INTRODUCTION
Anxiety is a common, normal emotion; most people experience occasional trepidation, fear, nervousness, “jitters,” or even panic. Mild anxiety may aid mental sharpness as uncertainty or pressure mounts. For some individuals, however, anxiety occurs as part of an anxiety disorder that is a prominent, persistent, and disruptive aspect of their daily lives. Among the general population in the United States, about 25% will experience an anxiety disorder at some time in their life, making anxiety more common than depressive disorders. At over $50 billion per year, the direct and indirect annual costs associated with anxiety disorders in the United States are similar to, and may even surpass, the economic burdens attributed to mood disorders.
The major anxiety disorders are shown in Table 26-1. They are often comorbid with depression and with one another (e.g., panic disorder [PD] and agoraphobia). Similar to depression, patients with an unrecognized anxiety disorder tend to present to general medical or specialist settings, rather than to the specialty mental health sector, as they generally complain of the prominent physical symptoms of the anxiety disorder rather than its emotional symptoms.
| Anxiety Disorder | Prevalence in Primary Care (%) |
| Acute stress disorder | 3–5 |
| Agoraphobia | 1–3 |
| Generalized Anxiety Disorder | 4–9 |
| Obsessive Compulsive Disorder | 1–2 |
| Panic Disorder | 1–6 |
| Post-traumatic Stress Disorder | 2–12 |
| Social phobia | 3–7 |
| Specific phobia | 8–13 |
| Adjustment disorder with anxiety | 4.5–9.2 |
| Anxiety disorder due to a general medical condition | 14–66 |
| Substance-induced anxiety disorder | Unknown prevalence |
| Anxiety disorder not otherwise specified (NOS) | Unknown |
It is important to distinguish among the various anxiety disorders and identify possible comorbidities because of differences in treatment, complications, and prognoses. Although cross-cultural epidemiologic research has shown that anxiety disorders are present in all cultures, ethnicities, and age groups, providers also must be alert to a variety of common medical conditions and medication side effects that can have symptoms resembling an anxiety disorder (Table 26-2).
• Cardiac Ischemic heart disease, mitral valve prolapse, arrhythmias |
• Endocrine/metabolic Hyperthyroidism, hypoglycemia, pheochromocytoma, carcinoid |
• Gynecologic Menopause, premenstrual syndrome |
• Neurologic Transient ischemic attacks, seizure disorders |
• Pharmacological Caffeine, alcohol, sympathomimetic agents, amphetamines, corticosteroids, theophylline, illicit drugs |
• Respiratory Asthma, chronic obstructive pulmonary disease |
DIAGNOSIS
Office-based screening instruments can improve the detection of anxiety and other mental disorders, and can be used to evaluate treatment response. Several instruments have been developed to aid in recognition of an anxiety disorder. A two-question screener, the GAD-2 subscale of the GAD-7, has been found to perform well as a rapid screening tool for the most common anxiety disorders. The GAD-2 questions are as follows: Over the last 2 weeks how often have you been bothered by the following problems: (1) Feeling nervous, anxious, or on edge; and (2) Not being able to stop or control worrying. A single “yes” response to the anxiety screening questions has a sensitivity of 94% and a specificity of 53% when compared to more formal assessment by a mental health professional. Other clinically useful screening questions are listed in Table 26-3.
| Disorder | Question |
| Generalized anxiety disorder (GAD) | Would you describe yourself generally as a nervous person? Are you a worrier? Do you feel nervous or tense? |
| Panic disorder (PD) | Have you ever had a sudden attack of rapid heartbeat or rush of intense fear, anxiety, or nervousness? Did anything seem to trigger it? |
| Agoraphobia | Have you ever avoided important activities because you were afraid you would have a sudden attack like the one I just asked you about? |
| Social anxiety disorder | Some people have strong fears of being watched or evaluated by others. For example, some people do not want to eat, speak, or write in front of people for fear of embarrassing themselves. Is anything like this a problem for you? |
| Specific phobia | Some people have strong fears or phobias about things like heights, flying, bugs, or snakes? Do you have any strong fears or phobias? |
| Obsession | Some people are bothered by intrusive, silly, unpleasant, or horrible thoughts that keep repeating over and over. For example, some people have repeated thoughts of hurting someone they love even though they do not want to; that a loved one has been seriously hurt; that they will yell obscenities in public; or that they are contaminated by germs. Has anything like this troubled you? |
| Compulsion | Some people are bothered by doing something over and over that they cannot resist, even when they try. They might wash their hands every few minutes, or repeatedly check to see that the stove is off or the door is locked, or count things excessively. Has anything like this been a problem for you? |
| Acute stress disorder (ASD) and posttraumatic stress disorder (PTSD) | Have you ever seen or experienced a traumatic event when you thought your life was in danger? Have you ever seen someone else in grave danger? What happened? |
Early recognition of anxiety disorders can help identify patients suffering from treatable problems and provide the patient and the clinician with a formal diagnosis to better explain the patient’s symptoms. It may also reduce patients’ medical expenses and risk of iatrogenic complications by decreasing or eliminating unnecessary medical testing and referrals to specialists to evaluate unexplained physical and somatic symptoms, and various “treatment” trials of pharmacological agents.
