either may lack adequate insight to recognize the unreasonableness of their condition or may be

too embarrassed to discuss the condition as unreasonable.

OCD frequently cooccurs with other disorders. The association with major depression is
particularly prominent, although comorbidity with panic disorder, phobias, and eating disorders
is also not uncommon. Finally, OCD exhibits a particularly interesting association with
Tourette's syndrome. Approximately half of all patients with Tourette's syndrome meet criteria
for OCD, although less than 10 percent of patients with OCD meet criteria for Tourette's
syndrome. There is also evidence of cotransmission of Tourette's syndrome, OCD, and chronic
motor tics within families.
History and Comparative Nosology
Patients with a syndrome of recurrent obsessions and compulsions were described in the 19th
century, when these conditions were viewed as a form of depressive state. Descriptions of OCD
also played a prominent role in Sigmund Freud's writings, as evidenced in the case history of the
Rat Man and in early learning-based theories that attempted to apply treatments developed for
patients with phobias to patients with OCD. A major change in research on OCD emerged with
the ECA Study in the early 1980s. Before this study, OCD was recognized as a discrete but rare
entity and stimulated only a modest degree of research. The ECA Study noted OCD to have a
prevalence in excess of 1 percent in the population and to be associated with marked impairment.
This observation led to extensive research on all aspects of OCD, including its phenomenology.
The main change in OCD from DSM-III to DSM-IV-TR involved the conceptualization of
compulsions. Whereas DSM-III-R viewed compulsions exclusively as behaviors, DSM-IV-TR
recognizes compulsions as either behaviors or mental acts designed to reduce the anxiety-
provoking nature of an obsession. The conceptualization of OCD in the ICD and DSM systems is
generally similar, with a few exceptions in the emphasis on specific features of the condition. For
example, ICD-10 emphasizes that a compulsive act must not be pleasurable. ICD-10 also
stipulates that obsessions or compulsions must be present most days for 2 weeks, a requirement
not included in DSM-IV-TR, and ICD-10 does not quantify the amount of time a patient must
spend on compulsions. Perhaps the primary difference between the DSM-IV-TR and ICD-10
views of the disorder involves categorization with respect to other anxiety disorders. DSM-IV-
TR recognizes OCD as one of the nine anxiety disorders discussed in this section. There has
been some debate, both in the United States and in Europe, as to whether OCD is more properly
classified in a distinct category. ICD-10 has adopted such a scheme, using the term OCD as a
label for a group of syndromes considered distinct from anxiety disorders.
Differential Diagnosis
A number of primary medical disorders can produce syndromes bearing a striking resemblance
to OCD. In fact, the current conceptualization of OCD as a disorder of the basal ganglia derives
from the phenomenological similarity between idiopathic OCD and OCD-like disorders that are
associated with basal ganglia diseases, such as Sydenham's chorea and Huntington's disease.
Hence, neurological signs of such basal ganglia pathology must be assessed when considering
the diagnosis of OCD in a patient presenting for psychiatric treatment. It should also be noted
that OCD frequently develops before age 30 years, and new-onset OCD in an older individual
should raise questions about potential neurological contributions to the disorder. Finally, among
children, there is some evidence of an association between an immune reaction to streptococcal
infections and either initial manifestations or dramatic exacerbation of OCD. This syndrome
appears to emerge relatively acutely, in contrast to a more insidious onset in other cases of
childhood OCD. Hence, in children with acute presentations, the role of such an infectious
process should be considered.
Obsessive-compulsive behavior is also found in a host of other psychiatric disorders, and the
clinician must also rule out these conditions when diagnosing OCD. OCD exhibits a superficial
resemblance to obsessive-compulsive personality disorder, which is associated with an obsessive
concern for details, perfectionism, and other similar personality traits. The conditions are easily
distinguished by the fact that only OCD is associated with a true syndrome of obsessions and
compulsions, as described above.
Psychotic symptoms often lead to obsessive thoughts and compulsive behaviors that can be
difficult to distinguish from OCD
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with poor insight, in which obsessions border on psychosis. The keys to distinguishing OCD
from psychosis are (1) patients with OCD can almost always acknowledge the unreasonable
nature of their symptoms, and (2) psychotic illnesses are typically associated with a host of other
features that are not characteristic of OCD. Similarly, OCD can be difficult to differentiate from
depression, as the two disorders often occur comorbidly, and major depression is often
associated with obsessive thoughts that, at times, border on true obsessions like those that
characterize OCD. The two conditions are best distinguished by their courses. Obsessive
symptoms associated with depression are only found in the presence of a depressive episode,
whereas true OCD persists despite remission of depression.
Finally, as noted above, OCD is closely related to Tourette's syndrome, as the two conditions
frequently cooccur, both in individuals over time and within families. In its classic form,
Tourette's syndrome is associated with a pattern of recurrent vocal and motor tics that bears only
a slight resemblance to OCD. However, the premonitory urges that precede tics often strikingly
resemble obsessions, and many of the more complicated motor tics are very similar to
compulsions.
Epidemiology
As noted above, although OCD was once considered relatively rare, recent epidemiological
studies place the prevalence in the range of 2 to 3 percent. The prevalence of the disorder is
approximately equal in men and women, although men tend to have an earlier onset than women
do.
Course
OCD typically begins in late adolescence, although onset in childhood is not uncommon. The
disorder tends to exhibit a waxing and waning course over the life span, with periods of
relatively good functioning and limited symptoms punctuated by periods of symptomatic
exacerbation. Small minorities of patients exhibit either complete remission of their disorder or a
progressive, deteriorating course.
Ms. B. presented for psychiatric admission after being transferred from a medical floor where
she had been treated for malnutrition. Ms. B. had been found unconscious in her apartment by a
neighbor. When brought to the emergency department by an ambulance, she was found to be
hypotensive and hypokalemic. At psychiatric admission, Ms. B. described a long history of
recurrent obsessions about cleanliness, particularly related to food items. She reported that
because she often had the thought that a food item was dirty, it was difficult for her to eat any
food unless she had washed it three or four times. She reported that washing her food decreased
the anxiety she felt about its dirtiness. Although Ms. B. reported that she had occasionally tried
to eat food that she had not washed (e.g., in a restaurant), she found that she became so worried
about becoming ill from eating such food that she could no longer dine in restaurants. Ms. B.
reported that her obsessions about the cleanliness of food had become so extreme over the past 3
months that she could eat very few foods, even if she washed them excessively. She recognized
the irrational nature of these obsessive concerns, but either could not bring herself to eat or
became extremely nervous and nauseated after eating.
