When evaluating a patient with anxiety-related distress, it is important to determine the temporal course of the symptoms. Patients whose anxiety problems are chronic, predating the onset of their cancer diagnosis, are likely to have a formal anxiety disorder. Whether or not an anxiety disorder has been previously diagnosed, it is useful to determine if the quality and pattern of anxiety symptoms are familiar to the patient. The stress of a cancer diagnosis, its treatment, or other life stresses coincident with cancer can exacerbate a long-standing anxiety problem. For example, patients with a history of panic disorder are likely to have more frequent or intense panic attacks. Similarly, patients with GAD are likely to have an increase in troublesome worry and so on. In patients with chronic anxiety states, previously effective management strategies are likely to give relief from recurrent symptoms.

If the anxiety complaints are new or qualitatively different from a pattern characteristic for the patient, the distress is more likely to be related to a specific event. Open-ended questioning about sources and causes of anxiety, focusing on temporal associations, will often give important clues about the source.

Fear differs from anxiety in that the source of the distressed feeling is obvious to the patient. Often, patients may have distress related to specific fears (e.g., dying, uncontrolled symptoms, loss of function, dependence on others, and family conflicts). For example, patients may paradoxically feel more
worried and distressed as the end of a prolonged course of treatment, such as a course of radiation therapy, approaches. While one might expect the end of a taxing course of therapy to be greeted with relief as the goal of completion is reached, patients often become accustomed to and comforted by close monitoring, supportive contact from treating staff, and the routine of care. Feelings of worry and apprehension about losing these positive aspects of the therapy can be distressing, all the more so because they are unexpected. It is important to determine early on whether there are specific worries and fears, as opposed to a more non-specific feeling of anxiety or tension. While anxiolytic medications may be of some help, specific fears and worries should be addressed with exploration of the problem and therapeutic approaches, including supportive or problem-solving therapy.

Often, patients with cancer are distressed by an acute sense of being out of control. Combined with worries about mortality, the disruption in life and routines caused by cancer, cancer-related symptoms, and cancer treatments can provoke a great deal of distress. Often described as being overwhelmed or “in a tailspin,” this experience can easily be misdiagnosed as clinical anxiety. Again, though anxiolytic medications may provide some degree of relief, they are not typically sufficient. Acute feelings of dyscontrol are often related to important milestones in illness (e.g., initial diagnosis, completing courses of radiation or chemotherapy treatment, and receiving bad prognostic news) or major changes in life roles and routines (e.g., job loss and separation from family). Much like specific fears, acute dyscontrol should be addressed with exploration of the problem and therapeutic approaches including supportive or problem-solving therapy.

The patient’s perspectives about causes and precipitants of anxiety are important to explore. Special attention should be paid to temporal associations between events and onset or worsening of anxiety symptoms. Are there specific worries, fears, or concerns? Have there been conflicts with family, friends, or care providers? Are there financial or transportation problems? Are there spiritual or existential concerns? Any of these items, alone or in combination, can lead to anxiety-related distress.

Are there other symptoms that cause or exacerbate the anxiety? Depression and anxiety are commonly comorbid, and addressing depression can reduce the burden of anxiety. Pain, dyspnea, and nausea are all symptoms that are commonly associated with anxiety. All these symptoms have an adaptive function making them a priority for the attention of the nervous system. Pain is a signal that attention needs to be paid to a source of tissue injury. Dyspnea is a signal that attention needs to be paid to a cause of poor oxygenation. Nausea is a signal that toxic contents of the gastrointestinal tract need to be expelled. These symptoms are hard-wired to be priority stimuli and, even when their presence is not an adaptively meaningful signal, persistence of these symptoms leaves the nervous system on “red alert” status, manifest as anxiety. Understandably, control of these and other distressing symptoms is anxiolytic.

Are there medications that are temporally related to the onset of anxiety symptoms? It is important to explore whether the onset of anxiety was associated with starting a new medication. It is also important to determine whether the onset of anxiety was associated with medication discontinuation, with particular attention paid to alcohol and sedative-hypnotic medications with potential for withdrawal states. Table 42.2 lists medications associated with anxiety.

