Treatment of Anxiety in the Medically Ill

By | March 12, 2015


An overemphasis on psychopharmacology in the care of medically ill patients may result in overlooking the value of psychotherapy. The first step in the treatment of anxiety is to spend time listening to and talking with the patient. Just as in psychotherapy with any patient, empathic listening is a powerful tool to relieve distress. With medically ill patients, the goal is to help patients understand and discuss their emotional reactions to their illness so that they can then manage these feelings by using their own coping mechanisms. Psychotherapeutic approaches include supportive, psychodynamic, and cognitive-behavioral therapies.

Supportive Therapy

Supportive therapy involves listening and providing reassurance, sympathy, education about the medical process and the underlying illness, advice, and suggestions. The process includes listening for fears and misperceptions about illness or its treatment and giving patients appropriate information so that they can be as prepared as possible. Effective communication, using language the patient and family can understand, can lead to a great decrease in anxiety. It is also helpful to give patients as much choice in their treatment decisions as possible so that they feel they have some control over the course of their treatment.

Reassurance is an important skill that all physicians use in treating patients. In some highly anxious patients, however, simple reassurance can actually cause increased anxiety and lead to a cycle of maladaptive behavior. For example, if a patient who has been told that a procedure is simple or painless subsequently experiences pain or untoward results, the resulting anxiety can lead to more reassurance-seeking behavior, mistrust, and decreased cooperation. Many anxious patients tend to interpret bodily symptoms as evidence of serious disease, and as a result, they may seek multiple consultations for reassurance. Understanding the patient’s beliefs, concerns, and perceptions can be helpful in challenging misperceptions, educating the patient about his or her illness, and devising a realistic plan to monitor symptoms. Having a realistic plan to help patients differentiate minor symptoms from those that may need medical attention will reduce anxiety and decrease the excessive need for reassurance. It is also important that the physician not assume that a patient’s anxiety is due to fear of dying. When reassurance is directed at the wrong fear, it may accentuate anxiety and lead patients to believe that their physician does not understand them.

The consultant can also serve as a liaison between the patient and the health care team. For example, the psychiatrist might help the primary physician understand the importance of clarifying the risks and benefits of treatment and of informing the anxious patient when there are delays in scheduling. It also may be helpful for the treatment team to consult directly with the psychiatrist about how to care for the anxious patient. Facilitating communication among the patient and the treatment team can help avoid misperceptions or mistrust that will only serve to heighten anxiety.

Another important aspect of supportive therapy is the involvement of the patient’s support system of family, friends, and religious community. Working with the support network is important to ensure that their anxiety and misperceptions do not add to the stress of the patient. Helping a patient to expand his or her social network can be an important component of a supportive program. In addition, hospital staff such as nurses, chaplains, social workers, volunteers, and other allied professionals can help provide support and encouragement to the medically ill patient.

Patients confronting life-threatening or terminal illnesses such as cancer may experience death anxiety. Relief of physical pain, dyspnea, and other physical symptoms is critical for the alleviation of anxiety. Some patients have strong religious or spiritual beliefs that may help reduce their distress, and pastoral counseling is often beneficial. Open discussions with patients about death help to reduce anxiety and distress, and psychological interventions alone can help patients manage their death anxiety. Maintaining hope is an important aspect of minimizing anxiety, although goals can change from full recovery to having more time to accomplish specific short-term goals. Helping patients find meaning and value in their lives, despite their illness and suffering, helps to relieve emotional distress. For example, anxiety can be reduced when patients see that they are still important to their families or that they still have unfinished business to address. The hospice movement has been instrumental in helping provide relief for many patients. Despite recent improvements in physician education, caregivers need more training to be able to overcome their own death anxiety so that they can provide comfort to end-of-life patients (see “Palliative Care”).

Supportive group interventions are very effective in reducing anxiety and distress in medically ill patients. HW, cancer, cardiac, and other support groups have proliferated in recent years. They can be quite helpful in providing emotional support and education in stress management, coping skills, and other behavioral techniques. Participants have been shown to have decreased stress levels and improved functioning.

