Anxiety is often manifested in individuals at various times during cancer screening, diagnosis, treatment, or recurrence. It can sometimes affect a person’s behavior regarding his or her health, contributing to a delay in or neglect of measures that might prevent cancer.    For example, when women with high levels of anxiety learn that they have a genetically lower level of risk of breast cancer than they had previously believed, they might perform breast self-examination more frequently.  Patients can experience moderate-to-severe anxiety while waiting for the results of diagnostic procedures.  For patients undergoing treatment, anxiety can also heighten the expectancy of pain,    other symptoms of distress and sleep disturbances, and can be a major factor in anticipatory nausea and vomiting. It has been shown that anxiety can lead to early death if untreated.  Anxiety, regardless of its degree, can substantially interfere with the quality of life of patients with cancer and of their families and should be evaluated and treated.   
Anxiety occurs to varying degrees in patients with cancer and may heighten as the disease progresses or as treatment becomes more aggressive.  Investigators have found that 44% of patients with cancer reported some anxiety; 23% reported significant anxiety.   Anxiety can be part of normal adaptation to cancer. In most cases, the reactions are time limited and ma 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.  (Refer to the PDQ summary on Adjustment to Cancer: Anxiety and Distress for more information.) 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. 
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,  functional limitations, lack of social support,  advancing disease, and history of trauma.   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.   Patients who have problems communicating with their families, friends, and physicians are also more at risk of developing anxiety. 
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.  Many of these factors can be managed when adequately assessed and properly treated.
Patients who have the following symptoms may be experiencing a specific anxiety disorder that was present before they became ill with cancer and that recurs because of the stress of the diagnosis and treatment: intense fear, the inability to absorb information, or the inability to cooperate with medical procedures. Somatic symptoms include shortness of breath, sweating, lightheadedness, and palpitations. Patients with cancer can present with the following anxiety disorders: adjustment disorder, panic disorder, phobias, obsessive-compulsive disorder, posttraumatic stress disorder, generalized anxiety disorder, or anxiety disorder that is caused by other general medical conditions. These patients are generally distressed about their symptoms and are usually compliant with behavioral and psychopharmacologic intervention. 
Adjustment disorder is diagnosed in patients who experience maladaptive behaviors and/or moods in response to an identified stressor. The maladaptive behaviors or moods include severe nervousness, worry, jitteriness, and impairment in normal functioning, such as the inability to work, attend school, or interact with others. These symptoms are in excess of normal reactions to cancer and occur within 6 months of the stressor event; however, this determination can be complicated in the patient with cancer, where the stressor is ongoing. Patients diagnosed with an adjustment disorder generally do not have a history of other psychiatric disorders. Patients with other chronic disorders, however, are likely to have had adjustment problems earlier in life that will recur in the cancer setting. Adjustment disorder is prevalent among cancer patients, particularly at critical times such as at diagnostic work-up, diagnosis, or relapse. Most patients with adjustment disorder respond to reassurance, relaxation techniques, low doses of short-acting benzodiazepines, and patient support and education programs.   (Refer to the PDQ Summary on Adjustment to Cancer: Anxiety and Distress for more information.)
In panic disorder, intense anxiety is the predominant symptom. Severe somatic symptoms can also be present. These include shortness of breath, dizziness, palpitations, trembling, diaphoresis, nausea, tingling sensations, or fears of going crazy. Attacks or discrete periods of intense discomfort can last for several minutes or for hours. Patients with panic attacks often present with symptoms that can be difficult to differentiate from other medical disorders, though a known history of panic disorder can help clarify the diagnosis. Panic disorder in patients with cancer is most often managed with benzodiazepines and antidepressant medications. 
Phobias are persistent fears or avoidance of a circumscribed object or situation. People with phobias usually experience intense anxiety and avoid potentially frightening situations. Phobias are experienced by cancer patients in a number of ways, such as fear of witnessing blood or tissue injury (also known as needle phobia) or claustrophobia (for example, during a magnetic resonance imaging scan). Phobias can complicate medical procedures and can result in the refusal of necessary medical intervention or tests. 
Obsessive-compulsive disorder is characterized by persistent thoughts, ideas, or images (obsessions) and by repetitive, purposeful, and intentional behaviors (compulsions) that a person performs to manage his or her intense distress. To qualify as obsessive-compulsive disorder, the obsessive thoughts and compulsive behaviors must be time-consuming and sufficiently distracting to interfere with the person’s ability to function in employment, academic, or social situations. Patients with cancer who have a history of obsessive-compulsive disorder may engage in compulsive behaviors such as hand washing, checking, or counting to such an extent that they cannot comply with treatment. For such patients, normal worry about the cancer diagnosis and prognosis can develop into full obsessive-compulsive symptoms and be severely disabling. Obsessive-compulsive disorder is most often managed with serotonergic antidepressant medications (selective serotonin reuptake inhibitors and clomipramine) and cognitive-behavioral psychotherapy. This disorder is rare in cancer patients who do not have a premorbid history.
