Treatment for Anxiety Disorders in the Medically Ill

By | January 9, 2015

Treatment of anxiety disorders in the medically ill depends upon the relationship between anxiety symptoms and physical disease. Some patients have persisting symptoms or exacerbations of anxiety disorders that existed before the onset of physical disease. In that case, treatment should be similar to that given to patients without comorbid illness. Other patients, perhaps the majority, have disorders the onset of which coincides with illness-related events. In these instances, treatment needs to take the emotional reaction to events into account. Still other patients will have disorders caused by the altered biology of a disease or its treatment. These are disorders due to medical conditions or substances, and their treatment should begin with the medical conditions, many of which are reversible.

The pharmacological treatment of anxiety disorders in the medically ill is complicated by physical disease and its treatment. Sometimes medications used for anxiety adversely affect the underlying medical problems or interact negatively with the drugs used to treat these problems. For example, a benzodiazepine may suppress respiration if given to an anxious patient with chronic pulmonary disease, or a serotonin reuptake inhibitor may alter the metabolism of drugs used to control cardiac rhythm in a patient with heart disease. Of course, the reverse is also true; physical disease and its treatment may contribute to anxiety in ways that are sometimes difficult to modify. In the face of progressive and life-threatening disease, anxiety-generating treatment (e.g., chemotherapy) may be necessary. When factors that are contributing to anxiety symptoms are recognized, they can be taken into account in weighing treatment options.

The psychological treatment of anxiety in the medically ill employs a number of management techniques. These techniques are usually not time-consuming nor do they call for special training, yet they are surprisingly effective (). For example, anxiety is best managed initially by providing emotional support and adequate information (). To do this, physicians should elicit and deal with the thoughts and feelings that are causing distress. Anxiety about procedures or treatments may be reduced by adequate preparation. Although the value of such simple measures is well documented, they are too often neglected (). Causes of anxiety to be explored include worry about practical matters such as finances, physical suffering, uncertainty about the future, loss of independence, loss of social role, fear of becoming a burden, fear of the manner of death, and spiritual concerns (). Many patients can be helped by an opportunity to share their concerns and to feel understood ().

In addition to supportive psychotherapy, anxiety management techniques (e.g., muscle relaxation), and cognitive behavioral interventions (e.g., modifying dysfunctional thoughts about illness) are often helpful.

Pharmacological treatment

Benzodiazepines

Benzodiazepines not only reduce anxiety but also induce sleep, promote muscle relaxation, control nausea and vomiting associated with chemotherapy, and bring about relaxation if not amnesia during procedures. There have been few controlled trials so that efficacy has not been established for most indications. In a controlled trial of patients with anxiety associated with cardiovascular disease, lorazepam in a dose of 3 mg daily proved superior to placebo (). Tollefson et al. (1991) reported that, in an open trial of alprazolam, patients with coexisting generalized anxiety disorder and irritable bowel syndrome showed a reduction in both anxiety and bowel symptoms. Similarly, Holland et al. (1991) found that both alprazolam and progressive muscle relaxation resulted in a significant reduction in anxiety and depressive symptoms among cancer patients.

Benzodiazepines have also been shown to significantly reduce the anticipatory anxiety as well as the nausea and vomiting that accompanies chemotherapy (). Patients who receive lorazepam experience less anxiety and more sedation as well as less nausea and vomiting. When the drug is given intravenously (2-4 mg), many patients do not remember the treatment. Patients receiving benzodiazepines have been pleased with their effects, and in some instances, have been willing to continue otherwise intolerable treatments ().

The choice of a benzodiazepine and its administration may be influenced by a patient’s age and physical status. The metabolism of drugs that undergo microsomal oxidation is slowed in the elderly. This prolongs the half-life of long-acting drugs and increases the risk of toxicity from accumulation (). The metabolism of drugs that undergo glucuronide conjugation, such as lorazepam, oxazepam, and temazepam, are little affected by age. Liver disease may also slow the metabolism and increase the risk of toxicity. In elderly patients, the starting dose of a benzodiazepine should be about half the usual dose.

Drugs that influence the activity of liver enzymes may alter the metabolism of benzodiazepines. Chronic sedative-hypnotic use can, by increasing enzymatic activity, increase the breakdown of benzodiazepines. Consequently, patients taking drugs like phenobarbital or phenytoin may require high doses. On the other hand, patients taking drugs that compete for metabolizing enzymes, such as cimetidine, disulfiram, isoniazid, erythromycin or estrogens, may require smaller doses. Elderly patients are more sensitive to the central effects of benzodiazepines including memory disturbance, drowsiness, depressed mood, ataxia, and falls.