POSTTRAUMATIC STRESS AND ACUTE STRESS DISORDERS
Symptomatology
Both PTSD and acute stress disorder are characterized by the onset of psychiatric symptoms
immediately after exposure to a traumatic event. As noted in Table 14.8-6, DSM-IV-TR
explicitly notes that such a traumatic event involves either witnessing or experiencing threatened
death or injury or witnessing or experiencing threat to physical integrity. Further, the response to
the traumatic event must involve intense fear or horror. Such traumatic experiences might
include being involved in or witnessing a violent accident or crime, military combat, assault,
being kidnapped, being involved in natural disasters, being diagnosed with a life-threatening
illness, or experiencing systematic physical or sexual abuse. Both PTSD and acute stress disorder
also require characteristic symptoms after such trauma. There is evidence of a dose–response
relationship between the degree of trauma and the likelihood of symptoms. The greater the
proximity and intensity of the trauma, the greater the probability of developing symptomatology.
Table 14.8-6 DSM-IV-TR Criteria for Posttraumatic Stress Disorder and Acute Stress
Disorder
Criteria for posttraumatic stress disorder (PTSD)
A. The person has been exposed to a traumatic event in which both of the following were
present:
1. The person experienced, witnessed, or was confronted with an event that involved actual or
threatened death or serious injury, or a threat to the physical integrity of self or others.
2. The person's response involved intense fear, helplessness, or horror. Note: In children this
may be expressed, instead, by disorganized or agitated behavior.
B. The traumatic event is persistently reexperienced in one (or more) of the following ways:
1. Recurrent and intrusive distressing recollections of the event, including images, thoughts, or
perceptions. Note: In young children, repetitive play may occur in which themes or aspects of
the trauma are expressed.
2. Recurrent distressing dreams of the event. Note: In children, there may be frightening
dreams without recognizable content.
3. Acting or feeling as if the traumatic event were recurring (includes a sense of reliving the
experience, illusions, hallucinations, and dissociative flashback episodes, including those that
occur on awakening or when intoxicated). Note: In young children, trauma-specific reenactment
may occur.
4. Intense psychological distress at exposure to internal or external cues that symbolize or
resemble an aspect of the traumatic event.
5. Physiological reactivity on exposure to internal or external cues that symbolize or resemble
an aspect of the traumatic event.
C. Persistent avoidance of stimuli associated with the trauma and numbing of general
responsiveness (not present before the trauma), as indicated by three (or more) of the following:
1. Efforts to avoid thoughts, feelings, or conversations associated with the trauma
2. Efforts to avoid activities, places, or people that arouse recollections of the trauma
 3. Inability to recall an important aspect of the trauma
4. Markedly diminished interest or participation in significant activities
5. Feeling of detachment or estrangement from others
6. Restricted range of affect (e.g., unable to have loving feelings)
7. Sense of a foreshortened future (e.g., does not expect to have a career, marriage, children, or
a normal life span)
D. Persistent symptoms of increased arousal (not present before the trauma), as indicated by two
(or more) of the following:
1. Difficulty falling or staying asleep
2. Irritability or outbursts of anger
3. Difficulty concentrating
4. Hypervigilance
5. Exaggerated startle response
E. Duration of the disturbance (symptoms in Criteria B, C, and D) is more than 1 month.
F. The disturbance causes clinically significant distress or impairment in social, occupational, or
other important areas of functioning.
Specify if:
Acute: if duration of symptoms is less than 3 months
Chronic: if duration of symptoms is 3 months or more
With delayed onset: if onset of symptoms is at least 6 months after the stressor
Criteria for acute stress disorder
A. The person has been exposed to a traumatic event in which both of the following were
present:
1. The person experienced, witnessed, or was confronted with an event that involved actual or
threatened death or serious injury, or a threat to the physical integrity of self or others.
2. The person's response involved intense fear, helplessness, or horror.
B. Either while experiencing or after experiencing the distressing event, the individual has three
(or more) of the following dissociative symptoms:
1. A subjective sense of numbing, detachment, or absence of emotional responsiveness
2. A reduction in awareness of his or her surroundings (e.g., “being in a daze”)
3. Derealization
4. Depersonalization
5. Dissociative amnesia (i.e., inability to recall an important aspect of the trauma)
C. The traumatic event is persistently reexperienced in at least one of the following ways:
recurrent images, thoughts, dreams, illusions, flashback episodes, or a sense of reliving the
experience, or distress on exposure to reminders of the traumatic event.
D. Marked avoidance of stimuli that arouse recollections of the trauma (e.g., thoughts, feelings,
conversations, activities, places, people).
E. Marked symptoms of anxiety or increased arousal (e.g., difficulty sleeping, irritability, poor
concentration, hypervigilance, exaggerated startle response, motor restlessness).
F. The disturbance causes clinically significant distress or impairment to social, occupational, or
other important areas of functioning or impairs the individual's ability to pursue some necessary
task, such as obtaining necessary assistance or mobilizing personal resources by telling family
members about the traumatic experience.
G. The disturbance lasts for a minimum of 2 days and a maximum of 4 weeks and occurs within
4 weeks of the traumatic event.
H. The disturbance is not due to the direct physiological effects of a substance (e.g., a drug of
abuse, a medication) or a general medical condition, is not better accounted for by brief
psychotic disorder, and is not merely an exacerbation of a preexisting Axis I or Axis II disorder.
From American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders.
4th ed. Text rev. Washington, DC: American Psychiatric Association; 2000, with permission.
In PTSD, the individual develops symptoms in three domains: reexperiencing the trauma,
avoiding stimuli associated with the trauma, and experiencing symptoms of increased autonomic
arousal, such as an enhanced startle. Flashbacks, in which the individual may act and feel as if
the trauma were recurring, represent the classic form of reexperiencing. Other forms of
reexperiencing include distressing recollections or dreams and either physiological or
psychological stress reactions when exposed to stimuli that are linked to the trauma. An
individual must exhibit at least one reexperiencing symptom to meet criteria for PTSD.
Symptoms of avoidance associated with PTSD include efforts to avoid thoughts or activities
related to the trauma, anhedonia, reduced capacity to remember events related to the trauma,
blunted affect, feelings of detachment or derealization, and a sense of a foreshortened future. An
individual must exhibit at least three such symptoms. Symptoms of increased arousal include
insomnia, irritability, hypervigilance, and exaggerated startle. An individual must exhibit at least
two such symptoms. Finally, the diagnosis of PTSD is only made when symptoms persist for at
least 1 month; the diagnosis of acute stress disorder is made in the interim. DSM-IV-TR
acknowledges three subtypes of PTSD, differentiating among syndromes with varying time
courses. Acute PTSD refers to an episode that lasts less than 3 months, whereas chronic PTSD
refers to an episode lasting 3 months or longer. PTSD with delayed onset refers to an episode
that develops 6 months or more after exposure to the traumatic event.
