Psychological Depression and Cardiac Surgery:
A Comprehensive Review
Phillip J. Tully, PhD, MPsych (Clin)
Department of Surgery, Flinders Medical Centre and Flinders University of South Australia, Bedford Park, SA, Australia; The School of
Psychology, The University of Adelaide, Adelaide, Australia; The Discipline of Psychiatry, The University of Adelaide, Adelaide, SA,
Australia; and The Heart Failure Self Management Program, Ambulatory and Primary Healthcare Directorate, Hampstead
Rehabilitation Centre, Northfield, Australia
Presented at the Perfusion Down Under Winter Meeting 2012, Queenstown, New Zealand, August 2–5, 2012.
Abstract: The psychological and neurological impact of cardiac
surgery has been of keen empirical interest for more than
two decades although reports showing the prognostic influence
of depression on adverse outcomes lag behind the evidence
documented in heart failure, myocardial infarction, and unstable
angina. The paucity of research to date is surprising considering
that some pathophysiological mechanisms through which depres-
sion is hypothesized to affect coronary heart disease (e.g., plate-
let activation, the inflammatory system, dysrhythmias) are known
to be substantially influenced by the use of cardiopulmonary
bypass. As such, cardiac surgery may provide a suitable exem-
plar to better understand the psychiatric mechanisms of
cardiopathogenesis. The extant literature is comprehensively
reviewed with respect to the deleterious impact of depression
on cardiac and neuropsychological morbidity and mortality.
Research to date indicates that depression and major depressive
episodes increase major cardiovascular morbidity risk after car-
diac surgery. The association between depressive disorders and
incident delirium is of particular relevance to cardiac surgery
staff. Contemporary treatment intervention studies are also
described along with suggestions for future cardiac surgery
research. Keywords: depression, depressive disorder, coronary
artery bypass, coronary artery disease, antidepressive agents.
The impact of psychological depression in the etiology
and prognosis of coronary heart disease (CHD) has been
empirically described for more than two decades in myo-
cardial infarction literature. Some of the earliest reports of
cardiac surgery reported an association between cardiopul-
monary bypass use and psychoses related to the stressors of
surgery (1) and susceptibility to neurological insult and
neurocognitive changes (2). Although the psychological
side effects of cardiac surgery have long been of interest,
the prevalence and influence of depression on patients
undergoing cardiac surgery lag behind the evidence
documented in heart failure, myocardial infarction, and
acute coronary syndromes (3). Rather, in cardiac surgery,
an emphasis has been placed on preserving cognitive func-
tion but not mental health function per se. This is surprising
considering that approximately 2–3% of patients undergo-
ing cardiac surgery experience a form of psychological
depression immediately leading up to and after surgery
(4–8). Moreover, some pathophysiological mechanisms
through which depression is hypothesized to affect CHD
(platelet activation, the inflammatory system, dysrhyth-
mias) are known to be substantially influenced by the use
of cardiopulmonary bypass (9). Therefore, cardiac surgery
may provide a suitable exemplar to better understand psy-
chiatric mechanisms of cardiopathogenesis. An overview of
research documenting a deleterious impact of depression
on cardiac and neuropsychological morbidity and mortality
is described. Part of the review describes the pathophysio-
logical mechanisms as relevant. Finally, contemporary
Received for publication October 19, 2012; accepted November 15, 2012.
Address correspondence to: Phillip J. Tully, PhD, MPsych (Clin), Cardiac
and Thoracic Surgical Unit, Flinders Medical Centre, 3 Flinders Drive,
Bedford Park, SA 5042, Australia. E-mail: email@example.com
The author has stated that the author has reported no material, financial,
or other relationship with any healthcare-related business or other entity
whose products or services are discussed in this paper.
The Journal of ExtraCorporeal Technology
treatment intervention studies are described along with sug-
gestions for future cardiac surgery research.
