Australian and New Zealand Journal of Psychiatry Obstructive Sleep Apnoea and Depression −− Diagnostic and Treatment Implications Robert Kaplan Aust N Z J Psychiatry 1992 26: 586 DOI: 10.3109/00048679209072093

The online version of this article can be found at:

Published by:

On behalf of:

The Royal Australian and New Zealand College of Psychiatrists

Additional services and information for Australian and New Zealand Journal of Psychiatry can be found at: Email Alerts: Subscriptions: Reprints: Permissions: Citations:

>> Version of Record - Dec 1, 1992 What is This?

Downloaded from at GEORGE MASON UNIV on June 8, 2014


Sleep apnoea (OSA), a common sleep disorder, is well recognised as a cause of morbidity including psychiatric disorders. There is increasing recognition of the link between OSA and depression. Sleep changes are intrinsic to depressive disorders, most notably disturbances of REM sleep; OSA causes predominantly REM sleep disturbances. The neuro-vegetative features of depression are similar or identical to the symptoms of OSA an issue which has not achieved wide clinical recognition. A growing number of studies confirm the statistical link between the two conditions. The implications are twofold :OSA needs to be excluded in cases of chronic or resistant depression and treatment of OSA will make it easier to treat the primary depressive disorder. A new method of treatment for OSA, the Sullivan continuous positive airway pump (CPAP), raises the theoretical possibility of treating depression by this means as well.


Australian and New Zealand Journal of Psychiatry 1992; 26586-591 Speculation about the nature of sleep goes back many centuries. The emerging discipline of sleep medicine has added considerably to our knowledge of sleep and related disorders. Research by pioneers such as Kleitman, Azerinsky and Dement [ 11 has reached fulfilment in the last two decades. with the establishment of research societies, journals and non-invasive sleep laboratory studies. Knowledge about the pathophysiology and clinical features of sleep disorders has increased exponentially. Environmental factors or physical illness can affect sleep patterns [ 2 ] ;alternatively, most psychiatric illness leads to secondary sleep disturbance. However the role of primary sleep disorders in causing

The Liaison Clinic, 4/328 Crown Street, PO Box 1026, Wollongong, New South Wales Robert Kaplan MBChB, FRANZCP, Consultant Psychiatrist

psychiatric symptoms or illness is less well documented. Because of its prevalence and morbidity, Obstructive Sleep Apnoea (OSA) is of great importance in sleep medicine. As a result of media publicity [3], there is greater awareness about the presentation of OSA. The typical patient is an obese middle-aged man, who smokes, drinks, snores heavily and leads an sedentary lifestyle. The symptoms are disturbed nocturnal sleep, daytime sleepiness to the point of hypersomnolence, poor concentration and memory, and sexual dysfunction. While the association of severe OSA with paranoid psychosis 141has been documented, the link between O S A of mild to moderate severity and other psychiatric disorders, most notably of mood, has not received as much comment. It is the intention in this paper to examine this relationship and to discuss the diagnostic and treatment implications.

