Medical Causes of Disturbed Sleep in Psychiatric Patients

Jul 01, 2006

When assessing a sleep-related problem in a psychiatric patient, investigating all possible causes may be more helpful than assuming the complaint is a result of medication or the underlying condition.

July 2006, Vol. XXIII, No. 8

Difficulties with sleep, including insomnia, provide an opportunity for mental health professionals to venture outside the realms of their respective disciplines. Sleep-related complaints are highly prevalent in our patient populations. These complaints are often presumed to be secondary to coexisting psychiatric disorders. Less appreciated, however, is the potential role of comorbid, and often subtle, medical and neurologic disorders in the genesis of these complaints. The purpose of this article is to help practicing psychiatrists look "outside the box" when a patient reports insomnia. Instead of presuming that sleep difficulties are the result of a patient's primary psychiatric problem or medication used to manage the disorder, a step back to look at all the possibilities may be of greater benefit in producing a definitive resolution of the patient's complaints.


A subjective complaint, insomnia is characterized by repeated difficulty with sleep initiation, duration, consolidation, and quality. It occurs despite adequate time and opportunity for sleep, and is associated with daytime impairments.


Patients with insomnia rarely report profound daytime sleepiness, characterized by falling asleep during the day at inappropriate times. More often, their complaint is one of fatigue, lack of energy, mental dulling, and a sense of disorientation that they attribute to disturbed, restless, and unrefreshing sleep. Daytime sleepiness, often leading to mishaps and accidents, is a typical consequence of sleep deprivation, whereas insomnia is the inability to obtain sufficient sleep despite the opportunity to do so. The term sleep deprivation implies that too little time is available for sleep and that the opportunity for sleep is therefore curtailed.


Insomnia can be associated with several comorbid medical conditions, including diabetes, myocardial infarction (MI), heart failure, angina, any condition that causes chronic pain, prostate disorders, gastroesophageal reflux disease (GERD), and chronic obstructive pulmonary disease (COPD).


Many of these contribute directly and causally to the development of insomnia (

Table 1


Psychiatric Times

, July 2006, page 9]).


The relationships among chronic conditions, patient-reported comorbidities, and insomnia were examined using a questionnaire given to 1814 patients who had at least 1 of 5 chronic conditions (hypertension, diabetes, heart failure, MI, and depression) at baseline and again 2 years later. At baseline, mild insomnia was present in 34% of participants, and 16% had severe insomnia. After 2 years, 59% of patients with mild insomnia and 83% of patients with severe insomnia at baseline still had difficulty in sleeping. The odds ratios of conditions present at baseline corresponding to mild and severe insomnia, respectively, were depression, 2.6 and 8.2; subthreshold depression, 2.2 and 3.4; heart failure, 1.6 and 2.5; obstructive airway disease, 1.6 and 1.5; back problems, 1.4 and 1.5; hip impairment, 2.2 and 2.7; and prostate problems, 1.6 and 1.4.

Most of the associations noted at baseline were still present 2 years later.2 The investigators concluded that clinicians should not automatically ascribe insomnia to affective disorders but should also consider the possibility of cardiopulmonary disease, musculoskeletal conditions, and prostate disorders. These findings echo those by Klink and colleagues,4 who conducted a large survey of an adult population to examine the relationship among current complaints of insomnia and obesity, snoring, comorbid medical conditions, and documented complaints of insomnia a decade or more earlier. The strongest risk factor for a current problem with insomnia was a history of insomnia (odds ratio, 3.5). In addition, female gender (odds ratio, 1.5), advancing age (odds ratio, 1.3), snoring (odds ratio, 1.3), and multiple types of comorbid medical conditions (odds ratios, 1.1 to 1.7) also increased the risk of a current complaint of insomnia.

