Issues in Psycho-Oncology: What Clinicians Need to Know

[[{"type":"media","view_mode":"media_crop","fid":"29494","attributes":{"alt":"psycho-oncology","class":"media-image media-image-right","id":"media_crop_8701231950864","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"3053","media_crop_rotate":"0","media_crop_scale_h":"151","media_crop_scale_w":"150","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"float: right;","title":" ","typeof":"foaf:Image"}}]]Strictly speaking, psycho-oncology is a “sub-sub-specialty.” That is, psycho-oncology is a specialized niche of psychosomatic medicine, or medical psychiatry. Psycho-oncologists include psychiatrists, psychologists, social workers, and other mental health practitioners who possess cancerrelated expertise in a variety of areas, including differential diagnosis, psychotherapy, psychopharmacology, and palliative/supportive care.

The field was developed under the leadership of pioneers such as Avery Weisman, Jimmie Holland, and William Breitbart. These individuals advanced the discipline through clinical work, teaching, research, activism, and creation of professional networks. A clinical psychiatrist and psychoanalyst at Massachusetts General Hospital in the mid-1950s, Dr Weisman oversaw a research initiative, Project Omega. He authored various books, including Coping With Cancer, which continue to serve as foundational learning for trainees in psycho-oncology.¹ The Department of Psychiatry and Behavioral Sciences at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York, founded in the late 1970s under the leadership of Dr Jimmie Holland, has contributed a plethora of clinical research to the field, much of which has involved veteran clinician and renowned researcher, Dr William Breitbart.

MSKCC, Dana-Farber Cancer Institute/Brigham and Women’s Hospital in Boston, and Princess Margaret Hospital in Toronto offer accredited PGY-5 fellowship programs in psychosomatic medicine with emphasis on psycho-oncology. Active professional networks include the American Psychosocial Oncology Society, International Psycho-oncology Society, and the psycho-oncology and palliative care special interest group of the Academy of Psychosomatic Medicine.

In 2007, the Institute of Medicine published Cancer Care for the Whole Patient: Meeting Psychosocial Health Needs.² This seminal report galvanized the oncology community to address quality of life (including psychological distress) alongside duration of life.² Even as the breadth of the field expands, the limited supply of psycho-oncology clinicians, particularly in non-urban settings, dictates that many cancer patients in need of mental health services receive care from general mental health providers.

In this article, we introduce select topics in clinical psycho-oncology, including assessment and management of delirium and brain lesions, mood and anxiety disorders, medication adverse effects, and existential death anxiety.

Delirium and brain lesions

The majority of advanced cancer patients experience delirium in the last 6 months of life. Somewhat unique to oncology, the syndrome often presents in the ambulatory setting. While some cancer or cancer treatment–specific causes of delirium require specialized consideration, remember that “common things occur commonly.” That is, regardless of cancer stage or treatment details, common causes of delirium must be assessed and treated. This includes medical assessment (eg, laboratory tests, urinalysis, chest radiography, blood and urine cultures, brain imaging) and medication review, with special attention paid to opioids and benzodiazepines (both used commonly in cancer patients) and to anticholinergics. These assessments should be followed by serial mental status examinations, preferably using objective measures such as the Montreal Cognitive Assessment.

Cancer patients at particularly high risk for delirium include those undergoing stem cell transplant; immunosuppression increases the risk of infection, including potential reactivation of dormant viruses such as BK, varicella-zoster, and herpes simplex. Patients with primary brain tumors, brain metastases, or leptomeningeal carcinomatosis; those receiving high doses of opioids or benzodiazepines; and those with endorgan failure are also at increased risk.

A common challenging clinical neuropsychiatric scenario is that of a patient with a newly discovered brain lesion. Some lesions may be psychiatrically “silent” and have little effect on mood or behavior, although the risk of mental status changes is high in the setting of larger space-occupying lesions with frontal or temporal localization. Other risk factors include hemorrhage, increased intracranial pressure/obstruction of cerebral spinal fluid flow, seizures, and leptomeningeal invasion. Premorbid psychiatric and cognitive disorders may complicate the interpretation of mental status changes in the setting of brain tumors; in these situations, neuropsychological testing (where available) may be particularly useful diagnostically and therapeutically.

CASE VIGNETTE

Alice presents with confusion and bizarre behavior. She is 60 years old and has a history of stage III lung cancer. She has no history of psychiatric problems and is not taking medications known to alter mental status. A toxic/metabolic workup is unrevealing. However, a brain MRI scan reveals a large right frontal metastatic lesion with areas of hemorrhage. Resection of the lesion returns the patient’s cognition to baseline, and dexamethasone taper (targeting brain edema) is started immediately following surgery. Three days later, Alice again presents with altered mental status, raising concern for nonadherence with the corticosteroid taper. On evaluation, she reports visual hallucinations and evidences episodic severe distractibility, with poor concentration and memory difficulties on formal testing.