Posttraumatic stress disorder is diagnosed when a person re-experiences a traumatic event with intrusive distressing recollections, dreams, flashbacks, or hallucinations. Though definitions of a traumatic event have been focused on those outside the range of normal human experiences (e.g., military combat, torture, and natural disasters), the diagnosis of a life-threatening illness now meets criteria for a traumatic stressor.  Additionally, the experience of hospitalization and/or some painful treatment may also reactivate traumatic memories. Cancer patients who have posttraumatic stress disorder can become very anxious before surgery, chemotherapy, painful medical procedures, or dressing changes. Anxiolytic medications given in preparation for treatment can foster adjustment and reduce distress. No specific medications, however, have been consistently demonstrated to be the most effective or have been studied in other populations of patients with posttraumatic stress disorders; psychotherapy remains the treatment of choice. (Refer to the Posttreatment Considerations section and refer to the PDQ summary on Post-Traumatic Stress Disorder for more information.)
Generalized anxiety disorder is characterized by ongoing, unrealistic, and excessive anxiety and worry about two or more life circumstances. Some examples are patients’ fears that no one will care for them even though they have adequate and willing social support and the fear of exhausting their finances even though adequate insurance and financial coverage is available. Frequently a generalized anxiety disorder is preceded by a major depressive episode. A generalized anxiety disorder is characterized by motor tension (restlessness, muscle tension, and being easily fatigued), autonomic hyperactivity (shortness of breath, heart palpitations, sweating, and dizziness), or vigilance in scanning (feeling keyed-up and on-edge, irritability, and having exaggerated startle responses).
|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, corticotropin-producing tumors, and insulinoma.|
|Anxiety-producing drugs||Corticosteroids, neuroleptics used as antiemetics, thyroxine, bronchodilators, beta-adrenergic stimulants, antihistamines, and benzodiazepines (paradoxical reactions are often seen in older persons).|
|Anxiety-producing conditions||Substance withdrawal (from alcohol, opioids, or sedative-hypnotics).|
|*Adapted from Massie. |
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.  
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 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 opioids, 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.  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.
Effective management of anxiety disorders begins with a thorough and comprehensive assessment and an accurate diagnosis. The normal fears and uncertainties associated with cancer are often intense. Often, there is not a clear distinction between normal fears and fears that are more severe and finally reach the criteria for an anxiety disorder.  Treatment should be initiated that is not based solely on the definition of the disorder but on consideration for the patient’s quality of life. To assess the severity of the anxiety, it is important to understand to what extent the symptoms of anxiety are interfering with the activities of daily living. Screening for anxiety could include a brief self-report questionnaire that, if a defined cutoff score is exceeded, could then be followed by a more thorough clinical interview. A variety of general screening questionnaires have been used for identification of distress. Other anxiety-specific self-report questionnaires (e.g., State-Trait Anxiety Inventory) have also been used and a questionnaire for the assessment of prostate cancer–related anxiety has been developed and validated.   
The following is a list of questions that may be used in dialogue with patients to explore their symptoms of anxiety and other disorders. Referral to appropriate specialists may be indicated based on patient response.
When anxiety is situational (i.e., produced by pain, another underlying medical condition, a hormone-secreting tumor, or a side effect of medication), the prompt treatment of the cause usually leads to immediate control of the symptoms.  Some effective coping strategies include encouraging fearful patients to confront the problem directly, to try to view the situation as a problem to be solved or as a challenge, to try to obtain complete information, to try to be flexible (taking things as they come), to think of major events as a series of step-by-step tasks, and to encourage the use of resources and support. 
