Anxiety, Depression, and Delirium in Terminally Ill Cancer Patient

Abstract

Most terminally ill cancer patients present some degree of anxiety, depression, or delirium. In many cases family concerns, the prognosis of the disease, the type of treatment, and its adverse effects aggravate these emotional symptoms to the point of turning them into severe affective disorders which severely complicate their emotional state, their physical condition and their disposition and response to treatment. Although these are high prevalence disorders in terminally ill cancer patients, they often go undiagnosed and therefore do not receive treatment. An early diagnosis and adequate treatment, that includes emotional accompaniment, can greatly help to maintain the quality of life or even improve it and make these patients and their families move in a dignified way toward death. The scope of this chapter is to establish the presence of anxiety, depression and delirium in terminally ill cancer patients through scientific evidence; review the opinion of experts in the field on the most appropriate treatment, and the influence on the beneficial impact of interventions with family members or support people to ensure a more positive approach to the circumstances of these patients and serve as support for the treatment of medical personnel.

“The truth is, once you learn how to die you learn how to live.

—Mitch Albom, Tuesdays with Morrie¹

1. Introduction

1.1 Cancer: definition and prevalence

Cancer is defined as the pathological tissue growth caused by a lengthy and persistent proliferation of abnormal cells which causes invasion and destruction of body tissues [1].

Cancer, neoplasm, or malignant tumors are generic terms used in an indistinct way to designate a wide group of diseases that can affect any part of the organism. But cancer has a definite characteristic: the accelerated multiplication of abnormal cells that extend far beyond their usual limits, even invading other body parts, which is called metastasis. The metastatic extension is the principal cause of death by the disease [2].

According to the World Health Organization (WHO), cancer is the principal cause of death worldwide, being almost one of six deaths registered annually and in 2020, the total amount of cancer-related deaths was nearly 10 million [2].

Approximately 400 thousand children get diagnosed with any type of cancer annually. However, the incidence rises with age due to the loss of cellular repair mechanisms and the accumulation of risk factors [2].

Besides age, smoking is another important cancer risk factor, being almost one-third of cancer-related deaths. Other risk factors are increased body mass index, a sedentary lifestyle, alcohol intake, and low fruit intake [2].

2. Anxiety: definition, prevalence, and clinical characteristics

Anxiety is a natural adaptive mechanism that allows the human being to be alert to potential dangers. In a way, it delivers a sense of precaution for usual dangers and, in moderate intensity and short intervals, can help us focus, maintain focus, and face challenges.

As with other emotions, when the anxiety presents disproportionately for a specific situation or even in the absence of any evident danger, the beneficial effect is exceeded.

According to WHO, in 2015 the world prevalence of anxiety disorders was 3,6%. As with depression, anxiety disorders are more frequent in women than in men (4.6% versus 2.6% worldwide) [3].

It is calculated that approximately 13% of the general population has a phobic anxiety disorder, like social phobia, whereas 7% of women and 4.3% of men have specific phobias. Generalized anxiety disorder (GAD) is presented in 3–5% of the adult population. Obsessive-compulsive disorder (OCD) affects almost 2.3% of adults. Panic disorder is less frequent and is diagnosed in less than 1% of the population. Posttraumatic stress affects at least 1% of the population, with higher incidences in war veterans and survivors of physical or sexual abuse [3].

As physical signs and symptoms, we can find palpitations, tachycardia, hyperventilation, excessive sweating, the feeling of chest oppression or dyspnoea, tremors, dizziness, and fainting. As mental signs and symptoms, we have constant worry, weariness, irritability, and trouble focusing and falling asleep [4].

The anxiety that occurs in a high level of intensity and extends for long periods begins to produce a psychosocial functioning deterioration, interfering with normal activities and in more than one sphere (social, family, academic, and work, among others). On the other hand, the intensity and duration also produce physiological damage.

It is important to promptly recognize these signs and symptoms and have an integral medical evaluation.

3. Depression: definition, prevalence, and clinical characteristics

Mental health problems, especially depression, represent a public health concern due to their high prevalence, morbimortality, and incapacity generated in a long term.

Depression is different from mood changes and brief emotional responses to the problems of daily life and can become a serious health problem, especially when it occurs recurrently and with moderate to severe intensity, being associated with suicide in some cases.

Depression is a common disease throughout the world, as it is estimated to affect 5% of adults and 5.7% of elderly adults (over 60 years of age) [5]. According to the WHO, it is estimated that, in 2015, the proportion of the world population with depression was 4,4%. Although since the start of the 2019 COVID pandemic, the prevalence of anxiety and depression has increased by up to 25% [6].

In general, depression is defined as a disease characterized by a state of persistent sadness that is accompanied by a loss of interest in previously enjoyed activities. In addition, the patient loses the ability to carry out daily activities. All of this occurs for at least two weeks. In many cases, when depression is chronic, it is difficult for the patient to identify sadness or even remember what activities generated enjoyment: the only thing noticeable is the difficulty to participate in their different spheres (social, sentimental, work, academic, etc.) [7].