The diagnosis of acute stress disorder is applied to syndromes that resemble PTSD but last less
than 1 month after a trauma. Acute stress disorder is characterized by reexperiencing, avoidance,
and increased arousal, much like PTSD. Acute stress disorder is also associated with at least
three of the dissociative symptoms listed in Table 14.8-6.
Because individuals often exhibit complex biological and behavioral responses to extreme
trauma, the clinician must identify other medical and psychiatric conditions in the traumatized
patient. The clinician must always evaluate whether neurological etiologies underlie trauma-
related symptoms, particularly after traumatic events that involve physical injury. Traumatized
patients also can develop mood disorders, including dysthymia and major depression, as well as
other anxiety disorders, such as generalized anxiety disorder or panic disorder, and substance use
disorders. Finally, recent research suggests that some psychiatric features of posttraumatic
syndromes can relate to a patient's state before the trauma. For example, patients with premorbid
anxiety or affective syndromes may be more likely to develop posttraumatic symptoms than
individuals who are free of mental illness before the trauma. As a result, the clinician should
consider the premorbid mental state of the traumatized
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patient to enhance understanding of symptoms that develop after a traumatic event.

History and Comparative Nosology
Astute clinicians have recognized the juxtaposition of acute mental syndromes and traumatic
events for more than 200 years. Observations of trauma-related syndromes were documented
after the Civil War and early psychoanalytical writers, including Freud, noted the relationship
between neurosis and trauma. Considerable interest in posttraumatic mental disorders was
stimulated by observations of battle fatigue, shell shock, and soldier's heart in both World War I
and World War II. Moreover, increasing documentation of mental reactions to the Holocaust, to
a series of natural disasters, and to assault contributed to the growing recognition of a close
relationship between trauma and psychopathology.
The syndrome of PTSD was first recognized in the DSM nosology with DSM-III in 1980,
whereas acute stress disorder was first identified in DSM-IV-TR in 1994. The recognition of
acute stress disorder came after observations suggesting that many individuals exhibit mental
syndromes immediately after trauma and that such
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individuals might face an elevated risk for PTSD. The original DSM-III definition of PTSD
required only one symptom of reexperiencing, two symptoms of “psychic numbing,” and one
symptom from a list of miscellaneous items, with no duration criteria. DSM-III-R added a
number of symptoms to the DSM-III definition and removed the DSM-III symptom of guilt.
DSM-III-R also adopted the symptom groupings that are found in DSM-IV-TR, in which
symptoms are classified as manifestations of either reexperiencing, avoidance, or hyperarousal.
The major change to the definition in DSM-IV-TR involved the definition of trauma. Whereas
DSM-III-R emphasized trauma as an event that was “outside of normal experience,” a number of
field studies suggested that the typical traumatic precipitants of PTSD were relatively common
events. As a result, DSM-IV-TR emphasizes the threat and fear-provoking nature of a trauma,
without reference to “normal experience.”
There are some differences between the DSM-IV-TR and ICD-10 definitions of PTSD and acute
stress disorder. Whereas ICD-10 acknowledges the same core group of symptoms for PTSD than
DSM-IV-TR does, including exposure to a trauma, reexperiencing, avoidance, and increased
arousal, ICD-10 provides considerably less detail for each of the criteria than DSM-IV-TR does.
For example, unlike DSM-IV-TR, ICD-10 provides only brief examples of reexperiencing or
avoidance symptoms. The broader views of PTSD and acute stress disorder also differ between
the DSM and ICD systems. As it does with OCD, ICD-10 groups PTSD and acute stress reaction
in a distinct category, stress-related disorders, rather than grouping them with other anxiety
disorders.
Differential Diagnosis
Because patients often exhibit complex reactions to trauma, the clinician must be careful to
exclude other syndromes as well when evaluating patients presenting in the wake of trauma. It is
particularly important to recognize potentially treatable medical contributors to posttraumatic
symptomatology. For example, neurological injury after head trauma can contribute to the
clinical picture, as can psychoactive substance use disorders or withdrawal syndromes, either in
the period immediately surrounding the trauma or many weeks after the trauma. Medical
contributors can usually be detected through a careful history and physical examination, as long
as the clinician remembers to consider such factors.
Symptoms of PTSD can be difficult to distinguish from both panic disorder and generalized
anxiety disorder, as all three syndromes are associated with prominent anxiety and autonomic
arousal. Keys to correctly diagnosing PTSD involve a careful review of the time course relating
the symptoms to a traumatic event. Further, PTSD is associated with reexperiencing and
avoidance of a trauma, features typically not present in panic or generalized anxiety disorder.
Major depression is also a frequent concomitant of PTSD. Although the two syndromes are not
usually difficult to distinguish phenomenologically, it is important to note the presence of
comorbid depression, as this may influence treatment of PTSD. Finally, PTSD must be
differentiated from a series of related disorders that can exhibit phenomenological similarities,
including borderline personality disorder, dissociative disorders, and factitious disorders.
Epidemiology
As acute stress disorder represents a new disorder in DSM-IV-TR, there has been minimal
research on its prevalence. Research on the psychological response to trauma, however, shows
that psychological reactions that resemble acute stress disorder are very common with exposure
to extreme trauma at close proximity. Estimates of PTSD prevalence depend on the population
studied, as exposure to trauma varies widely across communities. Recent studies generally
estimate the prevalence in the community to be between 2 and 15 percent.
Course
Much of the recent research on the course of psychological reactions to trauma has focused on
the time course of symptoms immediately after a trauma. The likelihood of developing
symptoms, the severity of such symptoms, and the duration of the symptoms are each
proportional to the proximity, duration, and intensity of the trauma. Many individuals develop
acute stress reactions when faced with close, persistent, and intense trauma. Moreover, many
individuals who develop PTSD exhibit features of the acute stress syndrome before developing
PTSD, although many individuals with acute stress syndromes do not develop PTSD. Finally, the
full syndrome of PTSD also exhibits a variable course, with some evidence that this also relates
to the nature of the trauma. A large minority of patients develop complete remissions, whereas
another large group exhibits only mild symptoms. PTSD is persistent or chronic in
approximately 10 percent of patients with the disorder.
Mr. F. sought treatment for symptoms that he developed in the wake of an automobile accident
that had occurred approximately 6 weeks before his psychiatric evaluation. While driving to
work on a mid-January morning, Mr. F. lost control of his car on an icy road. His car swerved
out of control into oncoming traffic, collided with another car, and then hit a nearby pedestrian.
