Medications
The pharmacologic mainstay of anxiety disorders is antidepressant medication. These agents may take 4 to 6 weeks for maximal effect but promise long-lasting symptom amelioration once fully active. Currently, escitalopram(Drug information on escitalopram), paroxetine(Drug information on paroxetine), and venlafaxine have FDA (US Food and Drug Administration) indications for the management of generalized anxiety disorder. Most SSRIs have been used successfully in the treatment of panic disorder. Typical dose ranges for these agents follow: paroxetine, 20 to 60 mg/d; escitalopram, 10 to 20 mg/d; sertraline(Drug information on sertraline), 50 to 200 mg/d; and extended-release venlafaxine, 75 to 375 mg/d (see Table 1).
Benzodiazepines Because of the delayed onset of antidepressant action, benzodia-zepines are often useful adjuncts to initial treatment. These medications have variable hypnotic, antiemetic, and muscle-relaxant effects useful in other aspects of supportive cancer care. Caution is required when using these agents in the settings of serious illness (because of the risk of additive sedation with other medications), advanced age, or CNS impairment (because of the risk of disinhibition or delirium). Benzodiazepines commonly used to treat anxiety in cancer patients are listed in Table 2.
Short-acting benzodiazepines, such as lorazepam(Drug information on lorazepam) and alprazolam(Drug information on alprazolam), have a rapid onset but relatively short duration of action, making them useful for treating intermittent paroxysmal anxiety or panic attacks. For the same reason, they are also useful in patients with severe medical illness. Typical doses are lorazepam 0.5 to 1.0 mg PO (by mouth)/IM (intramuscular)/IV (intravenous) every 4 to 12 hours or alprazolam 0.25 to 0.5 mg PO every 6 to 8 hours as needed. For patients with persistent anxiety, these medications can be given on a regular schedule. Lorazepam’s lack of active metabolites makes it a good choice in patients with hepatic or renal compromise.
Withdrawal develops more rapidly to short-acting benzodiazepines than to their longer-acting counterparts. Therefore, if short-acting agents are used for any length of time, they should be discontinued gradually.
Longer-acting benzodiazepines, such as diazepam(Drug information on diazepam) and clonazepam(Drug information on clonazepam), are useful for persistent anxiety. Their longer duration of action is such that they do not “wear off” quickly and leave patients unprotected.
Clonazepam is typically given at a dose of 0.25 to 1.0 mg every 8 to 24 hours and diazepam at a dose of 2 to 10 mg every 6 to 24 hours. These drugs have multiple active metabolites that can adversely affect the elderly and patients with renal or hepatic impairment. In such patients, it is best to avoid these medications if at all possible.
Other medications At low doses, antipsychotic medications, such as haloperidol(Drug information on haloperidol) (Haldol), olanzapine(Drug information on olanzapine) (Zyprexa), quetiapine(Drug information on quetiapine) (Seroquel), and risperidone(Drug information on risperidone) (Risperdal), may be used as anxiolytics. These agents are most appropriate for patients with a history of, or at high risk for, adverse reactions to benzodiazepines.
Delirium
Delirium is a syndrome of diffuse brain dysfunction incited, typically acutely, by aspects of medical illness or treatment. In some surveys, 15%–30% of cancer inpatients and up to 85% of those who are terminally ill experience the syndrome. Its presence is linked to increased length of hospital stays, morbidity, and mortality. For this reason, accurate diagnosis and identification of causes are critical. With neutralization of inciting factors, many cases of delirium are reversible.
Signs and symptoms
Waxing and waning impairments in attention, orientation, and memory are the hallmarks of the syndrome. Other features that occur more variably include disturbances in affect, mood, sleep pattern, level of agitation, insight, and perception; a delirious patient may, for instance, experience an altered sense of reality, whether in the form of an illusion or a hallucination. The presence of several of these signs and symptoms or history or an exam should raise the specter of the diagnosis.
Distractibility is the sine qua non of the syndrome. Delirious patients perform poorly on tasks requiring concentration. They may have trouble naming the months of the year in reverse, counting backward by 7’s from 100, or drawing a clock face set to a particular hour. Memory impairment is also prominent. Delirious patients often encounter difficulty encoding new information, for instance, registering three new words if specifically asked to remember them or recalling them after 5 minutes. They may also have difficulty with biographical information, such as their phone number or the ages of their children. Not infrequently, delirious patients prove to be amnestic to their delirious episodes. They are typically disoriented to time and place but rarely to person. These deficits wax and wane, and the presence of lucid intervals may seem to discount the diagnosis. For this reason, serial examinations are useful.
Etiology
Organic disturbances that can produce a state of delirium are multifold and range from primary intracranial abnormalities such as tumors to systemic diseases that secondarily affect the brain to substance intoxication or substance withdrawal. Life-threatening causes that are potentially reversible include substance withdrawal (including from alcohol(Drug information on alcohol), prescription drugs, and illicit drugs), hypertensive encephalopathy, Wernicke’s encephalopathy, hypoxia, hypoglycemia, intracranial bleeding, meningitis, encephalitis, and poisoning. Another potentially reversible cause is substance intoxication. Many medications used commonly in the context of cancer can trigger delirium. They include benzodiazepines, opioids, anticholinergic medications, corticosteroids, and chemotherapeutics.