People with depression often have several of the following symptoms: loss of energy, disturbances in sleep pattern, sleeping more or less than usual; changes in the appetite; anxiety; decreased concentration; indecision; concern; feeling worthless, guilty, or hopeless; and frequent thoughts related to death, with self-harm, suicidal thoughts or attempts that often lead to death [8].

People exposed to violence frequently experience a variety of reactions including anxiety, stress, frustration, fear, irritability, anger, difficulty concentrating, loss of appetite, and nightmares [9].

Depression interferes with daily life, the ability to work, sleep, study, eat and enjoy life [9]. On the other hand, people with depression present cognitive distortions, such as negative thoughts about themselves, the environment or the future, and alterations in cognitive performance such as difficulties with concentration, memory, and the ability to make decisions, which also influence the overall functioning of the person [8].

When talking about mental health, it is always important to emphasize that depression is not a sign of weakness. It can be treated with psychotherapy, antidepressant medication or with a combination of both methods, the latter being what has shown better and longer-lasting results. A second sphere that must be targeted, within the treatment, is the generation of healthy lifestyles.

It is very common for patients with depression to have a family history of the disease. However, depression can also occur in people without a family history.

The causes of depression are multiple since several genetic, biological, and environmental factors intervene in it.

Regarding genetic factors, several studies have reported that around 200 genes are related. These genetic factors are related to alterations of neurotransmitters, cytokines and hormones, whose actions induce structural and functional modifications in the central nervous system, the endocrine system, and the immune system, which increase the risk of suffering from major depression [10].

The biological causes are explained both by structural alterations in the brain as well as functional alterations in neurotransmitters (serotonin, norepinephrine, and dopamine). However, more studies are still needed to understand the mechanisms of the efficacy of antidepressants [11, 12].

Among the environmental or psychosocial factors, it has been observed that depression is associated with previous stressful events, especially when these occur at an early or older age if the subject has been subjected to prolonged stress. The stress that accompanies the first episode produces long-term changes in brain physiology that can produce variations at the structural level and in the functioning of different brain areas [13, 14].

4. Terminally ill patients

The importance of determining that a patient is in the terminal phase (end of life) of the disease is aimed at early identification of the needs and special care that help the patient and his family [15].

Thus, the terminal patient is the one who has an advanced, progressive, and incurable disease, with a lack of reasonable possibilities of responding to a specific treatment, who presents numerous problems or intense symptoms, with a loss of autonomy or progressive fragility that represent a great emotional impact for himself, his relatives and the therapeutic team that cares for him, and his situation being related, implicitly or explicitly, to the presence of death and a life expectancy of fewer than six months. All of this is associated with high demand and use of resources [16, 17].

5. Cancer patient in terminal phase

On the other hand, the cancer patient in the terminal phase is the one with a histological diagnosis of cancer demonstrated in clinical stage IV; brain, spinal cord, liver or multiple lung metastases; who have received effective standard therapy and/or are in a situation of little or no possibility of responding to active or specific treatment [18].

Medicine attempts to preserve life, we see life expectancy rates are increasingly higher, however, it is inevitable getting to prevent death in spite of the multiple human and technological efforts and the advance in science.

It is in light of this reality that medical practitioners face patients in terminal, a human being that encounters great fears—resulting from the disease itself – to face death as an imminent situation and along with the patient, relatives and friends surrounding them.

Just there is where the medical practitioner and the therapeutic team are faced to great challenges, on the hand, relieving physical symptomatology, and on the other hand, dealing with those psychological needs. Therefore, the awareness of healthcare personnel facing this critical situation is essential to effectively help in the relief of patient and their family.

According to the Institute of Medicine, the “Good death” is one that is: “free from avoidable distress and suffering for the patient, family and caregivers, in general accord with the patient’s and family’s wishes, and reasonably consistent with clinical, cultural, and ethical standards” [19, 20].

The objective of the health personnel who oversees the patient in palliative care must be to reach the “Good death” and the steps to get to that state are aimed at relieving the mental, physical, family state, etc. It is there that psychiatric disorders take on great importance, because, although they are very frequent and with a high incidence, many times they are not detected early [15].

6. Psychiatric disorders in cancer patients

Within the main psychiatric disorders, we focused on the most critical three, which are anxiety, depression, and delirium.

It is evident that assessing the symptoms and signs of the different psychiatric disorders is difficult in an oncological patient in a terminal state of illness, which is why it requires greater knowledge of the most frequent psychiatric pathologies, as well as the earliest possible management of the patient to achieve a better result that improves the quality of life of our patient, as well as a “good death”.