Cognitive-Behavioral Therapy

Cognitive-behavioral therapy has been proven to be as effective as medication in treating many anxiety disorders, including GAD and panic disorder. Cognitive techniques are used to uncover and correct misinterpretations and irrational thoughts that lead to increased anxiety and distress. Behavioral techniques, such as systematic desensitization, can also be used to help overcome irrational fears that can interfere with effective treatment, such as blood or needle phobias and claustrophobia during MRI. Since cognitive-behavioral therapy techniques usually take several sessions to be effective, medications may be needed initially to help reduce anxiety. A brief course of cognitive-behavioral therapy can have long-lasting effects, but occasional “booster” sessions may be needed.

A variety of therapies that involve teaching self-awareness and self-regulation of body functions have been found effective in reducing anxiety and physical symptoms in medically ill patients. These include muscle relaxation techniques (such as Jacobson’s progressive muscle relaxation), autogenic training (such as biofeedback, which uses technology to control internal processes), and relaxation techniques (such as meditation, breathing exercises, and self-hypnosis). Muscular conditions such as tension headaches and musculoskeletal disorders may respond better to muscle relaxation; migraine headaches and hypertension, to autogenic training; and anxieties and phobias, to more cognitive techniques; however, further research is needed. When used by a skilled practitioner with a patient who is open to this approach, all of these techniques may be helpful in reducing symptoms of various conditions exacerbated by anxiety and stress. Guided imagery with relaxation and hypnosis has also been an effective technique to reduce anxiety. Relaxation techniques have been used to decrease the use of medications in hypertensive patients, to decrease pain in patients with chronic pain, and to expedite recovery and decrease complications in postsurgical patients. Meditation has been shown to reduce panic attacks, and biofeedback and relaxation have been used to help wean patients from the ventilator as well as to reduce dyspnea and anxiety in patients with chronic obstructive pulmonary disease.

Psychodynamic Therapy

For patients who are not too ill and who have sufficient emotional resilience, brief dynamic psychotherapy can be useful in uncovering the conscious and unconscious meaning of the illness to the patient. Understanding patients’ developmental history, interpersonal dynamics, and defense mechanisms can help the psychiatrist to assist them in finding healthier ways to cope with medical illness. What coping strategies have helped in the past? When did the individual feel most fulfilled in his or her life? How can those memories and skills be used now, even in the presence of significant medical illness? Psychotherapy can uncover areas leading to increased distress, such as real or imagined guilt, unhealthy coping strategies like avoidance and denial, and recognition of past conflicted relationships that may be repeated in the current doctor-patient relationship. An understanding of the patient’s underlying dynamics can help identify and resolve conflicts with the treatment team that may be interfering with recovery. Psychotherapy started in the hospital may then be continued on an outpatient basis, to help patients cope with their illness and achieve optimal functioning. An understanding of psychodynamic principles can also help psychiatrists in working with the primary treatment team that is caring for the anxious patient.

Countertransference reactions can cause a number of problems for providers of anxious patients. For example, physicians may overidentify with their patients, leading to frustration because of lack of progress or poor prognosis. As a result, they may then overcompensate by offering excessive reassurance, or they may minimize or overlook symptoms in an unconscious attempt to reduce their own anxiety. Caregivers may also become withdrawn and distant, providing care mechanically with little empathy or awareness of the emotional needs of the patient. Psychiatrists can play a role in helping the health care team to be cognizant of these defenses so they do not interfere with the provision of optimal patient care. (See “Psychosocial Treatments,” for further discussion of psychotherapy for the medically ill.)


Psychotherapeutic techniques are often not sufficient to manage anxiety in the medically ill. An increasingly broad range of psychopharmacological agents can be used safely with this population.

TABLE Selected benzodiazepines used for anxiety in the medically ill

Medication Route Dosage Elimination half-life Comments
Alprazolam Oral 0.25-1.0 mg tid 9–20 hours Rapid onset.

Interdose withdrawal a problem, but new extended-release form is available.

Chlordiazepoxide Oral, intramuscular 5-2 5 mg qid 28–100 hours (including metabolites) Useful for alcohol withdrawal.
Clonazepam Oral 0.2 5-1 mg bid-tid 19–60 hours Also used for absence seizures, periodic leg movements, and neuropathic pain.
Diazepam Oral, intravenous 2-10 mg qid 30–200 hours (including metabolites) Also used as an anticonvulsant and muscle relaxant.
Lorazepam Oral, intramuscular, intravenous 0.5–2.0 mg up to qid 8–24 hours Intravenous availability is an advantage.

Metabolized by conjugation.