Mr. F. was trapped in his car for 3 hours while rescue workers cut through the car door. After
referral, Mr. F. reported frequent intrusive thoughts about the accident, including nightmares of
the event and recurrent intrusive visions of his car slamming into the pedestrian. He reported that
he had altered his driving route to work to avoid the scene of the accident and that he found
himself switching the TV channel whenever a commercial for snow tires appeared. Mr. F.
described frequent difficulty falling asleep, poor concentration, and an increased focus on his
environment, particularly when he was driving.
GENERALIZED ANXIETY DISORDER
Symptomatology
Generalized anxiety disorder is characterized by a pattern of frequent, persistent worry and
anxiety that is out of proportion to the impact of the event or circumstance that is the focus of the
worry, as shown in Table 14.8-7. For example, although college students often worry about
examinations, a student who persistently worries about failure despite consistently getting
outstanding grades shows a pattern of worry that is typical of generalized anxiety disorder.
Patients with generalized anxiety disorder may not acknowledge the excessive nature of their
worries, but they must be bothered by their degree of worry. This pattern must occur more days
than not for at least 6 months. Patients must find it difficult to control this worry and must report
at least three of six somatic or cognitive symptoms. Such symptoms include feelings of
restlessness, fatigue, muscle tension, and insomnia. Finally, worry is a ubiquitous feature of
many anxiety disorders, as patients with panic disorder often worry about panic attacks, patients
with social phobia worry about social encounters, and patients with OCD worry about their
obsessions. The worries in generalized anxiety disorder must exceed in breadth or scope the
worries that characterize these other anxiety disorders. Children with marked and persistent
worry can also be diagnosed with generalized anxiety disorder, but, unlike
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adults, they must only meet one of the six somatic or cognitive symptom criteria.
Table 14.8-7 DSM-IV-TR Criteria for Generalized Anxiety Disorder
A. Excessive anxiety and worry (apprehensive expectation) about a number of events or
activities (such as work or school performance) occurring more days than not for at least 6
months.
B. The person finds it difficult to control the worry.
C. The anxiety and worry are associated with three (or more) of the following six symptoms
(with at least some symptoms present for more days than not for the past 6 months). Note: Only
one item is required in children.
1. Restlessness or feeling keyed up or on edge
2. Being easily fatigued
3. Difficulty concentrating
4. Irritability
5. Muscle tension
6. Sleep disturbance (difficulty falling or staying asleep, or restless unsatisfying sleep)
D. The focus of the anxiety and worry is not confined to features of an Axis I disorder—e.g., the
anxiety or worry is not about having a panic attack (as in panic disorder), being embarrassed in
public (as in social phobia), being contaminated (as in obsessive-compulsive disorder), being
away from home (as in separation anxiety disorder), gaining weight (as in anorexia nervosa),
having multiple physical complaints (as in somatization disorder), or having a serious illness (as
in hypochondriasis), and the anxiety or worry does not occur exclusively during posttraumatic
stress disorder.
E. The anxiety, worry, or physical symptoms cause clinically significant distress or impairment
in social, occupational, or other important areas of functioning.
F. The disturbance is not due to the direct physiological effects of a substance (e.g., a drug of
abuse, a medication) or a general medical condition (e.g., hypothyroidism) and does not occur
exclusively during a mood disorder, a psychotic disorder, or a pervasive developmental disorder.
From American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders.
4th ed. Text rev. Washington, DC: American Psychiatric Association; 2000, with permission.
History and Comparative Nosology
Clinicians have documented symptoms of generalized anxiety disorder for more than 100 years.
Many of the syndromes that are considered related to panic disorder, such as DaCosta's
syndrome or neurocirculatory asthenia, also bear a close resemblance to generalized anxiety
disorder. In fact, before DSM-III, panic disorder and generalized anxiety disorder were both
subsumed under the broader category of anxiety neurosis.
The conceptualization of generalized anxiety disorder has changed gradually from DSM-III to
DSM-IV-TR. The disorder was originally conceived as a residual category in DSM-III for
anxiety disorders that did not fulfill criteria for another disorder. DSM-III only required a 1-
month duration of symptoms, and concerns arose about the low reliability of the diagnosis.
DSM-III-R increased the duration criterion to 6 months, placed more emphasis on the symptom
of worry, and added a list of 18 symptoms, out of which patients had to exhibit at least 6. DSM-
III-R also removed some of the hierarchical rules in DSM-III that had limited the diagnosis to
individuals who were free of other specific disorders. Finally, DSM-IV-TR brought further
revisions to the diagnosis. The list of associated symptoms was narrowed from 18 to 6, of which
adult patients had to exhibit at least three. More emphasis was also placed on the pervasiveness
of the patient's worry. DSM-IV-TR attempted to expand this emphasis on worry across
development. Whereas DSM-III-R included the diagnosis of overanxious disorder for use among
children, DSM-IV-TR integrated this DSM-III-R diagnosis with generalized anxiety disorder,
with the caveat that minor threshold differences apply when making the diagnosis in children
rather than in adults.
ICD-10 includes the diagnosis of generalized anxiety disorder and emphasizes the distinction
between generalized anxiety and panic disorders. Although ICD-10 places a similar emphasis on
worry to that in DSM-IV-TR, it approaches the other symptoms of generalized anxiety disorder
in a way that more closely resembles DSM-III-R than DSM-IV-TR. For example, in ICD-10, the
diagnosis requires four associated symptoms from a list of 22 symptoms.
Differential Diagnosis
Like other anxiety disorders, particularly panic disorder, generalized anxiety disorder must be
differentiated from both medical and psychiatric disorders. Neurological, endocrinological,
metabolic, and medication-related disorders similar to those considered in the differential
diagnosis of panic disorder must be considered in the differential diagnosis of generalized
anxiety disorder. Common cooccurring anxiety disorders also must be considered. These include
panic disorder, phobias, OCD, and PTSD. To meet criteria for generalized anxiety disorder,
patients must not only exhibit the full syndrome, but their symptoms also cannot be explained by
the presence of a comorbid anxiety disorder. To diagnose generalized anxiety disorder in the
context of other anxiety disorders, it is most important to document anxiety or worry related to
circumstances or topics that are either unrelated or only minimally related to other disorders.
Hence, proper diagnosis involves both definitively establishing the presence of generalized
anxiety disorder and properly diagnosing other anxiety disorders. Patients with generalized
anxiety disorder frequently develop major depressive disorder. As a result, this condition must
also be recognized and distinguished. Again, the key to making a correct diagnosis is
documenting anxiety or worry that is unrelated to the depressive disorder.
