reflux

Depression , anxiety , psychosis

Abnormal motor activity during sleep

Symptoms affecting daily activities

Excessive daytime sleepiness Neuropsychological symptoms Irritability Inability to concentrate Cognitive disorder Depressive symptoms Other psychological disorders

(somatisation,obsession-compulsion,hostility,nocturnal panic attacks,psychotic episodes

OSA, may easily mimic the symptoms of a major depressive episode.

Depression is the most common mood disorder in OSAS.

Pathophysiology Is it a primary consequence of OSAS? Does it develop secondary to OSAS –

related symptoms? Sleepiness Sleep problems Irritability Social problems Is it associated with other OSAS – related

factors ? Obesity Hypertension

Sleep structure in OSA and depression

Major depression PSG increase in sleep latency frequent nocturnal awakenings early morning awakenings decrease in deep sleep shortened REM latency increase in the ratio of REM

OSA Fragmented sleep Increase in initial sleep stages Increase in REM latency

OSA + depression decrease in sleep latency ( compared with cases without OSA, but with depression)

OSA + depression Increase in REM ratio

(compared with cases with OSA, but without depression)

Bardwell WA. Biol Psychiatry 2000; 48:1001-9

Possible mechanisms of the association between OSA and depression

Two factors considered to be responsible of depressive symptoms in OSA :

Sleep fragmentation Oxygen desaturation in sleep

Microarousals related with apneas and hypopneas sleep fragmentation primary cause of excessive daytime sleepiness depressive symptoms

Intermittant oxygen desaturations caused by respiratory events nocturnal hypoxemia

44 cases ( OSA ) Excessive daytime sleepiness ESS ve MWT results are correlated with

high depression scores. Sforza E. Sleep Med 2002;3:139-45

The impact of cognitive disorder in OSA is correlated with the severity of the hypoxic events.

OSA – related hypoxemia affects the mood.

Engleman HM, Sleep 2000;23 Suppl 4:5102-8 Kamba M. Am J Respir Crit Care Med 1997;156:296-

98

Recurrent nocturnal hypoxemia

cerebral metabolic disorder

McGown AD. Sleep

2003;26:710-716

Increase in the intensity of brain white matter is associated with depressive symptoms

This increase is more significant in severe cases with OSA compared with milder cases.

Sassi RB.J Affect Diord 2003; 77: 237-45

Firbank MJ. Am J Geriatr Psychiatry 2004;12: 606-12

Aloia MS. J Int Neuropsychol Soc 2004;10:772-85

A common neurobiological risk factor can be present in both disorders.

Serotoninergic system Mood disorder Sleep-wake cyclus Upper airway muscle tone control in

sleep

Functional decrease in serotoninergic neurotransmission is associated with depression

Adrien J. Sleep Med rev 2002;6:341-51

Transmission of serotonin to upper airway motor neurons is diminished during wakefulness dilator muscle activity is primarily decreased during sleep uyku apne

SSRI Antidepressant

effect Fluoxetine,

protryptiline, paroxetine

Common risk factors

OSA - related obesity, HT and DM should raise the suspicion of comorbid or underlying OSA in a depressive patient.

Depression and OSA have been shown to be independently related with metabolic syndrome and cardiovascular disease.

Gami AS. Eur Heart J 2004;25:709-11 Lett HS. Psychosom Med 2004;66:305-15

Insulin resistance is a contributing factor in the relation between depression and cardiovascular disease and in the pathophysiology of depressive disorder.

OSA is also independently related with cardiovascular risk factors compassing metabolic syndrome, primarily insulin resistance.

Coughlin SR. Eur Heart J 2004;25:735-41 Wilcox I. Thorax 1998;53 Suppl 3:S25-8

Since there is a complex relationship between OSAS and depression , current recommendation is as follows:

Mood disorder should be considered as secondary to the medical condition, but not a different psychiatric entity.

Prevalence

24-25 % of male OSAS patients has administered to a psychiatrist before because of anxiety or depression.

Guilleminault C. Arch Intern Med 1977;137:296-

300 In 40 % of 25 male OSA patients

depression risk was found to be increased in cases with excessive daytime sleepiness when investigated for affective disorder.

