Section 19

PRINCIPLES OF PSYCHO-ONCOLOGY

69

PRINCIPLES OF PSYCHO-ONCOLOGY
JIMMIE C. HOLLAND, MD JANE GOOEN-PIELS, PHD

Quality of life as an outcome variable for patients treated at all stages of cancer has received increasing attention in recent years. More concern also has been directed toward recognizing and treating the distressed patient or family member. Stresses on oncologists have also been identified, particularly those related to delivering bad news. Research is more actively exploring social, behavioral, and psychologic contributions to cancer prevention, detection, and survival. Psycho-oncology, which has emerged over the past two decades as a subspecialty of oncology, focuses on these psychosocial issues along the continuum of care, as well as those which affect prevention. A body of information is now available, training programs exist, and a research agenda has been formulated.1 Psycho-oncology addresses the two psychologic dimensions of cancer: first, the psychologic response of patients to cancer at all stages of disease, as well as that of their families and their caretakers (i.e., the psychosocial dimension). This aspect impacts on the care of all patients, irrespective of age, site of cancer, or treatment. The second dimension consists of the psychological, behavioral, and social factors that influence risk, detection, and survival (i.e., the psychobiologic dimension). To extend our knowledge of these aspects of oncology, we are training a group of multi-disciplinary clinicians and investigators, largely from psychology, psychiatry, social work, nursing, and clergy to serve as specialists in psycho-oncology in cancer centers. In addition, we have developed teaching modules for the training of all oncologic disciplines on the psychosocial aspects of patient care, particularly with attention to developing communication skills. Collaborative research is increasing in the psychologic, humanistic, ethical, and spiritual aspects of patient care. Clinical trials more frequently include quality of life as an outcome variable, often coupled with economic outcome data. Active research in neurological, immunological, and endocrinological links is occurring through the new field of psychoneuroimmunology, to explore possible psychobiologic relationships in cancer cause and survival.2, 3 Most cancer centers and oncology divisions now have a psychooncology or psychosocial unit, whose role is to treat patients and family members who are distressed and to serve as a teaching resource for the oncology staff.4 Only a few centers have programs that include

research and training. The disciplines most often represented in these programs are nursing, social work, psychology, psychiatry, and chaplaincy. Trained volunteers, particularly those who have experienced cancer, either personally or in their families, play an increasingly important role as well. Many of the volunteer organizations, such as the Wellness Community, Gildas Club, and Hope and Cope in Montreal, have been established and founded by such individuals. They provide free help and support to many patients with cancer. This chapter provides a historical context for the development of psycho-oncology, our knowledge of the psychological and social aspects of patient care and the common psychiatric complications and their management. The range of interventions available today are outlined, as well as standards of care and clinical practice guidelines.5 The references cited in this chapter show the rapidly expanding literature in the field, and they serve as a guide to find additional information in each area. HISTORICAL PERSPECTIVE The stigma that cancer equals death, which has been attached to the disease for centuries, led to the long-respected dictum that doctors should not tell patients that they had cancer. To do so was considered cruel and would take away patients hope (Table 69.1). For centuries, there was indeed no treatment, and both doctors and patients had a fatalistic attitude as they awaited the inevitable outcome. The advent of anesthesia and antisepsis led to possible surgical removal of some tumors. Near the end of the 19th century and early in the 20th century, it became important to counter the publics fatalistic attitude since cure was possible, but only if the cancer was detected in an early stage. The American Cancer Society was formed in 1913 to educate the public about the warning symptoms of cancer and to reduce their immobilizing fears. As radiation and surgery were combined to treat cancer, more cures were effected. The establishment of the National Cancer Institute (NCI) in the United States in 1937 reflected new enthusiasm for improving cancer treatment. The addition of chemotherapy to combined modalities resulted in the cure of several childhood tumors. This led to an increase in interest in the medical outcome of long-term survivors of cancer and provided a new opportunity for studying the psychological sequelae of cancer. By the early 1970s, as survival improved further and patients became more willing to reveal that they had cancer, the diagnosis of cancer began to be more frequently revealed to patients as well as to their families. At about the same time, concern for more humane care of patients at the end of life was seen, with the development of the hospice movement and greater interest in pain management and palliative

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Table 69.1. Historical Attitudes About Cancer and Development of Psycho-Oncology 1800s Prevailing attitude was cancer equals death Fatalistic acceptance of diagnosis Diagnosis never revealed to patient American Cancer Society formed to fight fatalism and educate public that early treatment by surgery could be curative National Cancer Institute formed to seek a cure for cancer Combined modalities lead to increased survival in Hodgkins disease, acute lymphocytic leukemia, and childhood tumors First studies of psychological response to cancer reported Debate about telling or not telling diagnosis and change to revealing the diagnosis; federally mandated guidelines for informed consent Prevalence studies of psychiatric and psychological sequelae in cancer Psycho-oncology units develop in larger cancer centers Education of public about lifestyle and cancer prevention; behavioral research in changing habits (e.g., smoking), diet, and lifestyle Health-related quality-of-life assessment was accepted as an outcome measure in clinical trials Intervention studies undertaken to impact quality of life and reduce distress Development of psychoneuroimmunology and exploration of its relevance to cancer and risk survival

late development of psycho-oncology within oncology, and still contributes to attitudes of patients today. HEARING THE DIAGNOSIS Patients respond with anxiety when they realize that they are going through tests and procedures to rule out a diagnosis of cancer. When the doctor delivers the news that the diagnosis is cancer, it is a crisis situation which calls for all the inner psychological resources of the patient to cope with the information. Recent attention has been given to the important role of how the doctor delivers bad news as a factor impacting on the patients response. Insensitivity in giving bad news is recalled even years later by the patient. Oncology training programs today are beginning to teach communication skills to doctors.6 Research is beginning to result in practice guidelines on how to present information, how to be sensitive to the patients response, and the importance of presenting a treatment plan in conjunction with the bad news.711 Communication at transition points in illnessat diagnosis, on evidence of recurrence or progression of disease, discussion of the do not resuscitate order, and participation in investigational protocolsis also critically important. Most people do not think very often about death, but the first thought on learning a cancer diagnosis is, I could die of this. This creates not only a psychological crisis, but an existential one as well. The person seeks to cope by searching for ways to meet the challenge (e.g., seek treatment) and maintain emotional control. This is often done by trying to put the information in a context that gives it a tolerable meaning.1214 Park and Folkman12 describe how the stressful information is processed cognitively, first by confronting the situation and changing, it if possible, but then by seeking positive aspects, trying to find meaning in it, and finally reconciling the meaning of the information (e.g., treatment requiring an amputation) with life goals that may have to be permanently altered (e.g., no longer able to pursue an athletic career). For many, the existential crisis elicits coping by calling on spiritual and religious beliefs that give a context of meaning to threat to life and the possibility of death.15 The diagnosis creates a period of crisis that is an expected and normal emotional upheaval (Table 69.2).16 The initial phase is characterized by disbelief and denial that the news is true. Patients often seek to prove that the diagnosis is not true (they must have mixed up the slides). High anxiety levels make it hard to process information, unfortunately at the time that treatment decisions must be made. Feeling numb and appearing not to understand the import are common reactions, but this usually lasts less than a week. Phase II follows, which is characterized by emotional turmoil and dysphoria during which the reality is slowly acknowledged. The person is anxious and depressed, has poor concentration, anorexia and insomnia, and inability to maintain a daily routine. Thoughts of illness
Table 69.3. Factors that Determine Psychological Adjustment to Cancer

19001920 1930 1950

196070

1980

1990

care. Greater openness in revealing the diagnosis, increased concern for the dying, and enhanced concern about quality of life and the rights of patients led to more attention to the supportive and psychological aspects of care. Evidence for the link of environmental exposures to cancer, particularly cigarette smoking, gave new impetus to examining the role of psychological and behavioral factors in cancer prevention. By 1980, the stage was set for greater interest in the psychological problems of patients with cancer. However, valid tools to assess these variables were few. Early investigators were forced to develop new instruments or modify those originally developed to assess patients with psychiatric disorders. Investigators with knowledge of research methods in both cancer and social science were few. Nevertheless, a small group of investigators around the world, largely in the United States and the United Kingdom, began to identify themselves as psychosocial or psycho-oncologists, and they began to study the prevalence of psychiatric comorbidity in cancer and to address key psychosocial questions. The investigators were associated with the early psycho-oncology units in a few cancer centers. Some developed programs to train young clinicians and investigators, who began to establish psycho-oncology units in other cancer centers. This brief history underscores the relative youth of this subspecialty of oncology which began in the late 1970s. It also points to the degree to which historical attitudes toward cancer contributed to the
Table 69.2.
Phase

Society-derived Open discussion of diagnosis versus unrevealed secret Knowledge of treatment options, prognosis, and participation as partner in treatment Popular beliefs (stress causes cancer) Patient-derived Intrapersonal Developmental stage at time of cancer and meaning of curtailed goals (e.g., marriage, children) Coping ability; emotional maturity at time of cancer; philosophic, spiritual, or religious beliefs that influence coping Interpersonal Spouse, family, friends (social support) Socioeconomic/social class Cancer-derived Site, stage, symptoms (especially pain) and prognosis Treatment required (surgery, radiation, chemotherapy) and sequelae (immediate and delayed) Altered body structure or function, rehabilitation/restoration available Psychological management by the treating staff

