Overview

Description And Etiology

Treatment

Post-treatment Considerations

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OVERVIEW

Anxiety occurs to varying degrees in patients with cancer and may heighten as the disease progresses or as treatment becomes more aggressive.[13] Investigators have found that 44% of patients with cancer reported some anxiety; 23% reported significant anxiety.[14] Anxiety can be part of normal adaptation to cancer. In most cases, the reactions are time limited and may motivate patients and families to take steps to reduce anxiety (e.g., gain information), which may assist in adjusting to the illness. However, anxiety reactions that are prolonged or unusually intense are classified as adjustment disorders. These disorders can negatively affect quality of life and interfere with a cancer patient's ability to function socially and emotionally. These anxiety reactions require intervention.[15] Other specific anxiety disorders such as generalized anxiety, phobia, or panic disorder are not as common among these patients and usually predate the cancer diagnosis. The stress caused by a diagnosis of cancer and its treatment may precipitate a relapse of pre- existing anxiety disorders. These disorders can be disabling and can interfere with treatment. They require prompt diagnosis and effective management.[16]

Some factors that can increase the likelihood of developing anxiety disorders during cancer treatment include a history of anxiety disorders, severe pain, anxiety at time of diagnosis,[17] functional limitations, lack of social support, advancing disease, and history of trauma.[13,18] Many medical conditions and interventions can cause anxiety disorders, including central nervous system metastases, lung cancer, and treatment with corticosteroids and other medications. A patient's experience with cancer or other illnesses may reactivate associations and memories of previous illness and contribute to acute anxiety. Certain demographic factors, such as being female and developing cancer at a young age, are associated with increased anxiety in medical situations.[19] Patients who have problems communicating with their families, friends, and physicians are also more at risk of developing anxiety.[19]

In the patient with advanced disease, anxiety is often not caused by the fear of death but by the issues of uncontrolled pain, isolation, abandonment, and dependency.[20] Many of these factors can be managed when adequately assessed and properly treated.

References:

1. Lauver D, Ho CH: Explaining delay in care seeking for breast cancer symptoms. Journal of Applied Social Psychology 23(21): 1806-1825, 1993.
2. MacFarlane ME, Sony SD: Women, breast lump discovery, and associated stress. Health Care for Women International 13(1): 23-32, 1992.
3. Gram IT, Slenker SE: Cancer anxiety and attitudes toward mammography among screening attenders, nonattenders, and women never invited. American Journal of Public Health 82(2): 249-251, 1992.
4. Lerman C, Kash K, Stefanek M: Younger women at increased risk for breast cancer: perceived risk, psychological well-being, and surveillance behavior. Journal of the National Cancer Institute Monographs 16: 171-176, 1994.
5. Jenkins PL, May VE, Hughes LE: Psychological morbidity associated with local recurrence of breast cancer. International Journal of Psychiatry in Medicine 21(2): 149-155, 1991.
6. Velikova G, Selby PJ, Snaith PR, et al.: The relationship of cancer pain to anxiety. Psychotherapy and Psychosomatics 63(3-4): 181-184, 1995.
7. Glover J, Dibble SL, Dodd MJ, et al.: Mood states of oncology outpatients: does pain make a difference? Journal of Pain and Symptom Management 10(2): 120-128, 1995.
8. Ferrell-Torry AT, Glick OJ: The use of therapeutic massage as a nursing intervention to modify anxiety and the perception of cancer pain. Cancer Nursing 16(2): 93-101, 1993.
9. Sirois F: Psychosis as a mode of exitus in a cancer patient. Journal of Palliative Care 9(4): 16-18, 1993.
10. Davis-Ali SH, Chesler MA, Chesney BK: Recognizing cancer as a family disease: worries and support reported by patients and spouses. Social Work in Health Care 19(2): 45-65, 1993.
11. Dahlquist LM, Czyzewski DI, Copeland KG, et al.: Parents of children newly diagnosed with cancer: anxiety, coping, and marital distress. Journal of Pediatric Psychology 18(3): 365-376, 1993.
12. Payne SA: A study of quality of life in cancer patients receiving palliative chemotherapy. Social Science and Medicine 35(12): 1505-1509, 1992.
13. Breitbart W: Identifying patients at risk for, and treatment of major psychiatric complications of cancer. Supportive Care in Cancer 3(1): 45-60, 1995.
14. Schag CA, Heinrich RL: Anxiety in medical situations: adult cancer patients. Journal of Clinical Psychology 45(1): 20-27, 1989.
15. Razavi D, Stiefel F: Common psychiatric disorders in cancer patients: I. Adjustment disorders and depressive disorders. Supportive Care in Cancer 2(4): 223-232, 1994.
16. Maguire P, Faulkner A, Regnard C: Managing the anxious patient with advancing disease--a flow diagram. Palliative Medicine 7(3): 239-244, 1993.
17. Nordin K, Glimelius B: Predicting delayed anxiety and depression in patients with gastrointestinal cancer. British Journal of Cancer 79(3/4): 525-529, 1999.
18. Green BL, Krupnick JL, Rowland JH, et al.: Trauma history as a predictor of psychologic symptoms in women with breast cancer. Journal of Clinical Oncology 18(5): 1084-1093, 2000.
19. Friedman LC, Lehane D, Webb JA, et al.: Anxiety in medical situations and chemotherapy-related problems among cancer patients. Journal of Cancer Education 9(1): 37-41, 1994.
20. Hackett TP, Cassem NH: Massachusetts General Hospital Handbook of General Hospital Psychiatry. 2nd ed., Littleton, Mass: PSG, 1987.

