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Insomnia and Depression Prior to Myocardial Infarction

ROBERT M. CARNEY, PHD, KENNETH E. FREEDLAND, P H D , AND
ALLAN S. JAFFE, MD
Insomnia is common among patients who subsequently experience an acute myocardial
infarction (MI), and is a major symptom of psychiatric depression. The purpose of this study
was to determine what proportion of patients reporting insomnia prior to MI have depression.
Of 70 patients with a recent MI, 27 (39%) reported having had insomnia for two weeks or
longer prior to their MI, 13 of whom (48%) met diagnostic criteria for a major depressive
episode (MDE). MDE accounted for a significant proportion of the patients reporting insomnia
prior to MI (p < 0.0001). Furthermore, those patients with insomnia who did not meet diagnostic
criteria for MDE nevertheless had three times as many depressive symptoms, excluding sleep
disturbance, as did those patients who did not experience insomnia prior to their MI (p <
0.0009). The implications of this finding are discussed, as well as possible explanations for the
relationship between insomnia, depression, and subsequent MI.

INTRODUCTION

Many patients who have suffered acute
myocardial infarction (MIj report insomnia in the weeks or months prior to the
event (1-3). Nearly half of such patients
reported frequent nocturnal awakenings
during the six months prior to the event
in a recent study. This incidence is greater
than the 33% incidence reported for a
group of hospitalized patients with noncardiac medical illnesses or 26% for a
sample of medically healthy controls (1).
The increased frequency of insomnia was
present even after controlling for the use
of stimulants such as coffee and cigarettes.
The etiology of this insomnia is unclear.
From the Departments of Psychiatry and Medicine, Divisions of Behavioral Medicine and Cardiology, Washington University School of Medicine, St.
Louis, Missouri.
Address reprint requests to: Robert M. Carney,
Ph.D., Jewish Hospital of St. Louis, Department of
Psychiatry, 216 S. Kingshighway Boulevard, St.
Louis, MO 63110.
Received for publication March 6, 1990; revision
received July 17, 1990.

Psychosomatic Medicine 52:603-609 (1990)
0033-3174/9O/5206-O6O3$O2 00/0
Copyright © 1990 by the American Psycho

It could result from episodes of nocturnal
myocardial ischemia which are known to
occur in some persons with coronary artery disease [CAD] (4). Another possibility, however, is that insomnia prior to MI
may be a symptom of clinical depression
that we and others have documented to
be common in patients with coronary artery disease.
A variety of psychological complaints,
including anxiety, dysphoric mood, "vital
exhaustion," fatigue, and general malaise,
have been commonly reported prior to
acute MI (1, 2). Insomnia, fatigue, and
general malaise are classic symptoms of
psychiatric depression. Thus, it is possible
that depression could account for the high
prevalence of insomnia, "vital exhaustion," and general psychological distress
observed in patients prior to acute myocardial infarction. The purpose of this
study was to determine whether the presence of major depressive disorder accounts for a significant proportion of patients reporting insomnia for two weeks
or more prior to their myocardial infarction.
603