DEPRESSION AMONG PATIENTS UNDERGOING
The term major depressive episode is used to refer to a
psychiatric diagnosis of unipolar depression episode as
distinct from bipolar depression, adjustment disorders,
and other types of mood disorders. The cardinal symptoms
of major depressive episode include depressed mood and/
or loss of interest or pleasure among other cognitive and
somatic symptoms described subsequently. The prevalence
of major depressive episode is 15–20% among patients
undergoing coronary artery bypass graft (CABG) surgery.
Comparatively, prevalence estimates among the general
population is 5–9% for females and 2–3% among males
(10). Collectively, research to date indicates that the num-
ber of patients affected by any depression (i.e., major, minor
or dysthymia) approximates between 20% and 30% of
patients undergoing CABG surgery depending on concur-
rent comorbidity rates, and a summary is provided in
Table 1. A notable limitation of these studies, however, is
the low sample size, highlighting a needfor further research.
Studies using self-report depression measures suggest
up to 50% of patients experience depressive symptoms
(9,11–13). Studies using self-report measures do not reflect
a clinical diagnosis of depression but, rather, depression
symptoms. Peterson and colleagues (14) explain that newly
developed depressive symptoms result from the stressors of
surgery that can produce an adjustment reaction or reactive-
type depression. In any case, as described further subse-
quently, identifying depression in the patient undergoing
CABG surgery is complicated by the somatic symptoms
experienced in CHD and the physical stressors of surgery.
The American Heart Association (15) recommended
the Patient Health Questionnaire (PHQ) (16) to screen
for depressive symptoms. In its expanded form, the PHQ-9
covers the full spectrum of symptoms reflective of a
major depressive episode, depicted in Table 2. As Carney
and Freedland point out (17), many different combina-
tions of symptoms fulfill criteria for a major depressive
episode. The American Heart Association and American
College of Cardiology Foundation (18) stated that a rea-
sonable level of evidence exists for depression screening,
stating it is reasonable in instances in which patients have
access to case management in collaboration with their pri-
not every cardiac surgery unit or medical center could fea-
sibly adopt a routine depression screening and follow-up
protocol. Indeed, close monitoring and follow-up for
patients describing thoughts of death or self-harm are
strongly recommended. Shemesh et al. (19) reported that
>12% of cardiovascular patients require immediate evalu-
ation of suicidal thought and intent, reiterating the practi-
cal requirements for referral pathways after assessment.
It has been suggested that a positive response to either
of the PHQ-2 questions should be followed up with
Table 1. Coronary artery bypass graft studies reporting prevalence of depression with structured diagnostic interview.
Reference Sample CharacteristicsDiagnosis Timing of AssessmentMajor Depression (%)Dysthymia (%)
563 open-heart surgery with CPB, Poland
309 CABG, US
260 CABG, Poland
158 CABG ± valve, Australia
124 CABG, Canada
50 CABG, Brazil
47 CABG, Italy
34 CABG, Germany
Post (1 month)
*Minor depression and dysthymia.
CABG, coronary artery bypass graft; CPB, cardiopulmonary bypass; CIS, Clinical Interview Schedule; MINI; MINI International Neuropsychiatric
Interview; NIMH, National Institute of Mental Health; Pre, preoperative period; Post, postoperative period; SCID, Structured Clinical Interview for
DSM Disorders; US, United States.
Table 2. Core depression symptoms assessed by the PHQ-9.
Over the past 2 weeks, how often have you been bothered by any of the
1. Little interest or pleasure in doing things
2. Feeling down, depressed, or hopeless
3. Trouble falling or staying asleep or sleeping too much
4. Feeling tired or having little energy
5. Poor appetite or overeating
6. Feeling bad about yourself or that you are a failure or have let
yourself or your family down
7. Trouble concentrating on things such as reading the newspaper or
8. Moving or speaking so slowly that other people could have noticed
or the opposite—being so fidgety or restless that you have been
moving around a lot more than usual
9. Thoughts that you would be better off dead of or hurting yourself in
Questions are scored: not at all = 0; several days = 1; more than half the
days = 2; nearly every day = 3. Refer to references (16,22).
