The benefits of early psychiatric treatment in patients with oncological pathology

1. Introduction

Patients confronted with oncological diseases have to face, besides the somatic symptoms inherent to their main pathology, adverse events of the chemotherapy, including central nervous system (CNS) manifestations, psycho-organic disorders, stress or adjustment disorders, depressive episodes, or anxiety disorders. Somatic symptoms reported in this population require a personalized approach, focused on disentangling cancer-related organic manifestations (e.g., pain, nausea, weight loss) from drugs’ adverse events (e.g., constipation, diarrhea, weight changes), other comorbid conditions, and from somatizations, which are considered symptoms of the aforementioned psychiatric disorders (e.g., diffuse pain, dizziness, paresthesias) – Figure 1. Also, psychiatric symptoms in this population are possibly integrated into paraneoplastic syndromes (e.g., depression, anxiety, cognitive impairments), or to the metastatatic CNS cancer, but they may be part of the reactive depressive disorders or similar psychiatric conditions, or they may be due to treatment-emergent adverse events or independent mental or behavioral disorders⁽¹⁾ (Figure 2). Regarding the last possibility, psychiatric conditions may have had their onset long before the diagnosis of cancer being made, and are exacerbated in this stressful context, thus requiring a new therapeutic approach.
 

Somatic and psychiatric symptoms may be influenced by relational aspects, such as communication with friends and family, the therapeutic relationship with the attending physician, and all the contextual factors that can determine the patient’s sense of well-being (e.g., comorbidities, accessibility of therapeutic resources, social support group, coping mechanisms, personal history of traumatic life events).

The importance of exploring these aspects derives from the high impact psychiatric and somatic symptoms have on the patient’s quality of life and well-being. There is a significant overlap in this population between mood disorders, psychoses, substance use disorders, anxiety disorders, posttraumatic stress disorder and somatic symptom disorder, highlighting the complex intertwining between psychiatric disorders and cancer⁽²⁾. Besides individual negative effects of these intricacies, there are also important socioeconomic costs derived from the need to approach concomitantly somatic and psychiatric conditions⁽²⁾. Furthermore, when considering the effects of such overlapping pathologies, caregivers’ burden should also be considered⁽³⁾.

In order to correctly evaluate the complex configurations of these overlapping conditions, the case management should include a multidisciplinary team. Mental health specialists are an important part of this team, as they are the only ones habilitated to screen for psychiatric disorders in oncological patients, to diagnose such conditions and to initiate and monitor psychotropic treatment, similar to what is reported in patients with other severe organic pathology⁽⁴⁾. The evaluation of the quality of life and overall functionality in these patients is also part of the mental health specialists’ attributions, as is the preservation of good communication with the patient’s caregivers and addressing their psychiatric needs when the case requires.

Based on all these arguments, a literature review focused on retrieving the most important symptoms that require psychiatric intervention and on the benefits of early psychotropic intervention is considered to be granted.

2. Palliative care and the characteristics of the terminal cancer patient

Palliative care is a difficult concept to define, but it has, nevertheless, been intensely explored during the last decades, due to its extremely important medical and societal consequences. This concept overlaps with end-of-life care, comfort care, and supportive care⁽⁵⁾. The inclusion of a patient in palliative care programs assumes the existence of a life-threatening illness, with no possibility of remission, stabilization, or modification of the course of the illness.

Sometimes, patients do not accept palliative care or the involvement of carers in it, due to dysfunctional defense or coping mechanisms that are difficult to approach directly⁽⁶⁾. Palliative care must be provided by a multidisciplinary team, with the participation of mental health specialists – i.e., psychiatrists, clinical psychologists, psychotherapists, social workers, etc.⁽⁶⁾

The case management of patients in terminal phases who require palliative care begins with a thoroughly conducted assessment of the inclusion criteria. In this direction, it is important to determine: (a) the presence of an advanced and incurable disease, (b) the failure to respond to specific treatment; (c) the presence of severe symptoms; (d) the major emotional impact on the patient, family, and therapeutic team; (e) a life expectancy less than six months⁽⁷⁾.

