David W. Kissane is an academic consultation-liaison psychiatrist, psycho-oncologist and psychotherapy researcher in cancer and palliative care. He is the incumbent in the Jimmie C. Holland Chair in Psycho-Oncology, attending Psychiatrist at The Memorial Hospital for Cancer and Allied Diseases, and Professor of Psychiatry at the Weill Medical College of Cornell University. He is a past President of the International Psycho-Oncology Society (2000-03) and recipient of their Arthur Sutherland Award for Lifetime Achievement in Psycho-oncology in 2008. He is the author of over 150 publications, including two books, Family Focused Grief Therapy (2002) and Handbook of Communication in Oncology and Palliative Care (2009). At Memorial Sloan-Kettering Cancer Center’s Department of Psychiatry and Behavioral Sciences, he has established a state-of-the-art Communication Skills Training and Research Laboratory and a Psychotherapy Research Laboratory.

Mario Maj is Professor of Psychiatry at the University of Naples, Italy. President of the World Psychiatric Association. Formerly President of the Italian Psychiatric Association; President of the Italian Society of Biological Psychiatry (since 1990); Secretary-General of the Association of European Psychiatrists (2001-2002); President of the Association of European Psychiatrists (2002). He is the Italian psychiatrist with the highest number of citations in indexed journals in the period 1981-2008.

Norman Sartorius, Association for the Improvement of Mental Health Programmes, Geneva, Switzerland. Professor Sartorius is President of the International Association for the Promotion of Mental Health Programmes. Honorary Fellow of the Royal College of Psychiatrists, of the Royal Australian and New Zealand College of Psychiatrists and of the American College of Psychiatry; Distinguished Fellow of the American Psychiatric Association. Member of the WHO Expert Advisory Panel on Mental Health. Member of WPA Council.

Depression and Cancer

John Wiley & Sons

Copyright © 2011 John Wiley & Sons, Ltd
All right reserved.
ISBN: 978-0-470-68966-0

Chapter One

The Prevalence of Depression in People with Cancer

Mary Jane Massie Department of Psychiatry and Behavioral Sciences, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

Mari Lloyd-Williams and Greg Irving Academic Palliative and Supportive Care Studies Group (APSCSG), School of Population, Community and Behavioural Sciences, University of Liverpool, UK

Kimberley Miller Princess Margaret Hospital, Toronto, ON, Canada

Depression is amongst the main causes of disability worldwide, leading to personal suffering and increased mortality. The US National Comorbidity Survey revealed a 12-month prevalence of major depressive disorder of 6%, with a lifetime prevalence of 16%, while high comorbidity exists with anxiety disorders, substance use disorders and impulse control disorders. In any twelve-month period, more than half the patients with major depressive disorder 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. Seedat et al. found that, across cohorts from 15 countries, women developed depression almost twice as frequently as men.

When comorbid with medical illness, depression increases the symptom burden and functional impairment, and worsens medical outcomes. 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%. In 1987, a retrospective review of 263 000 patients from 327 hospitals found that 24% of those receiving a psychiatric consultation were depressed. However, Snyder et al., using both clinical interview and DSM-III-R criteria reported less depression (6%), but more adjustment disorder with depressed mood (14%), in 944 medically ill patients referred for psychiatric consultation.

Wells et al. examined Epidemiological Catchment Area Study data regarding mental disorders amongst persons with at least one of eight chronic medical conditions. Six-month and lifetime prevalence rates of mental disorders were increased in those with versus without medical illness (25 and 42% versus 17 and 33%). Thirteen per cent 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%. 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.

PREVALENCE OF DEPRESSION IN CANCER PATIENTS

Using DSM-III criteria through a structured clinical interview, the Psychosocial Collaborative Oncology Group (PSYCOG) was one of the first groups to carefully determine the prevalence of mental disorders in 215 randomly selected hospitalized and ambulatory adult cancer patients in three cancer centres. Forty-seven per cent of the patients evaluated had clinically apparently psychiatric disorders. Of these patients, over 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 mental 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. This epidemiologically sound study has remained the gold standard for many years.