Also approved for chemotherapy-related nausea and vomiting.

Midazolam Intramuscular, intravenous Intramuscular: 5 mg single dose

Intravenous: 0.02–0.10 mg/kg per hour

1–20 hours (including metabolites) Used for preoperative sedation and intravenous induction.
Oxazepam Oral 10-30 mg qid 3–25 hours Metabolized by conjugation.

May also be useful for alcohol withdrawal.


For acute anxiety symptoms, the most immediately effective and frequently used agents are the benzodiazepines (Table Selected benzodiazepines used for anxiety in the medically ill). Diazepam and chlordiazepoxide were among the first of these to be used. They also have established efficacy for other conditions — diazepam as an anticonvulsant and muscle relaxant and chlordiazepoxide for alcohol detoxification. Diazepam can be given orally or intravenously but should not be given intramuscularly. However, newer benzodiazepines have better safety profiles and shorter half-lives, so they tend to be used more frequently.

Alprazolam works rapidly and is eliminated quickly, but as a result there may be rebound anxiety and withdrawal symptoms. Because lorazepam can be given orally, intravenously, or intramuscularly and does not have an active metabolite, it is often a preferred medication in hospitalized patients. Lorazepam can be given in an intravenous bolus or drip, but as doses increase to provide sedation and treat delirium tremens, respiratory status must be watched closely. Like lorazepam, oxazepam and the hypnotic temazepam are metabolized through conjugation and so are less problematic in patients with liver disease than the other benzodiazepines, which are oxidatively metabolized. Midazolam, a benzodiazepine with a very short half-life that can only be given intravenously or intramuscularly, is used for short-term procedures such as bone marrow biopsies, endoscopies, and MRI scans in claustrophobic patients.

For patients who need long-term benzodiazepines, it is often helpful to change to a medication with a longer half-life, such as clonazepam.

Hypnotics are commonly used in medically ill patients who are kept awake by their anxiety. Triazolam has been used less frequently in recent years because it can cause retrograde amnesia. Temazepam is occasionally still used for persons who tend to awaken when taking the shorter-acting hypnotics. Newer agents such as zolpidem and zaleplon are nonbenzodiazepines that act on the benzodiazepine receptor. They are preferred for short-term use because they have very short half-lives and as a result cause less daytime sedation, impaired coordination, and cognitive disturbance. Generally all of the hypnotics are best used for short intervals to decrease the chance of side effects, to maintain effectiveness (i.e., prevent tolerance), and to prevent dependence.

All benzodiazepines can cause excessive sedation. They may also cause motor and cognitive disturbances, especially in older persons and individuals with impaired brain functioning (e.g., due to dementia, head injury, or mental retardation). Therefore, they should be used with caution, if at all, in these patients. Anxiety in delirious patients is usually better treated with antipsychotics than with benzodiazepines. Benzodiazepines can cause respiratory suppression, so they should be used cautiously in persons with pulmonary disease who retain carbon dioxide, or in patients with sleep apnea. Because of potential teratogenicity, benzodiazepines should be avoided in the first trimester of pregnancy. They should also be avoided at the very end of pregnancy, because there are reports of sedation and withdrawal symptoms in the fetus. All benzodiazepines can lead to tolerance and dependence, so they should be avoided or used judiciously (i.e., for detoxification) in persons with a substance abuse history. However, compared with barbiturates and earlier sedative-hypnotics such as meprobamate, they are much safer in overdose and have fewer side effects. In persons who are conscientious and do not have a history of chemical dependence, benzodiazepines can often be safely used for years without causing problems or tolerance. As an individual ages, use should be reevaluated. Similarly, long-term benzodiazepine use may need to be reduced or discontinued among patients who develop specific medical conditions (e.g., end-stage liver disease, dementia, chronic obstructive pulmonary disease, and cerebellar dysfunction).