Normal Responses to Crises Encountered with Cancer

Symptoms Time interval

Phase I: Initial response Phase II: Dysphoria

Disbelief or denial or despair (I knew it all along) Anxiety, depressed mood, anorexia, insomnia, poor concentration, inability to function Accepts validity of information and begins dealing with options available Finds reasons for optimism and resumes usual activities

Usually less than 1 week Usually 1 to 2 weeks, but varies

Phase III: Adaptation

Usually by 2 weeks, but adaptation continues over months; may or may not be successful

and death intrude repeatedly and cannot be dispelled. This period may last 1 to 2 weeks, usually diminishing as the person begins treatment and becomes more hopeful as positive steps are taken. A therapeutic alliance with the doctor and a treatment plan make the future seem more hopeful. Phase III represents the longer-term adaptation, lasting from weeks to months, in which the patient adjusts to the diagnosis and treatment, finds reasons for optimism, and returns to normal routines and ways of coping that were characteristic and successful in the past. The quality of this adaptation depends on the patients prior level of adjustment and emotional maturity. It is important that family, friends, and staff be aware that there is no single best way to cope. Individuals have developed their own coping styles that, for better or for worse, have gotten them through prior life crises. There is a strong tendency in todays society to demand that individuals with cancer have a positive attitude to beat it. Patients are made to feel guilty if they do not cope that way, and they often are told that the absence of a positive attitude leads to faster tumor growth. While a positive thinking strategy works well for some individuals, it does not for others. It is critically important that the doctor respects and supports each individuals way of coping.2,3,17 This sequence of disbelief, dysphoria, and adaptation recurs with each new crisis in the course of illness. Depression becomes more prominent when the news is progressive disease or treatment failure. FACTORS IN ADAPTATION TO CANCER While the acute response to catastrophic news is similar in most patients at the time of diagnosis, individuals vary widely in how well or how poorly they adapt to illness over time. Therefore, it is important to recognize factors that predict good or poor adjustment, enabling early identification of particularly vulnerable individuals. Factors that contribute to adaptation derive from three areas: (1) society-derived factors, which are the social attitudes and beliefs about cancer that impact on the patient; (2) patient-derived factors, which are the personal attributes the person brings to illness; and, (3) cancer-derived

CHAPTER 69 / Principles of Psycho-Oncology 945

factors, which represent the clinical reality of the illness to which the patient must adapt (Table 69.3). SOCIETY-DERIVED FACTORS The society-derived factors are constantly changing since they reflect societys attitudes toward cancer and its treatment, as well as societys perceptions and knowledge of cancer at a given time. Long feared and stigmatized, cancer is somewhat less fearsome today. The diagnosis is more routinely given, and the public justifiably is more optimistic about the outcome, particularly among children and young adults. Coupled with societys demands for informed consent and for knowledge of treatment options, better communication between doctor and patient has been a positive spin-off. This has resulted, however, in an added burden for the patient because of the fuller knowledge of the realistic prognosis associated with each treatment option. In addition, patients who have finished cancer treatment are monitored far more carefully today with frequent scans and procedures to detect recurrent cancer, causing far greater anxiety and fears. Thus, awareness of an uncertain future is far greater today. An additional burden is the widely popularized belief that stress causes cancer. Some patients mistakenly feel that they themselves, by some stressful event or events they did not manage properly, caused their cancer to develop. Repeated reassurance that this is not true is necessary.2,3,18,19 PATIENT-DERIVED FACTORS The patient-derived factors that affect adaptation come from three sources: (1) intrapersonal (developmental stage and coping ability); (2) interpersonal (the social support from others); and (3) socioeconomic and social class (the material resources available). The developmental stage of the person at the time that cancer develops determines the meaning of an illness or treatment-related loss; for example, loss of fertility or altered appearance will impact differently, depending on the time of life that it occurs. An awareness of the individuals developmental stage, the associated biologic

Table 69.4.
Stage

Developmental Stages and Cancer

Tasks Disruption Intervention

Children Childhood (early)

Motor Speech Cognition Family bonding Socialization Confidence Prepubertal Peer relations Intellectual and physical prowess Menarche/puberty Peer acceptance Increasing independence Sexual experimentation Formation of identity Intimacy Marriage Parental role Work role

Developmental slowing Regression Separation anxiety Withdrawal Increasing fears (pain) Being different School phobia Death fears Alopecia/amputation differentness Decreasing school/physical performance Increasing dependence Conflicts about self and sexuality Impact of illness Decreasing attractiveness Sterility/impotence Decreasing family role Disruption of job performance Altered appearance Disrupted marital/family role Disrupted achievements Increasing physical/emotional Services to maintain Increasing dependence on others Increasing isolation Decreasing financial security

Physical/social stimulation Structured play Increasing family contact Continuity of staff Trust of staff Maintain appearance Minimize absences Discuss illness and monitor responses Maintain appearance Maintain peer contact Support independence Counseling Counseling Maintain appearance Sex counseling Homemaker Support children Decreasing job interruptions Maintain appearance Counseling (patient and family) Financial planning Health-related Care of self Social support system Promote social/familial network Financial planning

Childhood (late)

Adolescents and adults Adolescence

Adult (middle)

Changing hormonal status/menopause Older children Empty nest Peak of career Aging changes Physical limitations Adjustment to increasing losses Increasing social support needed Retirement

Adult (old)

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Table 69.5. Predictors of Poor Coping with Cancer

Social isolation Low socioeconomic status Alcohol or drug abuse Prior psychiatric history Prior experience with cancer (e.g., death of a relative) Recent losses/bereavement Inflexibility and rigidity of coping Pessimistic philosophy of life Absence of a belief/value system, from which to view life and death Multiple obligations
Adapted from Holland and Rowland.21

CANCER-DERIVED FACTORS The cancer-derived factors that contribute to adaptation are the clinical facts themselves of stage of disease at diagnosis, site, presence of symptoms (especially pain), the prognosis, the type(s) of treatment required and their immediate and long-term impact on function, and the extent of rehabilitation that is possible. These are the givens, but in addition, the psychological management by the oncology team is an important variable. The sensitive oncologist and nurse become important sources of psychological support for the patient and family. Concern, compassion and caring in the context of professional ministrations are invaluable aids to the patients ability to cope with illness.8,10,31 Absence of such a relationship with key staff is a negative factor in coping, which contributes materially to the under-recognition and treatment of distress.5 PSYCHOSOCIAL PROBLEMS Psychosocial problems of patients vary across the continuum of cancer. They can be considered in four broad categories: (1) those in patients receiving active treatment with cure as a goal; (2) psychosocial problems patients receiving palliative care, with the treatment of cancer aimed at control or comfort; (3) problems of patients who have completed active treatment and who are considered survivors; and (4) asymptomatic, healthy individuals who have a known enhanced genetic risk of cancer by family history. ADAPTATION TO ACTIVE TREATMENT In patients undergoing treatment aimed at cure, the goal of psychosocial intervention is to support their ability to cope with the stresses of treatment; to reduce their distress, by helping them to tolerate the short-term loss for the long-term gain; and to assist in symptom management (e.g., anxiety, nausea and vomiting, pain).3237 Some cancers, such as pancreatic cancer, have a less likely curative outcome and are associated with more distressing physical symptoms and depression.38 The known poor prognosis adds to the psychological burden. One study revealed that oncologists were able to perceive patients physical symptoms correctly, but they underestimated levels of anxiety and depression.31 Hospitalized patients have higher frequency of both psychosocial problems and psychiatric disorders due to level of illness.39,40 Ambulatory patients who have been screened in the waiting room for level of distress show that about a quarter to a third have significant distress (mixed anxiety and depressive symptoms) and should be referred for evaluation by a mental health professional.41,42 The goal of cure encourages most individuals to tolerate the temporary discomfort and side effects of surgery, chemotherapy, and radiation and to adapt to the permanent losses or organ-preserving procedures that may be necessary to achieve successful antineoplastic treatment.43 Control of anxiety, depression, delirium, and nausea and vomiting and encouraging adherence to treatment are areas in which symptom control and psychological support are helpful. McQuellon and colleagues utilized an orientation program for new patients, which gave them added information about what to expect. Anxiety and depression symptoms were reduced as compared with the usual care group.44 Counseling, support groups, cognitive-behavioral interventions, and psychopharmacologic agents all are useful to control distress. A broad range of psychosocial interventions have emerged.45 (See section Psychiatric and Psychosocial Interventions.) ADAPTATION TO PALLIATIVE CARE The transition from a curative approach to a palliative one is extremely difficult for the patient, family, and the physician who has worked with the patient through months of arduous treatment. This transition constitutes a crisis that carries greater anguish than that experienced at the time of initial diagnosis. The combination of physical symptoms, psychological distress, and the existential crisis constitutes the suffering associated with advanced cancer.46 Patients have a period of high distress on learning that the goal has shifted from cure to control of their cancer. However, they adapt remarkably well to the altered goal. Today, many people view cancer as a chronic disease at this stage, particularly those living with advanced prostate or breast cancers. They hold on to the hope that, while maintaining present treatment, a new therapy for cure might become available. It is only when treatments and investigational therapies begin to fail that end of life issues emerge more clearly