Downloaded from at GEORGE MASON UNIV on June 8, 2014


Obstructive sleep apnoea In OSA, the pathophysiology is due to an occluded upper airway with a reduced oropharyngeal lumen leading to cessation of respiration [ 5 ] . The causes of obstruction include: enlarged tonsils; nasal obstruction (e.g. septa1 deviation and rhinitis); deformities of the mandible (e.g. acromegaly, Pierre-Robins syndrome); enlargements of the tongue: and more systemic disorders, such as obesity, hyperthyroidism and the Pickwickian syndrome [6]. Any cause of impaired levels of consciousness, respiration, or muscle tone (notably alcohol and sedatives) exacerbates the problem. Voluntary muscles relax during sleep and are paralysed during REM (rapid eye movement) sleep. In OSA, as the intramural pressure increases, the airspace posterior to the soft palate narrows and obstructs, largely due to displacement of the soft palate and tongue [7]. Respiration will decrease to the point of cessation until brainstem reflexes are activated, restarting the breathing (and snoring) cycle. During apnoeas, blood oxygen saturation decreases, on occasions as low as 50% [8]. The duration of these intervals typically last 30 to 60 seconds and they can occur up to 60 times an hour. From a clinical perspective, the chief symptom, snoring, can be related to the above events. With any interference to sleep breathing, nasal respiration is replaced by mouth breathing. The natural obstruction created by the tongue and other pharyngeal structures means that inhaled air flows along a path at a very acute angle with corresponding turbulence. The margins of the soft palate and uvula, hanging down into the pharynx, have an effect similar to a reed valve, creating the acoustic vibrations known as snoring. The snoring reaches a peak in volume, followed by often audible intervals when breathing ceases, then re-starting and building up again in intensity. Apnoeas are often heralded by choking, gurgling, gasping and snorting sounds (initiated by diaphragmatic contractions) and alarmed spouses may wake up their partner, convinced that they have died in their sleep. Also associated is the tendency to have repeated episodes of brief awakenings during the night, often during the early hours of the morning when REM sleep intervals are predominant. Sufferers tend to ignore these episodes or assume they have wakened to urinate 191. They can awake with a start, have a sore or dry


throat, or be in a state of high arousal with a sensation of being suffocated or strangled [lo]. Sleep disturbances and parasomnias such as hypn a g o g i c h a l l u c i n a t i o n s , b r u x i s m , nocturnal myoclonus, sleep paralysis and REM behaviour disorder, are more common in OSA [ 1 I]. Sufferers wake in the mornings feeling dull, groggy, sluggish and apathetic. Explanations like “I feel I’m in a haze till midday”or “It takes me several hours to wake up ”are typical. Although patients will sleep longer at night if able to, this, if anything, makes them feel more tired during the day. It is one of the paradoxes of OSA that when patients have a shortened night’s sleep for whatever reason, they feel brighter and less tired the following day. Tiredness will increase as the day progresses, being at its worst in the afternoon and early evening: OSA is therefore a cause of the poskprandial torpor that sets in after the evening meal in front of the TV set. Patients struggle against an intense desire to sleep - often failing to resist this. Such sleeps are rarely refreshing and the desire may pass in an hour or two. In severe cases, the hypersomnolence may be irresistible, leading to sleeping during daytime activities. Recently, this has been linked with motor vehicle accidents, most notably truck driving (truck drivers are regarded as high risk group by virtue of their lifestyle) and will have increasing forensic importance [ 121. Other daytime symptoms of OSA do not receive as much recognition as they deserve. Impaired memory and concentration are common. In particular, there is poor short-term memory with the deficit, interestingly enough, being names, dates and numbers - at times almost resembling a nominal dysphasia [ 131. This is an important diagnostic clue. Young and middle-aged males, usually intelligent and competent, find this alarming and deal with it by denial because of fears of dementia. Sexual dysfunction in males usually resembles an organic impotence, with erectile and/or ejaculatory failure and reduction or absence of sexual desire [ 141. Physical changes are not uncommon. In addition to sore throat on arising. facial pain, headaches, puffy eyes and hearing difficulties can occur 191. Because of the disruption to the entire sleep cycle, especially in the later half, sleep phase disorders result in initial insomnia, that is, difficulty in falling asleep. This tends to obscure inquiry into the rest of the sleep cycle and is often inappropriately treated with hypnotics.

Downloaded from at GEORGE MASON UNIV on June 8, 2014



Weight gain, often a premorbid feature, may be exacerbated. This is largely due to the associated sluggishness and lack of physical activity but in part due to retention of fluid, which may remit dramatically with treatment of OSA.

