Depression and Congestive Heart Failure

CHF MAY/JUNE 2003DEPRESSION AND CHF 163

The prevalence rates of depression in congestive heartfailure patients range from 24%–42%. Depression is agraded, independent risk factor for readmission to thehospital, functional decline, and mortality in patientswith congestive heart failure. Physicians can assess de-pression by using the SIG E CAPS + mood mnemonic,or any of a number of easily administered and scoredself-report inventories. Cognitive-behavior therapy is thepreferred psychological treatment. Cognitive-behaviortherapy emphasizes the reciprocal interactions amongphysiology, environmental events, thoughts, and behav-iors, and how these may be altered to produce changes inmood and behavior. Pharmacologically, the selectiveserotonin reuptake inhibitors are recommended, whereasthe tricyclic antidepressants are not recommended for de-pression in congestive heart failure patients. The combi-nation of a selective serotonin reuptake inhibitor withcognitive-behavior therapy is often the most effectivetreatment. (CHF. 2003;9:163–169) ©2003 CHF, Inc.

Thomas P. Guck, PhD; Gary N. Elsasser, PharmD;Michael G. Kavan, PhD; Eugene J. Barone, MDFrom the Department of Family Practice, CreightonUniversity School of Medicine, Omaha, NE

Address for correspondence:Thomas P. Guck, PhD, Department of Family Practice,Creighton University School of Medicine, 1319 Leaven-worth Street, Omaha, NE 68102E-mail: [email protected] received January 31, 2002;accepted March 6, 2002

Major depression has been reported in 15%–22% ofpatients suffering from acute cardiovascular dis-ease, with as many as 65% reporting some symp-toms of depression.1 Further, depression has beenwell established as an independent risk factor con-tributing to poorer outcome and mortality in pa-tients with coronary heart disease.2–4

The relationship between depression and congestiveheart failure (CHF) has only recently been examined.Somewhere between 2 and 3 million Americans sufferfrom CHF.5,6 Approximately 400,000 new cases ofCHF are diagnosed each year.7 The prevalence rates ofdepression in CHF samples range from 24%–42%.8,9

Vaccarino et al.10 found that 35%, 33.5%, and 9% of asample of CHF patients 50 years of age or older re-ported mild, moderate, or severe depression, respec-tively. Jiang and colleagues11 reported that 13.9% of374 CHF patients 18 years or older met criteria for amajor depressive disorder, while 35.3% of the samplereported Beck depression scores of 10 or higher.

Depression has been found to be significantly relat-ed to reduced functional status, higher readmissionrates, and increased mortality in CHF patients. A re-cent study found a strong and graded relationship be-tween the severity of depressive symptoms at baselineand functional decline and death at 6 months follow-up. The strong relationship remained even after statis-tical adjustment for demographic factors, medical his-tory, baseline functional status, and clinical severity.10

Another study found that major depression was associ-ated with increased readmission and mortality at 3-month and 1-year follow-up, independently of age,New York Heart Association class, baseline ejectionfraction, and ischemic etiology of CHF. CHF patientswho had major depression were more than twice aslikely as nondepressed patients to be readmitted ordie.11 Clearly, these recent findings provide strong evi-dence that depressive symptoms are an independentrisk factor for patients with CHF, just as they are forpatients with coronary heart disease.

Due to the high prevalence of depression in patientswith CHF, it is important for physicians to accuratelyassess their patients for this disorder. Although figuresspecific to CHF are not available, it is estimated thatfewer than 25% of cardiac patients with major depres-sion are diagnosed as depressed, and only about onehalf of cardiac patients diagnosed as depressed re-ceived treatment for depression.12 Depression may beundiagnosed and untreated in cardiac patients

Depression and Congestive Heart Failure

CHF MAY/JUNE 2003164 DEPRESSION AND CHF

because: 1) physicians may be reluctant to ask; 2) pa-tients may be hesitant to report depressive symptoms;3) physicians and patients may mistakenly believe thatdepression is a normal reaction rather than a more se-rious but treatable disorder; and 4) many symptoms,such as fatigue, low energy, sleep disturbances, weightloss or gain, and concentration and memory problems,which are common in both CHF and depression, maybe diagnosed as symptomatic only of CHF.1,9

AssessmentA diagnosis of major depressive disorder requires thepresence of five or more of the following symptoms, asrecommended by The Diagnostic and Statistical Manualfor Mental Disorders (DSM), 4th Edition13: a) depressedmood; b) markedly diminished interest or pleasure inall, or nearly all, activities; c) significant weight loss orgain, or a decrease or increase in appetite; d) insom-nia or hypersomnia; e) psychomotor agitation or re-tardation; f) fatigue or loss of energy; g) feelings ofworthlessness or excessive or inappropriate guilt; h)diminished ability to think or concentrate, or indeci-siveness; and/or i) recurrent thoughts of death, suici-dal ideation, or suicide attempt. These symptomsmust be present nearly every day for a 2-week period,and at least one of the symptoms must be either de-pressed mood or loss of interest or pleasure. Thesesymptoms must represent a change from previousfunctioning, resulting in social, occupational, or otherlife impairment, and they cannot be the direct resultof a substance, medical condition, or bereavement.The mnemonic SIG E CAPS (Sleep, Interest, Guilt,Energy, Concentration, Appetite, Psychomotor, Sui-cide) + Mood, presented in Table I, is a useful way toremember these criteria.