As Stiefel et al. mention underdetection and undertreatment of depression is a serious problem in palliative care [21]. In palliative care patients, anxiety and depression need to be actively screened for and dealt with using a multidisciplinary approach [22].

7. Anxiety in cancer patients

It is also important to refer to specific situations that cancer patients experience, such as radiotherapy treatments, which will be an important factor in the patient’s quality of life. When the patient is presented with the different types of treatments, the first reactions to the proposed treatment arise first and special attention must be paid since many patients have preconceived ideas about side effects. This is where the role of the doctor is essential to start the new therapeutic approach, clarifying doubts [23, 24].

In the case of patients undergoing radiotherapy, some degree of anxiety has been observed, expressed mainly as concern about the treatment, side effects, what is going to happen in the near future, depression and social isolation caused mainly by fear of the treatment and its side effects and impact on quality of life [23, 24].

In this chapter we focus on the cancer patient in a terminal situation, therefore, the intention of the therapeutic treatment with radiotherapy will have the objective of improving the quality of life and not a curative intention.

Most of the effects of radiation therapy on normal tissue are attributed to cytotoxicity [25].

In the terminally ill cancer patient, the approach of the health personnel and especially of the doctor must be even more global than in any other circumstance.

We must always remember that we are dealing with a patient who not only has a feeling of uncertainty, of fear of what is going to happen, who has faced the diagnosis of “cancer” and who is also now in a terminal situation, with a logical and understandable increase of their fears, concerns, denial, physical and psychic pain, fear for their loved ones, with a very large and deep mixture of feelings that translate in a large majority of patients to some degree of anxiety, depression that the sooner we diagnose, we will be able to offer the patient and their family better adherence to treatment, a better quality of life and a more dignified death.

In studies such as the one carried out by Jung-Ah Min et al., it is observed how a high level of resilience contributes to less emotional stress in hospitalized patients. Likewise, they observe the same relationship in patients with metastatic cancer. Thus, it appears that the influence of resilience is independent of and not attributed to the potential effects of a well-known variety of factors contributing to emotional stress [26].

Resilience is defined as the dynamic capacity to successfully maintain or recover a healthy mental state in the face of significant life risks or adversities [27].

In the article published by R.L. Gould et al. evidence is shown for the feasibility and acceptability of acceptance and commitment therapy (ACT), an acceptance-based behavioral therapy, with a strong evidence base in pain and a growing evidence base in mental health conditions [4].

8. Depression in cancer patients

The diagnosis of cancer is often related to emotional and mental disorders such as depression and anxiety [26].

Psychiatric disorders, mainly anxiety and depression, occur between 25 and 50% of patients with advanced cancer; however, many of these are underdiagnosed since they are considered a part of the disease’s own discomfort [28].

The comorbidity between cancer and psychiatric problems can generate several complications, ranging from non-adherence to any treatment, isolation of the patient, greater symptoms and suffering, and increased complications of recovery from surgery [29].

However, making a psychopathological diagnosis of depression in cancer patients can be difficult, due to the confluence of psychological and somatic symptoms typical of neoplastic disease. The very nature of cancer generates emotional discomfort that can range from a normal adaptive reaction to the disease to the presence of a set of signs and symptoms that, depending on the intensity and psychosocial involvement of the patient, could require psychotherapeutic and psychopharmacological treatment [30].

Insomnia, and in general, sleep disorders associated with anxiety/depressive disorders are one of the most prevalent symptoms, affecting 40–60% of cancer patients. Despite the importance of adequate sleep in cell repair processes, insomnia is one of the most common symptoms and one that generates high levels of stress but often does not receive the attention it deserves when compared to other problems presented by these patients such as nausea and pain, etc. [31].

The use of antidepressants and other psychotropic drugs is necessary for the presence of feelings of worthlessness, guilt, or hopelessness associated with frequent thoughts of death, self-harm, or suicide attempts. Pharmacological treatment can also help with irritability, anger, loss of appetite, insomnia, and difficulty concentrating and making decisions [32].

9. Depression in terminally ill patients

The incidence of major depression in terminally ill patients is between 25 and 77% [33]. Treatment should be started as soon as possible, since a lapse of time is needed for the treatment to begin to take effect, and in terminally ill patients we do not have time, we must be able to early recognize the signs and symptoms of depression that allow us to start the most appropriate treatment for each patient [34].

The sign that can help physicians in diagnosing the presence of depression is when there is a poor response to pain management, despite using different treatments. In these cases, as Robert L. Fine MD points out in his article “Depression, anxiety and delirium in terminally ill patient” [33], revising the dose of analgesics and increasing it, as well as adding antidepressant treatment, has very good results.

10. Consequences of depression in cancer patients

Cancer by itself produces enough physical and emotional discomfort in those who suffer from it, as part of its own clinical picture and as a consequence of treatments. However, the sum of psychosocial stressors and physical alterations can trigger a depressive disorder. The association between cancer and depression worsens the suffering and quality of life of patients [34].

