Management of anxiety disorders

Anxiety is an uncomfortable state that has both psychologic and physical components. The psychologic component can be characterized with terms such as fear, apprehension, dread, and uneasiness. The physical component manifests as tachycardia, palpitations, trembling, dry mouth, sweating, weakness, fatigue, and shortness of breath.

Anxiety is a nearly universal experience that often serves an adaptive function. When anxiety is moderate and situationally appropriate, therapy may not be needed or even desirable. In contrast, when anxiety is persistent and disabling, intervention is clearly indicated.

Anxiety disorders are among the most common psychiatric illnesses. In the United States, about 25% of people develop pathologic anxiety at some time in their lives. As a rule, the incidence is higher in women than in men.

In this chapter, we focus on five of the more common anxiety disorders: generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, social anxiety disorder, and post-traumatic stress disorder. Although each type is distinct, they all have one element in common: an unhealthy level of anxiety. In addition, with all anxiety disorders, depression is frequently comorbid.

Fortunately, anxiety disorders often respond well to treatment—either psychotherapy, drug therapy, or both. For most patients, a combination of psychotherapy and drug therapy is more effective than either modality alone.

As indicated in Table 35–1, two classes of drugs are used most: benzodiazepines and selective serotonin reuptake inhibitors (SSRIs). Benzodiazepines are used primarily for one condition: generalized anxiety disorder (GAD). In contrast, the SSRIs are now used for all anxiety disorders. It should be noted that, although SSRIs were developed as antidepressants, they can be very effective against anxiety—whether or not depression is present.

TABLE 35–1

First-Line Drugs for Anxiety Disorders

Anxiety Disorder	Benzodiazepines	SSRIs	Others
Generalized Anxiety Disorder	Alprazolam Chlordiazepoxide Clorazepate Diazepam Lorazepam Oxazepam	Escitalopram	Buspirone Venlafaxine Duloxetine
Panic Disorder		Fluoxetine Paroxetine Sertraline	Venlafaxine
Obsessive-Compulsive Disorder		Citalopram Escitalopram Fluoxetine Fluvoxamine Paroxetine Sertraline
Social Anxiety Disorder		Fluvoxamine Paroxetine Sertraline	Venlafaxine
Post-traumatic Stress Disorder		Fluoxetine Paroxetine Sertraline	Venlafaxine

SSRIs = selective serotonin reuptake inhibitors.

Diagnostic criteria for the anxiety disorders are set forth in the Diagnostic and Statistical Manual of Mental Disorders (DSM). The criteria now in use, published in the fourth edition of the DSM (DSM-IV), were released in 1994. Revised criteria will appear in fifth edition of the DSM (DSM-5), scheduled for release in 2013. The proposed DSM-5 criteria for anxiety disorders, which are much like the criteria in DSM-IV, are presented in tables throughout this chapter.

Generalized anxiety disorder

Characteristics

Generalized anxiety disorder is a chronic condition characterized by uncontrollable worrying. Of all anxiety disorders, GAD is the least likely to remit. Most patients with GAD also have another psychiatric disorder, usually depression. GAD should not be confused with situational anxiety, which is a normal response to a stressful situation (eg, family problems, exams, financial difficulties); symptoms may be intense, but they are temporary.

The hallmark of GAD is unrealistic or excessive anxiety about several events or activities (eg, work or school performance) that lasts 6 months or longer. Other psychologic manifestations include vigilance, tension, apprehension, poor concentration, and difficulty falling or staying asleep. Somatic manifestations include trembling, muscle tension, restlessness, and signs of autonomic hyperactivity, such as palpitations, tachycardia, sweating, and cold clammy hands. Diagnostic criteria for GAD, as proposed for DSM-5, are shown in Table 35–2.

TABLE 35–2

Proposed DSM-5 Diagnostic Criteria for Generalized Anxiety Disorder

A Excessive anxiety and worry (apprehensive expectation) about two (or more) domains of activities or events (for example, domains like family, health, finances, and school/work difficulties).

B The excessive anxiety and worry occur on more days than not for 3 months or more.