changes at that age, and the psychological and social tasks demanded of that person helps to understand the impact of cancer and to derive interventions for each age. Table 69.4 outlines the developmental stages, the normal tasks that must be achieved at each age, the disruption in achieving expected life goals, and the interventions that can minimize the deleterious effects of illness. It is particularly important in treating childhood and adolescent cancers to assure that normal developmental milestones are reached and maintained as nearly as possible.20 Detailed developmental tables of the life cycle have been published elsewhere.21 The intrapersonal resources a person brings to the illness are those derived from personality, level of emotional maturity, coping strategies, and attitudes and beliefs about illness. There are several characteristics of personality that are associated with better adjustment to cancer: being optimistic by nature, facing illness directly as a challenge or problem, using humor, being able to find some positive meaning in the situation, despite its stress, and having a philosophy or belief system that puts the illness in a tolerable perspective.13,14 The strategies that patients use to cope with cancer must accomplish several goals: (1) to keep distress within manageable levels; (2) to maintain a sense of personal worth; (3) to restore or maintain relations with significant others; (4) to enhance recovery and physical function; and (5) to work out a socially acceptable post-illness status with maximal physical function.13 Taken overall, good coping strategies are important in maintaining a sense of control, optimism, and acceptance of the facts, while seeking constructive, positive approaches to illness and treatment. Sharing information and obtaining support from others is a helpful coping strategy. For many individuals, religion provides an existential view of life, death, and illness, as well as a supportive community of individuals who share their views.15 In terms of prior experience, among individuals diagnosed with cancer, some are at greater risk of distress if they have had a prior psychiatric problem or if they have experienced loss of a close family member to cancer earlier in life. The death of a relative from the same cancer adds a particularly heavy burden of painful memories. In addition, individuals who have survived extreme experiences earlier in life (e.g., Holocaust survivors or survivors of physical abuse) are more apt to experience post-traumatic stress disorder (PTSD) symptoms and may have more distress in coping with cancer.22 Table 69.5 outlines the major predictors of poor coping that can readily be elicited while taking a history, thus identifying patients who are most vulnerable.23 The patients social environment provides the important interpersonal resources of spouse or partner, family, and friends as social support which makes a concrete contribution. Increasing evidence suggests the central role that social support plays in both coping and survival. Isolated individuals have more trouble coping with illness and have a higher age-related mortality.2427 A third patient-derived factor which has emerged is that of the individuals socioeconomic and social class status. Increasing evidence points to these as important issues that impact on both morbidity and mortality, not only by limited access to appropriate care but also because poorer education and resources affect cancer treatment and outcome.2830 Research points to a social class gradient in which higher mortality correlates with lower social class that holds as a gradient across the five social classes, based on education and income.30

Table 69.6.

Psychosocial Sequelae in Cancer Survivors

CHAPTER 69 / Principles of Psycho-Oncology 947

Positive effect of appreciating life more Major psychiatric disorders are uncommon (1520% score in significantly distressed range) Subtle psychologic distress is common Anxiety about recurrence/illness/death (Damocles syndrome) Greater sense of vulnerability (less control, lower self-esteem) Reminders (smells, sights) of chemotherapy produce anxiety and nausea Post-traumatic stress disorder (around 15%), (including PTSD symptoms, around 25%) Sexual problems related to treatment: less sense of attractiveness, lower sexual desire, poorer sexual performance Career goals altered negatively (fewer risks, less ability to change jobs) Job and health insurance problems

Assurance of the physicians commitment to continued care and symptom control becomes more important. Appointing a health proxy and discussion of wishes about resuscitation and life-sustaining measures are best discussed early rather than late. Decisions about where continuing care will be given must be discussed, as well as assessing whether end-of-life care can be managed at home. When this is possible, both patient and family benefit psychologically from it.4749 Considerable information exists today about symptom control in advanced stages of illness, with better control of pain, anorexia, nausea, constipation, dyspnea, weakness, cachexia, and suffering (distress).5053 Portenoy and colleagues studied the prevalence of symptoms in patients with advanced cancer and found fatigue, weakness, pain, and emotional distress present in over two-thirds of patients.43 Palliative care in children is also better defined.54, 55 There is a growing number of controlled trials of medication and behavioral and psychological interventions to treat the psychiatric disorders which are common in advanced stages of illness: anxiety, depression, and confusion (delirium).48,50,56,57 The Academy of Psychosomatic Medicine has formulated guidelines on the psychiatric aspects of end-of-life care.58 Other studies have identified the role of the psychiatrist in managing psychiatric disorders associated with terminal cancer.46,59,60 Depression and requests for physician-assisted suicide require careful consideration.6165 Comfort care must focus on control of the physical, psychological, and spiritual aspects, as existential issues grow in importance. ADAPTATION TO BEING A SURVIVOR One of the growing and increasingly vocal group of patients are those who have completed active treatment and, on returning to their normal lives and routine, become advocates for themselves and others. The National Coalition of Cancer Survivorship (NCCS) is an advocacy group gaining a voice in health policy and care. It publishes practical and sensitive how-to books for survivors. Patient advocates are now members of committees in the NCIs policy bodies and in cooperative groups. Common concerns of survivors are fear of recurrence, worry about delayed physical effects, risk of second cancers, and sterility66 (Table 69.6 outlines the psychosocial sequelae). (See Kornbliths comprehensive review for further information.66) Neuropsychological tests have revealed cognitive changes caused by radiation and chemotherapy. The negative dose-related effects of cranial radiation in children have been found to result in underachievement in school and significant neuropsychological impairment.67 More recent reviews by Ahles and others suggest that even adjuvant chemotherapy for breast cancer produces subtle cognitive deficits that are apparent months after treatment on neuropsychological testing.68,69 A study by Ahles in the Cancer and Leukemia Group B (CALGB) showed that prophylactic cranial radiation in small cell lung cancer patients resulted in cognitive deficits which were not related to depression.70 Studies of young adult survivors of Hodgkins disease,71 acute leukemia, and testicular cancer reveal several psychosocial characteristics that apply to survivors across tumor sites (see Table 69.6).72,73 Most psychologically healthy individuals emerge from cancer treatment without serious psychological sequelae or significant psychiatric

disorders. However, there is a subset of survivors, around 15%, who do show significant problems. They are most often those with greater physical sequelae and fewer social supports.66 Survivors report persistent fears of recurrence and death (Damocles syndrome), a greater sense of uncertainty about the future, and a greater sense of vulnerability and lower self-esteem (see Table 69.6). Minor physical symptoms are feared to be signs of recurrent cancer. Anxiety and even panic occur before follow-up visits and scans. Anxiety diminishes over time, especially after the first 5 years associated with maximal risk of recurrence, but it continues to be exacerbated at times of periodic medical examinations or appearance of minor symptoms. Gonadal toxicity results in infertility and, in women, symptoms of premature menopause and sexual dysfunction. Even when no treatment-related gonadal toxicity is present, there often is decreased libido and poorer sexual satisfaction and performance in both men and women.7477 Career goals suffer due to difficulty in changing jobs and pursuing a chosen career; the difficulty is based, in part, on survivors realistic concerns about health insurance and the prejudice they are confronted with about having had cancer. Many survivors report subtle forms of discrimination.72 Chemotherapy results in longlasting, conditioned, Pavlovian responses to reminders of the treatment situation where nausea and vomiting occurred with cyclic chemotherapy.32,78 Cella and colleagues found that smells, tastes, and sights that were reminders of treatment, even as long as 11 years later, resulted in a sudden sense of unexplained anxiety and nausea (but rarely vomiting) that only on reflection was recognized as a reminder of prior treatment.79 A more generalized type of anxiety seen after aggressive cancer treatment, such as bone marrow or stem cell transplantation, is PTSD. Symptoms of hypervigilance, flashbacks, anxiety, depressive symptoms, poor self-esteem, and poor concentration are reported.22,8082 Studies suggest that about 10 to 15% of patients who received bone marrow transplantation have PTSD, but another 10 to 15% have some of the symptoms of PTSD without fulfilling all criteria for a definitive diagnosis. PTSD has also been diagnosed in a high percentage of mothers of children who have gone through cancer treatment.83 Cognitivebehavioral therapy with or without medication is the current treatment. ADAPTATION TO INCREASED GENETIC RISK OF CANCER Healthy individuals increasingly recognize that they are at risk of a particular type of cancer by virtue of cancers in others in their family.84,85 Currently, such persons are informed about the increased risk of breast, colon, ovarian, and prostate cancers among first-degree relatives, as well as of melanoma and endocrine tumors (MENS I and II).86 The psychological impact of this knowledge results in a new and increasing number of individuals who are healthy but fearful of disease, sometimes to pathological levels. They constitute the worried well, who must deal with knowledge of enhanced risk despite present good health. Some perceive themselves as walking time bombs. In a study by Kash and colleagues of women with two or more first-degree relatives with breast cancer, those most anxious were least able to carry out regular breast self-examination or have mammograms, despite the importance of surveillance because of high risk.87,88 Studies have been conducted to explore how to counsel those at risk.89 People usually overestimate their actual risk, and genetic counseling is helpful to give them accurate information about actual risk. Most studies have explored psychological responses to the risk of breast, ovarian84,85,9095 and colon cancers.86,89,96 Requests for genetic counseling have increased; however, requests for actual genetic testing are more carefully considered by most individuals as the potential discrimination in the workplace, health and life insurance, and breach of privacy regarding the information are recognized. In addition, there are many as yet unidentified gene mutations and hence results are often far from definitive. The potential harm to minors is particularly worrisome. Pretesting counseling must take into account the impact on psychologically vulnerable individuals. However, the concern about severe psychological sequelae has not been borne out by experience thus far, and most individuals who learn their genetic results tolerate the information well, even when the clinical significance of results are ambiguous. More studies are needed of