These studies underscore the importance of exploring comorbid medical conditions in patients with insomnia who also have depression, schizophrenia, or an anxiety disorder. Further, it is conceivable that the psychiatric condition of interest developed after a period of insomnia that was initially caused by a medical condition. Many studies that include longitudinal data now demonstrate that the presence of current insomnia predicts future psychiatric conditions, even many years later.5-11

Investigators using data from the National Institute of Mental Health Epidemiologic Catchment Area study questioned nearly 8000 communitysample respondents at baseline and at 1-year follow-up about sleep complaints and psychiatric symptoms. Of this group, 10.2% reported insomnia, and 3.2% reported hypersomnia at baseline. Of those persons with insomnia and hypersomnia, respectively, 40% and 46.5% also had a psychiatric disorder. Only 16.4% of those with no reported sleep problems had psychiatric morbidity. Compared to respondents without insomnia, patients with insomnia at both interviews had a much higher risk for major depression (odds ratio, 39.8). Of particular interest was the finding that the risk of new-onset major depression was much less for those who had insomnia that had resolved by the second visit (odds ratio, 1.6).5

In the Johns Hopkins Precursors Study, a long-term prospective study, investigators examined the relationship between self-reported sleep disturbances and subsequent clinical depression and psychiatric distress in 1053 men who attended medical school at The Johns Hopkins University between 1948 and 1964. Median follow-up was 34 years. The relative risk of new clinical depression developing was greater in those who reported insomnia in medical school (relative risk [RR], 2.0) compared with those who did not. The investigators concluded that insomnia in young male adults indicates greater risk for subsequent clinical depression.7

Restless legs syndrome

One of the most enigmatic medical conditions associated with insomnia is restless legs syndrome (RLS), a sensorimotor disorder with a strong genetic or hereditary component.


Patients experience an urge to move the limbs, especially the legs, and the sensation begins or worsens during periods of rest. Patients use numerous adjectives to describe the sensations, including "creepy-crawly," shock-like, grabbing, and even "Elvis legs."


The need to move the limbs abates, at least temporarily, if the patient gets up to walk or stretch. Symptoms are more pronounced in the evening or at night than during the day.


RLS can be confused with several other disorders. It is distinguished from periodic limb movement disorder (PLMD) by the fact that RLS is an office-based diagnosis, while PLMD is definitively diagnosed by polysomnography, during which repetitive bursts of electromyographic (EMG) activity are noted during the course of sleep, typically associated with brief arousals. However, 80% of patients with RLS also have PLMD. RLS is often difficult to distinguish from other medical and psychiatric disorders, such as peripheral neuropathy, whose symptoms may also worsen at night, yet whose symptoms typically do not improve with movement. Nocturnal leg cramps may improve with movement, but they usually are not associated with motor restlessness. Akathisia, a motor restlessness associated with the use of antidepressants, can also closely mimic RLS.

In a study conducted by Montplaisir and colleagues,14 94% of patients with RLS reported difficulty in falling asleep or staying asleep or both. Polysomnography revealed that as symptoms worsened, sleep latency was lengthened, the number of awakenings and arousals increased, and the efficiency of sleep decreased. The condition is common: In a telephone survey of 1800 adults conducted in Kentucky, the experience of restless legs on 5 or more nights per month was reported by 3% of participants aged 18 to 29 years, 10% of those aged 30 to 79 years, and 19% of those 80 years and older. The age-adjusted prevalence was 10.0%.15

Because of their insomnia, many of these patients have poor mental health characteristics, including difficulties with concentration and mental focus, a general feeling of being unwell, and feelings of despondency and depression. Patients with RLS may have suicidal thoughts, marital difficulties, and occupational deficits in addition to depression.14 These psychiatric symptoms and the insomnia complaints, therefore, are caused by a neurologic disorder, highlighting the pitfall of hastily ascribing insomnia to a psychiatric disorder. Massage, hot or cold baths, and distraction techniques have been used with mixed results in some patients with RLS. The only FDA-approved medication for the disorder is ropinirole.

Sleep-related breathing disorders

Obstructive sleep apnea syndrome (OSAS) is characterized by the cessation of air flow while the effort to breathe continues. Spells of apnea are often followed by arousals, with brief periods of increased electroencephalographic frequency from delta or theta to predominantly alpha frequency and/or increased EMG amplitude, which are thought to be important in terminating the apnea and restoring normal breathing. Rarely do these patients present with a complaint of choking or inability to breathe during sleep, which are more indicative of panic disorder and congestive heart failure. More typically, they present with disturbed and unrefreshing sleep, excessive daytime sleepiness, snoring, morning headache and disorientation, memory impairment, irritability, and depression.