DESCRIPTION AND ETIOLOGY

The following is a list of questions that may be used to ask patients with cancer about their anxiety symptoms.

1. Have you had any of the following symptoms since your cancer diagnosis or
treatment? When do these symptoms occur (i.e., how many days prior to treatment, at night, or at no specific time) and how long do they last? 2. Do you feel shaky, jittery, or nervous? 3. Have you felt tense, fearful, or apprehensive? 4. Have you had to avoid certain places or activities because of fear?
5. Have you felt your heart pounding or racing?
6. Have you had trouble catching your breath when nervous?
7. Have you had any unjustified sweating or trembling? 8. Have you felt a knot in your stomach? 9. Have you felt like you have a lump in your throat? 10. Do you find yourself pacing? 11. Are you afraid to close your eyes at night for fear that you may die in
your sleep?
12. Do you worry about the next diagnostic test, or the results of it, weeks
in advance?
13. Have you suddenly had a fear of losing control or going crazy?
14. Have you suddenly had a fear of dying?
15. Do you often worry about when your pain will return and how bad it will
get?
16. Do you worry about whether you will be able to get your next dose of pain
medication on time?
17. Do you spend more time in bed than you should because you are afraid that
the pain will intensify if you stand up or move about? 18. Have you been confused or disoriented lately?

Adjustment Disorder

Panic Disorder

Phobias

Obsessive-Compulsive Disorder

Post-Traumatic Stress Disorder

Generalized Anxiety Disorder

Anxiety Disorder Caused by Other General Medical Conditions

              Table 1: Possible Causes of Anxiety*
-------------------------------------------------------------------------------
    Medical Problem                      Examples
------------------------     --------------------------------------------------

Poorly controlled pain       Insufficient or as-needed pain medications.

Abnormal metabolic states    Hypoxia, pulmonary embolus, sepsis, delirium,
                             hypoglycemia, bleeding coronary occlusion, or
                             heart failure.

Hormone-secreting tumors     Pheochromocytoma, thyroid adenoma or carcinoma,
                             parathyroid adenoma, ACTH-producing tumors, and
                             insulinoma.

Anxiety-producing drugs      Corticosteroids, neuroleptics used as antiemetics,
                             thyroxine, bronchodilators, beta-adrenergic
                             stimulants, antihistamines, and benzodiazepines
                             (paradoxical reactions often seen in the elderly).

Anxiety-producing conditions Substance withdrawal (from alcohol, narcotic
                             analgesics, or sedative-hypnotics).
-------------------------------------------------------------------------------
*Adapted from Massie MJ: Anxiety, panic and phobias.  In Holland JC, Rowland
JH, eds., Handbook of Psychooncology: psychological care of the patient with
cancer.  New York: Oxford University Press, 1989, pp. 300-309.

Causes of anxiety in cancer patients may include other medical factors such as uncontrolled pain, abnormal metabolic states (e.g., hypercalcemia or hypoglycemia), and hormone-producing tumors. Patients in severe pain are anxious and agitated, and anxiety can potentiate pain. To adequately manage pain, the patient's anxiety must be treated.[5,6]

Acute onset of anxiety may be a precursor of a change in metabolic state or of another impending medical event such as myocardial infarction, infection, or pneumonia. Sepsis and electrolyte abnormalities can also cause anxiety symptoms. Sudden anxiety with chest pain or respiratory distress may suggest a pulmonary embolism. Patients who are hypoxic can experience anxiety; they may be fearful that they are suffocating.

