Depression, Anxiety and Obstructive Sleep Apnea - Clinical Implications

Introduction

There is a considerable overlap between symptoms of obstructive sleep apnea (OSA) and depression, resulting in under-diagnosis of OSA which is a common sleep disorder. Anxiety also develops in patients of OSA due to various reasons. This triad poses challenges to the clinician. The inter-relationships of the constituents of the triad and its clinical implications are discussed.

Obstructive Sleep Apnea

OSA is characterized by repetitive pharyngeal collapse in sleep, manifested chiefly by snoring and daytime sleepiness (OSA associated with excessive daytime sleepiness is commonly called OSAS -obstructive sleep apnea syndrome). This cyclical pharyngeal collapse results in cyclical hypoxia and cyclical stimulation of the sympathetic nervous system which is responsible for the adverse effects on various body systems. These consequences can be life threatening. Nocturnal symptoms mainly include loud and habitual snoring, choking, restless sleep, dry throat and nocturia. In elderly, nocturia and cognitive impairment are prominent symptoms. During daytime, OSA patients mainly experience fatigue, sleepiness and inability to concentrate. In fact, OSA patients may present with daytime symptoms only, as nocturnal symptoms are observed by the partner sharing the bedroom; who may consider snoring as a normal phenomenon. There is poor awareness of OSA in society at large with huge medical and economic burden on both themselves and the society. The delay in the diagnosis of OSAS is partly due to the nature of the syndrome as snoring and nocturnal respiratory pauses may not attract the attention of the partner sharing the bedroom. Therefore, better understanding of the disease and its complications are important.

Prevalence studies

(a) OSA - Although obstructive sleep apnea hypopnea syndrome can occur in any age group, the prevalence increases with age. The Wisconsin cohort study¹ reported that 24% of men and 9% of women had abnormal apnea hypopnea indices. In the US, the prevalence reported for obstructive sleep apnea hypopnea syndrome was 3% to 7% in adult men and 2% to 5% in adult women.² In India, Udwadia et al3 reported habitual snoring in 26% of the study population (middle aged urban Indian men) and the estimated prevalence of sleep-disordered breathing (SDB) was 19.5% and that of obstructive sleep apnea hypopnea syndrome (SDB with daytime hypersomnolence) was 7.5%. Several studies show that prevalence of sleep disordered breathing increases with age ranging from 5% to 15% in middle aged adults to approximately 24% in community dwelling older adults.⁴ Pattanaik S et al⁵ reported the prevalence of OSA in an Indian population using the STOP-BANG questionnaire as 13.7%. Also, the prevalence of OSA did not show any significant difference in various age groups and it was found that males had a higher prevalence of OSA as compared to females.

(b) OSA with Depression - An association between mood disturbances and anxiety disorder with OSAS has been shown in a large body of epidemiological studies.^6,7 Depression poses a major public health problem. Numbers of patients suffering from depression are rising day by day. Poongothai Subramani et al reported the prevalence of depression as 15.1%. This study involved 26,001 subjects belonging to urban south Indian population.⁸ Reddy and Chandrashekar⁹ in a meta-analysis reported the prevalence of depression to be 7.9 to 8.9 per thousand population and the prevalence rates were nearly twice in urban areas.

Clinical Presentations of OSA

The disorder can present as a sleep disorder or as a consequence of the disorder eg. hypertension, type 2 diabtes mellitus, anxiety, insomnia. The classical nocturnal symptoms of OSA include snoring often loud and habitual, witnessed apneas, choking, dyspnea, restlessness, diaphoresis, acid reflux, drooling, somniloquy, frequent change of posture in sleep, unable to sleep supine and bruxism. The daytime symptoms include sleepiness fatigue, morning headache, poor concentration, decreased libido or impotence, decreased attention, depression, decreased dexterity and personality changes. Mood swings and angry behaviour are often present, which may force the subject to seek psychiatric advice.