The association between cancer and depression also reduces therapeutic adherence and increases mortality and morbidity [35]. Depression also decreases the patient’s ability to cope with the disease and exacerbates the number and intensity of physical symptoms. In this way, the hospitalization time is prolonged, it can lead to suicide and the psychological burden on the family increases [34].

In a systematic review of patients with breast, lung, brain, skin, and blood cancer, mortality was 25% higher in patients with depressive symptoms and 39% higher in patients with major or minor depression, even when the known survival clinical prognostic factors are controlled [36].

It is common to find cancer patients with suicidal ideation. People with cancer are about 2 to 3 times more likely to commit suicide than the general population. This can be caused by the specific situations of each case, such as the location of the tumor, an advanced stage, the prognosis of the disease and obviously the presence of a depressive disorder that is not identified and treated in time [37].

For this reason, it is important to diagnose depression and other psychiatric disorders in oncological patients, since not treating them can seriously complicate the prognosis of the patient [37].

11. Depression assessment in cancer patients

Through this chapter, the great importance of timely detection of depression in cancer patients has been established. Achieving the correct diagnosis helps us carry out better management, not only of the symptoms caused by the oncological disease but also an adequate intervention regarding the symptoms of depression, allowing us even to achieve an intervention of some family members in the process [38].

Even though the diagnosis is clinical and the ICD 10 or DSM5 criteria can be used, it is also possible to use some evaluation questionnaires that also allow the case to be documented properly.

For more accurate detection of depression, an evaluation in which some exploratory questions are used at the beginning is recommended; if significant symptoms are detected, it is desirable to apply some specialized test that has been previously standardized [39].

The hospital anxiety and depression scale (HAD-Hospital Anxiety and Depression Scale-HADS, Zigmond and Snaith, 1983; see Table 1), has been the most used self-assessment instrument to detect emotional distress (anxiety and depression) in populations with physical illness. It is a short instrument (with 14 items) that has shown reliability and validity, being used both for diagnosis and for assessing the severity of the disorder and that has been adapted and validated in various populations and cultures, always showing adequate sensitivity and specificity to discriminate anxiety and depression [39].

Hospital Anxiety and Depression Scale questionnaire. To evaluate anxiety and depressive state of patients with physical symptoms, they were asked to attempt a questionnaire comprising 14 items. Note: Copyright © 1983. John Wiley & Sons, Inc. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983 Jun;67(6):361–370.14
A. Do you feel tense?	B. Are you able to enjoy yourself to the same extent as you used to?
Almost always	I enjoy myself exactly the same as before.
Usually	I enjoy myself less pleasure than before.
Sometimes	I enjoy myself only a little compared with before.
Never	I do not enjoy myself at all.
C. Do you have the dreadful feeling that something completely terrible might happen now?	D. Do you laugh to the same extent as you used to?
I have a clear dreadful feeling of something terrible happening.	I laugh the same as before
I sometimes have a dreadful feeling, but the degree is not terrible.	I do not laugh like I used to
I occasionally have a dreadful feeling, but I do not lake any notice.	I definitely do not laugh as much as I used to
I never get such a feeling.	I do not laugh at all
E. Do you ever feel worried?	F. Are you in a good mood?
Almost always	Not at all
Usually	Not often
Sometimes, but not frequently	Sometimes
Only occasionally	Almost always
G. Can you sit peacefully and relax?	H. Do you feel that you have delayed thoughts and reactions?
I can	I almost always do
I usually car	I often do
I can, but not frequently	I sometimes do
Not at all	I never do
I. Do you every feel so dreadful that you feel sick in the stomach?	J. Have you lost interest in your appearance?
Never	Yes, clearly
Sometimes	I do not pay enough attention to my appearance
Often	I may not pay enough attention to my appearance
Very often	I give plenty of attention to my appearance
K. Do you lack peace of mind to the extent that you must constantly move around?	L. Are you able to look forward to the future?
Very much so	To the same degree as before
Considerably so	Somewhat less than before
Not very much	Clearly less than before
Not at all	Almost not at all
M. Do you ever get sudden anxiety attacks?	N. Do you enjoy good books, radio, and television programs?
Yes, very often	Yes, often
Yes, somewhat often	Sometimes
Not often	Mot often
Never	Very rarely

Table 1.

HAD-hospital anxiety and depression scale-HADS, Zigmond y Snaith, 1983.

It consists of two subscales, HADA for anxiety and HADD for depression, of seven items each with scores from 0 to 3. It includes cognitive and affective dimensions and omits somatic aspects such as loss of appetite, fatigue, insomnia, and others to avoid attributing them to depression and not to the disease itself.

The authors themselves recommend the original cut-off points: eight for possible cases and > 10 for probable cases in both subscales [40].