OSA and depression Sleep is related to cardiovascular, thermal, respiratory, endocrine, circadian and sensory processes. Areas of the basal forebrain interact with cholinergic and aminergic areas of the brain stem. Affective disorder, which affects a wide range of structures and functions, alters sleep in a manner distinguishable from pseudodementia and may involve change in autonomic function [ 151. In major depressive disorder there are symptoms of middle insomnia, early morning wakening, diurnal mood swing, psychomotor retardation, poor concentration and memory, sexual dysfunction and melancholia. Sleep EEG changes in depression are consistently found in 90% of in-patients. These are: reduced REM latency, that is, time for the onset of the first REM sleep; and prolonging of REM sleep periods. Consequently, successful treatment of depression usually involves REM sleep suppression [ 161 and recurrence may be predictable by the so-called “delta sleep ratio” ~71. Recently, attention has been paid to the role of REM sleep deprivation for both diagnosis and treatment of depression. Since the sleep cycle involves the turning off of cortisol, and the turning on of growth hormone and prolactin [IS], it would appear that sleep abnormalities may affect neuroendocrine rhythms. These in turn could be related to the onset and intensity of affective illness. In their review 1191, Wu and Bunney assessed the evidence that prolonged wakefulness is antidepressogenic and complementary evidence that sleep is depressogenic. Their hypothesis is that sleep could release a substance associated with depression and that it is metabolised or stored during wakefulness, with a subsequent reduction in depression. This however is only one of many processes involved in CNS control of mood [20].

Linking OSA and depression The neuro-vegetative symptoms of major depressive disorder and OSA overlap considerably. First, both are associated with nocturnal awakenings. The distinction between middle insomnia and early morning wakening may not be questioned by clinicians. Patients with depression tend to wake in the early hours, and stay awake. In OSA, the tendency is towards multiple awakenings. Second, the other neuro-vegetative symptoms of depression are very similar to OSA and often impossible to distinguish clinically : - psychomotor retardation (confused with lethargy), - poor concentration and memory (similar in both), - reducedhbsent sexual drive (in both), and - diurnal mood swing (easy to confuse with hypersomnolence, which occurs in some cases of depression) (211. Not all patients lose weight in depression; 10-15% may gain weight [22]. OSA has a strong link with obesity, which is exacerbated by the apathy and lethargy. Another change typical of both OSA and depression is irritability and anger, leading to violence on occasions. Finally, OSA itself can cause depression [23]. Patients feel that they are in a continual tired haze, losing control of their lives and fearing early senility or madness. The mood in primary depression is likely to be deeper and more intense but not necessarily so, and the distinction can be difficult to make. In the author’s experience, the affect in OSA may seem blunted, less easy to empathise with or raising questions of neurotic or reactive disturbance. In severe cases, the mood may be labile, more typical of an organic brain syndrome [24]. In a study by Moskoet a/ [251, evaluating symptoms of a major affective disorder in patients presenting to a sleep disorder centre, 67% of patients reported an episode of depression within the previous 5 years, and 26% described themselves as depressed at presentation. The study suggests that sleep disorders should be considered in the differential diagnosis of affective disorders, and vice versa. As a corollary, a significant improvement of scores was noted with surgical treatment of those with OSA.

Downloaded from at GEORGE MASON UNIV on June 8, 2014


Polysomnography performed on 86 in-patients with affective disorders found that 15.1% had sleep apnoea 1261. The apnoea’s tended to be mild and were largely obstructive or mixed. The authors felt that routine polysomnography screening for OSA in affective disorders was not indicated. However, they did acknowledge that OSA and affective disorder can exist in the same patient, in which case the apnoeic symptoms are worse/more long standing in relation to other psychopathology. In another study by Reynolds ef al[27]. the authors reported depression to be frequent in sleep apnoea syndromes. In a sample of 25 consecutive male sleep apnoeics, 40% met Research Diagnostic Criteria for an affective disorder or for alcohol abuse. In a study of 55 patients with sleep apnoea [28], Millman and colleagues reported that 45% had SDS scores of over 50 or greater, consistent with depression. They conclude that OSA can produce prominent symptoms of depression that appear to be related to the severity of the underlying apnoea; furthermore, treatment of the OSA may result in the alleviation of these symptoms in certain patients. Consideration of the possibility of OSA may only emerge after an unsuccessful response to treatment of depression. Tricyclics may produce an early response that is usually not sustained. Tricyclics alleviate sleep disturbances related to depression (often before antidepressant effects are seen) and may prove effective in improving disturbed sleep related to sleep apnoea. Protriptyline, for example, has been used for symptomatic treatment of OSA on the basis of reducing REM sleep time [291. The reason that tricyclics produce a response in both OSA and depression can be explained by a model put forward by Hudson er al[30]postulating the “affective spectrum disorders” - a family of disorders characterised by a positive response to tricyclics. This includes such disparate conditions as irritable bowel syndrome, migraine, bulimia and cataplexy with depression. The model predicts that “a common physiological abnormality” will be found for all groups in the family. While sleep disturbance/change is not referred to in the paper, it is likely to be implicated. With time, it may be noted that the depressed patient’s complaints focus increasingly on sleepiness, poor memory, and appetite changes. Some patients previously categorised as having “atypical” depression would fall into this category. Patients seen in


