Anxiety Disorders

Jaesu Han MD

Michelle Park MD

Robert E. Hales MD, MBA

CLINICAL HIGHLIGHTS

Screening requires asking about both physical and psychological symptoms of anxiety.
The somatic presentation of anxiety disorders, where physical symptoms predominate, is common in the primary care setting.
Specific anxiety disorders are defined and categorized by the presence or absence of specific situational triggers.
More than 70% of patients diagnosed with an anxiety disorder in the primary care setting also have another comorbid Axis I condition, most commonly depression and another anxiety disorder. The AMPS screening tool is a quick and effective way to screen for anxiety, mood, psychotic, and substance misuse disorders.
Initial management of anxiety disorders includes establishing a trusting relationship while addressing psychosocial stressors in an empathic way.
General medical conditions can trigger as well as masquerade an anxiety disorder; both need to be treated.
Cognitive behavioral therapy or medication management with serotonin reuptake inhibitors are both first-line treatment options regardless of the specific anxiety disorder. In general, when treating an anxiety disorder, it is best to start with half the normal antidepressant starting dose because this may decrease irritability and anxiety during the first few weeks of treatment.
Success with medications relies more on providing good patient information and follow-up than prescribing a specific drug.

Clinical Significance

Anxiety disorders represent the most prevalent group of psychiatric disorders in the general population. This group of conditions accounts for at least $42 billion per year in lost productivity and results in a significantly lower quality of life for the affected patients (1). Data from the 12-year longitudinal, naturalistic Harvard/Brown Anxiety Disorders Research Program showed that, with the exception of panic disorder without agoraphobia, the course of anxiety disorders is both chronic and enduring (2). Twelve years after the original episode, the majority of patients with generalized anxiety disorder, panic disorder with agoraphobia, and social anxiety disorder never achieved recovery, and of those who did recover, nearly half had a recurrence during the follow-up period.

The economic and social costs of these chronic and recurrent disorders are compounded by the persistent underrecognition and undertreatment of anxiety disorders in the primary care setting. One recent study found that nearly one in five patients had at least one clinically significant anxiety disorder and that 41% of these patients were not receiving treatment of any kind (3). Clearly, with knowledge that effective treatment options are readily available for the anxiety disorders, proper screening and diagnosis are critical.

Diagnosis

Anxiety is commonly defined as excessive worrying, nervousness, or feeling “on edge.” The prompt and accurate diagnosis of anxiety disorders in the primary care setting can be challenging for several reasons. Anxiety itself is a very normal human emotion and it can be difficult to decide just when it is pathologic. For example, anxiety can be adaptive when it motivates one to complete a task but pathologic when it is
excessive and paralyzes one from taking a needed action despite the possible repercussions (or missed opportunities). In order to ensure an accurate diagnosis and effective treatment plan, it is important to document the disability, screen for an anxiety disorder, consider the differential diagnosis, and identify the specific anxiety disorder.

DOCUMENT DISABILITY

Pathologic and clinically relevant anxiety is excessive and persistent and creates disability, often in the form of avoidance behaviors. Essentially, “normal” anxiety helps the patient to maintain order, while “pathologic” anxiety creates disorder. Clinicians should ask questions such as, “What have you given up because of your symptoms?” or “Have your symptoms prevented you from doing something you wanted or needed to do?” In addition to ensuring that the anxiety is clinically significant, the documentation also provides tangible targets for treatment. Diagnosis should include documentation of specific functional impairment, which may include:

Social impairment: withdrawal from family, friends, and hobbies
Occupational impairment: job avoidance, inefficiency, lack of promotion, or even disciplinary action
Impairment with activities of daily living: inability to shop for groceries, take the bus, or drive a car