The main purposes of including a patient in palliative care are, according to the World Health Organization (WHO): (a) to provide comfort regarding symptoms, mainly pain; (b) to support life, but also to consider death as a natural process; (c) to integrate emotional symptoms, social and spiritual needs, etc. into palliative care; (d) to support the patient and family until the end; (e) to improve the patient’s quality of life⁽⁸⁾.

The rights of terminally ill patients are, according to the same source mentioned before: (a) the right to be treated as a human being; (b) the right to maintain hope but also to express their emotions; (c) the right to care, even if only comfort goals exist; (d) the right not to die alone, to die in peace, with dignity; (e) the right not to be judged for one’s beliefs; (f) the right to have one’s body respected after death⁽⁸⁾.

3. Symptoms of the terminal oncological patient

There are many somatic and psychiatric symptoms that a patient with cancer may be confronted with, and listing all of them is clearly outside the purpose of this review. Therefore, only the most important from the therapeutic and differential diagnosis perspective of a mental health specialist will be presented here (Figure 3). For better integration into case management, the symptoms in terminal oncological patients have been divided into two distinct categories – somatic and psychiatric –, although in clinical practice, they are almost always intertwined.
 

3.1. Somatic symptoms

Pain

Pain is one of the most common and dreaded consequences of cancer. Pain varies according to the primary localization of neoplasia, but also according to the degree of cancer progression⁽⁹⁾. Pain is an ongoing source of frustration for patients, but also for their caregivers, and even for their treating physicians. Patients are reporting the intensity of pain, which is modulated by a multitude of factors, like emotional discomfort or personal interpretations of the symptom’s significance, with increased pain intensity being a determinant factor for depression. Pain management is not always appropriate, as multiple considerations should be integrated into the case management concomitantly, like pharmacokinetic, pharmacodynamic, and toxicologic aspects of the analgesics. There are reported clinicians’ concerns about the side effects of these drugs and the risk of opioid dependence, but there may also be a tendency of the treating physician to focus on disease management rather than collateral symptoms. Sometimes, patients also contribute to the persistence of this symptom by not following recommended therapy, either by discontinuing or altering the doses that were recommended to them⁽¹⁰⁾.

Respiratory distress

Respiratory symptomatology, in the context of oncological diseases, is frequently reported⁽¹¹⁾. Respiratory manifestations may have a different etiology, ranging from inadequate oxygenation due to organic causes to anxiety and panic attacks. Also, certain chemotherapies can have a pneumotoxic effect, such as  lung radiotherapy when applied to all types of tumors located in the chest⁽¹¹⁾. However, most long-term survivors continue to experience respiratory symptoms, which cause the oncological patient’s quality of life to decrease. In patients with a pulmonary background, these symptoms are more severe and persist longer despite therapeutic interventions⁽¹²⁾.

Weakness or lack of energy

Fatigue or weakness are sometimes used as synonymous terms. These symptoms may be related to treatment, tumor progression, or emotional reactions^(13,14). Chemotherapy can have negative effects on muscle function and motility (influencing neuromuscular protein expression)^(15,16). Chemotherapy also causes nausea sometimes, vomiting, and lack of appetite, with weight loss and anemia, which can lead to increased sensation of weakness⁽¹⁷⁾. Psychological, social or behavioral factors may enhance the feeling of fatigue experienced by oncological patients. In this case, attention should be drawn to depressive-type symptoms, which are associated with hypoprosexia and/or anhedonia⁽¹⁸⁾.

Nausea and vomiting

Nausea and vomiting are probably some of the most common and uncomfortable symptoms reported by oncological patients. These can lead to metabolic disturbances, dehydration or exhaustion⁽¹⁹⁾. The emetogenic risk is different, depending on the primary cancer localization. Different studies have shown an increased emetogenic risk for genital cancer (over 40%), followed by gastric (over 30%), esophageal (over 20%), and lung cancer (around 14%). The area involved in the mechanism of the nausea is located in the lining of the fourth ventricle, outside the blood-brain barrier and vulnerable to metabolic and chemical triggers, and may involve acetylcholine, dopamine, serotonin, cannabinoids or opioids (pro- or anti-emetogenic) neurotransmitters⁽²⁰⁾. Unlike vomiting, nausea has also an important subjective component that is difficult to assess, which responds well to some of the psychiatric treatments⁽²¹⁾.

