I. Problem/Condition.

Anxiety is a common problem in hospitalized patients given the fear of an illness and its consequences on a patient’s livelihood. Anxiety is defined as a psychological and physiological state of worry with somatic, emotional, physical, and behavioral changes associated with it. It is a normal response to stress but when it becomes excessive, it can become an anxiety disorder.

Other words for anxiety, which may be better recognized by different patients, are worry, dread, angst, uneasiness, and nervousness. It is twice as common in women as it is in men. Additional predictors of anxiety include poverty, recent adverse life events and parental loss. The development of anxiety increases with medical illnesses including angina, arrhythmias, labile hypertension, chronic obstructive pulmonary disease, congestive heart failure and even irritable bowel syndrome. It can also be a predisposing factor for acute coronary syndromes, hypertension and cardiovascular morbidity.

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II. Diagnostic Approach

A. What is the differential diagnosis for this problem?

When a hospitalized patient seems anxious, it is important to thoroughly evaluate the patient to rule out other etiologies of the behaviors and physical manifestations of anxiety.

Common etiologies include medications (both prescription and illicit), withdrawal syndromes, hypoxia, metabolic derangements like hypocalcemia, hyperthyroidism or hyperparathyroidism, primary central nervous system (CNS) disease (enchephalitis, brain mass), or acute decompensation from pulmonary emboli (PE), stroke or acute coronary syndrome (ACS). Rare etiologies include pheochromocytoma, acute intermittent porphyria, and carcinoid syndrome.

Once you’ve determined that the patient indeed has a primary anxiety disorder, you need to consider the various diagnoses: generalized anxiety disorder (GAD), panic disorder (PD), post-traumatic stress disorder (PTSD), adjustment disorder (AD), hypochondriasis, social phobias, and obsessive compulsive disorder (OCD). It is also prudent to determine whether there exists an underlying component of depression.

GAD is characterized by excessive worry that can’t be controlled. Patients describe muscle tension, fatigue, irritability, poor concentration, and often have insomnia and vague somatic complaints. GAD symptoms must be chronic, lasting over 6 months. PD generally indicates recurrent episodes of intense anxiety with physical distress like palpitations, sweating, tremulousness, shortness of breath, fear of choking, dizziness, or fear of dying.

PTSD requires a prior exposure to a traumatic event with a real threat of death or serious injury. These can include motor vehicle accidents, natural disasters, physical or sexual assault, or military experience. Patients recurrently experience the same event in their mind and often respond with avoidance behavior, becoming numb to emotions, or alternatively becoming hypersensitive where they startle easy and overreact to situations.

AD includes symptoms of anxiety that occur within a period of 3 months after identification of a stressor(s).

Hypochondriasis is driven by a concern or fixation about a medically unexplained symptom and is often centered around a specific illness.

Most social phobias relate to very specific social or performance situations (e.g. stage fright). OCD is a distressing, time-consuming impairment related to intrusive obsessions (thoughts, images, impulses) or compulsions (repetitive behaviors) that the individual recognizes are excessive and unreasonable but can’t control them.

Medication side effect profiles may also mimic symptoms of anxiety and accurate medication reconciliation is imperative. Specific attention should be paid to corticosteroids, thyroid hormone and beta-adrenergic agents.

B. Describe a diagnostic approach/method to the patient with this problem

The key to diagnosing anxiety in hospitalized patients it to take a complete history and to thoroughly understand what the patient’s experience of their illness is. For example, if a patient lost her mother to breast cancer and is admitted with a concern for underlying malignancy, she will have considerable anxiety during the work-up.

Many patients are additionally informed by information on the internet, which can be misleading and cause great distress. The discussion needs to include the patient’s concerns about loss of function and control, feeling dependent on others, the costs of evaluation and treatment, privacy issues, and even just a fear of hospitals as scary places.

1. Historical information important in the diagnosis of this problem.

There are two questions as part of the two item GAD scale (GAD-2) that can help determine if an anxiety disorder exists by a score equal to or greater than 3.

  • How frequently do you feel nervous, anxious or on edge? 0 (none), 1 (several days), 2 (greater than 1/2 days), 3 (nearly every day).

  • How frequently are you unable to stop or control your worrying? 0 (none), 1 (several days), 2 (1/2 days), 3 (nearly every day).

You may also consider evaluation with the GAD-7 which is suggested to have a better overall specificity and sensitivity compared to other screening modalities.

2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.

In the physical exam, pay attention to vital signs, reflexes, and overall tremulousness. Rapid heart rate (HR) and elevated blood pressure (BP) would be expected for a diagnosis. Consider examination for thyromegaly if clinically appropriate. Hyperadrenergic states would also manifest with fever, diaphoresis, warm skin versus vagal stimulation coolness and pallor. Do a complete neurologic exam to rule out focal CNS disease.