“The advantage of the HADS over other instruments that assess anxious and depressive symptomatology is that it does not include somatic symptoms that can be explained by cancer or its treatment. Being a brief, easy-to-apply and reliable instrument for clinical practice and research in the cancer population, it is relevant to determine the magnitude of the problem, prevention and implementation of actions for treatment” [41].

On the other hand, the Beck Depression Inventory-II (structured by Beck, Steer and Brown, 1996; see Appendix A), a self-report instrument composed of 21 items developed to evaluate the symptoms corresponding to the diagnostic criteria of depressive disorders of the Manual Diagnosis and Statistics of Mental Disorders (DSM5) has also demonstrated to have good psychometric properties, being able to detect the presence of depressive symptoms with significant clinical levels, allowing to timely intervene in the comprehensive care of cancer patients to achieve a better prognosis and better quality of care [42].

12. Treatment of depressive symptoms in cancer patients

The treatment of depressive symptoms in cancer patients is not different from that of patients with depression. The recommendation is always a multidisciplinary intervention that includes the medical treatment of the underlying disease and mental health interventions (psychiatry and psychology), social work, physical therapy, and others that speed up the recovery process or delay patient deterioration [34].

Regarding mental health, pharmacological treatment is as important as individual, group, and family psychological interventions.

It is interesting to point out that in the systematic review carried out by Dwin Gayatri et al., on “Quality of life of cancer patients at palliative care units in developing countries” [43], they find that in developing countries, patients in palliative care over 65 years of age, married or ever married, with a high level of education, users of complementary or alternative medicine, who practice religious or spiritual activities, are more likely to obtain high levels of quality of life scores.

Also, they mention that spirituality and religiosity positively affect the ability of cancer patients to cope with this situation, among other things because it gives the patient greater social support and a belief system, offering a coping mechanism and influencing neuroendocrine and neuroimmunology mechanisms.

From the medical point of view, the main way of approaching depression from the somatic area is pharmacological management. There must be coordination between the medical oncologist and the psychiatrist to choose the appropriate medication based on the patient’s symptom profile, tolerability and risk-benefit, with the aim of designing a strategy for each patient [34].

Selective serotonin reuptake inhibitors (SSRIs) are effective in treating depression in cancer patients. However, it is important to consider the pharmacological interactions with antineoplastic agents that can reduce their efficacy or increase their toxicity. Fluoxetine, sertraline, paroxetine, and fluvoxamine inhibit transformation through CYP450 3A4 [44].

Other drugs like citalopram, and escitalopram, are weak inhibitors, which makes them a safer choice. Dual antidepressants have also shown efficacy due to their speed of action and their usefulness in collateral symptoms, such as vasomotor symptoms and pain. Mirtazapine is very useful in symptoms such as pain, nausea, insomnia, and anxiety [34].

Regarding the psychological approach, an intervention is important from the moment the patient is diagnosed with cancer. It should not be expected that the cancer patient manifests a psychological disorder. Primary prevention helps prevent the occurrence of subsequent clinical psychopathological conditions, such as depression [44].

Individual cognitive-behavioral psychotherapy is the one that has been more studied, proving its effectiveness. Its help is based on the restructuring of the exaggerated negative beliefs that the patient has about himself, the world and the future. The objective is that the patient can have a more realistic vision, which helps him to face life in general in a healthier way [45].

On the other hand, strategies such as mindfulness, or full attention, have become highly relevant in recent years for managing stress and somatic pain. Other strategies, such as relaxation and other imagery-based therapies, have been used in successful interventions, reported in numerous publications. Music therapy has also been shown to relieve patients’ pain and psychological symptoms [46].

Among the beneficial effects of these psychological interventions is the reduction of the stress impact on the body, reduction of fear of the illness, activation of the immune system, increased motivation for lifestyle changes, strengthening the “desire to live”, coping with despair and evaluation and modification of the patient’s beliefs regarding the disease [44].

Another important point to keep in mind is the role of family and friends as a source of social, personal, emotional, and financial support. For this reason, it is extremely important to carry out an adequate family/or social psychological approach, addressing the concerns and difficulties that arise in the family or social support group of the cancer patient [47].

Many times, family conflicts, the sadness of losing a loved one and feelings of guilt can worsen the course of the disease, while mutual supportive relationships, unity, and family skills in caring for the sick are important protective factors [47].

13. Delirium

Delirium is a complex neurocognitive and behavioral syndrome, characterized by alterations in the level of consciousness and attention, associated with cognitive and perception alterations [48]. It has an abrupt onset and a fluctuating course.

Although its presence is very frequent, it is highly underdiagnosed. In patients with oncological and terminal pathology, its frequency varies between 26 and 44% and in recent days up to 80–90% [49].

Predisposing and precipitating factors of delirium have been described that we must consider for an early diagnosis. As described by Rolfson D, a powerful model that encourages clinicians to delineate multiple predisposing factors or vulnerability aspects and also to clearly list the acute triggers [50].

