The desire for hastened death, death sooner than natural disease progression, and passive or active suicidal wishes in the setting of advanced disease are associated with depressive disorder and its feature of hopelessness. Chochinov et al. found that 8.5% of those admitted to the hospital for terminal illness in Canada wished to die sooner and most were depressed (15).

Some ambulatory cancer patients do have thoughts that they would be better off dead or the thoughts of hurting themselves. One study of almost 3,000 patients in Scotland found that 8% reported such thoughts in the previous 2 weeks (23). Those patients with suicidal thoughts were more apt to have clinically significant emotional distress, substantial pain, and to a lesser extent older age.

In the setting of a cancer diagnosis, the likelihood of suicide is greatest when the diagnosis is new and when it seems to the patient more likely to be advanced and progressive. The most common cancers associated with suicide are lung, stomach, oral cavity and pharynx, larynx, and pancreatic cancers. Even with pancreatic cancer, which had the highest rate, however, suicide is extremely rare (24,25). The presence
of suicidal thoughts should directly lead to further assessment of the diagnosis of depressive disorder.

The narrowed thinking that comes with depression makes it harder to see any window of light or any sense that an individual’s life matters. Often intoxicants like alcohol or the medications for a medical illness like narcotics contribute to impulsivity and distortions of thinking.

Questions about the wish to die should be part of a basic evaluation of depression. The seriousness and persistence of the thoughts and the seriousness of a plan convey the gravity of the danger for a patient. Safety is a priority. Sometimes, the idea of suicide offers patients a sense of ultimate control over a worse fate, untreated pain or helplessness, and loss of respect in illness. The caretakers’ attention to relief of pain, to hearing the patient out, to amplifying the patient’s control as much as possible has value. Evaluation and treatment for clinical depression, a syndrome that comes with suicidal thoughts even when patients are not physically ill, is critical. If there has been a suicide attempt, understanding what made the patient think that suicide was the best choice can open a dialogue. In the setting of depression, thinking is pessimistic and distorted. Self-esteem is small. Patients may acutely underestimate their ability to cope and underestimate what can be done, room for hope, and the caring of loved ones. Medical intervention to increase comfort, to treat depression, and to change the psychosocial reality becomes paramount.

Patients with clinical depression have a hard time concentrating and persisting in concentration. They may not read the newspaper or follow their favorite team as usual. However, usually when pressed to do basic cognitive functions, they are able to. In the setting of systemic illness, multiple medications, including especially narcotics and benzodiazepines, the likelihood of syndromes of cognitive impairment increases. The lack of function that comes with cognitive impairment may be misunderstood as depression. Once confusion is documented, medical interventions or reduction in medication to improve cognition becomes the first priority.

Sickness, that is, anything that causes injury and inflammation, triggers cytokines and sickness behavior that can mimic the vegetative somatic symptoms of major depressive disorder (26). Malaise is the syndrome associated with fever or flu syndromes like the syndrome caused by interferon treatment. It is listlessness, inability to concentrate, hypersomnia, social withdrawal, anorexia, loss of interest, and poor grooming. Interleukin (IL)-1 and tumor necrosis factor foster slow wave sleep. Proinflammatory cytokines, IL-α and IL-β, tumor necrosis factor-α, and IL-6, generally, can trigger a constellation of behavioral changes that include fatigue, sleep disturbance, and depressive-like symptoms in animal models. There is a fatigue syndrome that follows procedures like surgery and radiation treatment. Bower et al. found that among breast cancer patients after the complex initial multi-modal treatment of the first year, 25% had depressive symptoms and 60% were fatigued. Fatigue was associated with soluble tumor necrosis factor receptor II levels and with recent treatment with chemotherapy. Depressive symptoms were associated with fatigue but not with inflammatory markers. These data support the idea that systemic chemotherapy is followed by a somatic fatigue syndrome characterized by inflammation that is distinct from the fatigue of major depressive disorder (27).

The fatigue of depression is typically associated with a sense of effort, a dread of the day, and insomnia, rather than the sleepiness and lack of stamina that come with the fatigue of sickness behavior.

Demoralization is a condition seen in medically ill patients, experienced as existential despair, hopelessness, helplessness, and loss of meaning and purpose in life. According to Clark and Kissane, who wrote about this syndrome and its history in the setting of those with advanced illness, this condition is distinguished from depression by the emphasis on a feeling of subjective incompetence rather than anhedonia. Its hallmark is hopelessness and the wish to die. The demoralized “feel inhibited in action by not knowing what to do, feeling helpless and incompetent, in the face of uncertainty, a failure of knowing how to cope” (28). Kissane et al. have developed a scale with distinct dimensions of loss of meaning, dysphoria, disheartenment, helplessness, and sense of failure (29). Demoralization has been seen as a normal response to adversity analogous to grief. These authors called upon Frank’s description of demoralization in combat soldiers (30) and Schmale and Engel’s giving up-given up complex (31). Griffith and Gaby (32) suggested that a pragmatic explanation of demoralization in medically ill patients is a set of different existential postures that position a patient to retreat from the challenges of illness. Helplessness, despair, or meaninglessness may to different degrees combine in contributing to the sense of subjective incompetence. Shader (33) noted that it is difficult to distinguish the presence or absence of depressive disorder in the demoralized patient since such a patient would feel more helpless in the presence of a persistent negative mood. He argued that the recognition of demoralization implies, beyond somatic treatments, that the clinician must work with patients to promote a sense of mastery and return of hope.