mood disorder units, with intractable or chronic depression, would also include some cases of OSA.

Comment Sleep disorder psychiatric disorder The relation of sleep disturbance/disorder and psychiatric disturbance is biaxial with most attention hitherto being paid to the axis PD --->SD. A Medline review (post-1980) showed a scanty literature on the axis SD --->PD, with the exception of narcolepsy [311. Narcolepsy, a REM sleep disorder, is an under-diagnosed condition. The classical tetrad of symptoms and the tendency towards polymorphous psychiatric presentation are well described. The REM sleep changes and the response to “serotonergic” drugs, such as clomipramiiie, may have an heuristic association with depression and OSA. As far as other psychiatric conditions are concerned, there are a number of case reports about depression and psychosis due to severe OSA. Lee et al [24] comment that sleep apnoea can precipitate neuropsychiatric disorders and treatment thereof can lead to significant improvements in the management of bipolar affective disorder. OSA is widely distributed in the population, amongst both sexes and over a wide age range 1321. In younger populations, the prevalence is close to 10%; above the age of 60, it rises over 50% [33]. If 10% of these cases cause depressive disorders, this would imply that a number of misdiagnosed and mistreated patients are being seen in psychiatric practice. The role of OSA in mood disorders is more significant than hitherto appreciated. Awareness of the clinical features, and the distinction from affective disorders, will lead to higher recognition. Unlike mood disorders, the clinical diagnosis of OSA is confirmed by physical findings and special investigations [34]. Many patients are greatly relieved to have a precise physical explanation of their symptoms and this leads to a reduction in help-seeking behaviour. According to Mendelsonet al [ 171,OSA occurs with a higher incidence in patients with affective disorder, and the possibility should be explored that treating OSA can have benefits on cognitive and affective status. In most situations, treatment of both mood and OSA is needed, making management of the mood problem easier. As Akiskal and Lemmi [34] have commented, the presence of OSA can prevent full

Downloaded from at GEORGE MASON UNIV on June 8, 2014



recovery from major depressions; specific management will often render a resistant depression responsive to TCA's. Symptomatic treatment of upper airway obstruction should include attention to weight loss, stopping smoking and drinking, and inappropriate use of sedatives. Nasal obstruction can be easily cured by non-invasive or surgical methods [35]. A moderate improvement can occur with a two week trial of decongestant and cortisone nasal sprays. If these measures fail, or if the OSA is of moderate to severe intensity, then a polysomnogram is required. For psychiatrists who do not have experience with OSA, self-report questionnaires [36] can be useful in deciding which patients need further investigation. Treatment of OSA has been revolutionised by the Sullivan continuous positive airway pump (known as the CPAP) [37]. This is a unique non-invasive form of physical treatment. A column of air, admitted through a nasal catheter, acts as an internal splint to prevent the airway collapsing. This is now in wide usage and has virtually rendered the need for tracheotomy obsolete. In other cases, surgery on the nose or palate (uvulopalato-pharyngoplasty) may be indicated [38]. The International Classification of Sleep Disorders has recently had psychiatric recognition by being included in DSM-1 1 1R [39]. Studies to clarify the link between OSA and mood disorders will doubtless be undertaken in the next few years but there needs to be greater emphasis on recognition and treatment by psychiatrists. The CPAP can cure depression secondary to OSA : can it have a role in the treatment of primary depression ? Is there a role for other physical treatments of OSA in the management of depression as well'? For selected patients, an examination of the nasal passages and pharynx, a recommendation made by Lee and colleagues, is easily performed [24]. As awareness of OSA rises, it is anticipated that psychiatrists will include this examination more often on selected patients in future. As more cases of OSA and depression are diagnosed and treated by psychiatrists, knowledge about the intriguing link between the two disorders will doubtless lead to an expansion in our repertoire of treatments for affective disorders.