Many research groups have assessed depression in cancer patients along the years, and the reported prevalence varies quite widely (major depression 3 to 38%; depression spectrum syndromes 1.5 to 52%). The following databases were searched to retrieve references published between 1965 and 2009: PubMed, Embase, CINAHL (nursing), PsycINFO, Scopus, Science Citation Index/Social Sciences Citation Index, Cochrane Evidence Based Medicine database. The searches were limited to English language references and to studies with more than 100 subjects, where this information was indicated. Table 1.1 shows the 60 studies with more than 100 patients that provided information about the number of patients interviewed and cancer type(s), evaluation methods, and per cent with depression or affective syndromes. Most authors reported patient gender and hospitalization status. The reported prevalence 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.

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), or by a symptom such as depressed mood, or by some of these 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 are not accounted for. For example, although drugs can cause depression in some people, research groups usually have not presented data about cytotoxic drug or hormone use when describing their findings.

Several papers from Nemeroff’s group acknowledge 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), but 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 due to the pathophysiologic effect of the tumour (i.e. cytokine or paraneoplastic syndromes associated with breast, pancreas, testis or lung cancers), treatment effects or other unidentified factors remain to be discerned. Nonetheless, we confidently conclude that 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 include brain (41–93%), pancreas (up to 50%), head and neck (up to 42%), breast (4.5–37%), gynaecological (23%) and lung (11%). A large cross-sectional study of 8265 adult outpatients revealed higher levels of mixed anxiety/depression symptoms in patients with stomach (20%), pancreatic (17%), head and neck (15%) and lung (14%) cancers. A lower prevalence of depression is reported in patients with other cancers, such as colon (13%) and lymphoma (8%).

DeFlorio and Massie reviewed 49 studies of the prevalence of depression in individuals with cancer with a particular emphasis on gender differences. Twenty-three studies found no gender differences in the prevalence of depression at a significance level of p <0.05. However, 10 research groups found either gender differences in subsets of patients, non-significant trends, or differences in other parameters such as psychiatric morbidity, anxiety and denial.

In their study of 808 cancer patients, Kathol et al. found women were more depressed than men using Research Diagnostic Criteria; however, this finding did not persist when DSM-III criteria were applied. Sneed et al. found no gender differences in depression, anxiety, hostility, somatization, general psychological distress, or psychological well-being. Fife et al. also found no significant differences in depression in male and female cancer patients; however, they found that women made a more positive adjustment to cancer.

DEPRESSION BY CANCER TYPE

Depression in Women with Breast Cancer

Breast cancer is the cancer most studied in terms of psychosocial effects. The reported prevalence of depression ranges from 4.5% to 37%. One of the larger studies, examining 3321 early stage Danish breast cancer patients, recently found a 13.7% prevalence of major depression 12–16 weeks after surgery (17.9% in 18–35 year olds and 11.2% in 60–69 year olds). Independent risk factors for the development of depression included younger age, social status, ethnicity, comorbidity, psychiatric history, physical functioning, smoking, alcohol use and body mass index (BMI). Kissane et al., in 303 early stage and 200 metastatic breast cancer patients, found prevalence rates of major depression of 9.6 and 6.5% respectively. Fatigue, a past history of depression, and cognitive attitudes of helplessness, hopelessness or resignation were significantly associated with depression in both groups.

Some research groups have assessed the duration of psychological distress in breast cancer patients. In a prospective study of 160 women awaiting breast surgery, Morris et al. found a 22% prevalence of depression in women who had a mastectomy for breast cancer. This prevalence persisted at two years, compared to an 8% prevalence of depression in those with benign disease. One five-year observational cohort study of 222 early stage breast cancer patients revealed prevalence rates for depression and anxiety of 33% at diagnosis, 15% after one year and 45% after a recurrence was diagnosed.

Few researchers have correlated patients’ history of depression with current depression and/or functioning. In a study of 303 relatively young (mean age 46) women with early (Stage I or II) breast cancer at 3 months after breast surgery, using a structured diagnostic interview, Kissane et al. found that a past history of depression was associated with current depression. They also noted that women with few psychological symptoms and good emotional adjustment to cancer may have refused participation in the study, because these women were also being recruited into an intervention study. Pasacreta reported findings on a homogenous sample of 79 women evaluated with the Diagnostic Interview Schedule and the Center for Epidemiological Studies Depression Scale, three–seven months after their diagnosis of breast cancer. Women with elevated depressive symptoms had more physical symptom distress and more impaired functioning than subjects without depression.