As predisposing factors, we have advanced age, male, visual disturbances, dementia, depression, physical dependence, immobility, fractured femur, alcoholism, serious physical illness, and stroke [51].

As acute triggers, we have drugs, organic involvement of the central nervous system, severe acute illness; cardiac, renal, respiratory or hepatic failure, infections, metabolic disorders such as hyponatremia, hyperkalemia, hypomagnesemia, and hypoglycemia; dehydration, anemia, disseminated intravascular coagulation and major surgery [49, 51, 52].

Opioid and nonopioid psychoactive drugs have been identified as clear precipitating factors. Also, dehydration is associated with reversible delirium [53].

Knowing its high incidence, it is necessary to always have the suspicion of being faced with this pathology, even more so when there is a reversibility chance in 50% of the cases [49] and in the ones that are not reversible, symptomatic treatment can always be carried out. Hence the importance of making a correct diagnosis and a prompt treatment that help us avoid early deaths and reduce the suffering of the patient and their families.

The diagnosis is clinical, for which we have The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5), (DSM 5) criteria described in Table 2 [54, 55]. A differential diagnosis must be made with depressive episodes, psychotic events, and dementias.

DSM-5; Disturbance in attention (i.e., reduced ability to direct, focus, sustain, and shift attention) and awareness (reduced orientation to the environment. The disturbance develops over a short period of time (usually hours to a few days), represents an acute change from baseline attention and awareness, and tends to fluctuate in severity during the course of the day. An additional disturbance in cognition (i.e., memory deficit, disorientation, language, visuospatial ability, or perception). The disturbances in Criteria A and C are not better explained by a pre-existing, established or evolving neurocognitive disorder and do not occur in the context of a severely reduced level of arousal such as coma. There is evidence from the history, physical examination or laboratory findings that the disturbance is a direct physiological consequence of another medical condition, substance intoxication or withdrawal (i.e., due to a drug of abuse or to a medication), or exposure to a toxin, or is due to multiple aetiologies).

DSM-5 Diagnosis and Statistical Manual of Mental Disorders, fifth edition.

Table 2.

DSM-5 delirium diagnosis criteria.

Once the delirium has been diagnosed, an evaluation of the causes must be initiated, provided that the patient is not in a state of agony. All tests must be consistent with the patient’s clinical status and with the expected benefit of their practice [48, 49, 56].

Among the complementary tests to request we have hemogram, coagulation, blood biochemistry (ions), kidney function, liver function, urine sediment and culture, oxygen saturation, chest X-ray, and brain CT [57].

Regarding the pathophysiology of delirium, we know that there is a wide range of causes, ranging from pharmacological to alteration of cerebral metabolism [57].

Pharmacological as a consequence of exceeding the therapeutic margin, especially with those with anticholinergic action. Opioids can cause delirium by increasing dopamine and glutamate activity and decreasing acetylcholine activity. Corticosteroids have been related to the appearance of delirium due to alteration of the hypothalamic-pituitary-adrenal axis. The neurotransmitter Gamma-aminobutyric acid (GABA), activity is decreased in delirium due to benzodiazepine and alcohol deprivation, while in hepatic encephalopathy its levels are increased by the increase in ammonia that induces the elevation of glutamate and glutamine [58, 59].

Alteration of cerebral metabolism due to a deficiency of the substances required to maintain it (mainly glucose and oxygen), toxins, or excessive metabolic demand as occurs in fever.

Likewise, cytokines also seem to be involved in the appearance of some types of delirium.

Lesions on diffuse structures composed of the thalamus and bilateral hemispheric pathways have been related to the appearance of delirium. Other structures composed of the frontal and parietal cortex of the right hemisphere and damaged by infarction of the middle cerebral artery and the right cerebral artery have also been related [60, 61].

• Hypoglycemia and hypoxemia also reduce acetylcholine [49, 53].

• Decrease or increase in brain serotonin levels.

• Infections.

• Serotonin syndrome and hepatic encephalopathy.

14. Clinical manifestations of delirium

Three types of delirium have been established according to their clinical manifestations: hyperactive, hypoactive, and mixed [51, 62].

We must take special care when facing a hypoactive type of delirium, since it is often difficult to diagnose, leading to a misdiagnosis and thus inadequate treatment.

The consciousness alteration usually fluctuates throughout the day. Alertness can be both increased and decreased. There is an attention deficit, the patient does not usually follow the dialog and responds with answers that do not correspond to the questions. The thinking process is usually incoherent or disorganized. It can also be accompanied by a language disorder that can range from dysarthria to mutism: the patient has difficulty finding the right word (dysnomia) or confuses some words with others (paraphasias). There is an alteration in immediate, short-term, or long-term memory. Disorientation, paranoid ideas, or hallucinations can also be present. The sleep-wake cycle is also usually altered. The patient may manifest an increase in pain with increases in analgesic requirements, and constructive visual apraxia (inability to copy geometric figures or more complex drawings) [49, 51, 56].