SCREEN FOR AN ANXIETY DISORDER

The advantage of a screening tool includes the ability to administer and score a validated test prior to seeing the patient. However, unlike tools such as the Patient Health Questionnaire-9 (PHQ-9) for major depression, there is currently no commonly accepted screening tool for all anxiety disorders in clinical practice. One recently studied screening tool is the Generalized Anxiety Disorders Scale (GAD-7), which appears to be sensitive for panic disorder, generalized anxiety disorder, social anxiety disorder, and posttraumatic stress disorder in the primary care setting (Table 4.1) (4). This tool consists of a series of seven questions that incorporates the same Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV), diagnostic criteria of generalized anxiety disorder. The first two items (GAD-2 subscale) can be used as an ultrarapid screening tool. A score of 8 or more on the GAD-7 or 3 or more on the GAD-2 should prompt a more thorough investigation for major anxiety disorders.

The GAD-2 highlights the two key components of anxiety that are present regardless of the specific diagnosis: (1) psychiatric symptoms: excessive ruminations or worry, poor concentration, and racing thoughts and (2) physical symptoms: muscle tension, sweating, fatigue, restlessness, and tremors. During the screening interview, it is therefore important to inquire about both components. When one component predominates, the clinical presentation may change drastically.

Table 4.1 GAD-7

*How often during the past 2 weeks have you felt bothered by:*
1. Feeling nervous, anxious, or on edge?	0	1	2	3
2. Not being able to stop or control worrying?	0	1	2	3
3. Worrying too much about different things?	0	1	2	3
4. Trouble relaxing?	0	1	2	3
5. Being so restless that it is hard to sit still?	0	1	2	3
6. Becoming easily annoyed or irritable?	0	1	2	3
7. Feeling afraid as if something awful might happen?	0	1	2	3
Each question is answered on a scale of:
0 = not at all
1 = several days
2 = more than half the days
3 = nearly every day
A score of 8 or more should prompt further diagnostic evaluation for an anxiety disorder.
From Spitzer RL, Kroenke K, Williams JB, et al. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006;166:1092-1097.

When psychiatric symptoms (e.g., anxiety) predominate, the patient presents to seek confirmation of an anxiety disorder diagnosis. Sometimes the patient’s assessment of a specific anxiety disorder is correct, but at other times the diagnosis may be another psychiatric disorder or even a general medical condition. Although this presentation may be easier for clinicians to recognize because they are “primed” to consider an anxiety disorder, it is also the less common presentation.

When physical symptoms predominate, the patient usually does not consider a psychiatric cause. The somatic presentation is more common than the psychiatric presentation in the primary care setting and is more likely to lead to misdiagnosis (5). This may occur when a patient attributes the symptoms to such things as lack of sleep, stress, or poor diet, and the clinician halts further work-up. Alternatively, there may be an extensive work-up in response to multiple medically unexplained physical complaints such as chest pain, dizziness, gastrointestinal symptoms, or dyspnea before an anxiety disorder is considered.

SPECIFIC ANXIETY DISORDERS

The following brief descriptions are intended to distill some salient points that serve to distinguish the disorders from each other. Keep in mind that the symptoms of anxiety often manifest as a waxing and waning “blanket” of symptoms but may also include time-limited “bursts” of symptoms in the form of panic attacks. Panic attacks, sometimes referred to as “anxiety attacks,” are in themselves not considered a separate anxiety disorder. These attacks are required for the diagnosis of panic disorder when they occur spontaneously but may occur with other anxiety disorders in response to situational triggers. In a typical panic attack, patients experience a sudden onset of symptoms that typically peak
within 10 minutes and rarely last longer than an hour. During a panic attack, psychological symptoms often include fears of losing control, dying, or “going crazy.” Physical symptoms reflecting autonomic activation are equally intense and include a racing heart rate, sweating, shaking, shortness of breath, nausea, dizziness, and chest discomfort.

Figure 4.1 Diagnostic algorithm for anxiety disorders.

Differentiating among the anxiety disorders relies on distinguishing if these symptoms, including panic attacks, are precipitated by specific situational triggers or are pervasive and occur with a variety of events (Figure 4.1). The two disorders without specific situational triggers are panic disorder and generalized anxiety disorder. The disorders with specific situational triggers are social phobia, specific phobia, obsessive compulsive disorder, acute stress disorder, and posttraumatic stress disorder. Adjustment disorder with anxiety and anxiety disorder not otherwise specified are quite common and will be discussed separately.