3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.

Where there is high suspicion for an underlying physiologic cause of anxiety, appropriate testing should be sought. All patients should undergo complete basic chemistry, blood count, thyroid-stimulating hormone (TSH), electrocardiogram (ECG). The addition of a urine toxicology screen (for substance abuse) should be assessed especially in high-risk populations.

C. Criteria for Diagnosing Each Diagnosis in the Method Above.

The ultimate diagnosis of an anxiety disorder is made by history. The evaluation with a complete history, exam and basic laboratory assessments is done to rule out other potential causes of the anxiety the patient is experiencing.

D. Over-utilized or “wasted” diagnostic tests associated with the evaluation of this problem.

It is unnecessary to work-up every anxious patient for pheochromocytoma or carcinoid. These are rare conditions and should be considered in the right clinical context. Carcinoid patients report flushing (with or without precipitating factors), diarrhea, and peripheral edema while pheochromcytoma patients have episodic hypertension, weight loss, and period of crisis with headaches, palpitations, sweating, nausea and tremor.

III. Management while the Diagnostic Process is Proceeding

A. Management of anxiety

The overall treatment of anxiety disorders is through the use of selective serotonin reuptake inhibitors (SSRI) or serotonin-norepinephrine reuptake inhibitors (SNRI), with the most data supporting the SSRIs sertraline, citalopram or escitalopram. Fluoxetine and paroxetine inhibit cytochrome P450 2D6 leading to many drug-drug interactions so are of more limited use. The choice between sertraline, citalopram or escitalopram depends on the patient’s insurance program.

Remember that all of these drugs will take a minimum of 4 weeks, closer to 8 weeks, before you will be able to determine if the patient has had a response. In the interim, specifically in the hospitalized patient group, benzodiazepines are useful to help bridge the patient in the short run until the long-term drug takes effect. Consider benzodiazepines in those patients with severely debilitating symptoms of anxiety.

Examples of commonly used benzodiazepines include lorazepam, alprazolam and clonazepam. Lorazepam is available in oral, intramuscular and intravenous (IV) forms and has no active metabolites so has a more predictable effect than others. Alprazolam is the most studied but due to its short half-life, it must be dosed every 6-8 hours. Clonazepam has a long half-life and causes less rebound insomnia but it may be more difficult to titrate the dose with a propensity to accumulate in hospitalized patients.

The disadvantage of all benzodiazepines is the overall sedative effect with psychomotor impairment, an increase in falls (especially in patients over the age of 65 years), depressed respiratory drive, and even concerns for long-term dependency on these drugs. Short acting anxiolytic alternatives to consider include buspirone (no decrease in respiratory drive) or for refractory situations, quetiapine and risperidone. Cognitive behavioral therapy and stress management training can also help if it is available and is considerable beneficial in the chronic management of patients with anxiety. There is growing evidence in the area of mindfulness meditation with an early suggestion of better outcomes than traditional stress management.

B. Common Pitfalls and Side-Effects of Management of this Clinical Problem

It’s important to communicate the expectation of how quickly (or not) the medications will start to have an effect. Starting a SSRI or SNRI without using short-term (few days to one week) benzodiazepines will not be effective. Continue to communicate with the patient with considerable reassurance and address the specific concerns.

Generally IV doses of benzodiazepines are most effective. Lorazepam 1-2 milligrams per os (PO) every 4-6 hours however is generally an acceptable strategy for patients without contraindications like liver failure, malnourishment, or chronic benzodiazepine use with probable tolerance.

What's the evidence?

Hicks, D, Cummings, T, Epstein, SA. “An approach to the patient with anxiety”. Medical Clinics of North America. vol. 94. 2010. pp. 1127-39.

Zhang, X, Norton, J, Carrière, I, Ritchie, K, Chaudieu, I, Ancelin, M-L. “Risk factors for late-onset generalized anxiety disorder: results from a 12-year prospective cohort (The ESPRIT study)”. Transl Psychiatry. vol. 5. 2015 Mar. pp. e536

Herr, NR, Williams, JW, Benjamin, S, McDuffie, J. “Does this patient have generalized anxiety or panic disorder?: The Rational Clinical Examination systematic review”. JAMA. vol. 312. 2014 Jul 2. pp. 78

Hoge, EA, Bui, E, Marques, L, Metcalf, CA, Morris, LK, Robinaugh, DJ, Worthington, JJ, Pollack, MH, Simon, NM. “Randomized controlled trial of mindfulness meditation for generalized anxiety disorder: effects on anxiety and stress reactivity”. J Clin Psychiatry. vol. 74. 2013 Aug. pp. 786