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JNCI Monographs 2004 2004(32):57-71; doi:10.1093/jncimonographs/lgh014
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2004 © Oxford University Press

ARTICLE

Prevalence of Depression in Patients With Cancer

Mary Jane Massie

Correspondence to: Mary Jane Massie, MD, Department of Psychiatry and Behavioral Science, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 (e-mail: massiem{at}mskcc.org)


    ABSTRACT
 Top
 Notes
 Abstract
 Introduction
 Early Studies of Depression...
 Prevalence of Depression in...
 Assessment Methods
 Prevalence of Depression in...
 Prevalence of Depression in...
 Cancer Types Highly Associated...
 Gender Differences
 Depression by Cancer Type
 Markers and Correlates of...
 Quality of Life
 Conclusion
 References
 
Depression is the psychiatric syndrome that has received the most attention in individuals with cancer. The study of depression has been a challenge because symptoms occur on a broad spectrum that ranges from sadness to major affective disorder and because mood change is often difficult to evaluate when a patient is confronted by repeated threats to life, is receiving cancer treatments, is fatigued, or is experiencing pain. Although many research groups have assessed depression in cancer patients since the 1960s, the reported prevalence (major depression, 0%–38%; depression spectrum syndromes, 0%–58%) varies significantly because of varying conceptualizations of depression, different criteria used to define depression, differences in methodological approaches to the measurement of depression, and different populations studied. Depression is highly associated with oropharyngeal (22%–57%), pancreatic (33%–50%), breast (1.5%–46%), and lung (11%–44%) cancers. A less high prevalence of depression is reported in patients with other cancers, such as colon (13%–25%), gynecological (12%–23%), and lymphoma (8%–19%). This report reviews the prevalence of depression in cancer patients throughout the course of cancer.



    INTRODUCTION
 Top
 Notes
 Abstract
 Introduction
 Early Studies of Depression...
 Prevalence of Depression in...
 Assessment Methods
 Prevalence of Depression in...
 Prevalence of Depression in...
 Cancer Types Highly Associated...
 Gender Differences
 Depression by Cancer Type
 Markers and Correlates of...
 Quality of Life
 Conclusion
 References
 
Depression affects 121 million people and is among the leading causes of disability worldwide. Untreated depression leads to personal suffering and increased mortality. Although the prevalence of depression varies considerably globally, the most common symptoms of depression are depressed mood, insomnia, and fatigue, and depressed women out number depressed men 2 to 1. Americans have a one in five chance of developing depression in their lifetimes. Weissman and colleagues reported the lifetime rate of major (nonbipolar) depression to be 8%–17% for American women and 3.5%–8.6% for men (1). The 6-month prevalence of depression in adult Americans is 6%. The point prevalence of depression in "healthy community samples" is 4.5%–9.3% for women and 2.3%–3.2% for men.

Although major depression commonly has its onset in the late twenties, one in 10 children have persistent feelings of sadness, one of the hallmarks of depression. The point prevalence of depression in prepubertal children ranges from 1% to 3% and from 3% to 9% in adolescents (2); however, the lifetime prevalence through adolescence is estimated to be as high as 20% (3). Although there is no difference in the prevalence rate between sexes before puberty, females are at higher risk after puberty. Depression in children negatively affects a child's development and often manifests as behavioral problems or somatic complaints.

Depression commonly coexists with other syndromes and symptoms, such as anxiety disorders (e.g., posttraumatic stress disorder, panic disorder, generalized anxiety disorder) and pain. The National Comorbidity Survey data show that in a 12-month period, 51% of patients with major depressive disorders are diagnosed with an additional anxiety disorder. Patients with comorbid depression and anxiety disorders experience more severe symptoms, have a longer time to recovery, use more healthcare resources, and have poorer outcome than do those with a single disorder (4).

The symptoms of depression and personal suffering resulting from this disorder have been well described. The complex biological underpinnings result from disturbances in neurotransmitters and hypothalamic-pituitary-gonadal axis disregulation. The last two decades have produced exciting science and advances in our understanding of the neurobiology and pathophysiology of depression. Electrophysiologic studies, neuroimaging techniques (i.e., magnetic resonance imaging [MRI]; computed tomography [CT]; single photon emission computed tomography [SPECT]; positron emission tomography [PET]; functional magnetic resonance imaging [functional MRI]), and neuropsychologic studies are providing information about the neuroanatomical substrate of depression as we are learning more about how systemic disease effects vulnerability to depression.


    EARLY STUDIES OF DEPRESSION IN CANCER PATIENTS
 Top
 Notes
 Abstract
 Introduction
 Early Studies of Depression...
 Prevalence of Depression in...
 Assessment Methods
 Prevalence of Depression in...
 Prevalence of Depression in...
 Cancer Types Highly Associated...
 Gender Differences
 Depression by Cancer Type
 Markers and Correlates of...
 Quality of Life
 Conclusion
 References
 
When significant numbers of mental health professionals began working in oncology settings, they asked oncologists to describe their perceptions of the prevalence of psychiatric disorders in cancer patients. Common responses ranged from "everyone is depressed, and rightfully so, because they have cancer" to "no one is depressed; these are just normal people" and likely were a reflection of the respondent's mood and coping style.