Conservative estimates place the prevalence of sleep apnea at 2% to 4% of the population.16 Exacerbating factors include obesity, enlarged neck circumference, middle to older age, male gender, upper airway and craniofacial abnormalities, alcohol and sedative use, smoking, hypothyroidism, acromegaly, and a positive family history.16 Although certain physical characteristics—including upper body obesity, neck thickness (17 inches or greater in men; 16 inches or greater in women), hypertension, and obvious airway abnormalities—raise suspicions of OSAS in a patient who reports daytime sleepiness, irritability, or another suggestive symptom, the diagnosis is made in the sleep laboratory.

OSAS is more prevalent in certain populations, including patients with schizophrenia, of whom 40% to 50% referred for evaluation of sleep complaints have OSAS.17 The prevalence of the condition in other psychiatric populations, such as those with major depression, substance abuse, and bipolar disorder, is not known. The high rate among patients with schizophrenia may be associated with the high prevalence of obesity, a known risk factor for OSAS, in this group of patients. OSAS is associated with a number of risks, such as the development of arrhythmias, hypertension, hypercapnia, cerebrovascular disease, myocardial ischemia, cor pulmonale, and pulmonary hypertension.18,19 An increase in mortality has also been shown to be a function of an increasing apnea index, which is the frequency of apnea episodes per hour of sleep.20

Behavioral interventions for the management of OSAS include weight loss and avoidance of alcohol, sedatives, sleep deprivation, the supine sleeping position, and smoking. Medical interventions include continuous positive airway pressure (CPAP), bi-level positive airway pressure (BiPAP), and oral appliances. Success rates are highest with CPAP and BiPAP. Surgical alternatives attempt to diminish the redundant tissue in the upper airway or to reconstruct the upper airway and bypass it altogether. To date, none of these procedures have attained first-line status for the management of OSAS.

COPD is associated with several changes in sleep due to hypoxemia that results from increased airway resistance and pooling of secretions. During REM sleep, patients with COPD show decrements in oxyhemoglobin saturation that can last for 20 to 30 minutes. These changes are thought to lead to disturbance in sleep quality and continuity.

Sleep symptoms can also develop in patients with heart failure, who tend to experience sleep onset and maintenance insomnia owing to paroxysmal nocturnal dyspnea, and Cheyne-Stokes respiration (or central apnea) that can cause arousal. The repeated pattern of arousals can lead to poor sleep, daytime sleepiness, cognitive dysfunction, and depression.21 Insomnia in patients with heart failure can be treated successfully with CPAP and servoventilation. As treatment of heart failure leads to continued improvements in cardiac function, sleep symptoms also tend to improve.


Increasing age has profound effects on sleep and sleep quality. Significant decrements in deep sleep, increases in stage 1 shallow sleep, and an increase in wake time after sleep onset are among the most notable changes.22 Older persons tend to awaken with the urge to urinate more frequently than younger persons, but some evidence suggests that people who cite the need to urinate as a cause of insomnia may actually wake first, then decide to visit the bathroom. Pain, discomfort, cough, heartburn, and headache are also cited by older persons as reasons that sleep is interrupted.23

Any medical or neurologic condition that causes arousal can result in the complaint of insomnia. The list of potential disorders is huge, and includes conditions such as GERD, seizure disorders, strokes, and fibromyalgia.24 Numerous medications cause disturbed sleep. Diphenhydramine, which is often used to promote sleep, has not been studied adequately in this regard and can also cause sleep problems. In a study conducted among older hospitalized patients, disorientation, memory impairment, altered sleep-wake cycles, insomnia, delirium, and inattention were just a few of the problems that were more common among patients exposed to diphenhydramine than in those who were not exposed.25