PHQ, Patient Health Questionnaire.
PSYCHOLOGICAL DEPRESSION AND CARDIAC SURGERY 225
Table 3. Association between depression and mortality or cardiac outcome after cardiac surgery.
158 CAG ±
Median 2 years
n = 6 (3.8)
DASS ³ 10
6.24; 95% CI =1.18–32.98, p < .05
817 CAG, US
Mean 5.2 years
n = 122 (15)
LVEF, sex, age,
grafts 4 vs 2, DM,
adjusted HR 2.37
CES-D ³ 27
HR 1.08 (.70–1.67),
p = .723
89 CAG, US
n = 5 (5.6)
BDI > 10
Adjusted OR = 23.16
(95% CI =
1.38–389.08, p = .03
89 CAG, US
for MI or
n = 8 (9)
BDI ³ 10
<1 week 28.1%
History of MI,
c2= 4.24, p = .039
309 CAG, US
MI, PCTA, redo,
for angina, CHF,
n = 42 (14)
BDI ³ 10
MDD, LVEF, sex,
living alone, LOS,
Adjusted RR = 1.62
(.83–3.16), p = NR
309 CAG, US
MI, PCTA, redo,
for angina, CHF,
n = 42 (14)
LVEF, sex, living alone,
LOS, NYHA class,
Adjusted RR 2.31
(1.17–4.56) p = .01
309 CAG, US
Median 9.3 years
n = 62 (20.1)
Female sex, age, LVEF,
Adjusted HR 1.78
p = .04
309 CAG, US
Median 9.3 years
n = 117 (37.9)
Female sex, age, LVEF,
Adjusted HR 1.19
(.78–1.82), p = .42
119 CAG ±
CHD or surgery
n = 21 (17.9)
DASS-D ³ 10
(1.45–18.28), p = .01
HR = .97 (.25–3.79),
p = .96
Table 3. Continued.
232 CAG, AVR,
CAG ± AVR,
n = 21 (9.1)
HAM-D ³ 9
c2, p = .07
427 CAG, US
n = not stated
Unadjusted OR =
2.6; 95% CI =1.6–4.3, p < .05
n = 17 (9.4)
BDI > 10
NS, not reported
for angina, CHF,
n = 48 (26.2)
BDI > 10
infection, ICU days,
preoperative and post discharge
6th month STAI-T,6 month BDI scores
Adjusted HR = .980
(95% CI =
.917–1.047, p = .544)
440 CAG ± valve,
Median 5 years
n = 67 (15.2)
DASS-D ³ 10
Age, renal disease,
Adjusted HR = 1.61
(95% CI = .91–2.85),
p = .10
226 CAG, AUS
n = 72 (32)
DASS-D ³ 10
Anxiety, stress, age,
sex, LVEF, urgency,
lung disease, CHF,
DM, PVD, renal
disease, MI < 90 days,
HTN, CCS, psychoactive medication use
HR = .80 (.38–1.68),
p = .56
4 days postoperative
HR = 2.06 (.97–4.40),
p = .06
226 CAG, AUS
Median 4.9 years
MI, unstable angina,
n = 65 (28.8)
4 days postoperative
LVEF, age, respiratory
disease, CHF, renaldisease, DM
Adjusted HR = 1.36
(1.02–1.82), p = .04
AUS, Australia; BDI, Beck Depression Inventory; CAG, coronary artery graft; CCS, Canadian Cardiovascular Society; CES-D, Center for Epidemiological Studies-Depression; CHD, coronary
heart disease; CHF, congestive heart failure; CI, confidence interval; CPB, cardiopulmonary bypass time; CVA, cerebrovascular accident; DASS, depression, anxiety and stress scales; DIS,
diagnostic interview schedule; DM, diabetes mellitus; HAM-D, Hamilton Rating Scale for Depression; HR, hazard ratio; HUN, Hungary; HTN, hypertension; ICU, intensive care unit; LOS,
length of stay; LV, left ventricular; LVEF, left ventricular ejection fraction; MDD, major depressive disorder; MI, myocardial infarction; NYHA, New York heart Association; OR, odds ratio;
PCI, percutaneous coronary intervention; PCTA, percutaneous coronary transluminal angioplasty; PVD, peripheral vascular disease; RR, risk ratio; STAI-T, State Trait Anxiety Inventory-
Trait; US, United States.