One of the first efforts in psychooncology was to obtain objective data on the type and frequency of psychological problems in cancer patients. Using criteria from the Diagnostic and Statistical Manual of Mental Disorders-Third Edition (DSM-III) (5) classification of psychiatric disorders, the Psychosocial Collaborative Oncology Group determined the psychiatric disorders in 215 randomly selected hospitalized and ambulatory adult cancer patients in three cancer centers by structured clinical interview (6). Although 53% of the patients evaluated were adjusting normally to stress, the remainder (47%) had clinically apparently psychiatric disorders. Of this 47% with psychiatric disorders, more than two-thirds (68%) had adjustment disorders with depressed or anxious mood, 13% had a major depression, 8% had an organic mental disorder, 7% had a personality disorder, and 4% had a preexisting anxiety disorder. The authors concluded that nearly 90% of the psychiatric disorders observed were reactions to or manifestations of disease or treatment. Personality and anxiety disorders can complicate cancer treatment and were described as antecedent to the cancer diagnosis. The finding of 4% anxiety disorders was far below what would have been expected in the general population.

Thirty-nine percent of those who received a psychiatric diagnosis experienced significant pain. In contrast, only 19% of patients who did not receive a psychiatric diagnosis had significant pain. The psychiatric diagnosis of the patients with pain was predominately adjustment disorder with depressed or mixed mood (69%), but of note, 15% of patients with significant pain had symptoms of a major depression.

This early study conducted in 1983 was important for several reasons: first, it was a collaborative research effort by groups at three treatment facilities serving patient populations from different socioeconomic and cultural backgrounds (Baltimore, MD; New York City; and upstate New York); second, it was one of the first reviews of the prevalence of psychiatric disorders cancer patients providing useful data for mental health professionals to use to teach oncologists and oncology staff members about the psychological problems of cancer patients and the importance of hiring mental health professionals trained in the assessment and treatment of people with cancer; third, the researchers found support for an association between psychiatric morbidity and the presence of complaints, such as pain, and highlighted the importance of such correlations; and fourth, the findings helped mental health professionals and hospital administrators consider how best to staff clinical settings to effectively treat the psychological problems of cancer patients.

In two other early studies using both DSM-III criteria that were modified to eliminate physical symptoms characteristic of cancer and those that were validated by observer rating scales (Hamilton Rating Scale and Beck Depression Inventory [BDI]), Bukberg and colleagues (7) found a 42% (24% severe, 18% moderate) prevalence among 62 adults (30 female, 32 male) hospitalized on oncology units, and Plumb and Holland (8) found a 33% prevalence of depression among 80 (40 female, 40 male) hospitalized adults with advanced cancer.


    PREVALENCE OF DEPRESSION IN MEDICALLY ILL PATIENTS
 Top
 Notes
 Abstract
 Introduction
 Early Studies of Depression...
 Prevalence of Depression in...
 Assessment Methods
 Prevalence of Depression in...
 Prevalence of Depression in...
 Cancer Types Highly Associated...
 Gender Differences
 Depression by Cancer Type
 Markers and Correlates of...
 Quality of Life
 Conclusion
 References
 
To place depression in cancer patients in context, it is helpful to consider the prevalence of depression occurring in association with other medical illnesses. Early studies of depression in the medically ill used patient self-report and varied measures with a heterogeneous mix of hospitalized medical and surgical patients and reported prevalence rates ranging from 20% to 30% (9). A retrospective review of 263 000 patients from 327 hospitals found that 24% of those receiving a psychiatric consultation were depressed (10). However, Synder and colleagues (11), using both clinical interview and DSM-IIIR criteria, reported less depression (6%) but more adjustment disorder with depressed mood (14%) in 944 medically ill patients referred for psychiatric consultation.

Taking a different approach, Wells and colleagues (12) examined Epidemiological Catchment Area Study data regarding psychiatric disorders among persons with at least one of eight chronic medical conditions. Six-month and lifetime prevalence rates of psychiatric disorder were increased in those with medical illness (25% and 42% versus 17% and 33%). Thirteen percent of the chronically medically ill had a lifetime diagnosis of affective disorder, versus 8% of those free from medical illness.

Lifetime rates of depression in patients with neurological conditions range from 30% to 50% (Table 1) (13). In contrast to neurological disease, prevalence rates of depression in patients with other medical or systemic illnesses show a variable picture, with the highest rates observed with endocrine disturbances such as Cushing's disease and surprisingly low rates documented in end-stage renal disease (Table 2) (13). Overall, rates of depression in medical illness appear to be lower than those encountered in neurological illness. Some have hypothesized that this may be a function of the extent of the direct structural compromise of the central nervous system in the neurological conditions as opposed to the medical illnesses.


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Table 1. Secondary depressive disorders in selected neurological diseases*

 

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Table 2. Secondary depressive disorders in selected medical illnesses*

 
To what extent depression in the medically ill is a discrete entity, separate from depression arising in patients without comorbid physical illness is controversial. However, factors, including the absence of the usual female preponderance in affective disorder, no indication of genetic loading, treatment outcome, and long-term course, all favor the idea that these disorders are different.