Older antiemetic medications, and especially metoclopramide, can cause an adverse effect known as akathisia. Akathisia is a sensation of motor restlessness that is commonly seen with medications related to first-generation antipsychotic drugs. An elegant description of akathisia once provided by a patient is that the feeling is like “an itch in my muscles that can only be scratched by moving around.” While akathisia is primarily a feeling of motor restlessness, when unrelieved it can be quite distressing and the fidgeting and emotional upset it causes can easily be mistaken for anxiety. In extreme cases, patients are frankly agitated and restless and can complain of feeling like “jumping out of my skin.” Treatment centers on discontinuation of the offending drug.

Particularly in patients with a history of chronic anxiety or a formal anxiety disorder, inquiry should be made into what treatments were effective in the past. Were there anxiolytic medications that provided reliable relief? Were there nonpharmacologic approaches that were effective? How has the patient best managed these symptoms in the past? If the current anxiety-related distress is consistent with past episodes of anxiety, past treatment response is a good predictor of treatment response in the present.

Patients should be asked about actions or activities that worsen or relieve anxiety symptoms. Can the patient distract herself/himself from distressed feelings by engaging in pleasurable activities, hobbies, or conversation with families and friends? Are relaxation techniques, exercise, meditation, or prayer reliably effective? What are the sources of inner strength and social support available to the patient and how can he/she access them?

Though not all sources of anxiety-related distress are best treated with medication alone, prompt relief from a significant burden of anxiety usually requires a treatment plan that includes medication, if acceptable to the patient. Formal anxiety disorders are usually best managed with anxiolytics and/or antidepressants. Benzodiazepines and antipsychotic medications can reduce anxiety rapidly, while antidepressant medications may take longer to work. Explicit fears and worries should be addressed directly with supportive therapeutic intervention, though anxiolytic medication can be useful as an adjunct.

A panic attack, while not sufficient for a diagnosis in and of itself, is the essential feature of panic disorder. Panic attacks are discrete, brief, intense episodes of intense anxiety associated with symptoms such as

palpitations, pounding heartbeat, or tachycardia;

diaphoresis;

tremor;

dyspnea or a sensation of smothering;

a sensation of choking;

chest pain or discomfort;

nausea or gastrointestinal distress;

dizziness or lightheadedness;

derealization or depersonalization;

fear of losing control as a result of the panic attack;

fear of dying as a result of the panic attack;

paresthesias; and/or

chills or hot flashes.

The typical panic attack has rapid onset and crescendo to full intensity in a matter of minutes. Though the patient’s perception may be that a panic attack lasts much longer, the attack usually dissipates over the course of 15 to 20 minutes, though the experience may leave the sufferer tense, fearful, and apprehensive for some longer period of time. Panic attacks may occur as a response to a perception of overwhelming threat, a reaction to anxiogenic medications, or as a result of spontaneous misfire of the brain’s “fight or flight” response. Those who describe a persistent level of baseline anxiety as “panic” are not describing panic attacks.

Presence of panic attacks is necessary but not sufficient for a diagnosis for panic disorder, which is characterized by the presence of recurrent panic attacks that are frequently or typically unexpected and unprovoked. During a panic attack, the sufferer often attributes the attack to some unseen threat and has an urge to escape the environment, so those with recurrent panic may move suddenly and seemingly irrationally to another setting, avoid situations from which escape would be difficult or embarrassing, or (in extreme cases) avoid placing themselves in such settings altogether. Patients with recurrent panic attacks often live with fear and dread of recurrent attacks. The burden of recurrent panic, the impairment caused by ongoing dread of recurrence, and the disruption caused by maladaptive lifestyle adaptations are the hallmarks of panic disorder.

In one study of panic disorder among hospitalized cancer patients, approximately one-fifth of the patients referred
for psychiatric consultation suffered from panic anxiety (7). Reported complications of panic anxiety in this population included the urge to elope from hospital, requests for discharge against medical advice, disruptions in adherence to cancer therapy protocols, and a request for discontinuation of cancer therapy in order to hasten death (7).