Lack of appetite

Malnutrition is common in oncological patients. Its occurrence may be related to certain gastrointestinal symptoms (nausea, vomiting, diarrhea), to the location of the tumor (oral cavity or esophagus), or to specific treatments that may cause alterations in taste and smell (chemotherapy toxicity or radiotherapy-associated mucositis). About 50% of patients with advanced cancer suffer from a lack of appetite^(22,23). Weight loss of more than 5% of body weight predicts a poor prognosis, being accompanied by a poorer response to chemotherapy^(22,23). Cachexia, which involves satiety and early anorexia, results in decreased fat and body mass, increasing susceptibility to complications, which correlates with poor prognosis. When weight loss is around 30%, death can occur⁽²⁴⁾.

Psychological symptoms such as anxiety and depression may be associated with decreased appetite. There are psychiatric therapeutic agents that can intervene to improve appetite and emotional state, with long-term beneficial effects.

Constipation

Almost 15% of people in the whole population suffer from functional constipation before a chronic disease is diagnosed⁽²⁵⁾. Constipation is one of the most common problems in cancer pathology. Opioids used in the oncological context may secondarily cause constipation. In addition to these, there is an inadequate fluid intake and certain environmental conditions that can aggravate this condition (i.e., privacy in hospital settings)⁽²⁵⁾.

Oral cavity problems

The category of adverse effects of oncological treatments also includes oral complications – mucositis, dysgeusia, and local infections, which can become generalized⁽²⁵⁾. Mucositis is manifested by damage to the gastrointestinal tract, which may be caused by chemotherapy (including methotrexate) and/or radiotherapy. Mucositis presents in different ways, from erythematous patches to ulcerations, with varying degrees of intensity: mild, moderate, severe, or life-threatening oral mucositis⁽²⁵⁾.

Inflammatory cytokines, tumor necrosis factor, interleukins IL-1 and IL-6, and neutropenia are factors favoring bacterial or fungal superinfection, which can accentuate mucosal destruction, with increased severity of pain. Mucositis decreases the capacity for adequate oral intake and increases the risk of infection. Psychiatric medication has an effect on increasing appetite, reducing pain and improving the patient’s mental state.

Sleepiness

Fatigue and excessive sleepiness are common in oncological patients. Chemotherapy, radiotherapy, surgery and the associated side effects such as anemia, weight loss and biochemical changes seem to play an important role. In addition, stress, depression and anxiety can accentuate these symptoms⁽²⁶⁾. Although fatigue and sleep disorders are distinct manifestations, there is a strong correlation between them. Sleep disturbances, represented by disrupted sleep onset and/or maintenance, as well as reduced sleep quality, can lead to fatigue and increased daytime sleepiness. These problems can become chronic and can persist for months or years, even after the end of cancer-specific therapy^(27,28). Lung tumors are most commonly associated with fatigue and excessive sleepiness, and these persist most during the course of the disease evolution⁽²⁹⁾. Psychiatric treatments have a positive effect on anxiety and depressive symptoms, but they also may have an activating effect in the context of sleepiness caused by secondary organic factors.

Reduced mobility

Mobility is an important physiological component throughout life, and it may become especially important in oncological patients who are deprived of other physical resources. Impairment of mobility, independent of the oncological component, increases susceptibility to the development of depressive disorders, contributing to an increased need for institutionalization and increased mortality. Oncological patients may experience a decrease in mobility due to various causes, from anergia to pain, and from weight loss to anemia. According to the existing data in the literature, mainly pain and fatigue, which also imply reduced physical fitness, make a significant contribution to this reduction in mobility⁽³⁰⁾. Added to these are secondary oncological changes, which imply tumor progression. While in younger patients, the reduction in mobility may be reversible, in older patients, it may become permanent⁽³¹⁾.

Psychiatric medication, by reducing “mental fatigue” – i.e., the affective component – can increase mobility and prevent the chronicity of this impairment.