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Figure 69.1. Guidelines for triage. Evaluation/treatment guideline in oncology clinic.

individuals who are tested and their family members who indirectly learn of their own risk. The Institute of Medicine and the Human Genome Project have led in examining the social policy issues, suggesting the need for supervision of laboratories, assurances of confidentiality, and guidelines for counseling. Major education of the public and professionals also is needed.97 GUIDELINES FOR RECOGNITION OF PSYCHOSOCIAL DISTRESS As oncology care has shifted to ambulatory settings and as managed care has mandated shorter visits with patients, under-recognition and undertreatment of psychosocial problems have become an even greater issue, which has been addressed by a panel appointed by the National Cancer Centers Network.5 They identified the barriers that contribute to the under-recognition as coming from patients and physicians attitudes to psychological issues. Patients with cancer are reluctant to ask for help for fear of being labeled psychiatric or psychological cases. The panel comprising of oncologists, nurses, social workers, clergy, and patient advocates proposed using the word distress, which is more acceptable and is not as stigmatizing. Distress is understood to be normal if one has cancer but is understood also to exist on a continuum of severity which at maximum produces disabling symptoms. The distress may be caused by illness or treatment, but it may relate to family problems or severe anxiety or depression. A diagnosis of cancer also provokes a questioning of the meaning of life, with a need to explore beliefs about life and death, creating a spiritual

or religious crisis for some.98 For these reasons, the panel proposed the definition of distress in cancer as an unpleasant emotional experience of a psychological (cognitive, behavioral, emotional), social, and/or spiritual nature that may interfere with the ability to cope effectively with cancer and its treatment. Distress extends along a continuum, ranging from common normal feelings of vulnerability, sadness, and fear to problems that can become disabling, such as depression, anxiety, panic, social isolation, and spiritual crisis.5 The panel has developed guidelines for the primary oncology team in the office or clinic, which are based on an algorithm to ensure prompt referral of patients to psychosocial resources using a rapid screening tool in the waiting room. The goal is not only easier referral, but using a word such as distress opens a dialogue between the patient and the oncology team to discuss more personal problems without embarrassment. Several centers are testing brief screening instruments, such as questionnaires which patients are asked to fill out in the oncology waiting room. At Johns Hopkins Cancer Center, all patients fill out a short questionnaire that is scanned, and patients with scores indicative of high distress are called at home and given an appointment to see the social worker.99 The panel proposed the use of a simple distress thermometer, a 0-to-10 scale, which asks, How distressed are you?5 This is based on the successful use of the 0-to-10 scale used widely to ask patients to rate their pain. Roth and colleagues found that a score of 5 or greater on the thermometer correlated with significant distress on the hospital anxiety and depression scale.41 The thermometer is accompanied by a list of problems, on which the patient indicates the major sources of distress: physical, psychological, social, practical (e.g., finances), or spiritual problems. The nurse or social worker reviews the information rapidly and explores it further with questions to clarify the primary problem(s). If the patients distress level is above 5, this triggers referral to the proper psychosocial resource. If the problem is physical, then the oncologist addresses the problem in the visit. If it falls in the other areas, mental health, social work, or pastoral counseling, the concerned worker is contacted. Less severe psychosocial problems are also managed by the team. Figure 69.1 and 69.2 show the recommended guidelines for triage, the thermometer, and the problem list.42,100,101 When this model is used, psychosocial, psychiatric, and pastoral counseling are perceived by patients as being more integrated into their total care, which is acceptable to them. PSYCHIATRIC DISORDERS For the oncologist, the relevant clinical question is how to identify the point at which the normal distress associated with cancer (e.g., fear, worry, and sadness) has extended along the continuum of severity to become a psychiatric disorder.56,57 This is important to total

Figure 69.2.

Distress thermometer.

patient care, not only for its effect on the patients well being but also because of its negative impact on adherence to treatment. A study done in the 1980s at three cancer centers identified the prevalence of psychiatric disorders in patients with cancer (60% inpatients and 40% outpatients),102 but the cohort was uncontrolled for stage of disease. The study found that 53% of patients were coping adequately despite the stresses of illness, but 47% had levels of distress that reached diagnostic criteria for a psychiatric disorder. Among these patients, 32% showed a mixture of reactive depression and anxiety (adjustment disorder with depressed anxious mood, in the Diagnostic and Statistical Manual of Mental Disorders-III (DSM-III) classification of psychiatric disorders). Six percent had major depression, 4% organic mental disorders, 3% personality disorder and/or alcohol abuse, and 2% anxiety disorders. Data support the premise that most psychiatric disturbances in patients with cancer directly relate to illness.103 Indeed, the predominant symptoms seen in one-third of all patients were combined reactive anxiety and depression, with one or the other predominating. The most common problems in cancer are anxiety and depression, often occurring together in situational or adjustment disorders.45,103,104 Farber and colleagues,105 studying outpatients in oncology clinics, independently found that one-third had significantly high levels of distress. The percentage of distressed patients rises in hospitalized patients because of greater disability, pain, metabolic derangements, and confusional states caused by medications.106 These forms of distress from depression or anxiety and confusional states (organic mental disorders) constitute, by far, the most likely psychiatric diagnoses encountered. Pre-existing psychiatric disorders constitute a small but critically important group requiring psychiatric management during cancer treatment.48 ANXIETY DISORDERS Anxiety is the most common form of psychologic distress in patients with cancer. It occurs in four forms: (1) situational anxiety anticipating or related to a frightening aspect of illness or treatment; (2) disease-related anxiety; (3) treatment-related anxiety; and (4) an exacerbation of a pre-existing anxiety disorder (Table 69.7). Situational anxiety occurs at the time of diagnosis, with anticipation of a procedure or new treatment, at transitional points in illness, after treatment is finished (paradoxical anxiety), and as a continuing fear of disease recurrence, which is nearly universal. Anxiety also occurs when a new treatment produces frightening, unexpectedly severe side effects, like an anaphylactic shock reaction.

CHAPTER 69 / Principles of Psycho-Oncology 949

Table 69.8. Anxiety Related to Common Medical Problems in Cancer
Examples

Medical Problems

Poorly controlled pain Abnormal metabolic states Hormone-secreting tumors Anxiety-producing drugs

Side effects of treatment

Unresponsive or undertreated pain Hypoxia, pulmonary embolus, sepsis, fever, delirium, hypoglycemia, bleeding, coronary occlusion and heart failure, cardiac arrhythmia Pheochromocytoma, thyroid tumors, carcinoid, parathyroid adenoma, ACTH-producing tumors, insulinoma Corticosteroids, neuroleptics used as antiemetics, thyroxine, bronchodilators, (-adrenergic stimulants, antihistamines, (paradoxic reactions), withdrawal states (alcohol, narcotic analgesics, sedative-hypnotics) Allergic skin rash to antibiotics, unexpected toxicity (e.g., diarrhea)

Table 69.7.

Causes of Anxiety in Patients with Cancer

Situational Diagnosis of cancer, prognosis discussion Crisis, illness/treatment Conflicts with family or staff Anticipating a frightening procedure Awaiting results of tests Fears of recurrence after completing treatment Disease-related Poorly controlled pain Abnormal metabolic states Hormone-secreting tumors Paraneoplastic syndromes (remote CNS effects) Treatment-related Frightening or painful procedures (MRI, scans, wound dbridement) Anxiety-producing drugs (antiemetic neuroleptics, bronchodilators) Withdrawal states (opioids, benzodiazepines, alcohol) Conditioned (anticipatory) anxiety, nausea, and vomiting with cyclic chemotherapy Exacerbation of pre-existing anxiety disorder Phobias (needles, claustrophobia) Panic or generalized anxiety disorder Post-traumatic stress disorder (Holocaust survivors, Vietnam veterans, recall of the death of a relative with cancer) Obsessive-compulsive disorder
CNS = central nervous system; MRI = magnetic resonance imaging.