The hyperactive type predominates a psychomotor agitation, hallucinations, delusions, and a state of hyperalertness and agitation. While in the hypoactive type, a state of hypoalertness, lethargy, drowsiness, decay, and bradypsychia predominates. The mixed type is the most frequent, representing 66% of cases, characterized by alternating periods of lethargy and agitation [51, 56].

15. Treatment of delirium

Nonpharmacological measures are essential. With the environment, education and support should be carried out with the family group and close friends. Sleep hygiene, restoration of circadian rhythms, adequate environment with natural light, reducing extreme light, acoustic or thermal stimuli; avoiding if possible or at least minimizing any physical, manual or mechanical restriction, hearing and visual aids. Facilitate reorientation, transmit security and confidence to both family members and patients [57].

Neuroleptics are the drugs of choice and among them, haloperidol is the most used: it can be administered orally, intravenously, intramuscularly, and subcutaneously. Low doses of haloperidol 1–10 mg/day may usually be necessary. If it is started by the subcutaneous route, it can be started with a dose of 1.5–2.5 mg every 8 hours. It is necessary to schedule a rescue dose of 1.5–2 mg subcutaneous every 20–30 minutes. If necessary, at least 3 rescue doses can be used before switching to another, more sedating neuroleptic [49, 56, 57].

Chlorpromazine has a greater anticholinergic and sedative effect than haloperidol. However, its use is avoided subcutaneously because it is very irritating. It starts with a dose of 12.5 mg PO, IV, and IM every 4–12 hours. The same rescue dose can be used every 15–20 minutes up to a maximum of three doses before considering the use of a benzodiazepine [49, 56].

Levomepromazine has a greater sedative effect than chlorpromazine and can be indicated when the use of the subcutaneous route is needed and haloperidol is ineffective. It begins with doses of 12.5 mg PO, IM, IV, and SC every 4–12 hours, with rescue doses of 12.5–25 mg every 15–20 minutes [49, 56].

Olanzapine is an atypical neuroleptic with anxiolytic and sedative effects. The initial dose is 2.5–10 mg every 12 hours.

Risperidone is another atypical neuroleptic and can be used PO in the form of tablets or orodispersible and as an oral solution. The dose ranges between 0.25–3 mg/12–24 hours.

Benzodiazepines are indicated when neuroleptics fail to control agitation, when quick deep sedation is required, and as the first choice when delirium is precipitated by alcohol withdrawal or sedatives. Midazolam is commonly used since it can be administered by any route. The initial dose is 2.5–5 mg sc/ev every 5–10 minutes followed by a continuous infusion either sc or ev [49, 56].

In refractory cases of agitation, the use of anesthetic agents such as barbiturates or propofol may become essential.

Those cases in which the underlying cause is the use of psychotropic drugs, including opioids, and dehydration have a particularly good prognosis. We must not forget that 50% of cases of delirium are reversible, so an early and accurate diagnosis is essential.

16. Conclusions

Cancer is the principal cause of death worldwide and mental health pathologies represent a public health concern due to its high prevalence, morbimortality, and long-term disability.

The three most critical psychiatric disorders in terminally ill cancer patients are anxiety, depression, and delirium. Despite their frequency, they tend to go undiagnosed and undertreated.

The comorbidity between cancer and psychiatric disorders generates several complications, ranging from non-adherence to any treatment, social isolation of the patient, greater symptoms and suffering, increased complications during recovery from surgery, high risk of disease progression and decrease of quality of life and other issues being observed in terminally ill cancer patients. We must bear in mind that 50% of all cases of delirium are reversible, so early, and accurate diagnosis is paramount.

The early detection and management of both psychic and psychological symptoms will improve patients’ quality of life and good death, positively impacting not only the patients but also their caregivers.

Treatment of mental health problems in cancer patients is no different than in other patients. The recommendation is always to provide a multidisciplinary intervention that includes medical treatment of the underlying disease as well as of the mental health (psychiatry and psychology), social work support, physiotherapy and others that speed up the recovery process or delay the deterioration of the patient’s health.

Psychotherapeutic interventions should also be included for family and support group to help maintaining and improving the quality of life of these patients and allow them and their families to transition to death with dignity.

This depression inventory can be self-scored. The scoring scale is at the end of the questionnaire.

1. 1. 0. I do not feel sad.

   2. 1. I feel sad

   3. 2. I am sad all the time and I can’t snap out of it.

   4. 3. I am so sad and unhappy that I can’t stand it.

2. 1. 0. I am not particularly discouraged about the future.

   2. 1. I feel discouraged about the future.

   3. 2. I feel I have nothing to look forward to.

   4. 3. I feel the future is hopeless and that things cannot improve.

3. 1. 0. I do not feel like a failure.