3.2. Emotional symptoms

Anxiety and depression in the terminal oncological patient

Anxiety in oncological patients varies according to the explored reference, but it may reach up to 28%, this value being closely dependent on the stage of the disease^(32-34). Anxiety is related to the effectiveness of treatment, the results of investigations, and the way in which the results are transmitted to the patient. In the terminal phase of the disease, there is a risk of reactivating certain preexisting anxiety disorder manifestations. In fact, in the terminal phase of the disease, anxiety is determined both by emotional and psychosocial factors and by medical conditions, representing the organic part of anxiety. Psychopharmacological treatment can be combined with supportive psychotherapy, relaxation therapy, guided imagery, and hypnosis in order to access as many available residual resources as the patient may still have.

Depression varies in terminal patients, and it may reach 18%^(35,36). A patient’s history of depression or a familial history of mood disorders may increase the risk of developing depression. In addition, chemotherapy, radiotherapy, corticosteroids, hormone therapy and metabolic-endocrine complications may increase the risk of depression. In terminally ill patients, psychiatric medication is recommended in order to reduce anxiety and its oncological symptoms with an important affective component. Depression, like anxiety, has a negative impact on the evolution of the disease but also on the quality of life⁽³⁷⁾.

Caregivers’ anxiety

Family members of oncological patients have multiple emotional needs. Carers of such patients have increasing psychological needs in the context of the advancing stages of cancer disease. Levels of anxiety and depression among carers, especially in the terminal stage, are higher than in the general population. Anxiety and depression in the family lead to reduced work performance, and may also result in poorer quality of care for the oncological patient⁽³⁸⁾.

Existential anguish and discomfort due to unmet communicational needs

Certain needs seem to be of greater importance in terms of existence for terminally ill cancer patients: intrinsic respect for the person and information about the cancer disease⁽³⁹⁾. The search for the meaning of life is part of the human experience. Inner peace, spirituality and faith have a positive impact on existence, increasing the quality of life⁽⁴⁰⁾. Communication with friends and family and the medical information provided have a particular impact on the development of the terminal oncological patient.

Cancer is an overwhelming event for the patient, family, friends and health professionals who have been communicating with the patient for a long time. Terminally ill oncological patients seek medical information regarding the progress of their illness. They feel the need for support from family, friends and health professionals. As far as family members are concerned, communication problems involve the need to obtain medical information and the need to hide feelings towards the patient⁽⁴¹⁾. The benefits of communication between patients, families and health professionals cannot be overemphasized due to the importance of this interaction in decreasing the levels of anxiety and depression.

The exchange of medical information plays an important role, especially in oncology. The vast majority of patients expect to receive information about the disease, treatment to be followed, side effects, and prognosis⁽⁴²⁾. Both patients and their families also use secondary sources of information. However, the vast majority prefer information to be provided by healthcare professionals. Patients also want to be able to participate in treatment decisions⁽⁴³⁾.

Some patients say they are dissatisfied with the information they receive, but in fact, the dissatisfaction is related to the doctor-patient interaction⁽⁴⁴⁾. Sometimes, dissatisfaction with the information received is related to the news regarding the prognosis of the disease. Therefore, the communication of information must be individualized and express an appropriate level of hope⁽⁴⁵⁾. Also, the communication must take into account the potential cognitive dysfunctions in patients with psychiatric disorders and comorbid oncological diseases⁽⁴⁶⁾.

3.3. The need for psychotropic treatment in patients with cancer

Although oncological providers reported in almost equal proportion comfort and discomfort when prescribing psychiatric medication, according to a cross-sectional survey, the need for such drugs is obvious⁽⁴⁷⁾. The main barriers to prescribing psychotropics reported in that study were difficulty in maintaining a follow-up after discharge from the hospital, poor communication with other specialists, and inadequate mental health education for providers⁽⁴⁷⁾. The most frequently prescribed psychotropics were benzodiazepines, and the least prescribed category was mood stabilizers⁽⁴⁷⁾. In palliative care, according to a retrospective analysis, only 35% of the patients received psychotropic medication, and only in 25% of all the treated cases the psychiatrist initiated the specific treatment⁽⁴⁸⁾. Anxiety and benzodiazepine treatment were the most commonly reported, followed by depression and associated antidepressant drugs, and psychosis leading to antipsychotic treatment (50%, 22% and 18%, respectively)⁽⁴⁸⁾. More specifically, clonazepam, alprazolam, lorazepam, quetiapine, olanzapine, risperidone, haloperidol, selective serotonin reuptake inhibitors (SSRIs), mirtazapine, and amitriptyline were the most commonly prescribed psychotropics in this population⁽⁴⁸⁾.

