Anxiety is a diffuse, unpleasant, and often vague subjective feeling of apprehension accompanied by objective symptoms of autonomic nervous system arousal. The experience of anxiety is associated with a sense of danger or a lack of control over events. The psychological component varies from individual to individual and is strongly influenced by personality and coping mechanisms.

Many factors contribute to the experience of anxiety by individuals in our society. We live in a rapidly changing culture characterized by continuous technologic advancements, proliferation of ever more refined information, and a mass media and entertainment industry saturated with violence and sexuality, all of which promote feelings of insecurity. In the workplace, downsizing, restructuring, mergers, and specialization are commonplace; transient work relationships and the elimination of benefits such as health insurance and retirement provisions increase the sense of insecurity.

Anxiety is pathologic when it occurs in situations that do not call for fear or when the degree of anxiety is excessive for the situation. Anxiety may occur as a result of life events, as a symptom of a primary anxiety disorder, as a secondary response to another psychiatric disorder or medical illness, or as a side effect of a medication.

The majority of individuals with mental disorders receive psychiatric care from primary care settings, whereas fewer than 20% receive care in specialized mental health settings. Among mental disorders, anxiety disorders have the highest overall prevalence rate, yet only 23%-59% of anxious patients receive treatment. The estimated 1-year prevalence rate is 17% with a lifetime prevalence rate at 25%. Patients with anxiety disorders are at increased risk of other medical comorbidities, longer hospital stays, more procedures, higher overall health care costs, failure in school or at work, low-paying jobs, and financial dependence in the form of welfare or other government subsidies.

Biomedical Influences

Because the symptoms of anxiety are so varied and prevalent, several etiologies exist to explain them. A recent meta-analysis revealed a significant genetic component, especially for panic disorder, generalized anxiety, and phobias. Temperament, which has genetic roots, is a broad vulnerability factor for anxiety disorders.

The inhibitory transmitter g-aminobutyric acid (GABA) occupies about 40% of all synapses and is clearly implicated in the anxiety disorders, as is the endocrine system. Exposure to a stressor activates the release of an endogenous opioid, β-endorphin, which is co-released with adrenocorticotropic hormone.

Psychological and Social Influences

Family dysfunction and parental psychopathology are involved in the development and maintenance of anxiety. Families of anxious children are more involved, controlling, and rejecting, and less intimate than are families who do not manifest anxiety. Parents of anxious children promote cautious and avoidant child behavior.

Behavioral and cognitive explanations define anxiety as a learned response. Anxiety develops in response to neutral or positive stimuli that become associated with a noxious or aversive event. Fearful associations develop from the situational context and the physical sensations present at the time. The patient may generalize (ie, classify objects and events based on a common characteristic) and thereby establish new cues to trigger anxiety. Previously neutral situations become feared and avoided. By avoiding anxiety-arousing stimuli, anxiety is diminished.

As panic and avoidance become more chronic, the behaviors involved become more habitual and awareness of one’s thoughts in relation to these anxiety states diminishes. Information-processing prejudices such as selectively attending to threatening stimuli become involuntary and unconscious. A person’s appraisal of an event, rather than intrinsic characteristics of that event, defines stress, evokes anxiety, and influences the ability to cope. Failure to cope elicits fear and vulnerability.

Training in stress inoculation, relaxation training, and cognitive-behavioral therapy can be implemented through an integrated curriculum in public education during the early and middle years. School settings provide furtive environments for group modeling and an opportunity to reach large numbers of people. The work of Dr Martin Seligman (see Gillham et al) demonstrates the sizable advantages of such school-based programs.

Symptoms and Signs

Examination of the patient usually yields few clues to assist in establishing the diagnosis of an anxiety disorder. Diagnosis is complicated by the amount of symptoms and their overlap with other disease states; thus anxiety often becomes a diagnosis of exclusion. Table 53-1 lists various symptoms of anxiety by organ system.

Despite the variety and diffuse nature of many of these symptoms, anxiety disorders can often be identified by exploration of the patient’s history, along with a few laboratory values. The symptoms of each anxiety disorder are sufficiently specific to arrive at the diagnosis by taking a thorough history from the patient, including pertinent past, social, and family information. Recognition of anxiety subtypes is often made on the basis of history alone.