Depression in Women with Gynaecological Cancer

In a systematic review which included 18 studies of psychological distress in ovarian cancer patients, Arden-Close et al. found strong evidence for a relationship of younger age, more advanced disease at diagnosis, more physical symptoms and shorter time since diagnosis with increased levels of anxiety and/or depression. In the 12 studies rated as methodologically good, 21–25% of patients scored above the clinical cut-off for depression. In examining depression in ovarian cancer patients, Goncalves et al. noted that persistent clinical depression tended to be not prevalent (6%), and that the highest prevalence was at the beginning of treatment. Neuroticism and the use of antidepressants were independent predictors of depression. For women with gynaecologic cancer, Evans et al. found a 23% prevalence of depression and a 24% prevalence of adjustment disorder with depressed mood.

Depression in Patients with Head and Neck Cancer

Head and neck malignancies carry high risks of morbidity and mortality, with disease and treatment factors contributing substantially to disfigurement and loss of vital functions, such as eating, breathing and communicating. A systematic review of 52 studies found that depression is present throughout the trajectory of illness in patients with oropharyngeal cancers. Depression rates were highest at the time of diagnosis (13–40%), during treatment (25– 52%), and at six-month follow-up (11– 45%); the levels decreased three years after diagnosis (9–27%). Other correlates of depression in this review included: patient characteristics (male, unmarried, less education, history of past and current smoking, young age, lower physical functioning and low social supports); patient physical symptoms (pain, fatigue, insomnia and anorexia); and treatment characteristics (combined and aggressive treatments).

de Leeuw et al. assessed the predictive values of numerous pre-treatment variables. Tumour stage, gender, depressive symptoms, openness to discuss cancer in the family, available support, received emotional support, tumour related symptoms, and size of an informal social network were calculated six months to three 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 three years after treatment.

Hammerlid et al., studying 357 head and neck cancer patients, found that those who reported a higher level of mental distress had lower performance status and more advanced disease.

Depression in Patients with Lung Cancer

Lung cancer has often been associated with higher levels of distress and depression than other tumour sites. In a study of depression and anxiety in 129 lung cancer patients, before and after diagnosis, Montazeri et al. found that 10% of patients had severe anxiety symptoms and 12% had symptoms of depression at first presentation to their pulmonary physician. Depression, but not anxiety, increased by 10% at follow-up. Hopwood and Stephens 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 also more prevalent in patients with small cell lung cancer than non-small cell lung cancer.

In a study of 129 newly diagnosed patients with non-small cell lung cancer, using a clinical interview that generated a DSM diagnosis, Akechi et al. reported a high prevalence of mental disorders. The most common psychiatric disorder at baseline was nicotine dependence (67%), followed by adjustment disorders (14%), alcohol dependence (13%), and major depression (5%).

Depression in Patients Undergoing Stem-Cell Transplantation

Loberiza et al. prospectively studied 193 adults who received autologous or allogenic hematopoietic stem-cell transplantation using the Short Form-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 utilized. Thirty-five per cent of the patients satisfied the authors’ criteria for depressive syndrome, which was associated with high mortality in the 6–12 month period after transplantation.

Depression in Brain Tumours

In addition to the difficulty adjusting to an illness that contributes to considerable morbidity and mortality, psychiatric problems in brain tumour patients can also be directly caused by the disease process as well as by treatment, including chemotherapy, radiation and corti-costeroids. Arnold et al. found that 41% of 363 brain tumour patients had depressive symptoms, as assessed by a modified version of the Brief Patient Health Questionnaire. Female gender, lower education, lower tumour grade and previous psychiatric disorder were predictors of depression. Although not significant, being unmarried and having a past/current medical illness trended toward being predictors of depression. Although based on symptoms, Litofsky et al. found that 93% of 598 high-grade glioma patients reported depressive symptoms in the early post-operative period, compared to 15% recognized by their physicians, highlighting the potential for underdiagnosis of depression in this population. Of 60 brain tumour patients, Pelletier et al. found that 38% scored in the clinically depressed range on the Beck Depressive Inventory-II. Although depression, fatigue, emotional distress and existential problems were interrelated, depression was the most important independent predictor of quality of life, emphasizing the importance of its recognition and treatment.

(Continues…)

Excerpted from Depression and Cancer Copyright © 2011 by John Wiley & Sons, Ltd. Excerpted by permission of John Wiley & Sons. All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
Excerpts are provided by Dial-A-Book Inc. solely for the personal use of visitors to this web site.