Assessing for depression in the CHF patient requiresan understanding of the risk factors for depression.These risk factors include: female gender, previous his-tory of depression, family history of depression, lack ofsocial support, especially if living alone, and loss of

function or major life role. This information can be ac-quired in a complete interview with the patient and sig-nificant other. In addition, physicians may use any ofthe self-report measures presented in Table II when as-sessing depression in their patients with CHF.14–18 Anumber of these measures are readily available and canbe easily used within the medical setting. For example,the 20-item Zung Self-Rating Depression Scale,14 pre-sented in the Appendix, and the 21-item Beck Depres-sion Inventory15 cover most of the nine DSM-IV symp-tom categories for Major Depressive Episode. The Self-Rating Depression Scale is also available in over 30 lan-guages and thus has broad multicultural applications.The Geriatric Depression Inventory18 takes into ac-count the special considerations of older individuals.These instruments are sensitive to changes in depres-sion, and therefore are useful for monitoring treatment.Despite these benefits, the greatest risk associated withdepression-screening instruments involves the genera-tion of false-positives. This may result in harmful label-ing and unnecessary treatment or further testing. To re-duce this risk, patients with a positive depression scoreshould be interviewed more extensively to confirm orrule out depression.

Psychosocial TreatmentThe most effective psychosocial treatment for depres-sion is cognitive-behavior therapy (CBT). CBT assumespatients are active participants in treatment and thatthere are reciprocal interactions among environmentalevents, thoughts, behavior, and physiology. CBT em-phasizes short-term, problem-focused skill develop-ment in each of these key areas. With CBT, physiciansare encouraged to have patients monitor their thoughtsabout their condition and/or life events that may lead todepression. Patients are instructed to formulate alterna-tive ways to view the situation and then to take appro-priate action. For example, depressed patients withCHF often manifest a decreased perception of function-al ability despite objective evidence to the con-

Table I. SIG E CAPS Mnemonic: Symptoms of Depression

S Sleep (insomnia or hypersomnia)

I Interests (diminished interest or pleasure from activities)

G Guilt (excessive or inappropriate guilt; feelings of worthlessness)

E Energy (loss of energy or fatigue)

C Concentration (diminished concentration or indecisiveness)

A Appetite (decrease or increase in appetite; weight loss or gain)

P Psychomotor retardation/agitation

S Suicide (recurrent thoughts of death, suicidal ideation, or suicide attempt)


trary.9,11,19 Physicians can assess patients for irrationalthoughts and then assist them to confront thesethoughts by providing accurate information as to theirtrue functional abilities. Physicians can then encouragepatients to follow through with appropriate physicaland social activity. These efforts can improve patientself-efficacy, elicit better adherence, and lead to a morepositive approach to health and life.

Pharmacologic TreatmentWhen choosing an antidepressant for the CHF pa-tient, the physician must take into consideration effi-cacy and adverse effects. A consistent finding in the lit-erature is that there are few differences with respect toeffectiveness, not only among antidepressant agentswithin a particular class but also among classes ofagents. In addition, no differences have been found inthe treatment of mild to moderate depression.20,21

Consequently, efficacy issues may be a secondary con-cern, while the side effect profile of these agents andtheir potential for significant drug interactions be-come of prime importance. This is particularly true inCHF patients, as they are more likely to be elderlyand suffering from other comorbidities. In addition,the routine treatment of CHF requires the use of mul-tiple medications. Therefore, polypharmacy often isadvocated rather than avoided. All of these factors in-crease the likelihood of an antidepressant-related sideeffect or drug-drug interaction.22