Given the observation that sleep disturbances are often deeply enmeshed in many physical and psychiatric conditions, obtaining a complete history and physical examination is important in every patient who reports significant insomnia (Tables 2 [see Psychiatric Times, July 2006, page 10] and 3). Nevertheless, although clinical wisdom would suggest such an approach, the data available to substantiate the utility of a physical examination are scant.26 Blood tests, sleep questionnaires, sleep diaries, and psychological screening tests, such as the Beck Anxiety Inventory, can reveal important clues about the nature and/or origin of insomnia. Testing is driven by the differential diagnosis and may include polysomnography. Referral to a sleep specialist is prudent when OSAS is suspected or dangerous nocturnal behaviors are reported, daytime sleepiness is severe and dangerous, and when insomnia and its related symptoms fail to respond to appropriate behavioral or pharmacologic therapy.

Examination: Symptom- and diagnosis-driven

Testing: Driven by the differential diagnosis
• Laboratory tests
  – Chem 20, thyrotropin level, iron/total iron-binding capacity/ferritin, B12/folate levels
• Polysomnography indications
  – Obstructive sleep apnea, narcolepsy, restless legs syndrome, periodic limb movement disorder
  – Unexplained sleep disturbance, treatment failure


Beyond management of any underlying medical conditions, a variety of pharmaceutical and nonpharmaceutical treatments are available for sleep disorders. While a discussion of the available treatments is beyond the scope of this article, correction of inadequate sleep hygiene always deserves consideration when a patient reports insomnia. Attention to several principles of good sleep hygiene is part of any treatment for insomnia.

Many patients develop a habit of improper sleep scheduling, including frequent daytime napping, that interferes with sleep at night. Variable bedtimes and excessive time in bed may also contribute to scheduling problems. Routine use of alcohol, nicotine, and caffeine has well-characterized negative effects on sleep. Some patients have difficulty in getting to sleep if mentally stimulating, physically activating, or emotionally upsetting activities occur too close to bedtime. Working in bed, on a laptop computer for example, and an uncomfortable environment for sleeping also increase the risk of insomnia.1 All of these factors can be explored with the patient and the importance of good sleep hygiene can be emphasized.


When a significant problem with sleep is reported by a patient, the psychiatrist must think along the lines of multiple disorders, not only coexisting but also fomenting one another longitudinally. Insomnia may be an intermediary, rather than the primary condition. Medical disorders often present with psychiatric symptoms or can be comorbid with psychiatric disorders. Identification of the underlying cause before the initiation of management is key. Appropriate treatment of insomnia requires identification of the medical disorder that may have initiated the process, perhaps decades ago.

Dr Doghramji is professor of psychiatry at Jefferson Medical College and director of the sleep disorders center at Thomas Jefferson University Hospital, Philadelphia. He reports stock or other financial options with Cephalon, EI DuPont, Forest Laboratories, Medco Health, and Merck & Co, and is a consultant to or on the speaker's bureau or advisory board of Forest Laboratories, GlaxoSmithKline, Neurocrine Bioscience, Pfizer, PriCara (Ortho-McNeil), Sanofi, Sepracor, and Takeda.

Drugs Mentioned in This Article

Diphenhydramine (multiple brands)
Ropinirole (Requip)