Anxiety which is disease-related is seen often with poorly controlled pain; it usually disappears when pain is adequately controlled (Tables 69.7 and 69.8). Anxiety also occurs with abnormal metabolic states, such as hypoxia, pulmonary embolus, sepsis, delirium, bleeding, cardiac arrhythmia, and hypoglycemia. Hormone-secreting tumors that produce anxiety are pheochromocytoma, thyroid tumors, carcinoid, parathyroid adenoma, adrenocorticotropin hormone (ACTH)-producing tumors, and insulinoma. Paraneoplastic disorders (remote central nervous system effect) can also cause anxiety and mood change. Among treatment-related causes of anxiety, the most common are anxiety related to frightening or painful procedures, especially those occurring repeatedly, such as wound dbridement. Approximately 20% of patients have trouble tolerating imaging procedures, such as MRI, because of the small, enclosed space, which triggers claustrophobia. Approximately 5% are unable to tolerate it. Several drugs frequently used in cancer also produce symptoms of anxiety: corticosteroids, neuroleptics used as antiemetics, bronchodilators, thyroxine, and stimulants. Unexplained restlessness, anxiety, and agitation often develop in patients who receive large doses of metoclopramide or other neuroleptics for the control of chemotherapy-related nausea and vomiting. Akathesia and dystonia can be frightening and require immediate treatment with a benzodiazepine, which promptly reduces the restless movements, anxiety, and agitation. Withdrawal states from alcohol, narcotic analgesics, and sedative-hypnotics produce anxiety as a prominent symptom and must be kept in mind when dealing with unexplained anxiety. Some patients undergoing cyclic chemotherapy using an emetogenic regimen begin to develop anticipatory anxiety, nausea, and vomiting by about the third cycle, a few days to hours in advance of receiving the next cycle of treatment.32,107,108 This is a learned, conditioned, Pavlovian autonomic response to the repeated chemotherapy-related experience of nausea and vomiting (as described earlier in survivors). In fact, two-thirds of women receiving adjuvant chemotherapy for breast cancer develop conditioned anxiety and nausea, although usually not vomiting.78,80 The response has been seen as long as 11 years later on encountering smells or tastes that remind the person of the chemotherapy received for Hodgkins disease.79 More effective antiemesis regimens with steroids and ondansetron have reduced the frequency and severity of this problem. However, behavioral interventions and antianxiety medication are sometimes needed to control symptoms. Patients who have pre-existing phobias, panic attacks, generalized anxiety, PTSD, or obsessive-compulsive disorder (OCD) are at risk of their symptoms exacerbating during cancer treatment (see Table 69.7).109 Phobias of needles, blood, and hospitals, claustrophobia, or agoraphobia may complicate the patients ability to tolerate hospital procedures. In patients who have frightening physical symptoms, such as shortness of breath, panic attacks often occur and further complicate the physical symptoms.103,110 Panic attacks and generalized anxiety symptoms must be controlled to enable the patient to tolerate anxiety-pro-

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Table 69.9. Treatment of Anxiety Disorders
Components

Treatment Modality

Supportive psychotherapy Individual therapy Support group Behavioral Psychopharmacologic

Providing information, rehearsal of feared events, reassurance Relaxation, hypnosis Systematic desensitization Benzodiazepines Short-acting (alprazolam, lorazepam, oxazepam) Long-acting (diazepam, clorazepate, clonazepam) (-blockers (propranolol) Tricyclic antidepressants (amitriptyline, doxepin, nortriptyline) Monoamine oxidase inhibitors (phenelzine, isocarboxazid) Antihistamines Neuroleptics (thioridazine, trifluoperazine, haloperidol) Buspirone

Combinations of the above

voking medical treatments. During their illness and treatment, patients who experienced the Holocaust or have traumatic memories of war or frightening events earlier in life may have flashbacks of these painful events whose memories have been quiescent for many years.20,22 OCD can be a difficult psychiatric disorder complicating cancer treatment. The patient is often indecisive about accepting both cancer treatment and psychiatric intervention with a psychotropic medication. Fears of the future, phobias, and rigidity, make it difficult for them to cope with illness. Encouragement to take one of the several drugs which have clear benefit for OCD is important. The treatment of simple situational anxiety usually is handled adequately by the physician, who reassures the patient, reviews frightening anticipated events, allows the person to rehearse them, and engenders confidence (Table 69.9). The oncology nurse or social worker often is helpful in giving additional information and offering reassurance. For persistent or distressing anxiety, three types of treatment are available: (1) psychotherapy and counseling, (2) behavioral interventions, and (3) psychopharmacologic treatment. Counseling or formal psychotherapy using a psychoeducational, cognitive-behavioral, or supportive intervention model is helpful.111114 Fawzy and colleagues outlined the range of psychosocial interventions that have been proven efficacious in controlled trials.45 A meta-analysis of randomized controlled trials showed that a range of interventions are efficacious in
Table 69.10. Commonly Prescribed Benzodiazepines in Cancer Patients

improving quality of life and decreasing distress, but data were insufficient to support an effect on survival.115 Several forms of interventionspsychoeducational, interpersonal, supportive, and cognitive-behavioralare being tried. Several behavioral interventions are effective. Relaxation exercises with guided imagery and hypnosis are most frequently employed. These methods are particularly helpful to patients who wish to maintain and enhance their sense of control. Relaxation is a useful therapy for anxiety related to pain and for control of conditioned chemotherapyrelated nausea and vomiting.108,116,117 Significant anxiety symptoms most often are treated pharmacologically by sedative-hypnotics from the benzodiazepine class of drugs, but other types also are effective, such as antihistamines, betablockers, and neuroleptics in low doses (see Table 69.9). Many patients with anxiety feel it is a sign of weakness to accept medications and therefore need to be encouraged to use them during a crisis period. The benzodiazepine is chosen on the basis of the desired half-life and route of administration, with knowledge of its metabolism and active metabolites (Table 69.10). A shorter half-life provides better control and less likelihood of poor elimination and oversedation. Patients whose anxiety manifests as insomnia respond to a bedtime dose of temazepam, 15 mg; triazolam, 25 mg; clonazepam, 1 mg; or zolpidem, 5 mg. The antidepressants trazodone, 50 mg, and mirtazapine, 15 mg, are useful for bedtime sedation. Daytime anxiety responds to lorazepam, 0.5 mg; alprazolam, 0.25 to 0.50 mg tid or qid. Clonazepam, 0.5 mg bid, or diazepam, 5 mg bid, are longer acting. It is important to taper these medications to prevent a mild rebound in anxiety or withdrawal symptoms. Buspirone is useful because it has no sedating effects and is not addictive. The neuroleptic thioridazine is useful in low doses (10 mg qid) when a benzodiazepine is contraindicated, as in older individuals. Haloperidol, 0.5 to 1.0 mg bid, and chlorpromazine, 25 to 50 mg, also are useful.109 DEPRESSION While it is expected and normal for a patient to feel sad on learning a diagnosis of cancer or hearing news that another crisis related to illness has occurred, some individuals experience far greater distress, at a level that is abnormal and constitutes a diagnosable depressive disorder. It is important to keep in mind that depression does respond to treatment and should not be left untreated, even when it is based on reality. Depression is difficult to diagnose in patients with cancer because the neoplastic disease itself often produces the vegetative symptoms of cancer: fatigue, weakness, loss of libido, insomnia, loss of interest, and

Table 69.11.

Evaluation of Depression and Predisposing Factors

Findings

Evaluative Category

Family history Personal history

Depression; suicide Previous depression, bipolar disorder, suicide attempt, alcoholism, substance abuse Recent bereavement Psychologic Dysphoric mood (e.g., sad, depressed, anxious, crying, diurnal mood change) Feelings of hopelessness; helplessness Loss of interest and pleasure; anhedonia Guilt, burden on others, worthlessness Poor concentration Mood incongruent to disease outlook Suicidal thoughts or plans Delusional thoughts (psychotic symptoms rare, except in organic affective syndrome) Somatic (less interpretable in more physically impaired patients) Insomnia Anorexia and weight loss Fatigue Psychomotor retardation or agitation Constipation Decreased libido

Signs and symptoms

Drug Approximate Dose Equivalent Initial Dosage (PO) (mg) Half-Life (h)

Short to intermediate half-life Alprazolam Chlordiazepoxide Clonazepam Lorazepam* Oxazepam Temazepam Triazolam Zolpidem Long half-life Chlorazepate Diazepam

0.5 10.0 1.0 1.0 10.0 15.0 0.25 5.0 7.5 5.0

0.250.50 tid 1025 tid 0.5 bid 0.52.0 tid 1015 tid 1530 qhs 0.1250.250 qhs 5.010.0 qhs 7.515.0 bid 510

1015 530 1850 1020 515 1015 1.5 24 30200 2070

*Lorazepam also can be administered intramuscularly; other benzodiazepines are erratically absorbed when given intramuscularly. Hypnotic agents.

Table 69.12. Medical-Related Risk Factors for Depression in Patients with Cancer Poorly controlled pain Other chronic disease/disability; advanced stage Medications Corticosteroids Prednisone, dexamethasone Interferon and interleukin-2 Chemotherapeutic agents Vincristine, vinblastine, procarbazine, L-asparaginase Other medications Cimetidine Indomethacin Levodopa Methyldopa Pentazocine Phenmetrazine Phenobarbital Propranolol Rauwolfia alkaloids Tamoxifen Antibiotics (Amphotericin B) Other medical conditions Metabolic (anemia; hypercalcemia) Nutritional (B12 or folate) Endocrine (hyper/hypothyroidism; adrenal insufficiency) Neurologic (paraneoplastic syndrome) Sites of cancer Pancreatic, small cell lung, breast cancer, lymphoma (producing remote CNS effects) Table 69.13.