or severe mental impairment. The presence of a depressive disorder at the time of myocardial infarction was determined from the patients' retrospective report of the duration of the relevant symptoms that they had experienced prior to their myocardial infarction. (2) without history or evidence of a previous MI. Sixteen (23%) of the 70 patients met DSM-III-R criteria for a major depressive episode (MDE) during the same period. valvular heart disease (except mitral valve prolapse). four (29%) terminal. Modifications of the DIS included the addition of questions to determine the onset and duration of each symptom and questions regarding the specific type of insomnia (sleep onset. interval. Seven (54%) of these patients complained of early morning awakening with an inability to return to sleep (terminal insomnia). The first 70 patients who met these criteria and who agreed to participate were enrolled during the five to seven days immediately following the acute myocardial infarction. Two senior clinicians independently reviewed the interview results for each subject and rendered diagnoses according to DSM-II1-R criteria (10). Nine (64%) of these patients reported interval and terminal insomnia. The interview 604 was administered by two lay interviewers with extensive training and experience in administering the DIS. and frequent awakenings during the night (interval insomnia). Of the 54 patients who did not meet diagnostic criteria for MDE. The DIS is a structured interview developed by the National Institutes of Mental Health for epidemiologic studies of psychiatric disorder. patients were asked questions regarding the presence and time of onset of symptoms of medical and cardiovascular illnesses. Following the DIS. including angina. Infarction was documented in all patients by the presence of chest pain compatible with ischemia. and one (7%) sleep-onset insomnia alone. CARNEY et al. Patients were interviewed after agreeing to be enrolled in the study. (6) able to complete the psychiatric diagnostic interview and psychological testing. Thirteen of the 16 patients with MDE (81%) reported insomnia of at least two weeks' duration. RESULTS Twenty-seven (39%) of the 70 patients enrolled in the study reported insomnia for at least two weeks prior to acute infarction. or terminal) experienced by the patient. Three of the patients without MDE complained of hypersomPsychosomatic Medicine 52:603-609 (1990) . Patients admitted to the study had to be: (1) under 70 years of age. Procedure A modified version of the affective disorders section of the Diagnostic Interview Schedule (DIS) (6) was used to assess the presence of symptoms of depression and determine the presence and duration of sleep complaints. It has been shown in previous studies to be both reliable and valid (7-9). interval.R. (5) without present diagnosis of congestive heart failure. and a rising and falling pattern of MBcreatine kinase (MB-CK) characteristic of acute infarction with at least one level above the upper bound of the reference range (5). (4) without severe diabetes or other chronic medical illnesses. while six (46%) complained of these problems as well as a difficulty in falling asleep (sleep-onset insomnia). 14 (26%) complained of insomnia. (7) permitted by the patient's cardiologist to participate in the study. and sleep-onset. None of the patients met the diagnostic criteria for any of the other affective disorders described in the DSM-III-R nosology. None of the MDE patients reported hypersomnia. METHODS Subjects Subjects were recruited for this study from a sequential series of patients with documented acute myocardial infarction who were admitted to the Barnes Hospital Coronary Care Unit. (3) without history of angioplasty or coronary artery bypass surgery. All medical and demographic information was obtained from the patients' medical charts. One hundred percent agreement was achieved between the two clinicians. electrocardiographic changes. M.

Furthermore. Because there were only three patients who complained of hypersomnia.85 depressive symptoms during the same period (t = 3. while those patients without insomnia reported a mean of 0.INSOMNIA. df= 1.0001). The criteria for dysthymia Psychosomatic Medicine 52:603-609 (1990) require the presence of depressed mood and two or more additional depressive symptoms for at least six months. many reported depressive symptoms that had been present for several weeks prior to their myocardial infarction.36. DEPRESSION AND MYOCARDIAL INFARCTION nia. Thus.0009). The mean number of depressive symptoms excluding sleep disturbance present for two weeks or longer for patients without MDE who reported insomnia was 3. the remaining patients reporting insomnia had significantly more depressive symptoms than did those without insomnia. they were dropped from the remaining analyses. However. and to the 18% which we reported for CAD patients without myocardial infarction. We were able to compare the proportions of patients who were prescribed medications or who had known medical illnesses sometimes associated with insomnia. p < 0.004).. This rate is close to the 18% prevalence estimate of major depressive disorder reportedly recently by Schleifer et al. none of the patients without insomnia reported ever receiving psychiatric treatment (x2 = 8. p < 0.54. p < 0. Unlike some other psychiatric diagnostic systems (e.g. d/= 1.65. Demographic and medical characteristics of patients without MDE (with and without insomnia) and for patients with MDE were generally comparable. since adding them to the "noninsomnia" group could obscure important differences. Two of the patients were also taking anxiolytics during this time. as well as comparisons of additional demographic and medical information. DSM-III-R does not include a diagnosis of "minor" depression. Patients with insomnia who did 605 . (12) using the Research Diagnostic Criteria (11). 25% of the patients without MDE but with insomnia reported having received psychiatric treatment at some time in the past. df = 48. except for dysthymia. Twenty-three percent of the total sample of patients met the DSM-IIIR criteria for a major depressive episode. we were unable to obtain reliable information regarding caffeine consumption in the weeks preceding myocardial infarction. Unfortunately. DISCUSSION Nearly half of the patients who complained of insomnia for two weeks or longer prior to their acute myocardial infarction met criteria for a major depressive episode. The results of these analyses. All three of these patients were being treated for coronary artery disease prior to their myocardial infarction and were taking beta-blockers and other medications during the period of hypersomnia. are presented in Table 1. Although none of the patients without MDE met DSM-III-R criteria for dysthymia. we were unable to include them as a separate group in these analyses. The difference in the proportions of patients with insomnia between the depressed and nondepressed groups was statistically significant (x2 = 14. the Research Diagnostic Criteria) (11).02. Forty-eight percent of all patients reporting insomnia met DSM-III-R criteria for major depression. Additional analyses were planned in order to identify other potential causes of insomnia. although only 48% of the patients with insomnia met diagnostic criteria for MDE. except for a higher proportion of females in the MDE group. In contrast.