PSYCHOLOGICAL DEPRESSION AND CARDIAC SURGERY 227
administration of the PHQ-9 with scores ³10 on the PHQ-
9 requiring an even more comprehensive assessment such
as by a psychiatrist or psychologist (15). As previously
mentioned, the somatic-laden
criteria overlap CHD symptoms. Specifically fatigue,
loss of appetite, psychomotor retardation, insomnia, and
difficulty concentrating can be the direct physiological
response to a medical illness and hospitalization (20) and
have been documented to significantly increase in the first
month after CABG surgery (21). Important risk factors
associated with a major depression episode among patients
undergoing CABG surgery include female gender, youn-
ger age, a previous depression episode, and evidence of
a family history of depression (8). Patients at high risk
might warrant closer monitoring during the perioperative
period with respect to depression and related psychiatric
sequelae such as delirium, as described subsequently.
Brief psychological reactions to the impending stressors
of surgery and the postoperative recovery period may
spontaneously remit over time, thus requiring no further
intervention. Watchful waiting, monitoring, and brief
support of suspected depressed cases might serve as a
useful strategy before implementing psychological inter-
vention. The developers of the PHQ-9 describe recom-
mendations for what constitutes depression remission
and treatment efficacy in primary care populations (22).
With respect to identification of a major depressive epi-
sode, the only study to use receiver operating characteris-
tics in patients undergoing CABG surgery showed that a
self-report measure of depression yielded an area under
thecurveof.811and 70.4%sensitivityand77.1% specific-
ity (23). Without more research, the use of self-report
measures to identify depression in CABG populations
remains largely unknown.
DEPRESSION AND MORBIDITY AFTER
CORONARY ARTERY BYPASS
The recent depression research among patients undergo-
ing CABG surgery is described in Table 3. The association
between depressive symptoms at the time of CABG sur-
gery and late mortality has been corroborated by several
studies (4,9,24). In a study of 309 patients undergoing
CABG surgery, Connerney et al. (4) reported that a major
depressive episode, but not depressive symptoms, was
associated with cardiac events at 1-year follow-up (risk
ratio, 2.31; 95% confidence interval [CI], 1.17–4.56)
adjusted for ejection fraction, female sex, extended length
of hospital stay, New York Heart Association class, num-
ber of vessels revascularized, and living alone. Blumenthal
et al. (24) reported a similar finding for person with mod-
erate to severe depression symptoms and increased mor-
tality risk (hazard ratio, 2.4; 95% CI, 1.2–4.2). Evidence
implicating depression in nonfatal morbidity outcomes has
been reported for hospital readmissions (11,25–27), major
cardiac events (4,28), and poorer quality of life (29). For
example, patients reporting depressive symptoms 1 month
after cardiac surgery were found to have a greater propor-
tion of arrhythmias and return of angina symptoms at
5-year follow-up (12). Scheier et al. (30) reported that
depressive symptoms were associated with surgery,
CHD, and wound infection hospital readmissions among
309 patients at 6-month follow-up. In a study of 963 patients
undergoing CABG, improvement in physical health at
6-month follow-up was lower among patients with depres-
sive symptoms after adjustment for cardiac severity and
anxiety, and stress suggested that only depression was con-
sistently associated with quality-of-life measures of vitality,
With respect to specific clusters of depression symptoms,
two recent studies support a prognostic association between
cognitive depression symptoms (e.g., pessimism, past-
failure, self-criticalness, worthlessness) with nearly twofold
greater risk of cardiac morbidity and mortality after CABG
surgery (28,32). These findings suggest that the adverse
effects of depression after CABG surgery are independent
of any somatic depressive symptoms or medical comor-
bidity and diverge from findings with patients with myocar-
dial infarction. However, Carney and Freedland’s recent
review (17) generally does not support that any particular
subtype of depression confers greater CHD morbidity risk.