The pharmacological treatment of choice for GAD, panic disorder, posttraumatic stress disorder, obsessive-compulsive disorder, and social anxiety disorder is one of the selective serotonin reuptake inhibitors (SSRIs): fluoxetine, sertraline, paroxetine, citalopram, escitalopram, and fluvoxamine. Venlafaxine, which inhibits both serotonin and norepinephrine reuptake, has been approved for GAD and social anxiety disorder and will probably also be shown to be effective for other anxiety disorders. These medications have few side effects and therefore are generally quite safe for the medically ill; they do not result in cardiac conduction problems, orthostatic hypotension, or physical dependence. Because antidepressants may take 2-6 weeks to relieve anxiety, the patient may need initial treatment with benzodiazepines. Once the patient has been stabilized on the antidepressant medication, the benzodiazepines can usually be gradually withdrawn without recurrence of anxiety. The antidepressant should be used for at least 3-6 months before stopping it, and it should be tapered to avoid discontinuation symptoms. Antidepressants can be used safely on a long-term basis if anxiety returns.

One of the main drawbacks of the SSRIs and venlafaxine is a relatively high incidence of sexual dysfunction in both men and women. This side effect may be particularly problematic for persons with medical problems already associated with sexual dysfunction, such as diabetes or vascular disease (“Sexual Disorders”). In addition, psychiatrists must be concerned about the potential for drug interactions, for example, with fluoxetine and paroxetine (cytochrome P450 2D6 inhibitors) and fluvoxamine (a cytochrome P450 3A4 inhibitor; “Psychopharmacology”). Serotonin reuptake inhibitors may cause initial gastrointestinal distress and nausea, so they are generally given with food. It is important to reassure the patient with gastrointestinal disease that these side effects are almost always transient. SSRIs are also associated with the syndrome of inappropriate secretion of antidiuretic hormone, especially in older patients. In a small percentage of patients, venlafaxine produces a unique side effect of sustained blood pressure elevation, which is dose-related. Blood pressure should be monitored when this drug is being initiated and with each dosage increase. If diastolic blood pressure increases occur, the dosage should be reduced or the drug stopped. Although SSRIs may help some individuals with migraine headaches, they can also exacerbate headaches. It has been reported that SSRIs can exacerbate parkinsonism in individuals with Parkinson’s disease; however, this appears to be an uncommon side effect. Because all SSRIs are equally efficacious in studies, medication choice is often based on side-effect profile. For example, the more sedating SSRIs (e.g., fluvoxamine and paroxetine) may be advantageous for the highly anxious patient with insomnia, whereas fluoxetine may be more stimulating. For medically ill patients taking multiple medications, agents with the fewest drug interactions are preferred: sertraline, citalopram, escitalopram, and venlafaxine.

Mirtazapine — an alpha-adrenoceptor antagonist and an antagonist at serotonin 5-HT2A, 5-HT2C, and 5-HT3 receptors — may be helpful in reducing anxiety. Its use in medically ill patients has increased recently for two reasons: 1) it has few drug interactions, and 2) the side effects of sedation and increased appetite are helpful in patients who have insomnia and anorexia with weight loss. Nefazodone is another unique antidepressant with some anxiolytic properties, but it can be problematic for medically ill patients because of its inhibition of the cytochrome P450 3A4 enzyme, the need for gradual dose adjustment, and its recent black-box warning of rare liver toxicity. Neither of these medications causes sexual dysfunction.

Tricyclic antidepressants and monoamine oxidase inhibitors are well established as effective treatments for anxiety disorders as well as for depression. Tricyclics can be efficacious for the treatment of anxiety in the medically ill (e.g., in patients with chronic pain or diarrhea-predominant irritable bowel syndrome). The main reasons these medications are currently not used frequently as first-line treatment are their numerous side effects and their toxicity in overdose. Tricyclics often cause dry mouth, weight gain, constipation, sedation, orthostatic hypotension, urinary retention, and falls, especially in elderly patients. In addition, because of their quinidine-like effects, they can cause heart block and arrhythmias. Because there is a relatively small margin of safety between efficacy and toxicity, overdose can be dangerous and even fatal. Persons with liver and kidney disease may develop toxicity due to impaired metabolism and excretion. Monoamine oxidase inhibitors can cause dizziness, orthostatic hypotension, and weight gain. These side effects, as well as the potential for serious hypertensive crises, limit their usefulness in medically ill patients.