None of the patients who complained of insomnia had been previously diagnosed as having sleep apnea.9) 3.2) 30. or between those with or without insomnia.7(7. greater caffeine consumption in the weeks prior to the acute infarction cannot be excluded as a possible explanation for insomnia in at least some of the patients. CARNEY et al.R.2) 2. Thus. not meet full criteria for major depression nevertheless reported more than three times as many symptoms of depression than did patients with normal sleep patterns.7 8. They also were significantly more likely to have received psychiatric treatment in the past.2 4. Unfortunately.9 (9) 54.3 0. there was no difference in the proportion of women between those with or without insomnia. many of the patients with insomnia who did not have major depression may have experienced a "minor" or "subclinical" depression that included sleep disturbance.1 (10.71 2 0.96 NS 46% 14% 21% 40% 14% 0% 29% 7% 3% X == x 2 == x 2 == x 2 == x 2 == FETt X 2 == FET FET 56% 50% 38% 38% 25% 6% 25% 6% 6% 43% 21% 23% 58% 14% 0% 19% 3% 0% F = 0. M.6 NS 0. t FET.8(16. there was a higher proportion of women in the MDE group.02 NS NS NS NS NS NS NS * NS. not significant.5 1. TABLE 1. They were also no different from other patients with respect to age or any medical variable studied.8(15. one half of the total sample of women met criteria for a major depressive episode. their insomnia cannot easily be explained by the presence of other chronic medical illnesses or medications. Consistent with previous studies of MDE in patients with coronary artery disease (13). Means (Standard Deviations) and Frequencies of Selected Medical and Demographic Variables for MDE Patients and Non-MDE Patients with and without Insomnia Variables Mean age Mean number of alcoholic drinks weekly Mean number of cigarettes daily (current smokers) Current smokers Sex (% females) History of angina History of hypertension History of diabetes Chronic lung disease Receiving beta-blockers Receiving sleep medications Receiving psychiatric medications MDE N= 16 Non-MDE Insomnia N = 14 Non-MDE w/o Insomnia N = 37 P 53.1 (5)' F = 1. Thus.0) 27.5 0. we were not able to obtain reliable estimates of caffeine intake in the weeks preceeding the myocardial infarction.4 (8. Thus.6) F = 0. HowPsychosomatic Medicine 52:603-609 (1990) . No differences were found in the pres606 ence of anginal symptoms between those with or without MDE. Patients with insomnia were neither more nor less likely than the other patients to be taking medications that affect sleep.0(11.6) 4.8 (5) 52. In fact. Among patients without MDE.16 NS* NS 28. Fisher's exact test.