Epidemiology
It is difficult to provide a definitive estimate of the prevalence of generalized anxiety disorder,
given the changes to the diagnostic criteria since the 1990s. In general, most community-based
studies place the prevalence in the range of 2 to 5 percent, with the ECA suggesting a lifetime
prevalence as high as 8 percent. The disorder tends to be more common in women and usually
has its onset in late adolescence or early adulthood. However, cases are commonly seen in older
adults. There is also some evidence suggesting that the prevalence of generalized anxiety
disorder is particularly high in primary care settings.
Course
The lack of prospective epidemiological studies precludes firm conclusions about the course of
generalized anxiety disorder. Moreover, there is also insufficient prospective research even
among clinical samples. The most complete data on the course of the disorder are derived from
retrospective epidemiologically based studies. These studies suggest that generalized anxiety
disorder is chronic, as most patients report symptoms for many years before assessment. Given
the possible biases in such studies, no definitive statement on the course of the disorder can be
made.
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Ms. X. was a successful, married, 30-year-old attorney who presented for a psychiatric
evaluation to treat mounting symptoms of worry and anxiety. For the preceding 8 months, Ms.
X. noted that she had become increasingly worried about her job performance. For example,
although she had always been a superb litigator, she found herself worrying more and more
about her ability to win cases. Similarly, although she had always been in outstanding physical
condition, she increasingly worried that her health had begun to deteriorate. Ms. X. noted
frequent somatic symptoms that accompanied her worries. For example, she often felt restless
while she worked and while she commuted to her office, at which time she tended to think about
the upcoming challenges of the day. She reported feeling increasingly fatigued, irritable, and
tense. She noted that she had increasing difficulty falling asleep at night as she worried about her
job performance and impending trials.
Three other anxiety disorders will be discussed in less detail. Anxiety disorder not otherwise
specified will only be discussed briefly due to the limited research on this condition. Substance-
induced anxiety and anxiety disorder due to a general medical condition are only discussed
briefly, as these topics are considered in more detail in other chapters.
ANXIETY DISORDER NOT OTHERWISE SPECIFIED
Anxiety represents one of the most common psychiatric symptoms encountered in various
settings, including primary care settings, and it is relatively common to encounter patients who
exhibit impairment from anxiety but do not meet criteria for one of the disorders discussed in the
preceding sections. These patients are appropriately classified as having anxiety disorder not
otherwise specified.
Two clinical features of this disorder must be recognized to properly identify the condition. First,
the anxiety described by the patients must be distressing, interfering with some aspect of
functioning. Second, the anxiety must not be attributable to another psychiatric condition. For
example, patients with generalized anxiety disorder may not initially report sufficient associated
symptoms to meet criteria for this condition. However, on further probing, such symptoms may
be identified. It is important to establish that another anxiety disorder does not account for the
complaints, particularly in patients with long-standing anxiety. Perhaps the most consistent
research on this condition examines patients with mixed anxiety-depressive disorder, a condition
described in the Appendix of DSM-IV-TR.
Patients with mixed anxiety-depressive disorder exhibit symptoms of both depression and
anxiety that do not meet criteria for another mood or anxiety disorder. Such patients must show
signs of consistent low mood for at least 1 month, accompanied by additional symptoms that
include prominent worries. Longitudinal studies find a relatively high risk for later mood or
anxiety disorders with this condition, particularly major depression. Due to the paucity of data on
treatment for the condition, clinicians often use approaches that are effective in other mood or
anxiety disorders. Anxiety concerning an embarrassing medical problem or scenario is another
frequently encountered form of anxiety disorder not otherwise specified. For example, patients
who exhibit excessive concern regarding a dermatological condition might exhibit symptoms of
this syndrome.
SUBSTANCE-INDUCED ANXIETY AND ANXIETY DUE TO A GENERAL MEDICAL
CONDITION
Each of these conditions is characterized by prominent anxiety that arises as the direct result of
some underlying physiological perturbation. Hence, for patients with substance-induced anxiety,
clinically significant symptoms of panic, worry, phobia, or obsessions emerge in the context of
substance use—this can refer to either prescribed or illicit substances. For example, both
prescribed and illicit sympathomimetic substances can often produce relatively marked degrees
of anxiety. Similarly, for anxiety due to a general medical condition, symptoms develop in the
context of an identifiable medical syndrome. For example, panic attacks have been tied to
various medical conditions, including endocrinological, cardiac, and respiratory illnesses.
The first step in identifying an anxiety disorder due to either a medical condition or substance is
to confirm the presence of one or the other complicating factor. Clearly, practitioners should
routinely document the medical and substance use status of all patients. However, the clinician
should be particularly wary when encountering a patient with an unusual symptomatic
presentation. For example, changes in consciousness or neurological function almost never occur
in acute anxiety states unless there is also an underlying medical component to the syndrome. In
cases in which there is a suspicion of such complicating factors, the presence of substance use or
medical problems first must be definitively confirmed by obtaining the necessary medical history
or evaluative procedures. Next, the clinician must determine that this underlying problem is the
cause of the ongoing anxiety symptoms. Although there is no definitive test to establish such a
causal relationship, at least three factors can be helpful—the timing of the symptoms, the
existing literature pertaining to the strength of the association between anxiety and the potential
complicating factor, and signs or symptoms (e.g., changes in consciousness) that are atypical for
an anxiety disorder. Finally, even more suggestive evidence can be provided if alleviation of the
complicating medical factor produces an amelioration of the anxiety symptoms.
SUGGESTED CROSS-REFERENCES
Other aspects of these disorders are discussed elsewhere within this chapter, such as theories on
etiology (Sections 14.3, 14.4, 14.5, 14.6, and 14.7) and treatment (Sections 14.9 and 14.10).
Similarly, substance-induced anxiety disorder and anxiety disorder due to a general medical
condition as distinct anxiety disorders are also discussed in Chapter 11, on substance use
disorders, and Chapter 10, on the psychiatric complications of medical conditions.
REFERENCES
Angst J, Vollrath M: The natural history of anxiety disorders. Acta Psychiatr Scand.
1991;84:446.
Ballenger JC, Fyer AJ: DSM-IV in progress: Examining criteria for panic disorder. Hosp
Community Psychiatry. 1993;44:226.
*Barlow DH. Anxiety and Its Disorders: The Nature and Treatment of Anxiety and Panic. New
York: Guilford; 1988.
*Breslau N, Davis GC, Andreski P, Peterson E: Traumatic events and posttraumatic stress
disorder in an urban population of young adults. Arch Gen Psychiatry. 1991;48:216.
Carden E, Speigel D: Dissociative reaction to the San Francisco Bay Area earthquake of 1989.
Am J Psychiatry. 1993;150:474.