Understanding the signs, symptoms, and epidemiologic features of the various anxiety disorders can help the physician make an accurate diagnosis and initiate timely, appropriate treatment while avoiding invasive or unnecessary testing.
Anxiety disorders typically manifest with emotional symptoms (e.g., fear and nervousness), cognitive symptoms (e.g., worry, a sense of doom, or derealization), and physical symptoms (e.g., muscular tension, tachycardia, dizziness, and insomnia). General medical practitioners must, therefore, decide how much diagnostic investigation is both feasible and necessary to rule out other important nonpsychiatric diseases. For example, when should a patient with palpitations undergo cardiac monitoring, thyroid function studies, evaluation for pheochromocytoma, or referral for cardiac catheterization? When does a patient with episodic nausea and abdominal pain require upper and lower endoscopy?
CASE ILLUSTRATION 1
Gwen is a 28-year-old woman who was admitted for a “rule out” and evaluation of syncope after presenting to the emergency department (ED) with shortness of breath, tachycardia, and a sensation that she is going to faint. The episodes started approximately 4 months ago, shortly after her husband was temporarily laid off from his job, and are not associated with activity. They have been increasing in frequency to where she is now experiencing as many as four episodes per week lasting approximately 5–10 minutes each. Gwen is fearful that she may faint while driving or when out with her child. She is also worried about her heart, as her mother had heart disease in her early fifties.
Gwen was monitored overnight and had several tests, including thyroid function studies and a Holter monitor. She was told those test results were all “normal” and to follow-up with her primary care provider who after reviewing the history and test results recognizes that the symptoms are consistent with panic disorder. Further historical details eliminate other medical or substance-related illness, or new use of caffeine or over-the-counter herbal or other remedies. The physician then reassures Gwen that her symptoms are not unusual and that 2–4% of all people suffer from PD. Sensing Gwen might be embarrassed by a psychological diagnosis, the doctor explains the nature of PD emphasizing its biological basis and asks her if she thinks the new onset of her symptoms are possibly related to her concerns regarding her family’s financial security. To help Gwen learn more about PD, the doctor gives her a booklet and a web site address to read about self-managing her anxiety symptoms (see “Suggested Readings”) and schedules a follow-up visit in 2 weeks to review this information and see how she is doing.
At their follow-up encounter, Gwen asks about medication for her panic symptoms as she has become worried about experiencing new attacks Her physician recommends a selective serotonin reuptake inhibitor (SSRI), and advises that she use one-half of a tablet for the first week and then increase to a full tablet in 7–10 days. The doctor also advises Gwen that it may take 4–6 weeks before she notices any improvement from the medication, and recommends another follow-up visit in 2 weeks to see how she is feeling, review the self-help recommendations, and answer any new questions she may have. After a month on the medication Gwen’s symptoms resolve and she returns to full function.
Symptoms resembling an anxiety disorder can be triggered by use of or intoxication from over-the-counter cold medications, caffeine, cocaine, theophylline preparations, amphetamines, and marijuana or withdrawal from alcohol, benzodiazepines, barbiturates, sedative–hypnotic agents, and other central nervous system (CNS) depressants. These conditions are commonly referred to as “substance-induced anxiety disorder” (Table 26-2). Therefore, the astute clinician must review the patient’s list of medications and inquire about the use of over-the-counter medications including “herbal supplements” and performance-enhancing preparations (anabolic steroids), legal (alcohol, tobacco, and caffeine) and illegal substances (cocaine).
Many medical conditions also have symptoms resembling those of anxiety (Table 26-2). Some are relatively common and obvious to practitioners (arrhythmias and asthma) and others are less so (insulinoma, pheochromocytoma, and carcinoid). Anxiety symptoms may also develop as a consequence of a medical condition. Examples include patients who experience anxiety symptoms following a myocardial infarction or following a pulmonary embolism. Clues to help sort medical from psychiatric patient presentations to guide diagnostic testing, if any, include patient age and gender, past medical and psychiatric history, family history, and social history, Indeed, people who have been in excellent physical health and develop new-onset anxiety symptoms after the age of 50 years are more likely to have medical etiologies explaining their anxiety symptoms than those under the age of 25 years who have presented previously to several physicians and undergone extensive medical testing for evaluation of multiple unexplained somatic symptoms.