CHAPTER 69 / Principles of Psycho-Oncology 951

Commonly Used Antidepressants in Cancer
Starting Daily Dosage (PO) (mg) Therapeutic Daily Dosage (PO) (mg)

Drug

Tricyclic antidepressants Amitriptyline Doxepin Imipramine Desipramine Nortriptyline Second-generation antidepressants Bupropion Trazodone Selective serotonin-reuptake inhibitors Fluoxetine Paroxetine Sertraline Citalopram Tetracyclic antidepressants Mirtazapine Serotonin- and norepinephrinereuptake inhibitors Venlafaxine Nefazodone Heterocyclic antidepressants Maprotiline Amoxapine Monoamine oxidase inhibitors Isocarboxazid Phenelzine Tranylcypromine Lithium carbonate Psychostimulants Dextroamphetamine Methylphenidate Pemoline Benzodiazepines Alprazolam

25 25 25 25 25 75 50 20 20 20 20 7.5

75100 75100 75100 75100 50100 200450 150200 2060 2050 50150 2040 7.530

25 100 25 25 10 15 10 300 2.5 at 8 a.m. and noon 2.5 at 8 a.m. and noon 18.75 in a.m. and noon 0.251.00

75150 300600 5075 100150 2440 3060 2040 6001200 530 530 37.5150 0.756.00

poor concentration and motivation.118 The oncologist must depend on the psychological symptoms of dysphoric mood, helplessness, hopelessness, worthlessness, loss of pleasure (anhedonia), and suicidal thoughts.119 Table 69.11 outlines the history and symptoms that are present in patients with cancer who have major depression. A personal or family history of depression or bipolar illness, having poor social support, being socially isolated, and having experienced a recent bereavement, all suggest increased risk of depression during illness. Evaluation should explore mental status, mood, hopelessness, feeling of being a burden, and suicidal ideation. Insomnia, anorexia, fatigue, agitation, or psychomotor retardation may relate to illness and must be interpreted in light of that fact. Depressive symptoms in their mildest form are part of an adjustment disorder with depressed mood. Dysthymia is another form of depression which is chronic and may become worse during illness. These are often referred to as minor depression, compared with frank full-blown major depression, on the basis of severity of symptoms. Table 69.12 outlines the medication-related risk factors: greater level of debilitation, advanced disease, and presence of another chronic illness or disability. Several medications frequently contribute: steroids, some chemotherapeutic agents (interferon, vincristine, procarbazine, L-asparaginase), and medications given for other reasons.120 Depression appears as part of the metabolic picture of organ failure, with some nutritional, endocrine, and neurologic complications of cancer related to direct and remote effects. It is a common symptom of pancreatic cancer, which has led to speculation about a tumor-induced mood change, possibly through alteration of brain serotonergic function.121 These disease-related major depressions are called mood disorder with depressive features due to cancer, in the DSM-IV psychiatric classification. Depression is managed first by establishing good rapport with the patient and ensuring support from available family members or friends. Supportive psychotherapeutic as well as behavioral interventions and psychotropic agents, often combined, are important resources for the treatment of depression. Behavioral interventions are effective in depression, by using cognitive-behavioral methods that encourage the patient to reframe the problems more constructively and to approach each aspect as a challenge to be met, which often reduces

uncontrolled, distressing emotions. This has been particularly helpful in coping with pain, which is extremely frightening in cancer when it is assumed to be evidence of tumor progression.51 Cognitive approaches also can alter distressing sensations and responses to them.39,116,122 Psychotropic drugs have been shown in clinical trials to be effective in controlling depressive symptoms in the course of medical illness, including cancer.123 Table 69.13 lists the most frequently used antidepressant medications in patients with cancer and their starting and maintenance doses. The commonly used antidepressants are the tricyclics, second-generation antidepressants, heterocyclics, selective serotonin-reuptake inhibitors (SSRIs), monoamine oxidase inhibitors, psychostimulants, lithium carbonate, and benzodiazepines. The SSRIs are the first-line treatment now because of their efficacy and low sideeffect profile, with less sedation and fewer autonomic side effects than the tricyclics. Fluoxetine has been widely used, as well as paroxetine and sertraline, and more recently citalopram. They have a short halflife. Venlafaxine is available as a serotonin and norepinephrine-reuptake inhibitor. Nefazodone, which is similar in effect to trazodone is a safe and effective antidepressant. Buproprion is widely used both for antidepressant effects and as part of smoking cessation regimens. Tricyclics are less commonly used because of their side effects, such as dry mouth and constipation. They are started at a low dose (10 to 25 mg at bedtime) and slowly increased by 10 to 25 mg increments over 4- to 7-day intervals. Patients usually are maintained 4 to 6 months on a tricyclic, chosen, in part, for its side-effect profile. A tri-

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Table 69.14. Risk Factors for Suicide in Cancer

Table 69.16.

Suicide in Relation to Stage of Disease

Personal Prior history of depression or suicide attempt (personal or family) Prior psychiatric disorder Prior alcohol or drug abuse Depression and hopelessness Recent loss/bereavement Socially isolated Medical Pain Delirium with poor impulse control Advanced illness Debilitation, exhaustion, fatigue

Patients at all stages of cancer Suicidal thoughts are common and serve as a means to maintain a sense of control over the disease Carrying out the act is viewed as for the future when I need to do it Some maintain a means of suicide (e.g., drugs) to assure ultimate control over feared intolerable symptoms Patients in remission, with good prognosis Serious suicidal thoughts represent underlying psychiatric disorder (depression, substance abuse) Unlikely to appear rational; treat aggressively, including hospitalization Patients with poor prognosis and poorly controlled symptoms Thoughts of suicide often appear rational May request advice about physician-assisted suicide Need evaluation for presence of treatable depression Need attention to quality-of-life issues and comfort Suicidal wishes usually diminish with control of distressing symptoms Adequate symptom control by physician may hasten death (dual effect) but is not actual physician-assisted suicide Patients in terminal stage May request euthanasia by lethal injection from physician Request often reflects poor quality of life, hopelessness, and depression Need for control of symptoms, even when it hastens death

cyclic with sedating effects, such as amitriptyline or doxepin, is best for agitation and insomnia; psychomotor slowing is better treated with desipramine. Nortriptyline and desipramine should be used for patients in whom minimal anticholinergic effects are desired. The tricyclics also are helpful in controlling chemotherapy-related peripheral neuropathy, pain, and discomfort. Maprotiline, amoxapine, and trazodone are useful, especially trazadone for insomnia associated with depression. In general, they have side effects similar to the tricyclics. Maprotiline can lower the seizure threshold. Antidepressant effects may take 2 to 3 weeks to become evident with the drugs discussed above, and maximal benefit usually is obtained by 4 weeks. Among the other antidepressants, psychostimulants are most widely used to promote well being and counteract the fatigue from advanced illness. Drowsiness associated with opioids often is diminished by dextroamphetamine, methylphenidate, or pemoline, which is a noncontrolled stimulant, with no addictive potential. Alprazolam has the advantage of being effective against anxiety and depression, and it is useful when stronger antidepressants are contraindicated.123 All antidepressants should be started in a low dose in elderly and young adults and titrated upward as tolerated. SUICIDE AND CANCER The incidence of suicide is higher in patients with cancer compared with the general population, but it is not as high as often is assumed.124126 It is likely, however, that suicide by overdose at home during the terminal stages of cancer is underdiagnosed and under-reported due to fear of stigma. Suicide is more likely to occur in advanced disease, when depression, hopelessness, and the presence of poorly controlled symptoms (especially pain) are greatest. Table 69.14 outlines risk factors that predict the execution of suicidal thoughts. They are similar to factors predicting depression (see Table 69.11) and must be assessed when evaluating a patient for suicidal risk (Table 69.15). Evaluation of the patient with suicidal ideation should query the nature of suicidal thoughts (passive or active), past history of psychiatric problems, particularly depression or suicide attempts, recent loss or bereavement, family history of depression or suicide, present symptoms that the patient feels are poorly controlled, the patients understanding of disease and prognosis, and the availability of social support. Evaluation of suicidal thoughts and risk in cancer must take into account disease stage and prognosis, since management depends on
Table 69.15. Evaluation of Suicidal Risk

Establish rapport Ask about symptoms (pain, discomfort, and adequacy of their control) Ask about depression and suicidal thoughts at present or in the past Ask about suicidal thoughts (Are they passive [I wish I could die] or active [I am thinking of ways to do it]) Ask about family or friends and sense of support from others Ask about any recent loss of close person, especially if by cancer Ask about understanding of illness, presence of confusion, fatigue Asking does not cause suicidal thoughts; the patient is usually relieved to express them.