The exploration of drug-drug interactions (DDI) between psychotropics and chemotherapy is needed, and according to a study dedicated to this topic, such interactions are common, with more than 32% DDI reported, out of which 87.5% were considered of major risk⁽⁴⁹⁾.

After referring oncological patients to a specialized psycho-oncology service, the rate of using psychotropic drugs increased from 55.5% to 79%, suggesting the need for more detailed psychiatric exploration of this population⁽⁵⁰⁾. The most frequently reported drugs administered in this population were minor tranquilizers and antidepressants, with more than 20% of the patients receiving more than one drug⁽⁵⁰⁾.

Several principles of psychopharmacological treatment in oncological patients are: (a) psychotropics should be initiated at low doses and increased gradually, based on tolerability; (b) the minimum efficient dose is recommended; (c) DDI should always be explored⁽⁵¹⁾.

For patients with depression and anxiety, SSRIs, venlafaxine, desvenlafaxine, tricyclics, and mirtazapine are the most explored antidepressants in this population, and they must be associated with nonpharmacological approaches, like psychotherapy or psychological counseling. Buspirone and benzodiazepines may be added, when needed⁽⁵¹⁾. For patients with delirium or psychoses, after treating the possible organic causes, haloperidol, second-generation antipsychotics, in association with midazolam or lorazepam, and possibly cholinesterase inhibitors for delirium may be recommended⁽⁵¹⁾. For fatigue, psychostimulants and nutraceuticals have been explored, with partially positive results⁽⁵¹⁾. Regarding sleep disorders, there is no unanimously approved treatment, and any intervention targeting insomnia should not exceed 1-2 months⁽⁵¹⁾.

The anticipated benefits of initiating pharmacological treatment in these patients are: (a) a rapid decrease in psychiatric symptoms; (b) an increase in patients’ adherence to the oncological treatment; (c) increasing the quality of life and well-being; (d) an increasing of the overall functionality; (e) reducing caregivers’ burden related to auxiliary symptoms, not directly related to the organic pathology (Figure 4). The evidence to support all these presumed positive effects is still scarce, but future trials are expected to verify the utility of such a targeted treatment on psychiatric symptoms. Also, the possibility of guiding a psychotropic treatment according to pharmacogenetic data in a personalized approach is a future perspective that can be beneficial for patients with psychiatric disorders and oncological comorbidity^(52,53).
 

4. Conclusions

Terminally ill oncological patients experience particular emotional and spiritual experiences, which can sometimes be transformed into somatic symptoms. In terminally ill patients, there is a risk of clinicians downplaying depressive symptoms as “normal reactions”, leading to a deficiency in the diagnosis of depression, with decreased chances of adequately treating this disorder and decreasing associated discomfort.

Antidepressant medication is appropriate if the terminal patient has a life expectancy of several months. If an oncological patient has a life expectancy of fewer than three weeks, it may require an antipsychotic, whether or not combined with a benzodiazepine, in order to control core psychiatric symptoms and to avoid the 2-4 weeks expectancy for the onset of antidepressant effect. Antipsychotics also have a positive effect on oncological symptoms like nausea, vomiting, lack of appetite, etc., when a psychiatric component exists. Individual counseling, relaxation, imagery and spiritual guidance play an important role in these cases. In conclusion, in the terminal stage of cancer, all medical and spiritual resources must be directed towards the patient’s well-being, which favors the smooth crossing of the “from here to there” phase.   
 

Corresponding author: Cătălina Florescu E-mail: catalinaflorescu03@gmail.com