Disorders without a Situational Trigger

Panic Disorder Panic disorder (PD) is characterized by recurrent panic attacks that are experienced at least initially as spontaneous and unexpected. Careful review with the patient may reveal benign cues such as emotional stress from an argument or a slightly elevated heart rate from caffeine that is interpreted as a symptom of an impending attack.
Although panic attacks can be terrifying and temporarily disabling, it is the anticipatory anxiety of when the next attack will come and the worry about its implications that perpetuates the disability. Patients may undergo extensive testing to find the etiology of symptoms, such as chest discomfort or gastrointestinal symptoms, before a diagnosis of PD is made. PD is twice as common in women as in men and onset peaks in late adolescence and the mid-30s. Although the initial panic attack is by definition not caused by an obvious trigger, the majority of patients report some antecedent adverse life event in the year prior to onset of illness.

Over time, agoraphobia may develop when continued apprehension of a panic attack prevents patients from being in places or situations from which they cannot escape, where help is unavailable, or where it would be embarrassing to be seen in the throes of a panic attack. In this respect, panic disorder with agoraphobia can be thought of as an anxiety disorder with a situational trigger. Common avoided places include buses, trains, supermarkets, and traveling away from home. In severe cases, patients may be completely housebound. Those who manage to leave the home usually engage in compensatory behavior such as having a companion around for activities outside the house.

Generalized Anxiety Disorder Generalized anxiety disorder (GAD) is the other anxiety disorder that does not have a specific situational trigger. In fact, the hallmark of GAD is the lack of a central trigger and the presence of free-floating anxiety consisting of ruminations and worries over often trivial matters that are pervasive and excessive. Along with these psychological symptoms are physical symptoms such as muscle tension, restlessness, and fatigue. Symptoms have been present for at least 6 months, but many patients will describe themselves as chronic worriers. GAD may be relatively common among primary care patients whose main clinical problem is chronic insomnia.

Disorders with a Situational Trigger

Social Phobia Social phobia, also known as social anxiety disorder (SAD), is sometimes thought of as pathologic shyness. The hallmark is the fear of embarrassment or humiliation in front of others. This fear may be relatively mild and circumscribed to a specific situation such as public speaking or more severe and generalized to almost all social situations. Patients may report fears they will be negatively evaluated by others and “say something stupid” or fear that others will notice their physical symptoms such as blushing, sweating, or shaking. Panic attacks may occur but are situationally bound to the social trigger. Onset is usually in the early teenage years and patients will often have symptoms for over 10 years before seeking treatment. During this time important social activities may have been missed and job promotions avoided.

Obsessive Compulsive Disorder The hallmark of obsessive compulsive disorder (OCD) is the presence of obsessions and/or compulsions that serve as triggers for anxiety. Obsessions are recurrent, unwanted, and
intrusive ideas, thoughts, impulses, or images. Common themes include contamination, repeated doubts, need for order, horrific thoughts, and sexual imagery. Compulsions are ritualistic behaviors or mental acts carried out in response to an obsession. Examples include repeated handwashing, checking of locks, and counting.

Those with true compulsions are differentiated from “compulsive” shoppers, gamblers, drinkers, etc., because the latter group derives some pleasure from the activity. These obsessions and compulsions are usually quite distressing for the patient and consume at least 1 hour per day but often many more. In severe cases, patients may not recognize that the obsessions or compulsions are excessive and therefore have OCD “with poor insight.” Initially, onset of OCD symptoms usually occurs in the 20s, with a waxing and waning course. The onset of primary OCD after the age of 35 is unusual and should prompt a complete neurologic evaluation. Comorbid tic disorders and compulsive skin picking and hair pulling (trichotillomania) are common in OCD. These comorbid disorders may be the impetus for treatment. The physical stigmata of compulsions (e.g., raw and rough hands from excessive handwashing or hairless patches from hair pulling) may be evident on physical examination.