    ASSESSMENT METHODS
 Top
 Notes
 Abstract
 Introduction
 Early Studies of Depression...
 Prevalence of Depression in...
 Assessment Methods
 Prevalence of Depression in...
 Prevalence of Depression in...
 Cancer Types Highly Associated...
 Gender Differences
 Depression by Cancer Type
 Markers and Correlates of...
 Quality of Life
 Conclusion
 References
 
Depression has been studied in patients with cancer using a range of assessment methods. The methods (self-report, brief screening instruments, and structured clinical interviews) commonly used are the Hospital Anxiety and Depression Scale (HADS), BDI, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, and DSM criteria. In general, the more narrowly the term is defined, the lower the prevalence of depression that is reported. Please see Dr. Trask's comprehensive discussion of the issues and challenges of assessment in this volume (13a).


    PREVALENCE OF DEPRESSION IN CANCER PATIENTS REFERRED FOR PSYCHIATRIC CONSULTATION
 Top
 Notes
 Abstract
 Introduction
 Early Studies of Depression...
 Prevalence of Depression in...
 Assessment Methods
 Prevalence of Depression in...
 Prevalence of Depression in...
 Cancer Types Highly Associated...
 Gender Differences
 Depression by Cancer Type
 Markers and Correlates of...
 Quality of Life
 Conclusion
 References
 
Studies of the prevalence of depression in cancer patients referred for psychiatric consultation are one source of information about depression in cancer patients. Although one might expect to find a higher rate of depression in those noted to be distressed and referred for psychiatric evaluation, the five studies of depression in oncology patients referred for psychiatric consultation report a prevalence of major depression ranging from 9% to 58% (Table 3) (1418). Although Massie and Holland (17) reported a low prevalence of depression (9%), an additional 26% of the hospitalized and ambulatory patients studied had adjustment disorder with depressed mood according to DSM-III. Lack of standardization in terms of population studied, disease site and stage, sample size, assessment instruments, cutoff score, type of interview, and diagnostic criteria employed (including major depression verus adjustment disorder with depressed mood versus depressive symptoms) all contributed to the large variance in reported prevalence among these studies.


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Table 3. Psychiatric consultation studies of depression in cancer patients*

 

    PREVALENCE OF DEPRESSION IN CANCER PATIENTS
 Top
 Notes
 Abstract
 Introduction
 Early Studies of Depression...
 Prevalence of Depression in...
 Assessment Methods
 Prevalence of Depression in...
 Prevalence of Depression in...
 Cancer Types Highly Associated...
 Gender Differences
 Depression by Cancer Type
 Markers and Correlates of...
 Quality of Life
 Conclusion
 References
 
Depression, the psychiatric syndrome that has received the most attention in individuals with cancer, has been a challenge to study because symptoms occur on a spectrum that ranges from sadness to major affective disorder and because mood change is often difficult to evaluate when a patient is confronted by repeated threats to life, is receiving cancer treatments, is fatigued, or is experiencing pain.

However, depression in cancer has been essential to study because comorbid illnesses complicate the treatment of both and may lead to poor adherence to treatment recommendations and to less desirable outcomes of both conditions. Watson and colleagues' 1999 report (19) that depression is linked to a reduced chance of survival in women with early stage breast cancer supports the need for further study.

Many research groups have assessed depression in cancer patients since the 1960s, and the reported prevalence (major depression, 0%-38%; depression spectrum syndromes, 0%-58%) varies significantly (Table 4) (68,20104). These databases were searched to retrieve references published between 1965 and 2002 on the prevalence of depression in cancer: Medline, PreMedline, Embase (Excerpta Medica), PsycINFO (Psychological Abstracts), and CINAHL (Cumulative Index to Nursing and Allied Health Literature). Articles in English were reviewed; Table 4 shows the studies that provided information about the number of patients interviewed and cancer type or types, evaluation methods, and percentage with depression or affective syndromes. Most authors reported patient sex and hospitalization status. Please see Dr. Lawrence's evidence report on cancer-related depression in this monograph (104a).


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Table 4. Representative studies of the prevalence of depression in cancer patients

 
In early, typically cross-sectional studies, the rate of depression was usually reported for adults with mixed types and stages of cancer. Depression was reported by severity (borderline, mild, moderate, severe, and extreme), by a symptom such as depressed mood, or by some of the diagnostic categories—major depression, minor depression, depressive disorder, adjustment disorder with depressed mood, or dysthymia—limiting our ability to compare studies. Although many research groups reported the gender and age (usually older) of study subjects, findings usually were not reported by demographic variables, and racial minorities were always underrepresented.

A limitation of many studies is that the effects of cancer treatments and non-cancer-related variables that affect mood often are not accounted for. For example, although the corticosteroids, vincristine, vinblastine, procarbazine, L-asparaginase, amphotericin B, interferon, and tamoxifen cause depression in some people, research groups usually have not presented data about cytotoxic drug or hormone use when describing their findings.

Although Newport and Nemeroff and McDaniel and colleagues (105107), acknowledged the many reasons why it is difficult to compare studies (different definitions of depression, cancer type or stage, time since diagnosis, varying cancer treatments, personal history of depression, and treatment for depression), importantly, they underscore several general observations. The severity of medical illness, as manifested by significant pain, declining performance status, or the need for ongoing treatment, is associated with a high risk of comorbid depression. Whether high rates of depression associated with some cancers are caused by the pathophysiologic effect of the tumor (i.e., paraneoplastic syndromes associated with breast, testis, or lung cancers), treatment effects, or other unidentified factors remains to be described. Cancer, exclusive of site, is associated with a rate of depression that is higher than in the general population.