Many drugs can precipitate anxiety in the persons who are ill. For example, corticosteroids can produce motor restlessness, agitation, and mania as well as depression and thoughts of suicide. Bronchodilators and B-adrenergic receptor stimulants used for chronic respiratory conditions can cause anxiety, irritability, and tremulousness. Akathisia, motor restlessness accompanied by subjective feelings of distress, is a side effect of neuroleptic drugs, which are commonly used for control of emesis. Withdrawal from narcotics, benzodiazepines, barbiturates, nicotine, and alcohol can result in anxiety, agitation, and behaviors that may be problematic for the patient who is in active treatment.

Certain tumor sites can produce symptoms that resemble anxiety disorders. Pheochromocytomas and pituitary microadenomas can present as episodes of panic and anxiety.[7] Nonhormone-secreting pancreatic cancers can cause anxiety symptoms. Primary lung tumors and lung metastases can often cause shortness of breath, which can lead to anxiety.

References:

1. Razavi D, Stiefel F: Common psychiatric disorders in cancer patients: I. Adjustment disorders and depressive disorders. Supportive Care in Cancer 2(4): 223-232, 1994.
2. Forester B, Kornfeld DS, Fleiss JL, et al.: Group psychotherapy during radiotherapy: effects on emotional and physical distress. American Journal of Psychiatry 150(11): 1700-1706, 1993.
3. Jevne RF: Looking back to look ahead: a retrospective study of referrals to a cancer counseling service. International Journal for the Advancement of Counselling 13(1): 61-72, 1990.
4. American Psychiatric Association: Diagnostic and statistical manual of mental disorders: DSM-IV. 4th ed., Washington, DC: American Psychiatric Association, 1994.
5. Velikova G, Selby PJ, Snaith PR, et al.: The relationship of cancer pain to anxiety. Psychotherapy and Psychosomatics 63(3-4): 181-184, 1995.
6. Glover J, Dibble SL, Dodd MJ, et al.: Mood states of oncology outpatients: does pain make a difference? Journal of Pain and Symptom Management 10(2): 120-128, 1995.
7. Wilcox JA: Pituitary microadenoma presenting as panic attacks. British Journal of Psychiatry 158(3): 426-427, 1991.

TREATMENT

Initial management of anxiety includes providing adequate information and support to the patient. Psychologic approaches include combinations of cognitive-behavioral therapeutic techniques, insight-oriented psychotherapy, crisis intervention, couple and family therapy, group therapy, self-help groups, and behavioral interventions. Behavioral approaches (hypnosis, meditation, progressive relaxation, guided imagery, and biofeedback) can be used to treat anxiety symptoms that are associated with painful procedures, pain syndromes, crisis situations, anticipatory fears, and depressive syndromes.

     Table 2:* Commonly Prescribed Benzodiazepines in Cancer Patients**
-------------------------------------------------------------------------------
Drug Equivalent     Approximate      Initial          Elimination of
                    Oral Dose        Dose             Half-life Drug
                    (mg)             (mg)***          Metabolites(hr)
-------------------------------------------------------------------------------
Short-acting
 Alprazolam           0.5           0.25-2.0 TID-QID     10-15
 Oxazepam            10.5           10-15 TID-QID         5-15
 Lorazepam            1.0           0.5-2.0 TID-QID      10-20
 Temazepam           15.0           15-30 QHS            10-15


Intermediate-acting
 Chlordiazepoxide    10.0           10-50 TID-QID        10-40

Long-acting
 Diazepam             5.0           5-10 BID-QID         20-100
 Clorazepate          7.5           7.5-15.0 BID         30-200
 Clonazepam           1.0           0.5-2.0 BID-TID
-------------------------------------------------------------------------------
*Adapted from Breitbart W: Management of specific symptoms.  In Holland JC,
ed.: Psycho-oncology.  New York, NY: Oxford University Press, 1998, 439.
**For dosing information of antidepressants used for anxiety as described in
this summary,(refer to the PDQ summary on Depression.)
***QID = four times a day; TID = three times a day; QHS = at bedtime; BID =
twice a day.