Consequences of OSA

OSA is a risk factor for several cardiometabolic disorders, hypertension (important cause for secondary hypertension), ischemic heart disease, insulin resistance, Type 2 diabetes, metabolic syndrome, dementia and stroke. The list of consequences is ever increasing. Recently ophthalmological consequences have been reported.¹⁰

OSA and Depression

Many patients present with both OSA and major depression together. The common symptoms which occur both in OSA and depression are (i) sleep disturbance (ii) daytime sleepiness (iii) fatigue (iv) decreased alertness (v) anxiety (vi) restlessness (vii) poor concentration (viii) weight gain. Overlapping symptoms like passivity, loss of facial expression and slowed psychomotor function can be observed both in patients of OSAS and depression. This could make diagnosis of either disorder difficult. Owing to excessive daytime sleep, most OSA patients are not alert and demonstrate poor concentration, factors which can lead to traffic accidents and workplace accidents.¹¹ OSA patients can present with major depressive symptoms. Also, they have higher prevalence of depression than in general population.¹² Major depressive disorder (MDD) carries with it an 18% prevalence of associated OSA while OSA has a 17.6% prevalence of MDD. A co-linear relationship exists between OSA and major depressive disorder.¹³ Depression is a risk factor for coronary artery disease. Coronary artery disease when it occurs with depression has a greater morbidity and mortality risk as compared to patients without depression.¹⁴ There is impaired cognition in patients of OSA. Yaffe K et al reported that older women with OSA present with greater decline in cognitive function than without OSA.¹⁵ OSAS may also present with atypical symptoms like morning headaches, anxiety and insomnia.

Nocturia is often present in patients with OSA which disturbs sleep. It is a prominent symptom of OSA in elderly. At the termination of apnea, there is increased venous return to the right atrium stimulating the release of atrial natriuretic peptide (ANP) causing natriuresis. Nocturia can occur at fixed times awakening the patient like an alarm clock.¹⁶

Patients suffering from OSA and major symptoms of depression respond to continuous positive airway pressure (CPAP) therapy. There is resolution of depressive symptoms gradually with improvement in quality of life.¹⁷ Elderly with symptoms of depression need to be evaluated for OSA before administering anti-depressant drugs. These drugs may not be necessary if OSA is treated with CPAP. Dementia in elderly may be reversible. Elderly often suffers from multiple diseases which may be consequences of OSA. This approach helps in reducing the number of drugs prescribed and also improves quality of life. An important cause for falls in elderly is administration of drugs like anti-depressants, sedative/hypnotic drugs. Finally, depression evident on face, may be a pointer to hypothyroidism which can be present along with OSA and depression.

OSA, Depression, Sleep Deprivation and TSH

The distinct 24-hour temporal patterns of endocrine function and metabolism demonstrates a high degree of temporal organization. During acute sleep deprivation, the overall diurnal pattern of TSH is maintained. However, the sleep related inhibition of TSH secretion is absent, resulting in elevated peak and 24 hour mean levels of TSH with acute sleep deprivation.¹⁸ This can have implications in sleep deprivation of modern life style and that due to an intrinsic sleep disorder. Apart from OSA, depression can mimic hypothyroidism. There are several manifestations of chronic partial sleep deprivation, the primary being sleepiness. Rapid eye movement (REM) sleep deprivation is often present in those who sleep late and wake up early. Fast eating in REM sleep deprived subjects has been reported by us.¹⁶ Increased appetite and fast eating promotes obesity.

Anxiety

Anxiety is defined as a feeling of worry, nervousness or unease about something with an uncertain outcome. Anxiety also refersto anticipation of a future concern and is more associated with muscle tension and avoidance behaviour. Insomnia either due to depression or OSA can result in anxiety. There is often reduction in REM sleep in OSA patients which can also result in anxiety.

Rezaeitalab F et al¹⁹ in a cross sectional study conducted to determine the prevalence of depression and anxiety in patients diagnosed with OSAS found that snoring was most frequent in patients suffering from OSA (66.3%), followed by anxiety (53.9%) and depression (46.1%). This study also revealed that the incidence of choking in patients suffering from anxiety was almost two times more than those without anxiety symptoms. Also high BMI was not only associated with severity of OSAS but also increased the frequency of anxiety. Regarding depression, 48% male and 33% of female OSAS patients had depressive symptoms.

There is a triangle of OSA, anxiety and depression which needs to be dissected at the bedside in all patients with depression. Detailed sleep history will be of considerable help.

Conclusion

There seems to be a close relation between OSAS, anxiety and depression. The emotional swings in patients with OSAS are possibly related to mood disorders and anxiety. Correction of OSAS by continuous positive airway pressure is highly rewarding. Psychiatrists need to appreciate these in their clinical pratice. Further studies are required to understand the complex relationship of OSAS, depression and anxiety.

Conflicts of Interest

None.