    CANCER TYPES HIGHLY ASSOCIATED WITH DEPRESSION
 Top
 Notes
 Abstract
 Introduction
 Early Studies of Depression...
 Prevalence of Depression in...
 Assessment Methods
 Prevalence of Depression in...
 Prevalence of Depression in...
 Cancer Types Highly Associated...
 Gender Differences
 Depression by Cancer Type
 Markers and Correlates of...
 Quality of Life
 Conclusion
 References
 
Cancer types highly associated with depression include oropharyngeal (22%–57%) (36,100), pancreatic (33%–50%) (20,39), breast (1.5%–46%) (67,74), and lung (11%–44%) (84,86). A less high prevalence of depression is reported in patients with other cancers, such as colon (13%–25%) (20,21), gynecological (12%–23%) (37,53,79), and lymphoma (8%–19%) (40,41).


    GENDER DIFFERENCES
 Top
 Notes
 Abstract
 Introduction
 Early Studies of Depression...
 Prevalence of Depression in...
 Assessment Methods
 Prevalence of Depression in...
 Prevalence of Depression in...
 Cancer Types Highly Associated...
 Gender Differences
 Depression by Cancer Type
 Markers and Correlates of...
 Quality of Life
 Conclusion
 References
 
A meta-analysis of 58 studies conducted between 1980 and 1994 demonstrated that cancer patients were significantly more depressed than the general population and that there were significant differences among groups with regard to sex, age, and type of cancer (108). DeFlorio and Massie (109) reviewed 49 studies of the prevalence of depression in individuals with cancer with a particular emphasis on gender differences. Among the 49 studies they reviewed, 30 included both males and females. Six research groups did not examine (or report) gender differences; the remaining 23 found no gender differences in the prevalence of depression at a significance level of P<.05. However, 10 research groups found either gender differences in subsets of patients, nonsignificant trends, or differences in other parameters such as psychiatric morbidity, anxiety, and denial.

Four studies reported increased depression in the subsets of female patients. Craig and Abeloff (23) found a nonsignificant trend for females to have more psychological symptoms in a study of 30 (63% female) cancer patients. Lloyd and colleagues (30) found significantly higher psychiatric morbidity (anxiety and depression) among women in a study of 40 (38% female) hospitalized and ambulatory patients with different stages of lymphoma.

Pettingale and colleagues (46) studied 168 patients with breast cancer or with lymphoma and found that the women with lymphoma had a tendency to be more depressed and were more anxious than were men with lymphoma and women with breast cancer. Women were more anxious than men at 3 months and 1 year follow-up; women with breast cancer were more anxious than were other patients at 1 year. Men were more likely to believe their illness was not under their control.

Two studies reported more severe depression in men with cancer. Although Plumb and Holland (28) found no gender differences in overall depression in 80 (50% female) hospitalized patients with advanced cancer, more men than women (12 versus 5) were severely depressed. Males were more likely to have a history of poor impulse control, and females had a history of phobic symptoms. Holland and colleagues (38) found that men with either pancreatic or gastric cancer had depression and distress scores equal or slightly higher than women. Men with pancreatic cancer (but not women) had higher depression scores on the Profile of Mood States than men with gastric cancer. Whether this reflects a gender-based biological mechanism is unknown.

Three research groups reported mixed results depending on subsets of patients or diagnostic criteria. In their study of 808 cancer patients, Kathol and colleagues (51) using Research Diagnostic Criteria found that women were more depressed than men; however, this finding did not persist when DSM-III criteria were applied. Baile and colleagues (57) in a study of 45 (43% female) ambulatory patients with head and neck cancer found increased depression in women with early-stage disease and in men with late-stage disease.

Sneed and colleagues (60) found no gender differences in depression, anxiety, hostility, somatization, general psychological distress, or psychological well-being in 133 (67% female) patients with mixed cancer diagnoses. However, women with gynecological and breast cancer were found to have less depression, anxiety, hostility, somatization, and psychological distress, and greater psychological well-being, than women and men with other types of cancer. The authors believed this was secondary to their perception that their illness was less serious.

Fife and colleagues (110) found no significant differences in depression in male and female cancer patients; however, they found that women made a more positive adjustment to cancer. In a study comparing 46 (45% females) adult twins with a hematological malignancy with their identical twin bone marrow donor, Friedrich and colleagues (42) found that female cancer patients showed more depression and repression of feelings than their nonpatient female twins; no difference was found between the male patients and their nonpatient twins. There was no significant difference in depression between male and female cancer patients.


    DEPRESSION BY CANCER TYPE
 Top
 Notes
 Abstract
 Introduction
 Early Studies of Depression...
 Prevalence of Depression in...
 Assessment Methods
 Prevalence of Depression in...
 Prevalence of Depression in...
 Cancer Types Highly Associated...
 Gender Differences
 Depression by Cancer Type
 Markers and Correlates of...
 Quality of Life
 Conclusion
 References
 
Depression in Women With Breast Cancer

Breast cancer is the cancer most studied in terms of psychosocial effects, and not surprisingly, many studies of the prevalence of depression in cancer are studies of women with breast cancer. The reported prevalence ranges from 1.5% to 46%.