Acknowledgments Thanks to Dr Kwok Yan and Professor Mark Dickerson for assistance with the manuscript.

References 1. Benios GE. Feelings of fatigue and psychopathology : a conceptual history. Comprehensive Psychiatry 1990 3 1 : 140-15 1.

2. Sassin JF, Mitler MM. An historical perspective on sleep disorders. Psychiatric Clinics of North America 1987; 10:517-523. 3 . Usher R : The trouble with sleep. Time, 1989; June 26:42-46. 4. Berrettini WH. Paranoid psychosis and sleep apnoea syndrome. American Journal of Psychiatry 1980; 137:493-494. 5 . Edlund MJ, McNamara ME, Millman RP. Sleep apnoea and panic attacks. Comprehensive Psychiatry 1991; 32: 130-132. 6. Rodenstein DO, Dooms G, Thomas Y. Pharyngeal shape and dimensions in healthy subjects, snorers, and patients with obstructive sleep apnoea. Thorax 1990; 45:722-727. 7. Whyte KF, Allen MB, Jeffrey AA, Gould GA. Douglas NJ. Clinical features of the sleep apnoeahypopnoea syndrome. Quarterly Journal of Medicine 1989; 72:659-666. 8. Issa FG. Sullivan CE. Alcohol. snoring and sleep apnoea. Journal of Neurology Neurosurgery and Psychiatry 1982: 45: 53-59, 9. Homer RL, Shea SA, Mclvor J, Guz A. Pharyngeal size and shape during wakefulness and sleep in patients with obstructive sleep apnoea. Quarterly Journal of Medicine 1989; 72:7 19-735. 10. Guilleminault C. Obstructive sleep apnoea : the clinical syndrome and historical perspective. Medical Clinics of North Americal985: 69:1187-1203. 1 I . Editorial. Snoring. British Medical Journal 1991; 302:860-861. 12. Dement WC. Guillemenault C. Sleep apnoea syndrome and related sleep disorders. In: Williams RL, Karacan I, Moore CA, eds. Sleep disorders : diagnosis and treatment. New York: Wiley. 1987:47-72. 13. Guillemenault C. Obstructive sleep apnoea syndrome - a review. Psychiatric Clinics of North America 1987; 10:607-62 1. 14. Mellman TA, Uhde TW. Sleep panic attacks : new clinical findings and theoretical implications. American Journal of Psychiatry 1989: 149:1204-1207. 15. Bearpark, H. Cognitive and psychological changes in sleep apnoea syndrome before and after treatment with CPAP. Sleep Research 1987; 16:303. 16. Calesby L, Ware J. Evaluation of impotence : monitoring periodic erections penile during sleep. Psychiatric Clinics of North America 1987; 10:675-685. 7. Mendelson WB. Clinical neuropharmacology of sleep. Neurology Clinic.; 1990: 153-160. 8. Reynolds CF, Kupfer DJ. Sleep research in affective illncss : state of the art circa 1987. Sleep 1987; 10:199-215. 9. Kupfer DJ. Frank E, McEachran AB, Crochocinski VJ : Delta sleep ratio - a biological correlate of early recurrence in unipolar affective disorder. Archives of General Psychiatryl990; 47: I 1001105. 20. Wu JC, Bunney WE. The biological basis of an antidepressant response to sleep deprivation and relapse: review and hypothesis. American Journal of Psychiatry 1990; 147;14-21, 21. Cillin JC. Borbely AA. Sleep: a neurological window on affective disorders. Trends In Neurosciences 1985; 537-542. 22. Kwentus J, Schultz SC, Fairman P, Isrow L. Sleep apnoea : a review. Psychosomatics 1985; 26:7 13-724.