Posttraumatic Stress Disorder Exposure to a highly traumatic event as a victim or witness in which life or injury was threatened is the situational trigger for posttraumatic stress disorder (PTSD). This traumatic event is followed by symptoms of re-experiences (flashbacks, nightmares, intrusive memories of the event), avoidance/numbing (avoiding conversations, activities, and people associated with the event or that may trigger experiences of the event), and increased autonomic arousal (hypervigilance, restlessness, exaggerated startle). If symptoms resolve within 1 month following the traumatic event, the diagnosis of acute stress disorder (ASD) is made. Patients with symptoms lasting greater than 1 month are diagnosed with PTSD.

Groups at risk for PTSD include combat veterans, natural disaster survivors, terrorist attack survivors, victims of childhood abuse, and victims of sexual or physical trauma.

Sometimes the primary care provider will be aware that a traumatic event has occurred, for example, a recent motor vehicle accident or gunshot wound. However, at other times, patients may present with only nonspecific avoidance behaviors and physical symptoms and not mention the traumatic event. Reasons may include not recognizing the impact of the event and fear that they will be seen as damaged or unstable. Therefore, screening patients with these nonspecific symptoms for a recent traumatic event is important. PTSD is more likely to develop in patients with direct exposure to interpersonal trauma (e.g., rape) than indirect exposure and events such as natural disasters.

Other Clinically Relevant Anxiety Disorders

Adjustment Disorder with Anxiety Adjustment disorder with anxiety is commonly seen in the primary care setting. The hallmark of this
disorder is the close temporal relationship of the onset of anxiety symptoms to a stressful event, usually within days, and resolution within 6 months of the termination of the stressor. Although symptoms may initially be quite intense, they are generally short-lived and diminish with the passage of time. There is symptom overlap with other disorders, but the duration and threshold specifiers distinguish adjustment disorder from other anxiety disorders. For example, GAD requires symptoms to be present for at least 6 months and PTSD and ASD require the stressor to be extreme in nature. Unlike the other anxiety disorders, there is an expectation of good outcome with adjustment disorder once the offending stressor is removed. If the stressor persists, anxiety symptoms will be present in a more attenuated form. Treatment is supportive to help the patient resolve or manage the stressor. Pharmacotherapy with antidepressants and benzodiazepines is sometimes utilized, but there is little evidence to support this practice.

Anxiety Disorder Not Otherwise Specified Many patients in the primary care setting will not initially fit neatly into any of the major anxiety disorders noted above. Assuming the symptoms are causing significant clinical distress, a diagnosis of anxiety disorder not otherwise specified (NOS) can be made. As patients become more comfortable and provide additional history, a specific diagnosis may be more apparent. At other times, a more specific diagnosis is not possible due to confounding general medical conditions. For example, in the case of PD, a reasonable initial diagnosis may be anxiety disorder NOS, to rule out anxiety disorder due to a general medical condition versus panic disorder. Finally, some patients may never manifest the required number of diagnostic criteria for a specific anxiety disorder, yet the symptoms are clinically significant. For example, PTSD without autonomic hyperarousability may be diagnosed as anxiety disorder NOS.

Differential Diagnosis

The two common but different presentations of anxiety disorders highlight the need for a comprehensive patient assessment and differential diagnosis before a definitive diagnosis is made. Patient assessment begins with obtaining the medical history, and particular attention should be paid to the onset of symptoms because anxiety disorders tend to present in late adolescence and early adulthood. For example, new-onset anxiety symptoms in a previously healthy patient beyond the age of 35 years without a recent significant life event or trauma are suspicious for an underlying medical condition. A family history of mood and anxiety disorders increases the likelihood of a primary anxiety disorder. Assessment should also include knowledge of both prescription and over-the-counter medications. The social history is helpful when evaluating relational and occupational factors as well as potential substance abuse. Upon completion of a thorough physical examination, reasonable initial tests for a patient with a possible anxiety disorder include a complete blood count, thyroid-stimulating hormone, and a complete metabolic panel.