Longitudinal studies of depression in women with breast cancer. Some research groups have assessed the duration of psychological distress in breast cancer patients and survivors. In a prospective study of 160 women awaiting breast surgery, Morris and colleagues (24) found a 22% prevalence of depression in women who had a mastectomy for breast cancer. This prevalence persisted at 2 years compared with an 8% prevalence of depression in those with benign disease. Meyer and Aspergren (49) found a 30% rate of anxiety or depressive symptoms in a study of 58 ambulatory women who were 5 years posttreatment for breast cancer. Women who had partial mastectomy followed by radiation had better body image but similar amount of anxiety and depression symptoms and fear of recurrence as did women who had modified radical mastectomy.

Watson and colleagues (19) prospectively studied 578 women with early-stage breast cancer using the Mental Adjustment to Cancer Scale, Courtauld Emotional Control Scale, and HADS (4–12 weeks and 12 months after diagnosis) and found that a high helplessness/hopelessness score had a moderate effect on 5-year, event-free survival. However, a high score for depression was linked to a significantly reduced chance of survival. Although the authors cautioned that the latter result was based on a small number of patients and should be interpreted with caution, these findings are provocative and require further study.

Depression in breast cancer patients by surgical procedure. In many of these studies, research groups compared psychological outcomes of women undergoing different surgical procedures. Maraste and colleagues (59) found low levels of depression (1.5%) but higher levels of anxiety (14%) in 133 ambulatory breast cancer patients receiving radiotherapy after mastectomy or lumpectomy. Using a cutoff score of 10 on HADS, only two mastectomy patients (1.5%) were considered significantly depressed. If a HADS cutoff score of 8 was applied, then 6.7% (seven mastectomy patients, two conservative surgery patients) were depressed. In contrast, in a study of 123 women with breast cancer, Lasry and colleagues (43) found a high prevalence of depression (50% in mastectomy, 50% in lumpectomy with radiation versus 41% in lumpectomy only). These high percentages may have resulted from a use of a self-report depression scale (Center for Epidemiology Self-report Depression Scale [CES-D]) rather than a DSM-IIIR criteria-based clinical interview.

Maguire and colleagues (25) found 26% moderate or severe depression among women who had mastectomy compared with a 12% prevalence of depression in women with benign disease. Grandi and colleagues (44) reported a 22% prevalence of depression and postlumpectomy hospitalized stage II or III breast cancer patients. Similarly, Fallowfield and colleagues (50) found a 21% prevalence of major depression in women who had mastectomy and a 19% prevalence in those who had lumpectomy. Interestingly, there was less depression reported among women whose surgeons allowed them to choose the type of surgery (23% depression reported among women who chose mastectomy versus 38% who had mastectomy based on surgeons' recommendation).

Goldberg et al. (58) found a 32% prevalence of depression in 166 women scheduled for breast surgery that revealed cancer compared with a 24% prevalence of depression in 156 women who were found to have benign disease at the time of breast biopsy. The women with breast cancer were significantly less depressed (21% depressed) at 1 year follow-up. There was no significant difference in depression between mastectomy patients and those who had conservative surgery either preoperatively or at 6 and 12 months postoperatively.

Using the Diagnostic Interview Schedule, the CES-D, and the Hopkins Symptoms Checklist, Sneeuw and colleagues (67) found a 4.5% prevalence of major depression among 556 stage I and II breast cancer patients, 215 treated by radical mastectomy and 341 treated by breast-conserving therapy. At the time of evaluation all women were disease-free. No significant differences were found between women who received mastectomy as opposed to those who were conservatively treated or between patients treated recently (1–2 years before the interview) and those treated longer ago.

Prior History of Depression in Women With Breast Cancer

Few researchers have noted the time of onset of depression or correlated patients' history of depression with current depression or functioning. Notably, Pasacreta (82) reported findings on a homogenous sample of 79 women evaluated with the Diagnostic Interview Schedule and CES-D 3–7 months after their diagnosis of breast cancer. Nearly 18% of this sample had a past or current history of depression according to DSM-IIIR criteria. Women with elevated depressive symptoms had more physical symptom distress and more impaired functioning than subjects with depressive disorders and without depression.

In a cross-sectional study of 303 relatively young (mean age 46 years) women with early (stage I or II) breast cancer at 3 months after breast surgery using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and HADS, Kissane and colleagues (85) found that a past history of depression was associated with depression. They also noted that women with few psychological symptoms and good emotional adjustment to cancer may have refused participation in this study because these women were also being recruited into an intervention study.

Hormones and Depression in Women With Breast Cancer

Cathcart and colleagues (63) studied 257 women with lymph node-negative breast cancer, 155 of whom were treated with tamoxifen and 102 who were not. On the basis of clinical interview, 15% of the tamoxifen-treated group had depression compared with 3% of those not taking tamoxifen. Of the 23 women with depression, eight had mild symptoms and no change in tamoxifen dose was made, eight had significant depression requiring a dose reduction to relieve symptoms, and seven had to discontinue tamoxifen secondary to depression.