Downloaded from at GEORGE MASON UNIV on June 8, 2014


23. Stunkard AJ. Fernstrom MH. Price A. Frank E, Kupfer DJ. Direction of weight change in recurrent depression. Archives of General Psychiatry 1990: 47:857-860. 24. Lee S. Chiu HFK. Chen Char-Nie. Psychosis in sleep apnoea. Journal of the Royal Australian and New Zealand College of Psychiatrists 19x9;23:571-573. 25. Mosko S, Zetin M. Glen S, Garber D, DeAntonio M. Sassin J, McAnich J, Warren S. Self-reported depressive symptomatology, mood ratings. and treatment outcome in sleep disordered patients. Journal of Clinical Psychology 1989; 45:s1-60. 26. Reynolds CF. Coble PA, Spiker DG. Neil JF, Holzer BC, Kupfer DJ. Prevalence of sleep apnoea and nocturnal myoclonus in affective disorders. Journal of Nervous and Mental Disease 1982: 170:565-575. 27. Reynolds CF. Kupfer DJ, McEachran AB, Taska LS. Sewitch DE, Coble PA. Depressive psychopathology in male sleep apneics. Journal of Clinical Psychiatry 1984; 45:287-290. 28. Millman RP, Fogel BF. McNamara ME. Depression as a manifestation of obstructive sleep apnoea : reversal with positive airway pressure. Journal of Clinical Psychiatry 1989; 50:348-35 I . 29. Clark RW, Schmidt HS, Schaal SF. Sleep apnoea : treatment with protriptyline. Neurology 1979; 29: 1287- 1289. 30. Hudson JI. Pope GH. Affective spectrum disorder : does antidepressant response identify a family of disorders with a common pathophysiology? American Journal of Psychiatry 1990; 147:552-564.

59 1

31. Mitler M. Nelson S, Hajdukovic R. Narcolepsy, diagnosis, treatment and management. Psychiatric Clinics of North America, 1987; 10593-605. 32. Moran MG Thompson TL Nies AS. Sleep disorders in the elderly. American Journal of Psychiatry 1988; 145:1369-1378. 33. Bliwise DL. Yesavage JA, Tinklenber JR, Dement WC. Sleep apnoea in Alzheimer’s disease. Neurobiology of Aging 1989; 101343-346. 34. Akiskal H, Lemmi H. Sleep in affective disorders. In: Kryger MH, Roth T, Dement WC eds. Principles and practice of sleep medicine. New York: Saunders, 1989:413-430. 35. Tanaka Y, Honda Y. Nasal obstruction as a cause of decreased pC02 and disordered breathing during sleep. Journal of Applied Physiology 1989; 67,3:970-972. 36. Kapuniai LE. Andres DJ. Crowell DH, Pearce JW. Identifying sleep apnoea from self reports. Sleep 1988; 1 I :430-436. 37. Sullivan CE. Berthon-Jones M, Issa FG. Reversal of obstructive sleep apnoea by continuous positive airway pressure applied through the nares. Lancet 1981; 2362-865. 38. Harmon JD. Morgan W, Chaudhary B. Sleep apnoea : morbidity and mortality of surgical treatment. Southern Medical Journal 1989; 82:161-64. 39. American Psychiatric Association. Diagnostic and Statistic Manual of Mental Disorders 1987 (3rd Edition. Revised) (DSM1 1 1 R), Washington, DC; APA.

Downloaded from at GEORGE MASON UNIV on June 8, 2014

Obstructive sleep apnoea and depression--diagnostic and treatment implications.

Sleep apnoea (OSA), a common sleep disorder, is well recognised as a cause of morbidity including psychiatric disorders. There is increasing recogniti...
549KB Sizes 0 Downloads 0 Views