Diagnostic Criteria

The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) differentiates several anxiety disorders. Diagnostic criteria for each disorder are presented below.

Panic Disorder

A panic attack involves a discrete period of intense fear or discomfort that has a sudden onset, rapidly builds to a peak, usually in 10 minutes or less, and is often accompanied by a sense of imminent danger or impending doom and an urge to escape. Many describe this disorder as “a fear of fear” developing from interoceptive conditioning. These patients tend to overestimate the probability of panic. About 33%-50% of panic-stricken people from community samples have agoraphobia, a fear of being in places or situations from which escape might be difficult or embarrassing or in which help may not be available. Individuals suffering from panic disorder without agoraphobia have higher success rates than those with agoraphobia.

Simple Phobias

Phobia refers to significant, provoked, and irrational anxiety that a person experiences when near a specific object or situation that is feared. Patients with simple phobias do not usually seek treatment. They avoid the particular object or situation that evokes anxiety.

Social Phobia

This involves clinically significant anxiety that occurs when an individual is exposed to certain types of social or performance situations. The lifetime prevalence of social phobia is estimated to be as high as 13%. Social phobia affects most areas of life, particularly education, career, and romantic relationships.

The Mini-SPIN is a brief three-item derivative of the Social Phobia Inventory (SPIN) that has been validated for the use of screening for social phobias.

Obsessive-Compulsive Disorder (OCD)

This involves intrusive thoughts that cause marked anxiety or distress. Compulsions (compelling acts) neutralize anxiety. The disorder typically stages as Obsession → Anxiety → Compulsion → Relief. Onset is usually gradual and the course is typically chronic. Up to 80% of patients with OCD evidence depression, anxiety, substance abuse, work disability, or all of these findings.

Post-Traumatic Stress Disorder (PTSD)

This involves the patient reexperiencing an extremely traumatic event accompanied by symptoms of increased arousal and avoidance of stimuli associated with the trauma. Rape, war-related stress, assault, and accidents commonly precipitate PTSD. The traumatizing effect is linked to the fact that these events are unexpected, uncontrollable, or inescapable. Optimally, new experiences are assimilated and expressed. Acute stress disorder entails the same PTSD-type symptoms, which occur immediately in the aftermath of a traumatic event but resolve within 4 weeks.

Generalized Anxiety Disorder (GAD)

This involves at least 6 months of persistent and excessive anxiety and worry with an inability to stop worrying. Uncontrollable and unpredictable aversive events may play an important role in the development of GAD. Further, patients with GAD have much less tolerance for uncertainty and are especially disturbed by not being able to predict the future. These chronic worriers commonly display insomnia; feel irritable, tense, and tired; and have difficulty concentrating. The degree of comorbidity between GAD and other psychiatric disorders is high. Patients with GAD show higher general medical utilization than patients with depression.

Several validated tools have been developed to screen for GAD including the two-item and seven-item Generalized Anxiety Disorder scales (GAD-2, GAD-7). These self-report questionnaires are easy to use and can assist primary care physicians in assessing the severity of GAD as well.

Substance-Induced Anxiety Disorder

In this disorder, anxiety is a direct physiologic consequence of a drug of abuse, medication, or exposure to a toxin.

Adjustment Disorder with Anxious Mood

In patients with this disorder, clinically significant symptoms of anxiety occur in response to an identifiable stressor within 3 months after the onset of the stressor and resolve within 6 months after the termination of the stressor. However, symptoms may persist longer if they occur in response to a chronic stressor (eg, a disabling chronic medical condition) or to a stressor that has enduring consequences (eg, financial effects of a divorce).

Anxiety Disorder Due to a General Medical Condition

In this disorder, prominent symptoms of anxiety are judged to be a direct physiologic consequence of a general medical condition. It is estimated that up to 20% of medical patients experience anxiety during the course of their medical illness.

When organic etiology is ruled out for a somatizing presentation, the patients involved usually are less educated, have psychiatric disorders, and belong to a culture that deemphasizes emotional displays while focusing on bodily concerns. Many of these patients lack social support and have suffered trauma.