Fallowfield and colleagues (112) studied 488 British women, ages 33-67 years, who were at high familial risk of developing breast cancer in a longitudinal, randomized (tamoxifen 20 mg daily), placebo-controlled study. The participants' average General Health Questionnaire score was slightly lower than the average in a large British population study. Using four instruments, including the General Health Questionnaire-30, they found that 16.9% of women taking tamoxifen reported depression as having been somewhat/quite a bit/very much of a problem since taking part in the trial, in comparison with 21.4% of the placebo group. Although this study was of women at high risk (not women with breast cancer), it is of interest because placebo-treated patients had more depression than those taking tamoxifen.

Prevalence of Depression in Women With Advanced Breast Cancer

Studies evaluating the correlation of depression with disease progression in women with breast cancer have shown inconsistent results. Silberfarb and colleagues (26) found less depression in women with advanced breast cancer (4.5%) than in those with recurrent disease (15%). Physical disability did not relate to emotional disturbance. Hopwood and colleagues (54,55) reported that ambulatory advanced breast cancer patients had a 20% depression prevalence in one study and 9% depression in another. Jenkins and colleagues (56) found a 32% prevalence of depression in 22 women with local recurrence comparable with rates found with mastectomy. Pinder and colleagues (64) found a 13% prevalence of depression in advanced breast cancer patients (N = 139); increased levels of depression were found in those with lowest socioeconomic status, poorest performance status, and closer proximity to death.

Prevalence of Depression in Women With Gynecological Cancer

Evans and colleagues (37) studied 83 women with gynecologic cancer and found a 23% prevalence of depression and 24% prevalence of adjustment disorder with depressed mood. Krouse and Krouse (27) found more severe depression (prevalence not cited) and poor body image among gynecologic patients as compared with women with breast cancer undergoing mastectomy. Golden and others (53) found a 23% rate of major depression in 83 hospitalized women with cervical, endometrial, and vaginal cancer.

Prevalence of Depression in Patients With Orophargngeal Cancer

In a study of 107 newly diagnosed head and neck cancer patients, Kugaya and colleagues (94) reported that 16.8% had major depression or an adjustment disorder and 33.6% met the criteria for alcohol dependence, 6.5% for alcohol abuse, and 32.7% for nicotine dependence. An association of advanced cancer stage and living alone with psychological distress was also found to be significant. Baile and colleagues (57) found that alcohol use was prevalent in patients with both benign and malignant head and neck lesions.

In a study of negative and positive influences of social support on depression in patients with head and neck cancer, de Leeuw and colleagues (92) found that the availability of support led to fewer depressive symptoms, but the effect of received support was equivocal. In another report, de Leeuw and colleagues (102) assessed the predictive values of numerous pretreatment variables. Tumor stage, sex, depressive symptoms, openness to discuss cancer in the family, available support, received emotional support, tumor-related symptoms, and size of an informal social network were calculated 6 months to 3 years after treatment. They concluded that these variables could be used to accurately predict which head and neck cancer patients were more likely to become depressed up to 3 years after treatment.

In a study of 18 head and neck cancer patients, Hutton and Williams (103) found that the degree of depression and distress decreased with increasing age. Hammerlid and colleagues (87) studied 357 head and neck cancer patients and found that patients who reported a higher level of mental distress and frequently scored as a possible or probable case of psychiatric disorder were patients who had lower performance status and more advanced disease.

Prevalence of Depression in Patients With Lung Cancer

In a study of depression and anxiety in 129 lung cancer patients, before and after diagnosis, Montazeri and colleagues (86) found that 10% of patients had severe anxiety symptoms and 12% had symptoms of depression at first presentation to their chest physician. Depression, but not anxiety, increased by 10% at follow-up. Hopwood and Stephens (93) studied 987 lung cancer patients and found that depression was common and persistent and that it was more prevalent for those patients with more severe symptoms and functional limitations. Depression was more prevalent in patients with small cell lung cancer than those with non-small cell lung cancer (NSCLC).

In a study of 129 newly diagnosed NSCLC patients, using a clinical interview that generated a DSM-III diagnosis, Akechi and colleagues (98) reported a high prevalence of psychiatric disorders. The most common psychiatric disorder at baseline was nicotine dependence (67%), followed by adjustment disorders (14%), alcohol dependence (13%), and major depression (5%).

Kramer (88) used HADS as an assessment measure and reported that 50% of his sample of 60 patients with inoperable lung cancer were borderline depressed and 37% were depressed. Buccheri (84) reported that depressed lung cancer patients had a significantly lower rate of survival.

Prevalence of depression in patients undergoing stem-cell transplantation. Grassi and colleagues (77) studied 44 cancer inpatients with solid tumors undergoing autologous bone marrow transplant and found that depression and anxiety at the time of admission to the hospital and days spent in isolation were the best predictors of depression after the bone marrow transplant.

Loberiza and colleagues (113) prospectively studied 193 adults who received autologous or allogenic hematopoietic stem-cell transplantation, using the SF-36 and the Spitzer Quality of Life Index Scale. The authors controlled for patient, disease, and transplantation prognostic factors, but unfortunately, no standardized measure of depression was used. Thirty-five percent (N = 65) of the patients studied satisfied the authors' criteria for depressive syndrome. The authors reported that depressive symptoms among patients who have undergone stem-cell transplantation were associated with high mortality in the 6- to 12-month period after transplantation.