Initial management of anxiety includes providing adequate information and support to the patient. Initial symptoms, which may warrant a psychiatric or psychological consultation, may first be reported to the primary oncologist or surgeon.  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. Combining different approaches can be beneficial for some patients. One study examined the usefulness of a comprehensive intervention combining positive coping strategies based on cognitive behavioral therapy (e.g., calming self-talk or relaxation) with education about the disease, treatment, and potential side effects in 509 recurrence-free breast cancer survivors at 5 to 9 years posttreatment.  Findings from this study indicate that women in the intervention group (n = 244) regularly used the intervention components to deal with triggers of fears of breast cancer recurrence and long-term treatment side effects. Most women in the intervention group found the strategies very helpful.  Preliminary evidence suggests racial differences in the use and benefit of specific coping strategies (e.g., religious coping strategies such as prayer and hopefulness are used more by African American women and provide greater benefit for these women).  
|Drug Equivalent||Approximate Oral Dose (mg)†||Initial Dose (mg)||Elimination of Half-life Drug Metabolites (h)|
|Alprazolam (Xanax)||0.5||0.25–2.0 t.i.d.–q.i.d.||10–15|
|Oxazepam (Serax)||10.5||10–15 t.i.d.–q.i.d.||5–15|
|Lorazepam (Ativan)||1.0||0.5–2.0 t.i.d.–q.i.d.||10–20|
|Temazepam (Restoril)||15.0||15–30 at bedtime||10–15|
|Chlordiazepoxide (Librium)||10.0||10–50 t.i.d.–q.i.d.||10–40|
|Alprazolam (Xanax XR)||1.0||1–6 q.d.||10–15|
|Diazepam (Valium)||5.0||5–10 b.i.d.–q.i.d.||20–100|
|Clorazepate (Tranxene)||7.5||7.5–15.0 b.i.d.||30–200|
|Clonazepam (Klonopin)||1.0||0.5–2.0 b.i.d.–t.i.d.||19–50|
|t.i.d. = 3 times a day; q.i.d. = 4 times a day; q.d. = once a day; b.i.d. = twice a day.|
|*Adapted from Breitbart W: Management of specific symptoms. In Holland JC, Breitbart W, Jacobsen PB, et al., eds.: Psycho-oncology. New York, NY: Oxford University Press, 1998, 439.|
|†Refer to the PDQ summary on Depression for dosing information on antidepressants used for anxiety as described in this summary.|
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 a 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 3 times a day and can be increased to 15 mg 3 times a day. Buspirone can also be given twice a day. Low-dose neuroleptics (e.g., thioridazine, 10 mg 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 twice a day or risperidone, 1 mg twice a day. 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 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. If the symptoms are manifestations of a depressive disorder, however, pharmacologic management is best achieved with antidepressant medication that has sedative properties (e.g., amitriptyline or doxepin) or with a serotonin reuptake inhibitor.  One meta-analysis of pediatric antidepressant clinical trials  found antidepressants efficacious relative to placebo in the treatment of anxiety disorders, with strongest effects in non–obsessive-compulsive disorder (OCD) anxiety disorders (e.g., generalized anxiety disorder or social anxiety disorder) and intermediate effects in OCD. (Refer to the PDQ summary on Depression for a discussion of the risk of suicidal ideation/suicide attempt associated with antidepressant use.)
Akathisia usually can be quickly controlled by stopping or changing the offending drug (if possible) or by the addition of a benzodiazepine, or 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.
Check NCI’s list of cancer clinical trials for U.S. supportive and palliative care trials about anxiety disorder that are now accepting participants. The list of trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
After treatment, patients are confronted with a number of issues related to cancer survivorship. Typical issues involve fears about repeated medical follow-up and diagnostic tests. Fear of recurrence is also an ongoing concern that waxes and wanes over time. A number of specific issues can be a source of anxiety. Fears related to returning to work, such as discussing one’s treatment with employees, insurance-related problems, and concerns about discrimination, can cause distress. Fear of screening, follow-up, and risk of second malignancies are ongoing physical threats that are accompanied by anxiety for certain subgroups of patients. Body-image changes, sexual dysfunction, and reproductive issues can also cause anxiety. Posttraumatic stress disorder has been diagnosed in about 3% to 5% of patients who survive cancer and its effects, depending on site and intensity of treatment. In a study of women who were taking tamoxifen for breast cancer, trait anxiety was associated with a higher dropout rate from tamoxifen therapy due to a higher incidence of adverse physiological side effects.  (Refer to the PDQ summary on Post-Traumatic Stress Disorder for more information.) Survivorship programs and resources, including group and individual counseling, can help facilitate adjustment and can address specific concerns. (Refer to the PDQ summary on Transitional Care Planning for more information.)
For more information, U.S. residents may call the National Cancer Institute's (NCI's) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 8:00 a.m. to 8:00 p.m., Eastern Time. A trained Cancer Information Specialist is available to answer your questions.
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National Cancer Institute: PDQ® Anxiety Disorder. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://cancer.gov/cancertopics/pdq/supportivecare/anxiety/HealthProfessional. Accessed <MM/DD/YYYY>.
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