Indications for Antianxiety and Sedative-Hypnotic Agents
Anxiety is characterized by fear and apprehension that may or may not be associated with a clearly identifiable stimulus. It is a common reaction to significant life stress, is seen in conjunction with almost every psychiatric disorder, and is also a common component of numerous medical disorders (e.g., hyperthyroidism, hypoglycemia, pheochromocytoma, complex partial seizures, pulmonary disorders, acute myocardial infarction, intoxication with caffeine or various substances of abuse). Anxiety is almost invariably accompanied by physical symptoms such as
Tachycardia, palpitations, chest tightness, diaphoresis
Breathing difficulties
Nausea, diarrhea, intestinal cramping
Dry mouth
Anxiety is associated with an increased risk for medical illness such as coronary artery disease and functional gastrointestinal disorders (1,2). Further, 20% to 25% of cancer patients also meet diagnostic criteria for a depressive- or an anxiety-related disorder (3). The adrenal system, genetic predisposition, and environmental factors appear to mediate the interaction between anxiety and medical comorbidities (4).
According to the Epidemiologic Catchment Area (ECA) Study (1990), anxiety disorders are the most prevalent psychiatric conditions in the United States(5,6 and 7). Of the 11 categories listed in the Diagnostic and Statistical Manual of Mental Disorders, 4th ed, Text revision (DSM-IV-TR) (8), generalized anxiety disorder (GAD) may be the most commonly diagnosed, although its incidence may actually be lower than that of phobic and obsessive-compulsive disorder (OCD).
Before 1980, the term anxiety neurosis was used to describe a syndrome that included both chronic generalized anxiety and panic attacks. GAD and panic were first listed as discrete diagnoses in the DSM-III, in part because of observed differences in their response to available drug treatments (i.e., the former to benzodiazepines, the latter to antidepressants; for a more detailed discussion of panic disorder [PD], see Chapter 13).
Elucidation of the neurocircuitry of anxiety disorders with functional imaging implicates the anterior paralimbic areas (increased activity) and the heteromodal association cortex (decreased activity) (9). Examples include
Post-traumatic stress disorder (PTSD): hyperactive or altered function in “emotionresponsive” regions such as the amygdala and insula; hypofunction of “emotion-regulatory” regions such as the medial frontal cortex and anterior cingulate cortex (10)
OCD: the orbitofrontal-thalamo-striatocortical circuits, which are implicated in cognitive and emotional processing (11)
PD: the amygdala, the medial temporal lobes, and their functional connections with the orbitofrontal cortex and brain stem (12)
In the context of neurotransmitters, evidence supports involvement of the serotonin (e.g., 5-HT1A receptor) (15), γ-aminobutyric acid (e.g., GABAA receptor), dopamine (e.g., D2 receptor), glutamate
(e.g., N-methyl-D-aspartate [NMDA] receptor), and μ-opioid systems in the pathological processes of various anxiety disorders.
(e.g., N-methyl-D-aspartate [NMDA] receptor), and μ-opioid systems in the pathological processes of various anxiety disorders.
Finally, all these findings must be considered in the context of stressful environmental events. For example, Mathew et al. (16) argue for a comprehensive approach in reviewing the evidence for neurobiological mechanisms underlying social anxiety disorder (SAD), including
Relevant nonhuman primate models
Neurodevelopmental issues
Genetics
Clinical neurobiology (e.g., pharmacological probes)
Neuroimaging
Generalized Anxiety Disorder
To differentiate it from transient anxiety, the DSM-IV-TR defines GAD as persistent anxiety or excessive worry occurring more days than not for at least 6 months about a number of events or activities (such as work or school performance) (8). A requirement that the person must find it difficult to control the worry was added. In addition, Criterion C now has a 6-item set that is simpler, more reliable, and more coherent than the 18-item set in DSM-III-R. Now the patient must have at least three or more of the following symptoms:
Restlessness
Easy fatigability
Difficulty concentrating
Irritability
Muscle tension
Disturbed sleep
Additional associated issues include the experience of significant distress or impairment, symptoms that do not occur exclusively during another disorder (e.g., mood, psychotic), its occurrence in children, and an independent association with risk of suicidality (17). GAD may be diagnosed along with another Axis I disorder (including another anxiety disorder) provided that symptoms are present at least sometimes without symptoms of the other disorder and that the anxiety is not focused on the other disorder. The lifetime prevalence of GAD is about 5% and appears to be higher in women, adults (median age of onset 31 years), non-Latino whites, in those with a low income, or those who are single (e.g., widowed, separated, divorced).