C The anxiety and worry are associated with one or more of the following symptoms:

1. Restlessness or feeling keyed up or on edge

2. Being easily fatigued

3. Difficulty concentrating or mind going blank

4. Irritability

5. Muscle tension

6. Sleep disturbance (difficulty falling or staying asleep, or restless unsatisfying sleep)

D The anxiety and worry are associated with one or more of the following behaviors:

1. Marked avoidance of situations in which a negative outcome could occur

2. Marked time and effort preparing for situations in which a negative outcome could occur

3. Marked procrastination in behavior or decision-making due to worries

4. Repeatedly seeking reassurance due to worries

E The focus of the anxiety and worry are not restricted to symptoms of another disorder, such as Panic Disorder, Social Anxiety Disorder, Obsessive-Compulsive Disorder, Separation Anxiety Disorder (eg, anxiety about being away from home or close relatives), Anorexia Nervosa (eg, fear of gaining weight), Somatization Disorder (eg., anxiety about multiple physical complaints), Body Dysmorphic Disorder (eg., worry about perceived appearance flaws), Hypochondriasis (eg, belief about having a serious illness), and the anxiety and worry do not occur exclusively during Posttraumatic Stress Disorder.

F The anxiety, worry, or physical symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

G The disturbance is not due to the direct physiological effects of a substance (eg, a drug of abuse, a medication) or a general medical condition (eg, hyperthyroidism) and does not occur exclusively during a Mood Disorder, a Psychotic Disorder, or an Autism Spectrum Disorder.

Modified from the proposed diagnostic criteria for GAD, to be published in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Washington, DC: American Psychiatric Association. Expected publication date: May 2013. Copyright © American Psychiatric Association. The proposed criteria are from the DSM-5 web site—www.DSM5.org—accessed on November 11, 2011.

Treatment

GAD can be managed with nondrug therapy and with drugs. Nondrug approaches include supportive therapy, cognitive behavioral therapy (CBT), biofeedback, and relaxation training. These can help relieve symptoms and improve coping skills in anxiety-provoking situations. When symptoms are mild, nondrug therapy may be all that is needed. However, if symptoms are intensely uncomfortable or disabling, drugs are indicated. Current first-line choices are benzodiazepines, buspirone, and four antidepressants: venlafaxine, paroxetine, escitalopram, and duloxetine. With the benzodiazepines, onset of relief is rapid. In contrast, with buspirone and the antidepressants, onset is delayed. Accordingly, benzodiazepines are preferred drugs for immediate stabilization, especially when anxiety is severe. However, for long-term management, buspirone and the antidepressants are preferred. Because GAD is a chronic disorder, initial drug therapy should be prolonged, lasting at least 12 months, and possibly longer. Unfortunately, even after extended treatment, drug withdrawal frequently results in relapse. Hence, for many patients, drug therapy must continue indefinitely.

Benzodiazepines

Benzodiazepines are first-choice drugs for anxiety. As discussed in Chapter 34, benefits derive from enhancing responses to gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter. Onset of benefits is immediate, and the margin of safety is high. Principal side effects are sedation and psychomotor slowing. Patients should be warned about these effects and informed they will subside in 7 to 10 days. Because of their abuse potential, benzodiazepines should be used with caution in patients known to abuse alcohol or other psychoactive substances.

Long-term use of benzodiazepines carries a risk of physical dependence. Withdrawal symptoms include panic, paranoia, and delirium. These can be especially troubling for patients with GAD. Furthermore, they can be confused with a return of pretreatment symptoms. Accordingly, clinicians must differentiate between a withdrawal reaction and relapse. To minimize withdrawal symptoms, benzodiazepines should be tapered gradually—over a period of several months. If relapse occurs, treatment should resume.

Of the 13 benzodiazepines available, 6 are approved for anxiety. The agents prescribed most often are alprazolam [Xanax, Xanax XR, Niravam] and lorazepam [Ativan]. However, there is no proof that any one benzodiazepine is clearly superior to the others. Hence, selection among them is largely a matter of prescriber preference. Dosages for anxiety are summarized in Table 35–3.

TABLE 35–3

Dosages of Benzodiazepines Approved for Anxiety

		Dosage
Generic Name	Trade Name	Initial	Usual Range (mg/day)
Alprazolam	Xanax, Niravam Xanax XR	0.25–0.5 mg 3 times/day 0.5–1 mg once/day	0.5–6 3–6
Chlordiazepoxide	Librium	—	15–100
Clorazepate	Tranxene	—	15–60
Diazepam	Valium	—	4–40
Lorazepam	Ativan	0.5–1 mg 3 times/day	2–6
Oxazepam		—	30–120