Table 4.2 Medical Conditions with Anxiety-Like Symptoms

MEDICAL CONDITION	SUGGESTED BASIC WORK-UP
Cardiovascular: coronary artery disease, congestive heart failure, arrhythmias	ECG (esp. patients >40 years old with palpitations or chest pain)
Pulmonary: asthma, chronic obstructive pulmonary disease	pulmonary function test, CXR
Endocrine: thyroid dysfunction, hyperparathyroidism, hypoglycemia, menopause, Cushing disease, insulinoma, pheochromocytoma	TSH, basic chemistry panel
Hematologic: anemia	CBC
Neurologic: seizure disorders, encephalopathies, essential tremor	EEG, brain MRI
Substance abuse/dependence	Urine or serum toxicology
CXR, chest x-ray; CBC, complete blood count; ECG, electrocardiogram; EEG, electroencephalogram; MRI, magnetic resonance imaging; TSH, thyroid-stimulating hormone.

Common general medical conditions and basic laboratory work-up for symptoms of anxiety are listed in Table 4.2. Many of these conditions will manifest with concurrent non-anxiety-related symptoms and risk factors that will guide the extent of the diagnostic work-up. For example, a nonobese 35-year-old patient who has nonanginal chest pain and no risk factors for coronary disease is unlikely to have an acute coronary syndrome and therefore should not undergo invasive diagnostic cardiac procedures.

Medications may cause anxiety-like symptoms (Table 4.3) (6). For example, patients on antipsychotics may complain of akathisia, which consists of an intense sense of internal restlessness. It can be an extremely anxiety-provoking side effect that resolves after discontinuation of the medication. Stimulants such as methylphenidate used for attention deficit hyperactivity disorder (ADHD) can cause symptoms such as a fine tremor, tachycardia, and irritability that can be confused with anxiety. A general medical condition such as hypothyroidism can be overcorrected with levothyroxine and cause iatrogenic hyperthyroidism with generalized anxiety symptoms.

Other psychiatric disorders commonly coexist with the primary anxiety disorders. More than 70% of patients diagnosed with an anxiety disorder in the primary care setting also have another comorbid Axis I condition. Having an additional anxiety disorder (>60%) is the most common psychiatric comorbid condition followed by major depression (>40%) and substance abuse disorders (14%) (7). Somatoform disorders and personality disorders should also be considered. The importance of identifying comorbid illness is clear, because this will likely lead to quicker recovery and significantly decrease the likelihood of recurrence.

Unrecognized substance abuse and dependence can cause or exacerbate an anxiety disorder. Symptoms may present during the acute intoxication or withdrawal phase of substance use. Any work-up for anxiety disorders must include the nonjudgmental screening for use of
substances in the past month. If abuse or dependence is detected, the longitudinal history is helpful in determining if current symptoms represent a substance-induced state or comorbid substance abuse and anxiety disorder. History suggesting two separate disorders would include (1) onset of symptoms prior to first use of the substance and (2) continued symptoms despite sustained abstinence for at least 1 month. Management of comorbid substance abuse and anxiety disorders include treatment for the anxiety disorder in addition to the substance abuse treatment.

Table 4.3 Medications and Substances That Cause Anxiety-Like Symptoms

Stimulant intoxication	Caffeine, nicotine, cocaine, methamphetamines, phencyclidine (PCP), MDMA (ecstasy)
Sympathomimetics	Pseudoephedrine, methylphenidate, amphetamines, beta-agonists
Dopaminergics	Amantadine, bromocriptine, levodopa, levodopa-carbidopa, metoclopramide
Anticholinergics	Benztropine mesylate, meperidine, oxybutynin, diphenhydramine
Miscellaneous	Anabolic steroids, corticosteroids, indomethacin, ephedra, theophylline
Drug withdrawal	Alcohol, benzodiazepines, opiates