Davidson JRT, Foa EB: Diagnostic issues in posttraumatic stress disorder: Considerations for the
DSM-IV. J Abnorm Psychol. 1991;100:346.
Davidson JRT, Hughes DL, George LK, Blazer DG: The epidemiology of social phobia.
Findings from the Epidemiologic Catchment Area Study. Psychol Med. 1993;23:709.
Freud S. Inhibitions, symptoms and anxiety. In: Standard Edition of the Complete Psychological
Works of Sigmund Freud. Vol 20. London: Hogarth Press; 1966:77.
Freud S. Obsessions and phobias. In: Standard Edition of the Complete Psychological Works of
Sigmund Freud. Vol 3. London: Hogarth Press; 1966:71.
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Fyer AJ, Mannuzza S, Chapman T, Liebowitz MR, Klein DF: A direct interview family study of
social phobia. Arch Gen Psychiatry. 1994;50:286.
Gorman JM, Papp LA: Chronic anxiety: Deciding the length of treatment. J Clin Psychiatry.
1990;51(Suppl):11.
Gorman JM, Papp LA, eds. Anxiety disorders. In: Tasman, ed. Annual Review of Psychiatry.
Vol 11A. Washington, DC: American Psychiatric Association Press; 1992.
Horwath E, Wolk SI, Goldstein RB, Wickramaratne P, Sobin C, Adams P, Lish JD, Weissman
MM: Is the comorbidity between social phobia and panic disorder due to familial cotransmission
or other factors? Arch Gen Psychiatry. 1995;52:574.
Jarrell MP, Ballenger JC: Psychiatric comorbidity in patients with generalized anxiety disorder.
Am J Psychiatry 1993;150:1216.
Jenike MA, Baer L, Minichiello WE. Obsessive-Compulsive Disorders: Theory and
Management. 2nd ed. Chicago: Yearbook Publishing; 1990.
Keller MB: The lifelong course of social anxiety disorder: A clinical perspective. Acta Psychiatr
Scand Suppl. 2003;417:85–94.
Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB: Posttraumatic stress disorder in the
national comorbidity survey. Arch Gen Psychiatry. 1995;52:1048.
Klein DF: Delineation of two drug-responsive anxiety syndromes. Psychopharmacology.
1964;5:397.
Klein DF: False suffocation alarms, spontaneous panics, and related conditions: An integrative
hypothesis. Arch Gen Psychiatry. 1993;50:306.
Klein DF, Rabkin JG, eds. Anxiety: New Research and Changing Concepts. New York: Raven
Press; 1981.
Klerman GL, Weissman MM, Ouellette R, Johnson J, Greenwald S: Panic attacks in the
community: Social morbidity and health care utilization. JAMA. 1991;265:742.
*Liebowitz MR, Gorman JM, Fyer AF, Klein DF: Social phobia: Review of a neglected anxiety
disorder. Arch Gen Psychiatry. 1985;42:729.
*Magee WJ, Eaton WW, Wittchen HU, McGonagle KA, Kessler RC: Agoraphobia, simple
phobia, and social phobia in the National Comorbidity Survey. Arch Gen Psychiatry.
1996;53:159.
*Marks IM. Fears, Phobias, and Rituals: Panic, Anxiety, and Their Disorders. New York: Oxford
University Press; 1988.
McFarlane AC. The phenomenology of post-traumatic stress disorders following a natural
disaster. J Nerv Ment Dis. 1988;176:22.
Merikangas KR, Zhang H, Avenevoli S, Acharyya S, Neuenschwander M, Angst J: Longitudinal
trajectories of depression and anxiety in a prospective community study: The Zurich Cohort
Study. Arch Gen Psychiatry. 2003;60:993–1000.
Pigott TA: Anxiety disorders in women. Psychiatr Clin North Am. 2003;26:621–672.
Rapee RM, Barlow DH, eds. Chronic Anxiety. New York: Guilford; 1991.
Rapoport JL: The Boy Who Couldn't Stop Washing. New York: Dutton; 1989.
Stein MB, Walker JR, Forde DR: Public-speaking fears in a community sample: Prevalence,
impact on functioning, and diagnostic classification. Arch Gen Psychiatry. 1995;53:169.
Weissman MM: Panic and generalized anxiety: Are they separate disorders? J Psychiatr Res.
1990;24(2 Suppl):157.

14.9 Anxiety Disorders: Somatic Treatment

Murray B. Stein M.D.
Part of "14 - Anxiety Disorders"
Anxiety disorders are among the most common psychiatric syndromes, affecting approximately
25 percent of persons in the general population during their lifetimes. The psychosocial and
economic impact of anxiety disorders is substantial, with an estimated $40 billion per year spent
primarily on medical services. The toll on individuals, in terms of suffering and functional
disability, is enormous. Moreover, it is being increasingly recognized that anxiety disorders often
start early in life and provide a template on which other forms of comorbidity (e.g., major
depression, substance abuse) and adverse health outcomes (e.g., suicidal ideation) are layered.
For all these reasons, anxiety disorders are finally being recognized as serious public health
problems.
HISTORY
Treatment of anxiety disorders has markedly evolved since the 1950s. Until the middle of the
20th century, anxiety disorders were treated with psychoanalysis or barbiturates. Psychoanalysis,
while offering the promise of a deep understanding of the roots of anxiety, has yet to be
empirically demonstrated to be efficacious for anxiety disorders. Barbiturates, although powerful
in their antianxiety and sedating effects, were no doubt misused and overused, resulting in
physical dependence and substantial risk of overdose for some. Benzodiazepines, partial agonists
of the γ-aminobutyric acid type A (GABAA) receptors, were discovered in the 1960s and
achieved prominence in the pharmacological treatment of anxiety. These agents continue to be
widely used because of their high degree of therapeutic efficacy and good safety profile.
Another milestone in the pharmacological treatment of anxiety disorders came in the early 1960s
when Donald Klein and colleagues determined that a tricyclic antidepressant, imipramine
(Tofranil), reduced the frequency of spontaneous panic attacks in anxious-depressed patients.
This observation sparked interest in the pharmacological dissection of anxiety, which was a key
factor in the development of a nosology of anxiety disorders that featured discrete “anxiety
disorders” as opposed to anxiety and phobic “neuroses.” Although some investigators might
argue that this separation was premature, it had the monumental impact of stirring interest in the
treatment of anxiety with compounds other than barbiturates, benzodiazepines, or neuroleptics
(e.g., thioridazine [Mellaril]). Although tricky to use because of anxious patients' sensitivity to
their side effects, tricyclic and heterocyclic antidepressants assumed a prominent role in the
treatment of panic disorder and related syndromes. In the mid-1980s, the arrival of the selective
serotonin reuptake inhibitor (SSRI) fluoxetine (Prozac) heralded a next stage in the treatment of
anxiety disorders with antidepressants. Although sometimes associated with initial worsening of
anxiety, the use of SSRIs, beginning with low doses and gradually working upward, rapidly
became a mainstay of the pharmacotherapy of anxiety disorders whose influence has not yet
ebbed.