Hypotension is one of the most notable adverse ef-fects associated with the antidepressants. The α-adrenergic blocking activity of the tricyclic antide-pressants (TCAs) can have a direct blood pressure-lowering effect.23 Differences exist with both thepropensity and the magnitude for hypotension amongthe TCAs, with nortriptyline having the least effect.The cardiac effects of the TCAs and other selected an-tidepressants are presented in Table III. In a study byGlassman et al.24 of 15 heart failure patients treated

with imipramine, seven developed severe orthostatichypotension. Furthermore, the potential for signifi-cant orthostatic blood pressure changes is exaggeratedby agents frequently employed to treat CHF. Theseepisodes of hypotension may, in turn, predispose theelderly CHF patient to falls and a higher frequency ofhip fractures. In the previously mentioned study, sixof the seven patients fell as a result of an orthostaticdrop in blood pressure. The atypical antidepressanttrazodone has also been noted to produce hypoten-sion, while the selective serotonin reuptake inhibitors(SSRIs) have minimal influence on blood pressure.Bupropion likewise does not significantly lower bloodpressure. However, bupropion and venlafaxine havebeen associated with the development of treatment-emergent hypertension in approximately 6% and 3%of patients, respectively.25,26

Cardiac conduction has also been problematic inpatients taking TCAs. Conduction is delayed and thiscan lead to significant morbidity in the presence of apre-existing conduction disturbance. Eighteen percentof patients with a pre-existing bundle branch blocktreated with therapeutic concentrations of imipraminedeveloped a worsening of their condition, either as 2:1atrioventricular block or a 25% increase in QRS dura-tion.27 Alteration in cardiac conduction with theSSRIs, even in the event of overdose, is negligible.Symptomatic bradycardia has been reported in pa-tients taking fluoxetine but has not been substantiatedin clinical trials.28 There was no evidence of QRSwidening or conduction delays in 234 cases of fluoxe-tine overdose reported to poison control centers.29

The occurrence of life-threatening arrhythmiashas long been noted as a complication of TCA over-dose, and their proarrhythmic potential has beenwell documented elsewhere. Atypical antidepres-sants, such as trazodone and bupropion, as well asthe SSRIs, have not been noted to produce arrhyth-mias when taken alone, even in the case of overdose.

Of particular importance to the patient with

Table II. Self-Report Instruments for Depression*

SCALE POPULATION ITEMS FORMAT DSM-IV

Beck Depression Inventory15 Adults 21 Multiple choice 8/9Center for Epidemiologic Studies–

Depression Scale16

Adults 20 Likert scale 7/9

General Health Questionnaire17** Adults 28 Likert scale 3/9Geriatric Depression Inventory18 Older Adults (>55

years)30 Yes/no 6/9

Zung Self-Rating Depression14

ScaleAdults 20 Likert scale 9/9

DSM=Diagnostic and Statistical Manual; *no self-report instrument listed in table assesses DSM-IV exclusion criteria.**Only the seven items from the Depression Subscale are included to determine DSM-IV coverage.

CHF is the effect of an antidepressant on myocar-dial contractility. The small number of trials involv-ing human subjects has not demonstrated a signifi-cant detriment to left ventricular function with anti-depressants as a whole.24,30–32

With the addition of each medication, the clini-cian must be cognizant of the potential for signifi-cant drug interactions. Table IV highlights some ofthe more common interactions with respect to anti-depressants and drugs commonly utilized in pa-tients with CHF. Interference with drug metabolismthrough an interaction with the cytochrome P450system is a common mechanism. Not all antidepres-sants are equal with respect to their involvement

with the CYP450 system. Fluvoxamine has thegreatest potential for drug interactions, as it inter-acts with all of the major P450 isoenzymes. Fluoxe-tine and paroxetine are potent inhibitors of the 2D6isoenzyme. This isoenzyme is intimately involved inthe metabolism of a number of important drugs andits inhibition can result in delays in metabolism,higher drug serum concentrations, and possible tox-icity of 2D6 substrates. Citalopram, sertraline, andvenlafaxine appear to have the least potential forsignificant P450 mediated interactions.

Despite the plethora of available agents for treatmentof depression, the presence of CHF and other cardio-vascular diseases complicates selection. Given the fre-


Table III. Cardiac Effects of Selected Antidepressants23,32–34

HYPOTENSIVE

EFFECTS

CARDIAC

CONDUCTION

HEART

RATE

PROARRHYTHMIC

EFFECTS

Tricyclic antidepressants Amitriptyline (Elavil, others) Imipramine (Tofranil, others) Nortriptyline (Pamelor)

+++++++

+++++++++

++++++

+++++++++++

Atypical antidepressants Buproprion (Wellbutrin) Trazodone (Desyrel) Nefazadone (Serzone)

0/++++++

00/++

+00

0++0

Serotonin reuptake inhibitors Fluoxetine (Prozac) Sertraline (Zoloft) Paroxetine (Paxil) Fluvoxamine (Luvox) Citalopram (Celexa)

00000/+

0/–000?