Studies to date are not without their limitations such as
the low number of morbidity events experienced and lack
of control for conventional risk factors (28). Unfortu-
nately, these practices tend to bias the results in favor of
rejecting the null hypothesis and the resultant wide CIs
(e.g., 9,26,33) obscure the effect sizes and biological plau-
sibility of an effect for depression.
DEPRESSION AND NEUROPSYCHOLOGICAL
MORBIDITY AFTER CORONARY ARTERY
BYPASS GRAFT SURGERY
The cognitive outcomes from cardiac surgery and the
role for the perfusionist and cardiopulmonary bypass
circuit continue to be of empirical interest. A major depres-
sive episode also increases the risk for delirium among car-
diac surgery populations (34), which is the most common
psychiatric disorder observed on admission to healthcare
settings (35). A fluctuating delirious state is characterized
by disorientation to time, place, and persons; perceptual
disturbances; and hallucinations. The incidence of delirium
after cardiac surgery varies widely between 3.1% and 50%
(36–42). McAvay and colleagues (43) showed that dys-
phoric mood and hopelessness depressive symptoms were
228 P.J. TULLY
associated with incident delirium after hospitalization.
Kazmierski et al. (44) screened patients undergoing open
heart surgery for major depression episodes before surgery
and found more than a fourfold greater risk for delirium
after surgery (adjusted odds ratio [OR], 4.69; 95% CI, 1.84–
11.93). Our prognostic study with 158 patients undergoing
CABG (5) modified the diagnostic criteria for delirium to
reduce potential bias from overlapping delirium–depression
symptoms (e.g., concentration difficulties). Even with more
stringent delirium criteria, preoperative major depression
remained associated with incident delirium after CABG
surgery (5) (adjusted OR, 3.86; 95% CI, 1.42–10.52). Sur-
prisingly, parallel research concerning post-CABG neuro-
psychological function has produced predominantly null
findings or weak correlations between depression and cog-
nitive function in the short term (18,45) and long term
(13,46,47). At 6-month and 5-year follow-up, depression,
anxiety, and stress were not consistently associated with
neuropsychological dysfunction in regression analysis
among 75 patients undergoing CABG surgery and 36 con-
trol subjects (47). These results suggest that although
depression poses a risk for delirium, there is not a consistent
association with neuropsychological function.
MECHANISMS OF CARDIOPATHOGENESIS
An increased risk in CHD morbidity attributable to
emotional distress is explained by behavioral and biologi-
cal mechanisms. Epidemiological surveys suggest that
affective disorders are associated with larger body mass
index, hypertension, hypercholesterolemia, diabetes (48),
physical inactivity (49), and regular smoking and nicotine
dependence (50,51). Psychological distress has also been
associated with less concordance to exercise regimens and
smoking cessation 4 months after myocardial infarction
(52). The biological mechanisms of cardiopathogenesis
attributable to depression are multifactorial and include
the dysregulation of the hypothalamic–pituitary–adrenal
axis (53–55), reduced heart rate variability (56–58), altered
serotonergic pathways, inflammatory response (59), and
altered platelet aggregability (60). Reports among patients
undergoing CABG show that depression symptoms are
associated with peripheral vascular disease and diabetes
(14), impairment in left ventricular function (61), and
lower use of the left internal mammary artery (9).