In the past two decades, hundreds of large-scale clinical trials have been conducted to test the
efficacy of new therapeutic agents for anxiety disorders. These studies have led to the
development of a burgeoning evidence base for the pharmacotherapy of anxiety disorders. In
parallel, cognitive-behavioral therapists have developed and empirically verified the utility of a
cadre of potent psychological therapies for anxiety disorders. For the most part, the best
pharmacological therapies rival the best psychological (i.e., cognitive-behavioral) therapies in
terms of overall efficacy, although the latter seem to confer more long-lasting therapeutic
benefits. Current knowledge of what medications work has so far outstripped knowledge of how
they work in the treatment of anxiety disorders. It is presumed that the mechanism of action of
antidepressants in treating anxiety is similar (perhaps identical) to their mechanism of action in
treating depression; this is thought to involve alterations in neuronal serotonin metabolism with
accompanying changes in receptor sensitivity. Actions on other neurotransmitter systems in
specific neuronal circuits (e.g., involving the amygdala) or on neurotrophic factors in specific
brain regions (e.g., hippocampus) are also possibilities that are currently the subject of much
research. The good news for consumers is that, even though researchers' understanding of
mechanisms of action lag behind the awareness of what works, they now have at their disposal a
sizable menu of empirically proven treatments from which to choose.
APPROACH TO TREATMENT
Medical Evaluation
Before initiating any treatment, appropriate diagnosis is mandatory. Physicians must recognize
that physiological
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causes for anxiety are legion, and that it is their job to rule out other medically treatable
conditions before resorting to symptomatic treatment of an anxiety disorder.
Ms. A. C., a 43-year-old married mother of two, had seen her family doctor approximately 2
years before her death with the complaints of anxiety and insomnia. Her family doctor queried
her about her psychosocial circumstances and learned that she had been experiencing substantial
marital distress as a result of her husband's numerous extramarital affairs. He prescribed
alprazolam (Xanax)—which the patient did not take because she did not like the idea of taking
medication for “psychological troubles”—and referred her to a counselor.
Ms. A. C. saw the counselor intermittently over the ensuing 2 years and saw her family doctor
several times for mostly unrelated complaints. At several visits, the physician's case notes
revealed that she was continuing to experience “anxiety and stress” and that additional
counseling was recommended. No laboratory tests or additional investigations were ordered at
any visit.
Ms. A. C. was found dead on the couch by her husband upon his return from work. Autopsy
determined that the cause of death was thyrotoxicosis (“thyroid storm”) from Graves' disease.
The list of medical conditions that may present with or feature anxiety includes thyroid disease,
hypoglycemia, pheochromocytoma (a tumor of the adrenal medulla), hypoparathyroidism,
seizure disorders, arrhythmias and other cardiac conditions, asthma, and chronic obstructive
pulmonary disease. Most of these conditions can be ruled out by history and physical
examination, with the exception of thyroid disease, which can be occult and yet is easily detected
with an ultrasensitive thyroid-stimulating hormone (TSH) blood test. When treatment does not
proceed as expected, or if there is a change in the character or intensity of established anxiety
symptoms, then reconsideration of the diagnosis, along with further examinations (as
appropriate) should be undertaken.
Substance use may also contribute to anxiety symptoms.
Mr. J. T., a 28-year-old business executive, reported to his physician that he had been
experiencing anxiety attacks for the previous 3 months. These occurred “out of the blue” and
were associated with tachycardia and shortness of breath. The most recent attack occurred while
he was driving to work and necessitated that he pull his car over to the side of the freeway and
call 911 for assistance.
In the history, Mr. J. T. revealed to his physician that he had increased his coffee intake during a
period of increased pressure at work. He reported that he began the morning with two cups of
cappuccino brewed on his home espresso maker, followed by a “cup” (which, on further
questioning, was revealed to be a 36-oz travel mug) of coffee in the car on the way to work. He
drank coffee from the office coffee machine all morning long, had one or two 16-oz caffeinated
beverages with lunch, and typically had a double espresso in the late afternoon “to restore my
energy late in the day.” He refilled his travel mug for the trek back home on the freeway after
work, and then had one or two cups of cappuccino with his dessert after dinner.
Using the approximate rule of thumb of 100 mg of caffeine per cup (8 oz) of coffee, Mr. J. T.'s
physician estimated that he was consuming, on average, 2,000 mg of caffeine per day. He
recommended to Mr. J. T. that he cut down by one cup of coffee per day until he was consuming
no more than four cups of coffee per day. He recommended that he drink half-decaffeinated and
half-caffeinated cups to make the transition easier. Mr. J. T. returned to see his physician 4
weeks later and reported that his anxiety attacks had ceased (and that he was sleeping better and
feeling less “stressed” overall).
Taking a caffeine history should become a routine part of the evaluation of anxious patients.
Indeed, patients with panic disorder may be exquisitely sensitive to caffeine and other stimulants,
such that doses that might not bother the average individual can exacerbate panic attacks.
Persons with panic disorder (or a family history thereof) should be cautioned to limit their daily
caffeine intake to 200 mg (i.e., no more than two or three 8-oz cups) per day. Other stimulants
(e.g., ephedrine, contained in many over-the-counter cold remedies), including illicit drugs such
as cocaine or methamphetamine, can result in pathological anxiety symptoms, as can alcohol
abuse (particularly during withdrawal). Careful history taking, supplemented if appropriate with
drug testing, can sort out this differential diagnosis in most cases. Once a nonpsychiatric medical
etiology has been ruled out, the clinician can then proceed with treatment based on the primary
considerations of diagnosis and patient preference.
Choosing a Treatment Modality
For most patients, pharmacotherapy, empirically proven psychotherapy (e.g., cognitive-
behavioral therapy [CBT]), or some combination thereof are appropriate initial treatment
options. Which of these, then, should be instituted for a given patient? This becomes an issue of
individual choice, negotiated between the physician and the patient, but there are some
considerations that may help guide this process. If a patient is seriously depressed in addition to
experiencing pathological anxiety, then some experts would argue that pharmacotherapy with an
antidepressant should be instituted (either alone or with CBT). If a patient has a prior history of
good response to pharmacotherapy (or a family history thereof), then serious consideration
should be given to restarting that particular medication, with the expectation that a similarly
good outcome will be obtained. (Costs and formulary restrictions may also, by necessity,
influence the selection of treatment modality. Here, it should be remembered that CBT, although
more expensive in the short term, might be very cost-effective in the long run.) Beyond that,
patient preference and physician experience should together form the basis for an informed
decision about which route (i.e., pharmacotherapy or empirically proven psychotherapy) to take.