Reynolds CF.J Clin Psychiatry 1984;45:287-90

26 % depressive symptoms 58 % major depression ( according to

DSM-lll criteriae ) Mosko S. J Clin Psychol 1989;45:51-60

Depression scores are two-fold higher in OSA cases than primary snorers

Aikens JE. Sleep 1999;22:355-59

Epidemiologic study UK, Germany, Italy, Portugal and Spain 18,980 patients In 17 % of patients with sleep-disordered

breathing major depression (+) Ohayon MM. J Clin Psychiatry 2003;64:1195-

200;quiz,1274-6

Early reviews related with OSAS and mood alterations are not systematic

Andrews JG. Clin Psychol Rev 2004;24:1031-49

El-Ad B.Int Rev Psychiatry 2005;17:277-82 Sateia MJ. Clin Chest Med 2003;24:249-59

Recent research findings January 1995-June 2006 55 manuscripts SaunamakiT. Acta Neurol Scand 2007 ;116:277-

88

Number of cases: 8-1635 44-69 age Male : 13-100 % Median:83%

Depression prevalence 7-63 % Mild in the majority Prevalence of anxiety 11-70 %

No significant difference in depressive symptoms in older cases with mild OSA ( AHİ > 5 ), in comparison with the control group ( AHİ < 5 ) in 5-years follow up.

Phillips BA. Chest 1996;110:654-658

2271 , mostly male, with OSA No relation between respiratory disorders and

depression score (Symptom Check List 90 ) Pillar G. Chest 1998;114:697-703

Depressive symptoms are more common in women

Smith R. Chest

2002;121:164-72 Shepertycky MR. Sleep

2005;28:309-14 Pillar G. Chest

1998;114:697-703 Quintana –Gallego E. Respir

Med 2004;98:984-9

Relation between the severity of OSAS and depression

Heterogenous patient groups No correlation was detected in a few

studies including homogenous patient groups

Even in studies including mild OSAS cases prevalence of depression is 16-41 %

Engleman HE. Am J Respir Crit Care Med 1999;159:461-7

Barnes M. Am J Respir Crit Care Med 2002;165:773-80

The severity of depression is more correlated with excessive daytime sleepiness than hypoxemia.

Zung Self-Rating Depression Scale In 45 % of the patients depressive

symptoms Depression scores are higher in patients

with high AHI

Millman RP. J Clin Psychiatry 1989;50:348-51

204 cases ( 101 female, 103 male ) Anxiety and depression scores

negatively correlated with OSAS severity

Fidan F. Toraks Dergisi 2006;7(2):125-29

56 cases Long duration of symptoms in OSAS ( >

5 years ) increases the frequency of anxiety and depression.

Şahbaz S. ERS Congress 2006

CLINICAL ASSESSMENT

Primary attention is required in the evaluation of mood disorders.

Some of the methods may actually reflect sleep quality or daytime sleepiness , not the mood.

Personal sleep history ESS, FOSQ Atypical OSA clinic ( in women ) Irritability Fatigue Fragmented sleep Inability to concentrate General decrease in psychomotor performance

In a depressive case, presence of sleep-wake complaints and the beginning of these complaints before the development of depressive psychopathology should be considered as underlying or comorbid OSA.

Comorbid disorders related with OSA should also be carefully evaluated.

When antihypertansive or antidepressant drugs are recommended, possibility of OSA should be investigated.

Depressive patients suspected of OSA, should be referred to sleep centers for PSG.

Patients with OSA should be systematically evaluated for depressive symptoms with standardized questionnaire forms in sleep centers.

However, since these questionnaires are not arranged specifically for the evaluation of depression in patients with OSA, they may not be appropriate in this group.

Typically, if symptoms of severe depressive patients are not improved with OSA treatment, or their fatigue continues, they should be referred to a psychiatrist.

25 cases 25 controls Anxiety, somatization and sleepiness are

high Positive behaviour towards getting

psychologic help.