The development of anxiety disorders involves multiple factors, including biological abnormalities, past and present psychological stressors, maladaptive cognitions, and environmentally conditioned behaviors. Abnormalities in the CNS associated with anxiety disorders relate to the gamma-aminobutyric acid (GABA) receptor as well as to the locus ceruleus. Animal studies have shown that stimulation of the locus ceruleus produces hyperarousal states similar to those seen in anxious humans. Gamma-aminobutyric acid is an inhibitory neurotransmitter found throughout most of the CNS. It may decrease anxiety by inhibiting locus ceruleus activity and modulating the reticular activating system, another area of the brainstem thought to affect alertness and fear. Benzodiazepines, a class of medications commonly used to treat anxiety, bind to specific sites on the GABA receptor. When the benzodiazepine molecule binds the GABA receptor, the effect of GABA on the GABA receptor is enhanced, reducing anxiety. Two other neurotransmitters, serotonin and norepinephrine, are also under investigation based on therapeutic responses to medications that affect these systems (e.g., SSRIs and serotonin norepinephrine reuptake inhibitors [SNRIs]). Poor regulation of the adrenergic system is also suspected as beta-adrenergic agonists induce symptoms of panic and alpha-adrenergic agonists decrease symptoms of anxiety.
Genetic factors also likely play a role in anxiety disorders, as evidenced by twin studies showing a higher concordance for PD and obsessive-compulsive disorder (OCD) among monozygotic twins than among dizygotic twins.
Cognitive behavioral therapy (CBT) holds that behavior is driven by underlying beliefs or cognitions. Patients with anxiety typically overestimate danger or threats and underestimate their ability to effectively cope. These patients subsequently feel “stressed” or anxious and select avoidant or other maladaptive coping strategies.
Conditioned learning may also play a pivotal role in the development of anxiety disorders and the resulting avoidance often seriously compounds patients’ anxiety-related functional impairment. For example, patients may notice some unusual autonomic arousal or physical sensation while driving a car. They may misinterpret this initially random and benign sensation as a life-threatening event (e.g., “I’m having a heart attack!”), which further intensifies the autonomic response, fuels the misinterpretation, and snowballs into a full-blown panic attack. They may learn to associate the physical sensation and the subsequent attack with the act of driving and feel heightened anxiety—fueled by catastrophic thinking—when they drive or anticipate driving. Initially, the association between driving and panic is coincidental (driving is not the event provoking the initial sensation or the panic attack). Eventually, however, a patient may completely stop driving for fear that another panic attack will occur. This conditioned learning between driving and panic may gradually become so strong that driving becomes a precipitant of panic attacks. Thus, the driver mistakenly becomes conditioned to fear driving.
Traumatic, highly stressful, and catastrophic life events are also key factors leading to anxiety disorders, particularly PTSD. Posttraumatic stress disorder and adjustment disorder with anxiety are examples of disorders in which these events play a specific causal role. Other research suggests that childhood trauma, sexual assault, battle exposure, and terrorism can predispose individuals to develop hyperactive physiologic responses to everyday stressors, placing them at greater risk for developing anxiety and other mood disorders.
SPECIFIC DISORDERS
A panic attack is characterized by a discrete period of intense fear accompanied by the abrupt onset of several cognitive and somatic symptoms. Cognitive symptoms may include but are not limited to racing thoughts, preoccupation with health concerns, catastrophic misinterpretation of somatic symptoms, or believing one is going insane. Somatic symptoms may include a choking sensation, racing heartbeat, sweating, “jelly” legs, nausea, shaking, chest pain, numbness, or feeling detached or unreal. Frightening physical symptoms are commonly prominent and scare many patients into seeking urgent medical care. Primary care providers can usually be reassuring, as panic attacks are often infrequent, self-limited, and not related to any serious mental or physical disorder. Panic attacks are categorized as follows:
Unexpected (untriggered or uncued);
Situationally bound (always environmentally or psychologically cued); or
Situationally predisposed (sometimes, but not invariably, cued).
Panic attacks can be comorbid with a number of other anxiety disorders including social and specific phobias, OCD, and PTSD. The presence and type of a panic trigger help clinicians make a correct diagnosis. Uncued panic attacks are characteristic of PD, whereas cued attacks suggest other psychiatric conditions such as the following:
Social phobia (attack triggered by fear of embarrassment in social situations);
Specific phobia (fear of places or things);
OCD (triggered by exposure to the object of an obsession, such as contamination); or
PTSD (triggered by an event resembling the original trauma).
Panic attacks are quite common; most people experience a subclinical or limited-symptom attack at some time. Only about 9% of the general population ever experiences a full-blown panic attack.
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