Benzodiazepines may inhibit respiratory drive in patients with chronic pulmonary disease. This inhibition is usually only a problem in patients with chronic carbon dioxide retention. According to Stoudemire & Moran (1993), most asthmatic and chronic emphysematous patients are able to tolerate small doses of benzodiazepines. Use of a benzodiazepine is dangerous in patients suffering from sleep apnea because of respiratory suppression. Buspirone, because it is a mild respiratory stimulant, may be useful in patients with chronic obstructive lung disease. Open trials have indicated efficacy ().

Lorazepam, alprazolam, and clonazepam are the benzodiazepines most frequently prescribed for medically ill patients. Lorazepam has no active metabolites and is unlikely to accumulate. Unlike most other drugs in this class, it may be administered by the oral, intramuscular, and intravenous routes, making it versatile. Control of anxiety is rapid, often occurring within the first few days. Drowsiness and fatigue, the most common side-effects, usually respond to dose adjustment or the passage of time. Alprazolam has antidepressant properties and may be tried where depressive symptoms coexist. Clonazepam is a longer-acting drug that has little interdose rebound that may be a problem with shorter-acting drugs (). Midazolam, a short-acting benzodiazepine that is available only in injectable form, is also used to control procedure-related anxiety.

Other antianxiety drugs

Several other classes of drugs are used to control generalized anxiety symptoms in the medically ill. These include azapirones, beta-blockers, and antihistamines. Buspirone, an azapirone, is a partial serotonin agonist that is free of sedation and effects on cognition (). It does not appear to interact with drugs used in the medically ill. In addition to its value in pulmonary disease, it may control anxiety and agitation in patients with dementia and brain trauma (). The dose for elderly patients is similar to that for younger ones (i.e., 40-60 mg) ().

Propranolol and other beta-adrenergic blocking agents relieve anxiety by blocking the peripheral autonomic response (). As with buspirone, they are useful for milder forms of anxiety but have little effect on panic disorder. Non-selective beta-blockers, such as propranolol, should not be used in patients with a history of asthma or obstructive pulmonary disease. Cardioselective agents, such as atenolol, may be used cautiously in such patients and may be best for patients with diabetes as they do not interfere with glycogenesis. Less lipophilic drugs, such as atenolol, have fewer central nervous system side-effects. Hydroxyzine and diphenhydramine, Hl-histaminic blocking agents, are commonly used to treat mild anxiety and insomnia. Although considered safe, they may cause drowsiness and cognitive impairment in the elderly and medically ill. Also, they have anticholinergic and other side-effects to which elderly persons are particularly sensitive.

Although benzodiazepines are useful for the rapid control of more severe anxiety, other drugs, including the serotonin uptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors are also used to treat anxiety in the medically ill. The efficacy of these classes of drugs for various anxiety disorders has been reviewed elsewhere (). The relative absence of cardiovascular effects has made the serotonin uptake inhibitors popular for treating anxiety and depression in the medically ill (). They may alter the metabolism of a number of drugs used to treat medical illness because of their inhibition of cytochrome P450 liver enzymes. Consequently, possible interactions must be taken into account when they are prescribed. Drugs with mild stimulant properties, such as fluoxetine, may be more difficult for anxious patients to tolerate initially than drugs such as paroxetine or sertraline. In higher doses these agents may produce akasthisia that may be mistaken for worsening anxiety.

Cyclic antidepressants are well established antipanic agents and their efficacy for generalized anxiety has also been demonstrated (); however, in the medically ill they have a number of potentially serious effects. These include orthostatic hypotension, anticholinergic effects, quinidine-like effects, and sedation. Nortriptyline has less potential for hypotension, and established blood levels are a useful guide to dosing. It is wise to begin with low doses (e.g., 10-25 mg) and increase gradually using electrocardiographic monitoring. Monoamine oxidase inhibitors may also be used in medically ill or elderly patients. Their superior efficacy for anxious depression and their energizing effects make them especially valuable for some patients. If no harmful drug interactions are anticipated, orthostatic hypotension is the chief concern with drugs such as phenelzine or tranylcypromine. Patients using these drugs must adhere to a tyramine-free diet and avoid indirect-acting sympathomimetic agents, some of which are available in over-the-counter cold preparations. Hypertensive crises resulting from such interactions are, fortunately, rare.