An anxiolytic medication is often needed alone or in combination with psychologic approaches. The choice of a benzodiazepine depends on the duration of action that is best suited to the patient, the desired rapidity of onset needed, the route of administration available, the presence or absence of active metabolites, and metabolic problems. Dosing schedules depend on patient tolerance and require individual titration. The shorter-acting benzodiazepines (alprazolam and lorazepam) are given 3 to 4 times per day. Short-acting benzodiazepines, particularly those that can be administered by multiple routes (lorazepam and diazepam) are effective for high levels of distress. Benzodiazepines decrease daytime anxiety and reduce insomnia. (Refer to the PDQ summary on Sleep Disorders for more information.) The most common side effects of benzodiazepines are dose dependent and are controlled by titrating the dose to avoid drowsiness, confusion, motor incoordination, and sedation. Buspirone, a nonbenzodiazepine, is useful in patients who have not previously been treated with benzodiazepine and in those who may abuse benzodiazepines (e.g. those with a history of illicit substance abuse or alcoholism). Buspirone is also useful in the geriatric population as an augment to fluoxetine for the treatment of anxiety and depression. The beginning dose is 5 mg given 3 times a day and can be increased to 15 mg given 3 times a day. Buspirone can also be given 2 times a day. Low-dose neuroleptics (e.g., thioridazine 10 mg given 3 times a day) are also used to treat severe anxiety when an adequate dose of a benzodiazepine is ineffective or if the patient might be expected to respond poorly to benzodiazepines (e.g., patients with brain metastases). Low-dose neuroleptics can also be used when benzodiazepines are not helpful or when there is the possibility of delirium, dementia, or other complications. For anxiety symptoms of another medical origin, reversal of the physical cause is the best treatment, if possible. Otherwise a benzodiazepine (e.g., lorazepam or clonazepam), a neuroleptic (e.g., thioridazine or haloperidol), or a combination of these classes of drugs can be used. Anecdotally, clinicians have prescribed atypical antipsychotics in low doses such as olanzapine, 2.5 mg BID or risperidone, 1 mg BID. Unstudied, these medications relieve anxiety and are associated with less akathisia.

All benzodiazepines can cause some degree of respiratory depression, though generally it is minimal in patients who have not used benzodiazepines in the past. They should be used cautiously (or not at all) for respiratory impairment. Standard precautions should be considered when using any sedative drug in patients who have borderline respiratory function. Ongoing assessment of this population is important. Low doses of the antihistamine, hydroxyzine (25 mg given 2-3 times a day), can be used safely in such situations. In patients with hepatic dysfunction, it is best to use short-acting benzodiazepines that are metabolized primarily by conjugation and excreted by the kidney (e.g., oxazepam, temazepam, or lorazepam). Another advantage of using lorazepam is its lack of active metabolites. Conversely, other benzodiazepines should be selected for renal dysfunction.

Patients with cancer often have symptoms of both anxiety and depression that are caused by cancer-treatment stressors. These symptoms of distress often are resolved with psychologic support alone. However, if the symptoms are manifestations of a depressive disorder, pharmacologic management is best achieved with antidepressant medication that has sedative properties (e.g., amitriptyline or doxepin) or with a serotonin reuptake inhibitor.[1]

Akathisia usually can be quickly controlled by stopping or changing the offending drug (if possible) or by the addition of a benzodiazepine, a beta- blocker such as propranolol. Treatment of withdrawal depends on the particular agent. Sometimes the goal is to stabilize the patient on the agent (e.g., a benzodiazepine) and sometimes a suitable substitute can be given (e.g., a benzodiazepine for ethanol).

In general, patients with cancer need to be encouraged to take sufficient amounts of medication to relieve anxiety. Medications are readily tapered and discontinued when symptoms subside. Concerns about addiction are exaggerated in patients with cancer and often interfere with adequate symptom relief.

References:

1. Massie MJ: Anxiety, panic, and phobias. In: Holland JC, Rowland JH, eds.: Handbook of Psychooncology: Psychological care of the patient with cancer. New York, NY: Oxford University Press, 1989, pp 300-309.
2. Breitbart W: Identifying patients at risk for, and treatment of major psychiatric complications of cancer. Supportive Care in Cancer 3(1): 45-60, 1995.
3. Johnson J: I Can Cope: Staying Healthy with Cancer. 2nd ed., Minneapolis, MN, Chronimed Pub., 1994.

POST-TREATMENT CONSIDERATIONS

Date Last Modified: 10/2002

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