Several clinical pearls are worth discussing. A clinician confronted with such a patient must consider the neuropsychiatric adverse effects of corticosteroids-including insomnia, irritability, anxiety, depression, hypomania or mania, psychosis, and cognitive impairment.³ In patients with a newly diagnosed and resected brain lesion, neuropsychiatric aberrations may be caused by a combination of clinical factors, including corticosteroids, the possible presence of undiagnosed seizures, and the direct deliriogenic impact of the lesion and its resection. If neuropsychiatric symptoms worsen with corticosteroid taper, consider unchecked inflammation as a possible cause.

In Alice’s case, the clinical examination (most notably, intermittent grossly impaired attention, with pauses in speech production) suggests the possibility of complex partial seizures. Indeed, an electroencephalogram reveals partial status epilepticus, a significant finding because neither adjustment of the corticosteroid dose nor addition of an antipsychotic would have led to symptom resolution. Ultimately, Alice receives 3 antiepileptic medications to control seizures and normalize mental status.

Mood and anxiety disorders

The available evidence for the prevalence of clinical depressive disorders in the cancer population is variable and influenced by study design and method of assessment. A recent systematic review noted the prevalence of depression as 5% to 16% in outpatients, 4% to 14% in inpatients, 4% to 11% in mixed populations, and 7% to 49% in palliative care. Notably, it was found that when studies used expert interviewers (such as psychiatrists and clinical psychologists), prevalence estimates were lower.⁴ In practice, the most common diagnosis made in the outpatient cancer setting is that of adjustment disorder. The suicide rate is 2 to 3 times that of the general population and is particularly high immediately following a cancer diagnosis.⁵

We recommend using validated tools (eg, Generalized Anxiety Disorder 7-item [GAD-7], Patient Health Questionnaire [PHQ-9]) to screen for major depression and anxiety disorders; however, even results of these screenings can sometimes be misleading. The presence of fatigue, poor appetite, poor concentration, and sleep disturbance that results in high PHQ-9 scores can often be explained by the effects of cancer or its treatment, as opposed to clinical depression. It is therefore also crucial to evaluate psychological constructs such as anhedonia, demoralization, self-esteem, attitude toward the future, hopelessness, helplessness, and meaning. Similarly, a patient can appear to have anxiety disorder as measured by the GAD-7, while the true pathology is akathisia (a movement disorder) as a result of prochlorperazine or metoclopramide, both commonly prescribed for nausea in cancer patients.

The treatment of adjustment, mood, and anxiety disorders in cancer patients is rooted in general psychiatry principles and includes psychotherapy and/or psychopharmacotherapy with antidepressants and, on occasion, stimulants and benzodiazepines. Medications such as venlafaxine XR, sertraline, citalopram, and escitalopram are preferred for the treatment of depression and anxiety because of their limited drug-drug interactions.

Mirtazapine is frequently used for its appetite-stimulating and soporific properties (particularly beneficial in cachectic patients and those with poor sleep) as well as for its very low likelihood of causing or exacerbating nausea (because of its serotonin type 3 antagonist properties). Bupropion also has utility in patients with depression and without prominent anxiety. Historically, there has been concern about prescribing medications with marked cytochrome P-450 (CYP) 2D6 inhibition (eg, paroxetine and fluoxetine) for patients receiving tamoxifen for adjuvant treatment of breast cancer; however, more recent data are mixed regarding a relationship between CYP2D6 activity and cancer recurrence. In patients with carcinoid tumor or syndrome, in whom endogenous serotonin production is elevated, atypical antidepressants such as mirtazapine and bupropion may be theoretically preferred because of their nonserotonergic mechanisms of action. However, in practice, most patients with such tumors tolerate conventional SSRI treatment.

Finally, benzodiazepines are frequently used for anxiety and nausea in cancer patients, but they should be deployed cautiously and usually in short-acting formulations, given their deliriogenic liability (particularly when coadministered with opioids). Haloperidol and atypical antipsychotics, such as quetiapine and olanzapine, given in low doses, are good alternatives for managing anxiety and insomnia, and off-label use may be less problematic in individuals with a limited life expectancy. For individuals with the common symptom cluster of nausea, anxiety, and insomnia, olanzapine may be especially helpful because of its potent antiemetic, anxiolytic, and potentially soporific properties.