Laboratory Findings

There are no gold standard laboratory studies to diagnose anxiety disorders. It is reasonable to perform a limited empiric evaluation to identify the etiology of the symptoms as well as evaluate for comorbid medical problems that may complicate the treatment. This evaluation may include a complete blood count, electrolyte, glucose, creatinine, calcium, liver panel, and thyroid function test. Further testing should be tailored on an individual basis, depending on the clinical circumstances. Urine drug screening should be considered, because illicit drug use and withdrawal may be a possible differential diagnosis and patients with anxiety may self-medicate with drugs of abuse.

Imaging Studies

Imaging studies are completed only to preclude any laboratory abnormalities or organic disease that may mimic anxiety or panic. Such studies include, but are not limited to, thyroid scan and cardiac diagnostics. Functional magnetic resonance imaging (MRI) is a technique that enables one to map cognitive, affective, and experiential processes onto brain substrates. It is a proxy measure about how complex processes are implemented in different neural systems. Magnetic resonance spectroscopy (MRS) is a noninvasive in vivo method used to quantify metabolites that are relevant to a wide range of brain processes. Recent studies have shown that there are significant metabolic differences between patients with anxiety disorders and healthy controls in various regions of the brain.

Special Tests

Psychological tests resort to self-report of symptoms and are major assessment tools for anxiety. This is unfortunate given that most other medical diagnoses (eg, diabetes mellitus) rely on both symptom self-report and systematic biomedical measurements (eg, the glucose tolerance test).

The State-Trait Anxiety Inventory measures the frequency and intensity of transient anxiety processes and anxiety proneness as a character trait. Other validated measures are the Anxiety Sensitivity Inventory, Agoraphobic Cognitions and Body Sensations Questionnaires, and the Panic Belief Questionnaire.

Comorbidity can comprehensively be assessed by the Minnesota Multiphasic Personality Inventory-II (MMPI-2), a test composed of 567 true-false test items that can be completed in about 2 hours. The Profile of Mood States (POMS) primarily measures mood states in psychiatric outpatients. Its advantage over the MMPI-2 is a completion time of about 10 minutes.

Because anxiety is a ubiquitous symptom of numerous conditions, family physicians must be alert to the possibility of alternative medical causes. A thorough evaluation and workup is essential to alleviate patients’ concerns that their symptoms are due to other chronic or severe medical conditions.

The first step in planning a diagnostic evaluation is to perform a thorough history and physical examination. Table 53-2 presents the differential diagnosis of other medical conditions that may present with anxiety-like symptoms. The clinician must rule out psychiatric disorders and ascertain if symptoms of anxiety are secondary to a medical illness or to a side effect of a medication. If anxiety did not predate a medical illness, subsequent anxiety may represent an adjustment disorder with anxious mood. The most likely organic cause of anxiety is alcohol and drug use (withdrawal or intoxication). Caffeine toxicity and increased sensitivity to caffeine also commonly mimic symptoms of anxiety.

Symptoms of cardiovascular abnormalities such as chest discomfort, shortness of breath, and palpitations are also cardinal symptoms of anxiety. Many anxious patients function poorly because they believe that they have heart disease. The electrocardiogram can be a useful tool to differentiate anxiety from a significant cardiac abnormality. Further evaluation should be considered based on the patient’s symptoms and risk profile.

A careful auscultatory examination of the heart may reveal evidence of mitral valve prolapse, the most common valvular abnormality in adults. Long-term studies have shown that complications from mitral valve prolapse are rare, but often these patients present with palpitations and a generalized sense of being unwell that may mimic anxiety.

Musculoskeletal pain syndromes and esophageal disorders, including esophageal motility disorders and gastroesophageal reflux disease, are the most common noncardiac explanations of chest pain. Anxiety exacerbates gastrointestinal conditions such as colitis, ulcers, and irritable bowel syndrome. Treating anxiety often resolves or improves gastrointestinal symptoms and its associated chest pain.

Most patients with chronic unexplained chest pain have concomitant psychiatric diagnoses, especially anxiety. When further cardiac evaluation yields normal results, the anxious patient is more effectively reassured.