   2. 1. I feel I have failed more than the average person.

   3. 2. As I look back on my life, all I can see is a lot of failures.

   4. 3. I feel I am a complete failure as a person.

4. 1. 0. I get as much satisfaction out of things as I used to.

   2. 1. I don’t enjoy things the way I used to.

   3. 2. I don’t get real satisfaction out of anything anymore.

   4. 3. I am dissatisfied or bored with everything.

5. 1. 0. I don’t feel particularly guilty.

   2. 1. I feel guilty a good part of the time.

   3. 2. I feel quite guilty most of the time.

   4. 3. I feel guilty all of the time.

6. 1. 0. I don’t feel I am being punished. .

   2. 1. I feel I may be punished.

   3. 2. I expect to be punished.

   4. 3. I feel I am being punished.

7. 1. 0. I don’t feel disappointed in myself.

   2. 1. I am disappointed in myself.

   3. 2. I am disgusted with myself.

   4. 3. I hate myself.

8. 1. 0. I don’t feel I am any worse than anybody else.

   2. 1. I am critical of myself for my weaknesses or mistakes.

   3. 2. I blame myself all the time for my faults.

   4. 3. I blame myself for everything bad that happens.

9. 1. 0. I don’t have any thoughts of killing myself.

   2. 1. I have thoughts of killing myself, but I would not carry them out.

   3. 2. I would like to kill myself.

   4. 3. I would kill myself if I had the chance.

10. 1. 0. I don’t cry any more than usual.

    2. 1. I cry more now than I used to.

    3. 2. I cry all the time now.

    4. 3. I used to be able to cry, but now I can’t cry even though I want to.

11. 1. 0. I am no more irritated by things than I ever was.

    2. 1. I am slightly more irritated now than usual.

    3. 2. I am quite annoyed or irritated a good deal of the time.

    4. 3. I feel irritated all the time.

12. 1. 0. I have not lost interest in other people.

    2. 1. I am less interested in other people than I used to be.

    3. 2. I have lost most of my interest in other people.

    4. 3. I have lost all of my interest in other people.

13. 1. 0. I make decisions about as well as I ever could.

    2. 1. I put off making decisions more than I used to.

    3. 2. I have greater difficulty in making decisions more than I used to.

    4. 3. I can’t make decisions at all anymore.

14. 1. 0. I don’t feel that I look any worse than I used to.

    2. 1. I am worried that I am looking old or unattractive.

    3. 2. I feel there are permanent changes in my appearance that make me look unattractive

    4. 3. I believe that I look ugly.

15. 1. 0. I can work about as well as before.

    2. 1. It takes an extra effort to get started at doing something.

    3. 2. I have to push myself very hard to do anything.

    4. 3. I can’t do any work at all.

16. 1. 0. I can sleep as well as usual.

    2. 1. I don’t sleep as well as I used to.

    3. 2. I wake up 1–2 hours earlier than usual and find it hard to get back to sleep.

    4. 3. I wake up several hours earlier than I used to and cannot get back to sleep.

17. 1. 0. I don’t get more tired than usual.

    2. 1. I get tired more easily than I used to.

    3. 2. I get tired from doing almost anything.

    4. 3. I am too tired to do anything.

18. 1. 0. My appetite is no worse than usual.

    2. 1. My appetite is not as good as it used to be.

    3. 2. My appetite is much worse now.

    4. 3. I have no appetite at all anymore.

19. 1. 0. I haven’t lost much weight, if any, lately.

    2. 1. I have lost more than five pounds.

    3. 2. I have lost more than ten pounds.

    4. 3. I have lost more than fifteen pounds.

20. 1. 0. I am no more worried about my health than usual.

    2. 1. I am worried about physical problems like aches, pains, upset stomach, or constipation.

    3. 2. I am very worried about physical problems and it’s hard to think of much else.

    4. 3. I am so worried about my physical problems that I cannot think of anything else.

21. 1. 0. I have not noticed any recent change in my interest in sex.

    2. 1. I am less interested in sex than I used to be.

    3. 2. I have almost no interest in sex.

    4. 3. I have lost interest in sex completely.

Interpreting the beck depression inventory

Now that you have completed the questionnaire, add up the score for each of the twenty-one questions by counting the number to the right of each question you marked. The highest possible total for the whole test would be sixty-three. This would mean you circled number three on all twenty-one questions. Since the lowest possible score for each question is zero, the lowest possible score for the test would be zero. This would mean you circles zero on each question. You can evaluate your depression according to the Table below.

Total score	Levels of depression
1–10	These ups and downs are considered normal
11–16	Mild mood disturbance
17–20	Borderline clinical depression
21–30	Moderate depression
31–40	Severe depression over
40	Extreme depression

http://www.med.navy.mil/sites/NMCP2/PatientServices/SleepClinicLab/Documents/Beck_Depression_Inventory.pdf