1. American Sleep Disorders Association. The InternationalClassification of Sleep Disorders: Diagnosticand Coding Manual. 2nd ed. Westchester, Ill:The American Academy of Sleep Medicine; 2005:1.
2. Katz DA, McHorney CA. Clinical correlates of insomniain patients with chronic illness. Arch Intern Med.1998;158:1099-1107.
3. Richardson G, Doghramji K. Insomnia: specialistsedition. Clinical Symposia. 2005;55:2-39.
4. Klink ME, Quan SF, Kaltenborn WT, et al. Risk factorsassociated with complaints of insomnia in a generaladult population. Influence of previous complaints ofinsomnia. Arch Intern Med. 1992;152:1634-1637.
5. Ford DE, Kamerow DB. Epidemiologic study of sleepdisturbances and psychiatric disorders. An opportunityfor prevention? JAMA. 1989;262:1479-1484.
6. Breslau N, Roth T, Rosenthal L, et al. Sleep disturbanceand psychiatric disorders: a longitudinalepidemiological study of young adults. Biol Psychiatry.1996;39:411-418.
7. Chang PP, Ford DE, Mead LA, et al. Insomnia inyoung men and subsequent depression. The JohnsHopkins Precursors Study. 1997;146:105-114.
8. Livingston G, Blizard B, Mann A. Does sleep disturbancepredict depression in elderly people? A studyin inner London. Br J Gen Pract. 1993;43:445-448.
9. Weissman MM, Greenwald S, Nino-Murcia G. Themorbidity of insomnia uncomplicated by psychiatricdisorders. Gen Hosp Psychiatry. 1997;19:245-250.
10. Eaton WW, Badawi M, Melton B. Prodromes andprecursors: epidemiologic data for primary preventionof disorders with slow onset. Am J Psychiatry.1995;152:967-972.
11. Mallon L, Broman JE, Hetta J. Relationship betweeninsomnia, depression, and mortality: a 12-year follow-up of older adults in the community. IntPsychogeriatr. 2000;12:295-306.
12. Allen RP, Picchietti D, Hening WA, et al;International Restless Legs Syndrome Study Group.Restless legs syndrome: diagnostic criteria, specialconsiderations, and epidemiology. A report from therestless legs syndrome diagnosis and epidemiologyworkshop at the National Institutes of Health. SleepMed. 2003;4:101-119.
13. Winkelmann J, Wetter TC, Collado-Seidel V, etal. Clinical characteristics and frequency of the hereditaryrestless legs syndrome in a population of 300patients. Sleep. 2000;23:597-602.
14. Montplaisir J, Boucher S, Poirier G, et al. Clinical,polysomnographic, and genetic characteristics ofrestless legs syndrome: a study of 133 patients diagnosedwith new standard criteria. Mov Disord.1997;12:61-65.
15. Phillips B, Young T, Finn L, et al. Epidemiologyof restless legs symptoms in adults. Arch Intern Med2000;160:2137-2141.
16. Young T, Palta M, Dempsey J, et al. The occurrenceof sleep-disordered breathing among middleagedadults. N Engl J Med. 1993;328:1230-1235.
17. Winklemann JW. Schizophrenia, obesity, andobstructive sleep apnea. J Clin Psychiatry. 2001:61:8-11.
18. Yaggi HK, Concato J, Kernan WN, et al. Obstructivesleep apnea as a risk factor for stroke and death.N Engl J Med. 2005;353:2034-2041.
19. Arzt M, Young T, Finn L, et al. Association of sleepdisorderedbreathing and the occurrence of stroke.Am J Respir Crit Care Med. 2005;172;1447-1551.
20. He J, Kryger MH, Zorick FJ, et al. Mortality andapnea index in obstructive sleep apnea. Experiencein 385 male patients. Chest. 1988;94:9-14.
21. Lesman-Leegte I, Jaarsma T, Sanderman R, et al.Depressive symptoms are prominent among elderlyhospitalised heart failure patients. Eur J Heart Failure.2006;[Epub ahead of print].
22. Williams RL, Karacan I, Hursch CJ. EEG of HumanSleep: Clinical Applications. New York: Wiley;1974.
23. National Sleep Foundation. Sleep in America Poll.Available at:

. Accessed May 7, 2006.
24. Provini F, Lombardi C, Lugaresi E. Insomnia in neurologicaldiseases. Semin Neurol. 2005;25:81-89.
25. Agostini JV, Leo-Summers LS, Inouye SK.Cognitive and other adverse effects of diphenhydramineuse in hospitalized older patients. Arch InternMed. 2001;161:2091-2097.
26. Sateia MJ, Doghramji K, Hauri PJ, Morin CM.Evaluation of chronic insomnia. An AmericanAcademy of Sleep Medicine review. Sleep. 2000;23:243-308.
27. Schenck CH, Mahowald MW, Sack RL. Assessmentand management of insomnia. JAMA.2003;289:2475-2479.