these factors (Table 69.16). It is helpful to consider the issue from four perspectives: (1) the suicidal thoughts which occur transiently in all patients with cancer; (2) suicidal thoughts in patients who are in remission with a good prognosis; (3) suicidal thoughts in patients with poor prognosis/poor symptom control; and (4) suicidal thoughts in patients in terminal stages. First, almost all patients who receive a diagnosis of cancer, even when the prognosis is good, carry a secret thought: I wont die in pain with advanced cancer. Ill kill myself first. Some patients maintain a hidden supply of a drug for this purpose. It usually serves as a steam valve, and with this, the person is able to maintain a sense of ultimate control over the disease and an intolerable future. The thought actually serves as a protective coping device that must be recognized by the physician and the psychiatrist as a means of maintaining control. For most patients, the time never comes to take the drug, and life becomes dearer as death approaches. The intensity of suicidal thoughts is greater among patients who have seen a relative die with poor control of pain, as was more typical of earlier times, and especially if it was the same cancer. It is important that the physician listen to these fears and concerns. Much of the societal concern about the right to physician-assisted suicide derives from the fear of loss of control. Serious ruminations about suicide in a patient in whom the disease is in remission or in whom a good prognosis exists, is not rational. In fact, careful evaluation very likely will elicit the presence of major depression, a history of substance abuse, or recent bereavement. A study by Hietanen and Lonnqvist127 of all suicides in Finland in 1987 found that 4.3% had cancer. Surprisingly, half these patients with cancer were in remission at the time of the suicide; they had greater prior psychiatric problems, particularly substance abuse, than those who committed suicide in advanced stages of cancer. It is important that these patients be recognized and aggressively treated for depression and suicidal risk, including psychiatric hospitalization, if necessary.126 Patients with a poor prognosis, advanced disease, and poorly controlled symptoms often have thoughts of suicide that are more likely to be viewed as rational.128 They may request a physician to write a prescription for a drug they intend to use to commit suicide. The sensitive physician should indicate his/her concern and express the importance of exploring further what the reasons are for suicidal wishes. A refusal to help without trying to find the reason for the patients request is not useful. Ideally, these patients should be referred to a psychiatrist to be evaluated whether they have a treatable major depression which is fueling their suicidal ideation. Chochinov and colleagues61,63 found that the persistent desire for death in the terminally ill is closely associated with the diagnosis of depression. It is particularly important to

evaluate the presence of hopelessness, which is a greater predictor of suicidal risk than depression itself.126 The other intervention needed is careful attention to any uncontrolled physical symptom, especially pain. Suicidal ideation diminishes when there is good control of pain and depression. Adequate pain control by the physician may actually have the dual effect of hastening death, but few physicians have difficulty in carrying out such a treatment aimed at comfort. Most physicians do not regard this as assisted suicide but as appropriate treatment geared to maximal comfort.57 Patients who are in the terminal stages and are too weak to carry out a suicidal act are those most likely to request euthanasia by a lethal injection from the physician. While the societal debate has been intense, support for Kevorkian-like legalized euthanasia has not occurred in Oregon, where physician-assisted suicide has been legalized. Only 11 patients died in this way in the first year. Federal action now prohibits the use of FDA-controlled substances for this purpose, and the societal debate continues. In our experience, hospitalized patients with advanced disease who are suicidal usually have poorly controlled pain (or nausea and vomiting), and they often have beginning organ failure with a mild metabolic encephalopothy resulting in poor judgment and poor impulse control.129 Depression and hopelessness are prominent as well as the feeling that there is no quality to my life and no pleasure. Patients are given a 24-hour companion, preferably a family member who understands the patients compromised state and who can provide emotional support. We begin aggressive management of their distressing physical symptoms (e.g., pain control with opioids) and institute an antidepressant along with supportive psychotherapeutic visits aimed at helping the person find some perspective from which he or she can find positive meaning despite the overall situation (e.g., My children need me and I must carry on.). Often, the suicidal wishes diminish with adequate attention to their distress. DELIRIUM Delirium, or encephalopathy, is a nonfocal, global cerebral dysfunction characterized by waxing and waning levels of consciousness, disordered thinking, disorientation and confusion, psychomotor slowing or agitation, and altered behavior, judgment and sleep-wake cycles. It is often worse at night, hence the term sundowning. It is usually contrasted with dementia by its being reversible; however, in advanced stages of cancer, due to organ failure and metabolic derangements, it is not reversible. The goal is to control the symptoms that are distressing or harmful to the patient or others (e.g., pulling out lines, combative behaviors). Family members need to understand that the cause is brain dysfunction, not a change in personality. They should be given explanation and guidance in dealing with the behavior. In patients with cancer, especially those in the advanced stages of disease, a sudden change in mood or behavior is most often related to a change in neurologic, vascular, or metabolic status; a functional basis is far less likely. In fact, in advanced and terminal illness, 75% of hosTable 69.17. Common Causes of Delirium in Cancer
Causes Examples

CHAPTER 69 / Principles of Psycho-Oncology 953

Table 69.18.
State

Behavioral Symptoms of Delirium in Patients with Cancer

Symptom

Early, mild

Late, severe with behavioral changes

Change in sleep pattern with restlessness, attempts to get out of bed, transient periods of disorientation Unexplained anxiety and sense of dread Increased irritability, anger, temper outbursts Withdrawal, refusal to talk to staff or relatives Forgetfulness, not previously present Refusal to cooperate with reasonable requests; pulling out tubes and lines Angry, swearing, shouting, abusive Demanding to go home, pacing corridor Illusions (misidentifies staff, visual and sensory clues) Delusions (misinterprets events, usually paranoid, fears of being harmed) Hallucinations (visual and auditory)

pitalized patients were found to develop a confusional state (delirium) during the period before death. Common causes of delirium in cancer are outlined in Table 69.17.130 A change in behavior in which the person becomes irritable, uncooperative, agitated or somnolent, and misinterprets sounds or objects is probably exhibiting early signs of delirium. This picture may be followed by delusions, usually paranoid (there are people here trying to hurt me), frank hallucinations, and difficulty in being held in their bed and hospital room because of mental aberrations (Table 69.18). Management begins with attention to the patients safety. It is important to have one-to-one observation, preferably by a person who can correct the patients misinterpretations of what is happening. Limiting the number of new faces and experiences is useful while enhancing awareness of time and place. Older patients are most prone to become confused, and delirium may be superimposed on dementia. Physical restraints must sometimes be used to prevent removal of vital intravenous lines and bandages and to prevent falls. Pharmacologic restraint may be necessary. The most common management is with low-dose haloperidol, a potent dopamine blocker, 0.5 to 1.0 mg bid to qid. Lorazepam reduces agitation in doses of 0.5 to 1.0 mg tid to qid but, alone, may increase confusion. Haloperidol and lorazepam often are given together to reduce confusion and diminish agitation.131 Table 69.19 outlines the drugs which are useful and their routes of administration, since access is sometimes a problem. Correcting the underlying metabolic or neurologic problem is not always possible, however, and comfort for the patient and family may depend, in practical terms, on being able to control the patients symptoms of confusion and agitation. Patients with psychomotor slowing may be safely observed without treatment, but significant degrees of confusion with agitation must be treated.59,129 This is often seen in terminal stages, and achieving sedation may be the goal to provide comfort and safety for both patient and family.
Table 69.19. Medications for Managing Delirium in Cancer Patients
Approximate Daily Dosage

Metabolic encephalopathy because of vital organ failure Electrolyte imbalance Treatment side effects

Infection Hematologic abnormalities Nutritional causes Paraneoplastic syndromes Metastatic or primary brain tumor

Liver, kidney, lung (hypoxia), thyroid, adrenal Sodium, potassium, calcium, glucose Narcotic/analgesics Anticholinergics Phenothiazines Antihistamines Chemotherapuetic agents Steroids Radiation therapy Septicemia Microcytic and macrocytic anemias, coagulopathies General malnutrition, thiamine, folic acid, vitamin B12 Remote effects of tumors Hormone-producing tumors

Generic Name

Neuroleptics Haloperidol Thiorodazine Chlorpromazine Molindone Risperidone Methotrimeprazine Benzodiazepines Lorazepam Midazolam Anesthetics Propofol
Reprinted from Breitbart and Cohen.129

0.55 mg every 212 h, PO, IV, SC, IM 1075 mg every 48 h, PO 12.550 mg every 412 h, PO, IV, IM 1050 mg every 812 h, PO 13 mg every 12 h, PO 12.550 mg every 48 h, IV, SC, PO 0.52.0 mg every 14 h, PO, IV, IM 30100 mg every 24 h, IV, SC 1050 mg every h, IV

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Table 69.20. Quality-of-Life Measurement: Functional Areas of Living Assessed Physical Functional Psychologic Sexual Social Work Symptoms of disease and treatment of side effects Ability to perform usual activities Mood, sense of well being Desire, performance Family, friends, leisure Usual level of activity