Fatigue

While certainly not a psychiatric issue, the management of cancerrelated fatigue is well within the purview of the psycho-oncologist. Individual studies vary; however, the prevalence of fatigue in patients being treated for cancer approaches 100%.⁶ Validated measures such as the Brief Fatigue Inventory may be used to track a patient’s level of fatigue, although in practice we often use a Likert scale (range, 0-10), in which the patient rates his or her current, average, and most severe levels of fatigue.

While medications may be helpful, a program of exercise has the strongest evidence base supporting its efficacy. Medically ill patients may wake for various physical reasons during the night (cough, pain, dyspnea, sleep apnea, frequent urination, management of tubes/lines, etc). Maintenance of good sleep hygiene is crucial and can help minimize the impact of sleep disruption on the patient’s overall functioning. Blood transfusions often have a robust effect on fatigue, but this benefit may be short-lived in the setting of ongoing cancer treatment.

Erythropoietin-stimulating factors are avoided by many oncologists because of the increased risk of deep venous thrombosis and possible cancer progression. Pharmacological options for cancer-related fatigue (all off-label, non–FDAapproved) include stimulants (such as methylphenidate), modafinil, and armodafinil.

Premorbid psychiatric or substance use disorders

Cancer patients with serious mental illness and/or substance use disorders are monitored closely by the psycho-oncologist, often in collaboration with the individual’s preexisting mental health providers. While case reports document the safe use of clozapine in patients receiving cytotoxic chemotherapy, such patients must be observed carefully in collaboration with the laboratory and dispensing pharmacy. Similarly, patients receiving lithium may require closer monitoring in the setting of chemotherapy fluid shifts. Atypical antipsychotics and valproate are preferred options for de novo management of hypomania/mania in cancer patients. Ensuring adequate treatment of pain and other symptoms in these patients can be challenging. For those with substance use disorders, behavioral contracts, random urine drug screening, and prescription monitoring programs are essential, along with limiting the quantity of opioids and benzodiazepines prescribed at any given time.

Existential death anxiety

Perhaps the greatest challenge facing psycho-oncology practitioners is the management of existential death anxiety, which can occur regardless of the type or stage of cancer and is not infrequently outside a patient’s conscious awareness. Obtaining a detailed narrative regarding the events leading up to cancer diagnosis is critical in understanding coping style and particular triggers for death anxiety. Perhaps the most important service provided by psycho-oncologists is the ability to recognize and address the patient’s defense mechanisms and coping styles, which will ultimately help the patient face mortality.

Conclusions

Despite the many advances in clinical oncology, there unfortunately still exists a cohort of individuals, including children, who will rapidly succumb to their disease. At times, psycho-oncologists bear witness to severe emotional and physical suffering. The field of psycho-oncology offers extensive opportunities for personal/existential growth through meaningful relationships with patients and their families; deep satisfaction in relieving anguish and improving quality of life through psychotherapy and psychopharmacological treatments; and rich collaborations with multidisciplinary oncology teams.

Disclosures:

Dr Yuppa is a staff psychiatrist at Dana-Farber Cancer Institute and Instructor in Psychiatry at Harvard Medical School, Boston. Dr Braun is a staff psychiatrist and Chief, Division of Adult Psychosocial Oncology at Dana-Farber Cancer Institute, and Assistant Professor of Psychiatry at Harvard Medical School. Dr Meyer is a staff psychiatrist at Dana-Farber Cancer Institute; Director, Medical Student Education in Psychiatry at Brigham and Women’s Hospital; and Assistant Professor of Psychiatry at Harvard Medical School.

References:

1. Weisman AD. Coping With Cancer. New York: McGraw-Hill; 1979.

2. Institute of Medicine. Cancer Care for the Whole Patient: Meeting Psychosocial Health Needs. Octo-ber 15, 2007. http://www.iom.edu/Reports/2007/Cancer-Care-for-the-Whole-Patient-MeetingPsychosocial-Health-Needs.aspx. Accessed October 7, 2014.

3. Dubovsky AN, Arvikar S, Stern TA, Axelrod L. The neuropsychiatric complications of glucocorticoid use: steroid psychosis revisited. Psychosomatics. 2012;53:103-115.

4. Walker J, Holm Hansen C, Martin P, et al. Prevalence of depression in adults with cancer: a systematic review. Ann Oncol. 2013;24:895-900.

5. Fang F, Fall K, Mittleman MA, et al. Suicide and cardiovascular death after a cancer diagnosis. N Engl J Med. 2012;366:1310-1318.

6. Weis J. Cancer-related fatigue: prevalence, assessment and treatment strategies. Expert Rev Pharmacoecon Outcomes Res. 2011;11:441-446.