––0–0

00000/+*

Phenethylamine Venlafaxine (Effexor) 0** + 0/+ 0/+*Fatalities associated with suicide implicated arrhythmias as a possible cause of death; **can produce a sustainedincrease in blood pressure; periodic monitoring is recommended

Table IV. Antidepressant Drug Interactions 23,35–39

INTERACTING DRUG ANTIDEPRESSANT POTENTIAL EFFECT AND MANAGEMENT

Clonidine

Quinidine, flecainide,encainide, verapamil

Warfarin

Metoprolol, propranolol

HMG-CoA reductase inhibitors,diltiazem, nifedipine, valsartan,irbesartan, losartan

TCAs

TCAs, fluvoxamine, fluoxetine

TCAs, fluoxetine, paroxetine,sertraline, fluvoxamine

Fluoxetine

Fluvoxamine

Hypertensive crisis; avoid coadministration

Prolonged QT interval; avoid coadministration

Elevates prothrombin time; monitor INR

Bradycardia; monitor heart rate

Inhibits metabolism; avoid coadministration

TCAs=tricyclic antidepressants; HMG-CoA=3-hydroxy-3-methylglutaryl coenzyme A; INR=international normalized ratio

quency of TCA-related side effects, the SSRIs should beconsidered as preferred therapy. Further considerationshould be given to an agent with the least potential forsignificant interactions with drugs commonly used inthe treatment of CHF and other concomitant illnesses.

General Treatment ConsiderationsCBT might be considered if any of the following condi-tions exist: 1) depression is not severe; 2) depression isnot chronic; 3) psychotic features are absent; 4) a previ-ous response to CBT was positive; 5) CBT services areavailable; 6) a medical contraindication to medicationsexists; 7) recovery has not been achieved with medica-tion alone; and/or 8) complicated psychosocial circum-stances exist. Antidepressants might be considered withany of the following conditions: 1) depression is severe;

2) depression is chronic or recurrent; 3) psychotic fea-tures are present; 4) there has been a previous positiveresponse to medication; 5) there is a family history ofdepression; and/or 6) the patient is unable to do thework required in psychotherapy.40 When selecting anantidepressant the STEPS acronym can be helpful:Safety, Tolerability, Efficacy, Payment, and Simplicity.41

A combination of CBT and medication may be bestused when symptoms of depression are severe orchronic, fail to resolve with either therapy alone, and ifthere are significant psychosocial issues.

SummaryDepression is an independent risk factor for func-tional decline and death in CHF patients. Frequent-ly, depression is not assessed or treated adequatelyor at all. Clinicians may gather information on de-


Appendix. Zung Self-Rating Scale for Depression

Name________________________________

Age_____Sex_____Date_________________

None or alittle of thetime

Some of thetime

Good part ofthe time

Most or all ofthe time

1. I feel downhearted, blue and sad.

2. Morning is when I feel the best.

3. I have crying spells or feel like it.

4. I have trouble sleeping through the night.

5. I eat as much as I used to.

6. I enjoy looking at, talking to and beingwith attractive women/men.

7. I notice that I am losing weight.

8. I have trouble with constipation.

9. My heart beats faster than usual.

10. I get tired for no reason.

11. My mind is as clear as it used to be.

12. I find it easy to do the things I used to.

13. I am restless and can’t keep still.

14. I feel hopeful about the future.

15. I am more irritable than usual.

16. I find it easy to make decisions.

17. I feel that I am useful and needed.

18. My life is pretty full.

19. I feel that others would be better off ifI were dead.

20. I still enjoy the things I used to do.

SDS Raw Score ____

pression by using the SIG E CAPS mnemonic and/orby administering one of several self-report instru-ments. CBT is the most effective, skill-based psycho-logical treatment for depression. Though well de-signed studies are still needed, it would appear thatthe newer agents, particularly the SSRIs, are pre-ferred over the TCAs, which should be avoided whentreating depression in patients with CHF.

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Appendix. Key for Scoring the Self-Rating Depression Scale (SDS)a,b (continued)

SDSItem no.

None or a littleof the time

Some ofthe time

Good partof the time

Most or allof the time

1. 1 2 3 42. 4 3 2 13. 1 2 3 44. 1 2 3 45. 4 3 2 16. 4 3 2 17. 1 2 3 48. 1 2 3 49. 1 2 3 410. 1 2 3 411. 4 3 2 112. 4 3 2 113. 1 2 3 414. 4 3 2 115. 1 2 3 416. 4 3 2 117. 4 3 2 118. 4 3 2 119. 1 2 3 420. 4 3 2 1

aFormula for converting raw scores to SDS index: (Index = Raw Score Total × 100)Maximum Score of 80

bSDS Index Equivalent Clinical Global ImpressionsBelow 50 Within normal range50–59 Presence of minimal to mild depression60–69 Presence of moderate to marked depression70 and over Presence of severe to extreme depression

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Depression and Congestive Heart Failure