Nevertheless. Psychiatric patients with depression have higher rates of myocardial infarction than do patients with other psychiatric disorders (17). DEPRESSION AND MYOCARDIAL INFARCTION ever. secondary to or independent of depression. A recent study of insomnia in the general population reported by Ford and Kamerow (14) showed a strong relationship not only between insomnia and depression. and nearly two times the expected mortality due to cardiovascular disease (18). and include a follow-up assessment of psychiatric status. is of primary importance. The interview employed in this study focused primarily on affective disorders. we were unable to rule out the possibility that some patients had this disorder. The use of a retrospective self-report interview to assess the presence of depression and insomnia is a limitation of this study. For this reason. such as sleep EEG. the nature of the relationship between insomnia and depression and subsequent myocardial infarction remains unclear. Clearly. suggesting that sleep disturbance in many cases may be an early symptom of depression. Although depression may account for many cases of insomnia in persons who subsequently experience a myocardial infarction.INSOMNIA. 16). Unfortunately. and they have a greater REM density during each sleep cycle (23). Medically well persons with major depression tend to begin rapid eye movement (REM) sleep earlier than do nondepressed persons (20-22). it is still unclear whether depression is the crucial factor. that sleep disturbance associated with depression is of primary importance. If insomnia and depression play an etiologic role in MI. but also between insomnia and anxiety disorders. We have speculated previously that increased sympathetic tone associated with depression may be responsible for this relationship by placing additional stress on the cardiovascular system (15). Because of the difficulty in accurately predicting myocardial infarction. Many studies that have investigated the relationship between stages of sleep and the incidence of nocturnal myocardial ischemia have reported an in607 . it is difficult to study this question prospectively. Ford and Kamerow (14) also found that the risk of developing major depression within one year after the first interview was over 20 times greater for patients who continued reporting insomnia. patients with recent myocardial infarction may not accurately recall symptoms that occurred just prior to their infarction. The DIS has been carefully validated and has been used in medical as well as psychiatric populations to assess depressive symptoms. we did not obtain a follow-up interview of subjects in this study and thus have no information concerning how many of Psychosomatic Medicine 52:603-609 (1990) these patients subsequently developed a major depression. It is possible. even among high risk patients with known coronary disease. or may reflect an underlying process of affective disturbance. Our data must therefore be interpreted with caution. so it was not possible to determine whether other psychiatric disorders were also associated with some of the cases of insomnia. of documenting sleep disturbance. Depression is associated with an increased risk of myocardial infarction and other cardiac events (15. however. and depression and insomnia are highly prevalent in these patients. or if sleep disturbance. future studies of insomnia prior to an infarction should evaluate patients for other psychiatric disorders. it is also difficult to use more reliable means. or by accelerating the progression of atherosclerosis (19).

R. On the other hand. 58-59 2. and Peggy Boyd. Thus. Lung and BJood Institute. Judith SkaJa. but it may reduce their incidence of acute myocardial infarction. United States Public Health Service Grant No. Adriaantje teVeJde. a major depressive episode was diagnosed in nearly half of the patients who reported insomnia for at least two weeks prior to an acute myocardial infarction. although only a small number of patients reported having episodes of anginal pain at any time before their infarction. REFERENCES 1. In summary. particularly if associated with getting out of bed. March 19-22. Clearly. Appels A: Sleep complaints. depression may be significant in the etiology of myocardial infarction only because it is often associated with insomnia. and the National Research Demonstration Center Grant. CARNEY et al. Nevertheless. Perhaps silent ischemic episodes lead to sleeplessness. 1978 608 Psychosomatic Medicine 52:603-609 (1990) . it is possible that patients with depression are at greater risk for nocturnal ischemia as a result of some alteration of REM sleep. Adv Cardiol 2561-72. The possibility that ischemic episodes may in fact be the cause of sleep disturbance must also be considered. Washington DC. Although the mechanisms underlying the relationship between stages of sleep and nocturnal ischemic episodes are not well understood (26). vital exhaustion and depression. more research needs to be done to explore these various possibilities. (4) suggests that being awake. and myocardial infarction. SCOR in Ischemic Heart Disease. the diagnosis and treatment of major depression in patients at risk for myocardial infarction may be especially important. and especially getting out of bed. Supported in part by the Heart. Kuller L: Prodromata of sudden death and myocardial infarction. more often precedes the ischemic event. Proceedings of the Eighth Annual Scientific Session of The Society of Behavioral Medicine. The remaining cases of insomnia were associated with more than three times as many symptoms of depression than were reported by those patients without pre-MI insomnia. National Institutes of Health. HL17646. can produce silent ischemic episodes in patients with CAD (4). 1987. but a clear his- tory describing these symptoms was not elicited by the clinicians caring for the patients studied. Grant No. Falgar P. Schouten E. Laurie Smith. creased frequency of anginal episodes during REM sleep. at least in a subset of patients (24. 25). simply being awake at night. The authors wish to acknowledge the contributions to this study of Karen Clark. Not only can treating depression be expected to improve the quality of life for these individuals. The significance of the relationship between insomnia and depression and subsequent acute myocardial infarction remains unclear. although the study by Barry et al. M. 1 ROl HL4242701. We further cannot definitively exclude the possibility that some instances of insomnia could have been related to manifestations of congestive heart failure such as orthopnea and paroxysmal dyspnea. An increased rate of ischemic episodes could place the patient with sleep disturbance at greater risk for myocardial infarction or sudden cardiac death. Maryland. Bethesda.

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