Ateş N.Akciğer Arşivi 2006

TREATMENT

2 months CPAP treatment 7 cases Significant drop in Total Mood

Disturbance score Increase in slow wave sleep

Derderian SS. Chest 1988;94:1023-27

4 weeks CPAP treatment Improvement in mood and cognitive

evaluation scores in mild- moderate OSAS patients.

Engleman HM. Lancet 1994;343:572-75

Engleman HM. Thorax 1997;52:114-19

1-3 months CPAP treatment Drop in depression scores Sanchez Al. Psychiatry Clin Neurasci 2001;55:641-

646 Ramos Platon MJ. Int J Neurosci 1992;62:173-195

CPAP therapy, decreases daytime sleepiness along with depressive symptoms in patients with OSA.

McMahon JP. Wmj 2003;102:36-43

Patients with OSAS with high anxiety and depression scores improve with CPAP therapy.

Fidan F. Tüberküloz ve Toraks Dergisi

2007;55(3):271-77

In severe OSAS patients, nasal CPAP improves quality of life decreasing depression.

Kawahara S. Internal Medicine 2005;44:422-27 Akashiba T. Chest 2002;122:861-65

No decrease in depression scores after 3-12 months CPAP treatment in severe OSAS cases

Borak J. J Sleep Res 1996; 5:123-27 Munoz A. Eur Respir J 2000; 15:676-81 Henke KG. Am J Respir Crit Care Med

2001;163:911-17

Depressive symptoms may develop in spite of effective treatment:

Chronic CPAP usage Awareness of the symptomatic , but not

curative nature of therapy Behavioral and personal characteristics

of the patients

Munoz A. Eur respir j 2000;15:676-81

Consisting a good control ( placebo ) group for CPAP treatment is hard.

Sham-CPAP CPAP kompliance may be lower in

depressive patients. Edinger JD. Percept Mot Skills 1994;78:1116-18

There is no correlation between basal depression scores and CPAP usage in the first month.

Lewis KE. Sleep 2004;27:134-38

The most important factor to explain the differences between the studies : The variability in the severity of the initial depressive symptoms

OSA severity itself , does not have a different impact on the improvement of mood after CPAP therapy

The severity of OSA - related depressive symptoms may affect the response to CPAP therapy.

While OSA patients with severe mood symptoms show more improvement with CPAP, patients with less severe or no symptoms do not show any improvement.

Millman RP. J Clin Psychiatry 1989;50:348-51

OSA IN DEPRESSION

17 older cases, with major depression 17.6 % OUA in control group 4.3 %

Reynolds CF. J Clin Psychiatry 1985; 46:257-61

OSA in general may be a confounding factor in mood disorders studies. Further studies of OSA are needed in primary depression.

Sedative antidepressants and adjunct therapies

Hypnotics used in the treatment of depression-related insomnia can exacerbate OSA.

Miles LE. Sleep 1980;3:1-220

Guilleminaut C. Am J Med 1990;88:255-85 Schröder CM. Annals of General Psychiatry 2005;4:13

CONCLUSION

OSA may be present in 20% of cases with depression.

This relation can vary with the general demographic and health characteristics of the research population and age, gender, and AHI.

Future clinical investigations should be conducted primarily in depressive patient groups regarding different subtypes of mood disorders.

Limitations of studies on mood disorders should be regarded in studies.

Diagnosis of the clinical entity requires psychiatric consultation.

In middle aged, obese patients with sleep problems diagnosed as mood disorders , OSAS should be investigated as a cause of depressive symptoms.

In the majority of the cases, depression and anxiety seem to be secondary to the medical condition, however, it should not be forgotten that mood disorders seen in OSAS may be due to a primary emotional state.

It is primarily important in depressive cases resistant to treatment.

OSA should be excluded in this case, because treatment of OSA not only increases the compliance to pharmacologic antidepressants, but also increases the treatment response for depression.

CPAP can improve depressive and anxiety symptoms, but there are a few long term follow-up studies investigating the efficiency of CPAP on mood.

If OSA is diagnosed in a depressive case, improvement in depressive symptoms can be observed with close follow-up .

Basic research is required investigating potential mechanisms by which both disorders interact and the association between depression and OSA.

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