PSYCHIATRIC AND PSYCHOSOCIAL INTERVENTIONS There has been a great increase in the number of controlled trials of well-defined psychotherapies which show efficacy in terms of decreased distress and improved quality of life, an effect that persists for months.113,114,132,133 Brief crisis counseling134 and combined psychosocial and educational interventions have proven to be of value in patients with cancer in helping them cope more effectively.135 Problem-solving counseling has emerged as a cognitive approach that is helpful for patients and family members.116 Twillman and Manetto37 have shown the efficacy of concurrent psychotherapy and pharmacotherapy in the management of depression and anxiety. Other studies have compared antidepressants.136138 Kissane and colleagues have taken a cognitive-existential approach in treating women with breast cancer that acknowledges the awareness of the crisis of meaning.139 Group counseling models have been developed from trials directed at both early and advanced disease, with evidence of efficacy.35,139142 They are effective in reducing distress and in helping to control pain. The widespread use of groups and the developments in psychoneuroimmunology has led to questions of whether psychosocial interventions can extend life. The one meta-analysis which has been done by Meyer and Mark115 showed an overall effect on quality of life but not on survival. There is little doubt that effective coping assures adherence to treatment and indirectly affects survival. However, whether interventions have any direct effect on survival is far from conclusive. Studies by Spiegel and colleagues,143 and Fawzy,144 reported 10 years ago, remain to be replicated. Studies are ongoing, and data should become available soon. However, several negative studies have been reported with group intervention, which showed no survival advantage.140,145,146 BLURRING OF CONVENTIONAL PSYCHOSOCIAL AND BEHAVIORAL INTERVENTIONS WITH ALTERNATIVE/ COMPLEMENTARY THERAPIES Behavioral interventions have been well tested and accepted in cancer patients. Relaxation, meditation, and systematic desensitization are all effective in reducing anxiety, conditioned responses from chemotherapy-induced nausea and vomiting, and pain.80,147 These behavioral interventions are often coupled with cognitive therapy approaches.116 The value of art therapy has also been shown.148 With the explosion of complementary/alternative medicine (CAM) in the United States, there has been a tendency, in cancer, to identify all interventions except surgery, chemotherapy, and radiation as CAM. For example, patients use of prayer, relaxation, meditation, psychotherapy, support groups, pastoral counseling, exercise, and nutrition have all been classified as CAM in one often-used survey instrument.149 It is inappropriate to lump the range of proven behavioral interventions and other counseling modes and common sense approaches to improve quality of life and well being as CAM. A study by Burstein and colleagues150 explored the use of CAM by women in the year following initial breast cancer treatment. Women who had used CAM (as defined above) were more depressed, more worried about the future, and had poorer quality of life. The data suggest that many who used CAM were more distressed and were seeking treatment for their psychological symptoms by using CAM. One explanation for this is that many are not being recognized by their oncologist as being distressed and hence are not referred to psychosocial resources within their traditional cancer care system.151 This fact adds weight to the importance of clinical practice guidelines for oncologists, which includes a triage system that assures that cancer patients who are distressed are referred to proper treatment resources5 (see guidelines above). QUALITY-OF-LIFE ASSESSMENT The definition of health-related quality of life (QOL) is the level of performance in the major domains of life function as reported by patient self-report.47,152 In the 1990s, clinical trials have increasingly included the assessment of quality of life in the outcome variables.153

Interest in quality of life grew after 1984, when the U.S. Food and Drug Administration (FDA) demanded that the efficacy of new anticancer agents be demonstrated by improved survival or evidence of enhanced quality of life. Coupled with patients involvement in their treatment decisions and concerns about informed consent, issues regarding quality of life with one treatment versus another led to heightened interest in finding ways to measure this variable. Karnofsky and Burchenal actually described in 1949 that in addition to survival, subjective improvement was equally important in the evaluation of patients responses to treatment.154 Despite that early observation, however, today only selected trials assess QOL, usually when there is a small likely treatment advantage (e.g., trials of chemotherapy agents in pancreatic cancer) or when a highly effective new treatment has significant side effects (e.g., stem cell transplantation).155 Today, six domains of function generally are included in multidimensional QOL measures: physical, functional, psychologic, social, sexual, and work-related (Table 69.20). No gold standard of measurement, however, currently exists to assess QOL, but there are several frequently used scales employed to monitor function and the effects of treatment. Initially, the most widely used was the functional living index-cancer (FLIC).156 A 22-item scale with physical well being and emotional subscales, the FLIC has largely been replaced by scales specifically for use with cancer that provide broader information. The cancer rehabilitation evaluation system (CARES) is a scale that consists of 139 items concerning cancer problems across the six QOL domains.157 A series of QOL measures were developed and tested by the European Organization for Research and Treatment of Cancer (EORTC).158 The scales have a core of questions that are applicable to the QOL for all patients with cancer and modules which are attached to query the specific issues related to a disease site (e.g., prostate, breast, lung cancers). A similar approach has been used by Cella and colleagues159 in the development of the functional assessment of cancer therapy (FACT), which adds an aspect of patient assessment regarding the discrepancy between prior and present functions. In addition to the FACT-G, the core questions, Cella has developed modules for major cancer sites and common problems requiring subjective assessment, such as nausea, vomiting, and pain. Aside from the Karnofsky performance rating scale, Spitzer and colleagues quality of life index (QL-index) is the only observer-rated measure of QOL that is used with any frequency.160 Additional scales, not developed specifically for cancer but widely used, are the psychosocial adjustment to illness scale (PAIS) and the sickness impact profile (SIP).161,162 The PAIS, in particular, has been used extensively with several chronic illnesses, including cancer. The SIP scale is similar in format to CARES, in that it lists 136 problems that can result from illness that affect QOL. Most QOL scales presently being developed are designed for selfreport or to be completed in response to structured interview questions.163,164 Traditionally, such forms were administered at the time of clinic visits; however, the use of trained telephone interviewers in cooperative group trials in the CALGB has been found to be not only a more practicable approach but more effective because it takes the collection of QOL data away from the rushed clinic setting.155 The method ensures consistency in terms of evaluation and promotes better compliance as well as patient satisfaction. There are fewer missing data points because answers can be clarified immediately with the patient by the interviewer. Using this type of telephone approach, in which the patient has the written questions and responds to them at the interviewers request, findings were comparable with those attained using face-to-face interviews.

Recent efforts in QOL research have concentrated on the development of a unitary measure that might combine length of survival and QOL, referred to as quality-adjusted life years or QALY. TWIST (time without symptoms or toxicity), is another QALY method developed by Goldhirsch and colleagues.165,166 In this method, the number of months in which the patient experienced symptoms (weighted as to toxicity) or was in relapse is subtracted from overall survival time, yielding a QALY score. In QALY research, weights, which are either empirically derived or chosen arbitrarily, are assigned equally to disabilities and symptoms in the two treatment arms. In this manner, the effects of difference between symptoms on QOL can be mathematically taken into account. These methods, coupled with economic analysis, are providing increasing information to assist patients in making decisions about cancer treatments. FAMILY ISSUES Families have emerged as a significant overburdened but underrecognized component of health care today.167 Families are often viewed as being difficult in the hospital by staff who focus on the patient. However, discharge planning is done hurriedly and frequently inadequately, and the patient with a greater level of illness than in the past is suddenly returned home for care by the family. Today, the level of expectation of family members to give physical care and carry out medical procedures is also far greater. An estimated 25 million households in the United States are caring for a chronically ill family membermany are in homes of the economically deprived.168 Attention is slowly being given to the greater needs of families today by health policy planners. But, in addition to economic stresses, there are profound psychological and social stresses.169,170 These issues are compounded when the care at home is being given for advanced and terminal stages of cancer.49 The oncologists responsibility to the patient extends to the evaluation of the caregiver as well and the ability of that key person to cope with the demands. GRIEF IN SURVIVING FAMILY MEMBERS Oncologists who treat patients with cancer often come to know family members well, especially during the terminal stages of illness. They are in a unique position to provide support to the family when the patient dies and ensure care for grief in the surviving caregiver and family members, especially children.171 They need to be able to recognize abnormal reactions and refer the grieving relative for bereavement counseling. Hospice programs include this as part of their services. It is important to be aware in ones community of both support groups for the bereaved and of mental health professionals who offer one-on-one bereavement counseling. Severe or protracted grief reactions often lead to major depression that requires intensive psychiatric treatment. There has been much interest in whether grief results in increased risk of cancer or whether it promotes progression or recurrence in survivors. Several studies have found no higher mortality from cancer among parents in Israel who had lost a child by accident or war 10 years earlier172 or in parents in Denmark who had experienced death of their child from cancer.19 Similar results were found for loss of spouses followed up 10 years later.173 Zonderman, following a community sample of individuals who had depressive symptoms or clinical depression, found no excess mortality from cancer 10 years later.174 A study from the CALGB, to be published shortly, used a nested case-controlled design to study women who had received adjuvant chemotherapy for breast cancer 7 years earlier. When controlled for expected predictor variables of survival, loss of child or spouse in the 7 year interval did not predict shorter time to recurrence or death. These epidemiologic data suggest that grief does not increase the risk of cancer or lead to its recurrence or progression in survivors. This information is reassuring for individuals who fear that their grief is making them more vulnerable to cancer or its progression. SUMMARY The subspecialty of psycho-oncology is a recent development within oncology, reflecting the increased interest in the behavioral, psychological, ethical, and social factors in cancer prevention and the

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quality of life for patients with cancer at all stages. Quality-of-life issues are different in patients under active treatment, during palliative care, for survivors, and for healthy individuals who are at known increased genetic risk. Early identification of patients who are not coping well with the diagnosis and treatment is important, both for treatment compliance and control of distress. It is important to recognize and diagnose common psychiatric disorders, such as anxiety and depressive symptoms (adjustment disorder, with mixed features), major depression, specific anxiety disorders, and delirium caused largely by medications and complications of cancer. The modalities available to treat these symptoms are psychoeducational, psychosocial, psychotherapeutic, behavioral, and pharmacologic. Referral to a mental-health professional familiar with the care of patients with cancer is often important, both for evaluation and treatment. The measurement of health-related quality of life that assesses the patients functioning in the major domains of life has been a valuable addition to clinical trials research, permitting assessment of not only survival but also the quality of that time. This merger of data from two diverse areas augurs well for future research in oncology which addresses the total care of the patient. REFERENCES
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