Therapeutic approaches for panic disorder center on pharmacologic therapy to reduce the frequency and intensity of panic attacks, restore functioning, and improve quality of life (8). However, a thorough assessment to rule out medical causes of panic anxiety (e.g., secondary panic related to medical problems producing episodic hypoxia) is an indispensible first step. Another important aspect of care is patient education about the nature and causes of panic attacks to maximize a sense of control and minimize misattribution of symptoms (e.g., misinterpretation of panic symptoms as a manifestation of disease progression or a heart attack). Cognitive-behavioral therapy (CBT) is among the nonpharmacologic therapies recommended for the treatment of panic disorder (8).

Recommended pharmacologic therapies generally include anxiolytic antidepressants and benzodiazepines (8,9). Most antidepressant medications are reliably effective for anxiety disorders, including panic disorder, but may take weeks of daily administration to have optimal effect. Benzodiazepines have the advantage of rapid onset of relief, but they have liabilities including the potential for misuse and addiction. For this reason, benzodiazepines are often co-prescribed with anxiolytic antidepressants at the onset of treatment for panic disorder and then tapered to discontinuation as the antidepressant medication has time to take effect. This approach can also help reduce the risk of anxiety exacerbation sometimes seen in the first few days of initiation of an antidepressant for a primary anxiety diagnosis (9). Some patients with panic disorder may need chronic co-administration of anxiolytic antidepressants and benzodiazepines or a small amount of benzodiazepines for PRN use to abort panic attacks.

GAD is characterized by a pattern of excessive worry that the patient has difficulty controlling. Typically, others in the patient’s social network would readily identify him or her as an excessive worrier. The worrying itself becomes a distressing or even disabling problem and is associated with other symptoms, such as

restlessness, feeling keyed-up, or feeling on edge;

fatigue;

problems with concentration;

irritability;

muscle tension; and

disturbance in sleeping.

The worrying is a long-standing pattern of behavior, is pervasive, and involves worry about a broad range of things (not just having a medical illness such as cancer). That said, a diagnosis with cancer, especially an illness with poor prognosis or high symptom burden, can exacerbate the level of worry-related distress in a patient with GAD to new heights.

Patients with GAD are managed primarily with anxiolytic antidepressants. A meta-analysis of randomized controlled trials of pharmacotherapy for GAD found that while a broad range of antidepressant medications are effective for GAD, fluoxetine ranked first among those drugs studied, in terms of response and remission rates (10). Sertraline was the besttolerated drug studied in this meta-analysis (10). Nutt recommends venlafaxine as the initial pharmacologic approach to GAD (9). The non-antidepressant, non-benzodiazepine serotonergic agent buspirone is also effective for GAD (9). CBT and other non-pharmacologic therapies aimed at reducing the burden of worry and worry-related distress are also helpful.

Posttraumatic stress disorder (PTSD) is one of the few mental disorders in DSM-IV with a known etiology, though this etiology is determined by definition. PTSD is a pervasive pattern of distress developing as a consequence of an overwhelmingly traumatic experience. The characteristics of the kinds of experience that cause PTSD include a sudden and unexpected nature of the traumatic event, a traumatic threat that is outside one’s control, a realistic threat of death or severe injury to oneself or others, and a response to this event that involves fear, helplessness, or horror. Symptoms of PTSD are manifest as re-experiencing phenomena, avoidance of reminders of the trauma, increased startle response and hyperarousal, and emotional numbness or detachment. The re-experiencing phenomena (e.g., nightmares, flashbacks, intrusive daydreams, and ruminations) usually feel more like a virtual recurrence of the traumatic event than an intense memory. A variety of factors appear to increase the chance that a given person will develop PTSD in response to trauma, including having recurrent traumas, the intensity of the fear produced (related to the patient’s interpretation of the severity of the threat), and innate coping capacities.