It should be noted that the validity of these diagnostic criteria is often debated and continue to evolve (13,17).Further, the overlap of symptoms and some commonalities in the neurobiology of GAD and major depressive disorder (MDD) have led to an increasing interest in studying these disorders together and discussions about categorizing GAD as a mood disorder (13,18). Important differential psychiatric diagnostic considerations include
Substance-induced disorders (e.g., caffeine intoxication)
Adjustment disorder with anxious mood (characterized by lack of full symptom criteria for GAD and the presence of a recognized psychosocial stressor)
Mood, psychotic or eating, disorders in which anxiety is related to the underlying condition
Further complicating diagnosis is the high rate of comorbidity with various psychiatric disorders, which increases the risk for impairment, disability, and suicidality (18).
Although few long-term follow-up studies exist, available evidence indicates that GAD may last for many years with waxing and waning symptoms and, as noted earlier, is often complicated by other intercurrent physical or psychiatric disorders (19,20). Although a DSM-IV-TR-derived diagnosis requires an anxiety duration of at least 6 months, clinicians often encounter very symptomatic patients who do not meet this criterion (21,22). Thus, clinical judgment and experience are critical in deciding when anxiety is a discrete disorder requiring primary treatment and when it is a manifestation of another disorder. This crucial differentiation requires that clinicians know that GAD and other anxiety disorders are lifelong, biologically based, often crippling, cause moderate-to-severe suffering, can handicap an otherwise healthy person, and are usually confirmed by a careful history. Freud emphasized these facts when he wrote (23):
The expectation that every neurotic phenomenon can be cured may, I suspect, be derived from the layman’s belief that the neuroses are something quite unnecessary which have no right whatsoever to exist. Whereas in fact they are severe, constitutionally fixed illnesses, which rarely restrict themselves to only a few attacks but persist as a rule over long periods or throughout life.
Phobic Disorders
All phobic disorders are characterized by disabling anxiety (at times also associated with panic attacks) and avoidance resulting from exposure to
Places or situations from which one cannot readily escape
Certain types of social or performance situations
A specific feared object or situation (e.g., heights)
AGORAPHOBIA
Agoraphobia (literally, fear of the marketplace) is the dread of being in places or situations from which escape might be difficult. This condition includes worry about suddenly developing embarrassing or incapacitating panic-like symptoms (e.g., loss of bladder control, dizziness) for which help might not be available. As a result, the agoraphobic patient often
Restricts travel
Needs a companion when away from home
Endures intense anxiety when confronted with a feared situation
Agoraphobia may accompany PD, but ECA data indicate that the majority of patients either fail to meet lifetime criteria for PD or have no history of panic symptoms (5). Questions about the validity of diagnosis have been raised, since many with agoraphobia and no history of PD are eventually found to have specific phobic disorders (24,25).
SOCIAL ANXIETY DISORDER (SAD)
SAD involves anxiety about social situations that is excessive and impairs functioning (8). Formerly called social phobia and one of the least studied of the major psychiatric disorders, SAD is the object of increasing research. As a result, we are filling in previous gaps concerning definition, prevalence, etiology, pathophysiology, assessment, and treatment (26).
SAD may present as a persistent fear of being judged by others and/or of embarrassing oneself in public (e.g., of being unable to answer questions in social situations, of choking when eating in front of others). Exposure to the feared situation provokes an immediate anxiety response. Thus, the phobic situation is preferably avoided or endured with intense anxiety. Secondarily, anticipatory avoidant behavior can interfere with occupational or social functioning (but need not be incapacitating), or there is marked distress about having the fear. Typically, the person is aware of the excessive and/or unreasonable nature of these concerns. The diagnosis is not made if one simply avoids social situations that normally provoke some distress, such as public speaking. If an Axis III or another Axis I disorder is present, SAD is diagnosed only if the fear is unrelated to these conditions. Two subtypes are recognized:
Generalized (i.e., fear most social situations)
Nongeneralized (i.e., fear a limited number of specific situations)
The US lifetime prevalence is estimated to be 12% to 13% based on the National Comorbidity Survey and its replication (27,28). Those with the generalized subtype typically exhibit more functional impairment and more comorbidities (29). This disorder usually occurs in adolescence, persists into adulthood, and can produce lifelong disability and increase the risk of other psychiatric comorbidities (e.g., MDD, alcoholism). Differential diagnosis includes
Separation anxiety disorder
Avoidant personality disorder, characterized by marked anxiety and a long-standing, pervasive, habitual, and active withdrawal from social relationships (30)
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