Prevalence of depression in patients with lymphoma, pancreatic, gastric, and colon cancer. There are fewer studies of the prevalence of depression in adults with lymphoma, pancreatic cancer (Table 5), gastric cancer (Table 6), and colon cancer. Wide ranges in the reported prevalence of depression are noted, but in general, patients with lymphoma, gastric cancer, or colon cancer have a less high prevalence of depression than those with pancreatic cancer. The high prevalence of depression in patients with pancreatic cancer is believed to be related to underlying biologic mechanisms.


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Table 5. Prevalence of depression in pancreatic cancer patients*

 

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Table 6. Prevalence of depression in gastric cancer patients*

 
Prevalence of Depression in Terminally Ill Patients

The reported prevalence of depression in patients with advanced cancer varies widely. Bukberg and colleagues (7) found that greater physical disability measured by the Karnofsky Rating Scale (the lower the score, the greater the disability) was associated with depression in their study of 62 patients with cancer. They found a 42% overall prevalence of depression, but a range of from 23% (in those with Karnofsky scores greater than 60) to 77% (in those with Karnofsky scores less than 40).

In the last 10 years, studies reporting the prevalence of depression in the terminally ill have ranged from 12.2% to 26%. In a study of 410 terminally ill cancer patients, De Walden-Galuszko (76) found 37% psychological morbidity, 18% of the 37% resulting from adjustment disorders (Table 7). Regardless of instrumentation (a single-item interview to DSMIII-R criteria), the prevalence of depression in the terminally ill falls within the range of the prevalence of depression in the general cancer population.


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Table 7. Prevalence of depression in terminally ill cancer patients*

 
In a recent study, Chochinov and colleagues (114) found that depression among terminally ill cancer patients is three times greater among patients who did not acknowledge their terminal prognosis. Breitbart and colleagues (90) found a 17% prevalence of depression and a 17% prevalence for a desire for hastened death in a study of 92 terminally ill cancer patients. Chochinov and colleagues (115) noted that hopelessness significantly contributed to the prediction of suicidal ideation in terminally ill cancer patients, even when the levels of depression were controlled.

Prevalence of Depression in Children With Cancer

Although there are fewer studies of depression in children and adolescents with cancer, in the last decade several groups have made significant contributions to our understanding of this issue (Table 8). It is commonly reported that children with cancer are no more depressed than are healthy children (80).


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Table 8. Prevalence of depression in children and adolescents with cancer*

 
Mulhern and colleagues (69) studied the severity of physical and depressive symptoms among 99 children with cancer (0.1-13 years from diagnosis) during a 6-week interval (evaluated at two time points: time 1 and 4-6 weeks later, to coincide with their clinic visit/treatment). Twenty-nine percent of the sample was black. Children were aged 8-16.8 years, with leukemia or solid tumors; all were in remission but were receiving treatment. Using the Children's Depression Inventory (CDI) and a modified CDI (excluding physical symptoms), the authors found that less than 10% of the children exhibited symptoms at or above the threshold for mild depression.

In their first report of their longitudinal study, Allen and colleagues (80) described their assessment of 42 adolescents (12–20 years of age) in the United Kingdom with various cancers (predominately sarcoma, followed by lymphoma, leukemia, and Wilms tumor) who completed the BDI and the State-Trait Anxiety Inventory on their first cancer outpatient visit (median time since diagnosis was 3 months). They found that adolescents with cancer were no more depressed (or anxious) than the control group (composed of 173 like-age students); girls in both groups were significantly more depressed than boys.

Using the CDI, Cavusoglu (100) studied children ages 9-13 years who were 1 or more years following initial cancer diagnosis (leukemia, lymphoma, sarcoma, retinoblastoma, and Wilms's tumor) and compared them with 50 healthy school children. Sixty-six percent of the children were in remission; 34% were being treated. Only 16% reported that they knew they had cancer; 62% could define (or point to) the location of the tumor. Twenty-two percent of the children with cancer had a score of 19 or higher on the depression scales; these scores were significantly higher than those of the healthy children. The children who stated they had cancer had higher depression scores.


    MARKERS AND CORRELATES OF DEPRESSION
 Top
 Notes
 Abstract
 Introduction
 Early Studies of Depression...
 Prevalence of Depression in...
 Assessment Methods
 Prevalence of Depression in...
 Prevalence of Depression in...
 Cancer Types Highly Associated...
 Gender Differences
 Depression by Cancer Type
 Markers and Correlates of...
 Quality of Life
 Conclusion
 References
 
Prevalence of Depression in Cancer Patients Who Experience Pain

Consistent with the findings of the 1983 Psychosocial Collaborative Oncology Group study, Chen and colleagues (91) reported that the prevalence of anxiety and depression was significantly higher for Taiwanese cancer patients with pain than for those without pain. In another recent study, Ciaramella and Poli (101) assessed depression among cancer patients using the Structured Clinical Interview for DSM-III-R, Endicott criteria, and Hamilton Depression Rating Scale. They found that depressed patients had more pain and metastasis than nondepressed patients but that depressed patients did not have more lifetime depression than nondepressed patients. Age and sex did not have any influence on the assessment of major depression among the 100 cancer patients studied.