Psychological treatment

Medically ill patients may benefit from a variety of psychosocial interventions designed to reduce general distress, procedure-related discomfort, and acute anxiety. Few controlled trials have examined the effectiveness of such therapies for anxiety (). A review of controlled studies of psychological therapies in medically ill patients in 1981 found only 13 methodologically adequate trials, and a similar review in 1996 found just 14 (). In their review of controlled studies in cancer patients, Fawzy et al. (1995) identified several types of relatively brief interventions that have demonstrated efficacy. These included education, behavioral interventions, cognitive therapy, individual psychotherapy, and group therapy. Few of the studies specifically examined change in anxiety but included it among measures of psychological distress. Also, most interventions were compared to ineffective procedures which showed they were better than no treatment but not how they compared with other approaches.

Behavioral methods have been used in conjunction with many medical interventions to reduce physical as well as psychological distress, and these methods have, in general, proved beneficial. Techniques have included progressive muscle relaxation, hypnosis, deep breathing, meditation, biofeedback, and guided imagery (). As reviewed by Goldberg (1982), these self-regulatory techniques reduce anxiety by evoking the relaxation response (). Most are easily taught and quickly learned. Efficacy in medical populations has been demonstrated (). For instance, Davis (1986) reported significant improvement in anxiety among breast cancer patients receiving biofeedback and cognitive therapy, and other investigators observed reduced anxiety among cancer patients who received muscle relaxation and guided imagery (). Similar methods have been applied to patients with lung disease ().

Behavioral techniques may also be useful for managing anxiety related to investigations or procedures (). Relaxation training, systematic desensitization, and positive reinforcement have been used to reduce anxious and phobic reactions to medical treatments (). Behavioral approaches, especially those for children undergoing painful procedures, usually involve a combination of positive motivation, emotive imagery, and hypnosis. Patients with claustrophobia or needle/blood phobia may be rapidly and successfully treated with behavioral methods (). For needle/blood phobia, Ost et al. (1989) developed a technique called applied tension that may produce results quickly.

Cognitive therapy, an effective treatment for anxiety, is increasingly being used in the medically ill (). This therapy focuses upon dysfunctional beliefs, especially those involving the illness itself, interaction with health care professionals, and the perceived impact on the patient’s life (). The onset of physical illness often involves life-threatening events to which some patients, by virtue of their cognitive style, are vulnerable. Cognitive therapy begins with an exploration of a patient’s understanding of his or her illness. The approach is educational and leads to the acquisition of skills that can be applied to present and future problems. Specific techniques have been developed for patients with such problems as cancer and chronic pain. Sensky (1993) has reviewed the efficacy of cognitive therapy in a variety of patient populations.

Individual psychotherapy has, in some controlled trials, resulted in reduced psychological distress and better coping in patients with neoplas-tic and other diseases (). In a study that attempted to reduce psychological morbidity including anxiety, Greer et al. (1992) examined the effect of adjuvant psychological therapy. At 4 months and again at 12 months, patients who had received the therapy had significantly lower scores on anxiety than did controls (). Also, fewer therapy patients fell in the clinical range for anxiety than did controls. The study – one of the few to address anxiety specifically – demonstrated that a brief psychological intervention can not only reduce distress but also the rate of caseness a year afterward. Controlled studies have also shown psychotherapeutic interventions useful in reducing the distress following myocardial infarction (). In one such trial, patients who received counseling from coronary care nurses reported significantly lower levels of anxiety than controls immediately after admission as well as 6 months later ().

Psychotherapy with medically ill persons is based on an understanding of the illness dynamics or factors affecting an individual’s response to a specific disease at a particular time in his or her life (). Illness is experienced as both a threat and a loss and typically precipitates a grief reaction accompanied by anxiety (). Supportive rather than intensive psychotherapy is usually appropriate for anxiety resulting from illness (). Winston et al. (1986) and Green (1993) have outlined the goals and techniques to be employed with this form of therapy. Blacher (1991) and Groves & Kucharski (1991) describe a series of brief intervention strategies that may be used by psychiatric consultants.

Group intervention may also be beneficial in medically ill patients (). Group techniques include education, emotional support, stress management, coping strategies, behavioral training, and others. In an important study by Spiegel et al. (1981), patients who participated in psychological support groups for a year reported less tension and fewer phobias than did controls.

Selections from the book: “The anxiety disorders” (1998)