INTERVENTION AND TREATMENT
With respect to pharmacological management, clini-
cians should be aware of the possible proarrhythmic and
cardiotoxic effects of tricyclic antidepressants in cardiac
patients and the common use of tricyclics such as amitrip-
tyline for pain management (62,63). Selective serotonin
reuptake inhibitors (SSRIs) on the other hand have been
hypothesized as safe among cardiac patients as a result of
the serotonin transporter affinity and attenuation of plate-
let functioning. Safety, tolerability and efficacy of SSRIs
among cardiac patients have been reported in some stud-
ies (45,64) but not others (65–67). Possible risks for
patients undergoing CABG surgery specifically include
increased bleeding attributable to SSRIs; however, this
has not been consistently supported (68–70). One study
suggested an increased mortality and readmission risk
after CABG surgery attributable to SSRIs (71) and others
have indicated greater morbidity but not mortality risk
(70). The largest study from a Swedish registry of 10,884
CABG procedures reported a 40–45% increased hazard
ratio in adjusted analyses for rehospitalization and death
respectively (72). Two recent systematic reviews of ran-
domized, controlled trials (RCTs) in patients with CHD
both corroborated SSRI and placebo were not associated
with reductions, or increased risk, in mortality (50,51).
A diverse range of behavioral and psychological RCT
interventions have been reported and cognitive–behavioral
therapy or collaborative care constitutes Class IIa evidence
(i.e., additional studies with focused objectives are needed,
and it is reasonable to administer treatment) (73). Freedland
et al. (74) compared cognitive behavior (n = 41) or support-
ive stress management (n = 42) vs. usual care (n = 40) and
found significant 3-month depression remission rates in the
treatment arms (71%, 57%, and 33%, respectively; p = .002).
Group differences were sustained at 9-month follow-up,
whereas cognitive–behavioral therapy intervention was
found to be superior with respect to measures of anxiety,
hopelessness, stress, and quality of life. Four sessions of
psychoeducation and skills training in a RCT treatment
group (n = 48) were associated with reduced depressive
symptoms 4 weeks after surgery by comparison to a usual
care group (n = 48) (53). A biweekly, nurse-led telephone-
8 months reported modest effect sizes (.30; 95% CI,
.17–.52) for mental health quality of life (54), and a trend
toward favorable cardiac hospital readmission rates. One
disconcerting finding for mental health professionals was
the low mental health service visits (4% intervention vs.
6% usual care), suggesting that patients undergoing
CABG surgery may not be suited to this particular form
of psychological support (55). Together with the findings
of lower cardiac events in patients randomized to a stress
intervention over 12 months in Finland (56), these studies
suggest that sustained depression remission can be achieved
with a diverse range of interventions. However, more com-
prehensive psychological interventions appear to be
required for clinically significant reductions in cardiovascu-
lar complications. Also, as the developers of the PHQ-9
point out (22), severe depression episodes require combina-
tions of antidepressants and psychotherapy; thus, neither
treatment modality can be recommended over the other.
PSYCHOLOGICAL DEPRESSION AND CARDIAC SURGERY 229
CONCLUSIONS AND FUTURE RESEARCH
Although a concerted effort has been made to improve
patient cognitive outcomes after cardiac surgery, far less
intervention has been invested in improving the mental
health outcomes of patients undergoing cardiac surgery.
Indeed, the interaction between depression pathophysiol-
ogy and effects of cardiopulmonary bypass is a potentially
fruitful avenue of research in cardiac surgery to better
understand mechanisms of psychiatric cardiopathogenesis.
Naturally, the rates of depression after cardiac surgery high-
light a requirement for appropriate identification, support,
and intervention efforts. One suggestion for future depres-
sion focused research in CABG surgery would be to inves-
tigate the impact of closely related psychological constructs,
particularly anxiety (57,58). Collaboration between psy-
chologists and psychiatrist specialists with cardiac surgeons,
cardiologists, and cardiac nurses may enhance the research
basis for improved patient outcomes. It is commonly hoped
that intervention might mitigate the deleterious impact of
depression on subsequent morbidity and mortality.
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