Do Depressed Cancer Patients Receive Evaluation and Treatment?

Determining whether people who are found to be in need of further evaluation and treatment for depression receive it has been of interest to several groups. Payne and colleagues (116) evaluated 275 women with breast cancer attending ambulatory breast cancer clinics in two sites (New York City and Long Island, NY), using a visual analogue scale, HADS, and Brief Symptom Inventory. A subsegment of the sample was evaluated by use of the Structured Clinical Interview for DSM-III-R. The authors found that the patients at the cancer center most in need of psychiatric services had already been referred for evaluation. In contrast, Berard and colleagues (83) evaluated 456 outpatients with solid tumors (breast cancer, lymphoma, and head and neck cancer), using the HADS, BDI, and structured psychiatric interview, and found that only 14% of the patients identified as depressed had been identified and treated for depression. Using the HADS, Pascoe et al. (96) found that the majority of cancer patients with psychological distress were not receiving counseling or psychological treatment. All of these research groups addressed the need for routine screening for depression in oncology settings and for the implementation of cost-effective treatment for those who need psychiatric services.


    QUALITY OF LIFE
 Top
 Notes
 Abstract
 Introduction
 Early Studies of Depression...
 Prevalence of Depression in...
 Assessment Methods
 Prevalence of Depression in...
 Prevalence of Depression in...
 Cancer Types Highly Associated...
 Gender Differences
 Depression by Cancer Type
 Markers and Correlates of...
 Quality of Life
 Conclusion
 References
 
In a study predicting depression among male cancer patients, Godding and colleagues (72) reported that social support and quality of life accounted for 31.5% of the variance in Beck Depression Inventory scores. In another study, Grassi and colleagues (78) found significant correlation between depression scores and impairment in quality of life in advanced, home-care-assisted cancer patients.

Biological Markers

Several groups have recently studied the association between psychosocial factors, endocrine function, immune function, and survival and mediation by immune mechanisms. Cohen and colleagues (117) examined the association between hormonal profiles before the start of cancer treatment and subsequent psychological symptomatology in 27 patients with renal cell carcinoma and 18 patients with malignant melanoma. Patients were evaluated by Impact of Event Scale at three time points, and urine cortisol, norepinephrine, and epinephrine levels were measured at baseline. Both baseline cortisol and norepinephrine levels were positively associated with depression at follow-up. Sachs and colleagues (74) studied lymphokine-activated killer cell and natural killer cell activity in breast cancer patients before surgery and reported that lymphokine-activated killer cell activity is a state marker of existing depression before surgery.

Other Factors Related to Morbidity and Depression in Cancer Patients

In a study of the psychiatric morbidity among cancer patients, Alexander and colleagues (61) reported that psychiatric morbidity was less common in patients unaware of their cancer or in those who considered their treatment as curative.

Aass and colleagues (79) reported that impaired social life, impaired professional work, and previous psychiatric problems were significantly correlated with depression, anxiety, physical function, fatigue, and pain in cancer patients. Depression, but not anxiety, increased in the presence of distant metastases, relapse, or progression and also increased when the diagnosis was made less than 1 month before assessment. They also found gender and age had no influence of the prevalence of depression.

In a recent study of 148 postoperative breast cancer patients undergoing no active cancer treatment except hormones, Akechi and colleagues (98) used the HADS and found that biomedical factors (disease stage, performance status, physical symptoms) were not significant determinants of psychiatric morbidity. In their study, family problems and coping responses were found to be more important.


    CONCLUSION
 Top
 Notes
 Abstract
 Introduction
 Early Studies of Depression...
 Prevalence of Depression in...
 Assessment Methods
 Prevalence of Depression in...
 Prevalence of Depression in...
 Cancer Types Highly Associated...
 Gender Differences
 Depression by Cancer Type
 Markers and Correlates of...
 Quality of Life
 Conclusion
 References
 
Depression is common in the general population and in adults and children with cancer and frequently coexists with anxiety and pain. Depression has been challenging to study because symptoms occur on a spectrum that ranges from sadness to major affective disorder and because mood change is often difficult to evaluate when a patient is confronted by repeated threats to life, is receiving cancer treatments, is fatigued, or is experiencing pain. Untreated depression results in significant morbidity and mortality. Although the reported prevalence of depression in more than 100 studies of cancer patients ranges from 0% to 58%, cancer, exclusive of site and stage of illness, is associated with a high degree of depression.

Future research must focus on establishing diagnostically reliable criteria, developing standard instruments for measuring depression, correlating past psychiatric history of depression and anxiety with current depression, characterizing the causative role of antineoplastics in depression, and identifying biological markers for depression.


    NOTES
 
The author thanks Elaine Bernstein, Theresa Carpenter, Alex Pisani, and Isabel Sulimanoff for their assistance with the preparation of this manuscript and William E. Pelton and Sylvia Rosenberg for their continued generous support of her work.


    REFERENCES
 Top
 Notes
 Abstract
 Introduction
 Early Studies of Depression...
 Prevalence of Depression in...
 Assessment Methods
 Prevalence of Depression in...
 Prevalence of Depression in...
 Cancer Types Highly Associated...
 Gender Differences
 Depression by Cancer Type
 Markers and Correlates of...
 Quality of Life
 Conclusion
 References
 

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