Antipsychotic medications are not approved for the treatment of anxiety, although there are limited data clearly supporting their efficacy. Nonetheless, psychiatrists often find them to be efficacious and safe to use in selected medical populations. Because antipsychotics do not cause confusion or respiratory compromise, they may be preferable to benzodiazepines for the more severe anxiety associated with agitation or delirium or in patients with respiratory compromise. For example, antipsychotics may be helpful in assisting the anxious patient who is being weaned from a ventilator. Of the older, or typical, antipsychotics, the agent used most often in medically ill patients is haloperidol, which can be given orally, intramuscularly, or intravenously. In acutely agitated patients who may be violent or psychotic, 5-10 mg of haloperidol is often given orally or intramuscularly, usually in conjunction with a benzodiazepine such as lorazepam, and sometimes with benztropine to prevent a dystonic reaction. In medically ill patients who are delirious, haloperidol rarely causes extrapyramidal side effects or dystonia. For mild agitation, 0.5-2.0 mg might be given, but much higher doses can be used. If a high-potency typical antipsychotic such as haloperidol is used in treating anxiety, it is important to monitor for akathisia because it can be mistaken for worsening anxiety. Newer atypical antipsychotics such as olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole are also used selectively in the management of anxiety, especially in lower doses. Ziprasidone is the only one available in intramuscular formulation at this time. Compared with the older agents, they have relatively favorable side-effect profiles. There are no data regarding their use for anxiety in general and specifically in medically ill populations, but they can be a safe alternative for those who might not do well with benzodiazepines, such as delirious patients or those with respiratory compromise.


Buspirone is a partial serotonin agonist approved for treatment of GAD. It may be useful in treating medically ill patients with anxiety because there are few drug interactions; it does not cause sedation, respiratory depression, or cognitive problems; and its metabolism is not greatly affected by liver disease. The main drawbacks with buspirone are that it may take 2-4 weeks to become effective, and its benefits seem modest. Because of its short half-life, buspirone needs to be given 2-3 times a day. Some patients complain of dizziness and excessive sedation when first beginning the medication, but it is usually well tolerated.


Beta-adrenergic blockers produce anxiolytic effects by blocking autonomic hyperarousal (elevated pulse, elevated blood pressure, sweating, tremors) associated with anxiety responses. They work best for specific anxiety-producing situations, such as performance anxiety and public speaking, and are less efficacious for panic disorder and social phobias. All beta-blockers are contraindicated in persons with asthma or chronic obstructive lung disease, and they can worsen peripheral vascular disease. Patients with insulin-dependent diabetes should not be prescribed nonselective beta-blockers; because those medications block the sympathetic nervous system response to hypoglycemia, the patient may be unaware of symptoms and may be less likely to respond appropriately. Central nervous system side effects such as nightmares, hallucinations, and sleep disturbance are infrequent. They may be more likely to occur with lipophilic drugs such as propranolol and pindolol, which cross the blood-brain barrier, and less likely to occur with atenolol, nadolol, and timolol. The reported association between beta-blockers and depression has not been supported by data from clinical trials.


Sedating histamine H1 receptor blockers are sometimes used to treat anxiety and insomnia. Hydroxyzine has been shown to be as effective and safe as benzodiazepines in treating anxiety in a general study population. Diphenhydramine, which is often used to treat insomnia, is available in over-the-counter preparations. Because these medications are not addicting, many physicians consider them to be benign. However, they can cause dizziness, excessive sedation, incoordination, and confusion, especially when used with alcohol or other central nervous system depressants. Elderly patients and those with brain disease or injury are more sensitive to these medications and may become delirious even with low doses. Despite these risks, these medications are still an option when benzodiazepines must be avoided due to concerns about dependence or respiratory depression.


Anticonvulsants are primarily prescribed by psychiatrists for patients with bipolar disorder who cannot tolerate or do not respond to lithium, but they can also be helpful for some individuals with anxiety. Patients with recurrent panic attacks and temporal lobe electroencephalographic abnormalities may respond to anticonvulsants. Gabapentin works on the gamma-aminobutyric acid system and can be effective for relief of neuropathic pain. It has also been shown to have efficacy for panic disorder and social anxiety disorder. Because gabapentin is not metabolized through the liver, it has few drug interactions and can be used safely in persons with liver disease. Side effects include sedation, headache, and dizziness. Divalproex sodium and carbamazepine have been found to be helpful in calming agitated, anxious patients, especially those with brain injury, mental retardation, or dementia. The newer anticonvulsants lamotrigine, topiramate, and tiagabine show some promise in treatment of mood disorders and may also prove to be beneficial for the treatment of anxiety.


Selections from the book: “Textbook of Psychosomatic Medicine”, 2005.