Some patients are of the opinion that taking a medication for emotional problems should be
avoided, and although education by the physician can help change these beliefs, it is usually an
uphill battle. For such patients, many of whom are much more comfortable with the idea of
actively participating in a course of learning tools and techniques for coping with anxiety, CBT
may be a much better choice. On the other hand, some patients will espouse a strong belief that
their anxiety is biological and that a medication designed to correct their “chemical imbalance” is
just the ticket. For such patients, beginning with pharmacotherapy is eminently reasonable.
Either way, patients (and physicians) should keep in mind the fact that they are not wed to a
particular treatment. If the initially chosen treatment modality, after a reasonable course of
treatment (usually several months in the case of either CBT or most forms of pharmacotherapy
for anxiety disorders), is not yielding the expected symptom resolution and improvement in
functioning, then a switch to another treatment modality (or an alternate form of the same
modality, e.g., switch to a different class of anxiolytic medication) should be made.
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PHARMACOTHERAPY
Once a decision is made to proceed with pharmacotherapy (either alone or in conjunction with
CBT or some other form of psychotherapy), numerous choices of medication class and type are
available. Ideally, decisions about which medication to use will be based on a good
understanding of the patient's personal and family history of response to psychopharmacologic
agents, in conjunction with a strong awareness of the evidence base for use of particular
medications for particular anxiety disorders. To the extent that randomized controlled trials are
available for these indications, the following information emphasizes information garnered from
such studies. This information will be supplemented with the author's clinical experience over
the past 20 years in treating patients with anxiety disorders. Readers are also encouraged to read
some of the treatment guidelines and algorithms (e.g., for panic disorder, published by the
American Psychiatric Association [APA]) that have become available in recent years and to stay
attuned to anticipated updates to these guidelines as the evidence base changes over time to
reflect newly accrued data.
Medications for Anxiety in Predictable Situations
There are basically two different ways to use medications for anxiety. One is to use them on an
as-needed (or prn) basis. Only certain medications can be used this way, however, and only for
certain indications, and the medication can only be used when the situation is predictable and
arises only occasionally.
Mr. A. Z. is a 49-year-old salesman with a major hirsutism relief organization, Werewolves
Anonymous. He presents to his family doctor asking for something to help him with his fear of
flying. He admits that he has coped with his fear in the past by imbibing copious quantities of
alcohol before and during flights, but that he is traveling with his boss and does not want to come
across “like a lush.” The flight is tomorrow.
After cautioning him against combining anxiolytic medication with alcohol, the physician
provides Mr. A. Z. with a prescription for a benzodiazepine (lorazepam [Ativan], 0.5 mg) to be
taken 1 hour before the flight and, if necessary, once during the flight. She also provides Mr. A.
Z. with a referral to a therapist with a good reputation for helping people overcome their fear of
flying using a combination of behavioral techniques and exposure supplemented with virtual
reality therapy. She encourages Mr. A. Z. to contact the therapist upon his return to work to
overcome his fear in anticipation of future flights.
Specific phobias are often treated with as-needed benzodiazepines, but exposure therapy is
recommended if the goal is to eventually overcome the phobia. Another example where as-
needed medication may be used is for social phobia (also known as social anxiety disorder), in
those instances in which the individual's symptoms are limited to anxiety only in performance
situations, such as speaking in front of large crowds. (Many patients with social phobia have the
generalized type of the disorder and fear and avoid many situations in addition to public
speaking. For those individuals, as-needed medication is usually insufficient.) A reasonable
approach would be to recommend that the individual participate in a local Toastmasters group or
similar self-help organization. If this has already been tried (or will be tried in the future, but
something more immediate is required because of an impending speaking engagement), then the
use of as-needed benzodiazepines or β-adrenergic antagonists may be recommended.
β-Adrenergic Receptor Antagonists
β-Blockers can be useful on an as-needed basis for performance anxiety. β-Blockers that are
sometimes used for this purpose include propranolol (Inderal) and atenolol (Tenormin). Some
clinicians recommend titrating the dose to yield an approximate 10-beats-per-minute reduction in
heart rate compared to pretreatment, whereas others simply try one or two fixed doses (typical
starting doses are 20 to 40 mg per dose for propranolol and 25 to 50 mg per dose for atenolol). β-
Adrenergic antagonists are believed to work for performance anxiety by reducing tachycardia
(racing heart) and tremor (shaking). Some people with performance anxiety have a heightened
awareness of their heart racing or their hands shaking, which makes them even more nervous. By
reducing some of these symptoms of social anxiety, the β-blockers can help some individuals
focus less on their bodily symptoms and more on the task at hand—for example, speaking in
public. β-Blockers are sometimes used by people in oral test-taking situations (e.g., medical
students before their practical examinations) or by professional musicians (e.g., concert
violinists). β-Blockers are typically taken 30 to 60 minutes before the performance situation.
Although the published literature suggests that β-blockers have a high success rate for public
speaking anxiety, the author's experience is that they are helpful in fewer than 50 percent of
cases. When they do not work, prn short-acting benzodiazepines (e.g., lorazepam, 0.5 to 1.0 mg)
may provide a reasonable alternative for most patients.
β-Blockers used on an as-needed basis are generally well tolerated with few side effects.
Occasionally, however, they can result in feelings of dizziness, lightheadedness, or fatigue. It is
important to ask patients to try the medication on one or two occasions before the real
performance situation to determine how it affects them and to find the right dose. β-Blockers
should not be prescribed to patients with bradycardia or heart block, asthma or chronic
obstructive pulmonary disease, angle-closure glaucoma, or diabetes.
Benzodiazepines
Another option to help with performance anxiety is a relatively short- or intermediate-acting
benzodiazepine, such as lorazepam or alprazolam. Like β-blockers, benzodiazepines can be used
on an as-needed basis to treat performance anxiety and are typically taken 30 to 60 minutes
before the performance situation. The potential for abuse and misuse has led to this class of
medication becoming notoriously disliked in the medical community. In fact, when used to treat
anxiety under appropriate medical supervision, benzodiazepines are often an excellent choice
given their high safety margin (e.g., in overdose) and their overall excellent efficacy and rapid
onset of action. If an individual has a history of alcohol or other substance abuse, however, then
benzodiazepines (with some exceptions, e.g., if other classes of medications have been tried first
and not worked) should not be prescribed. Adverse effects of the benzodiazepines are generally
few and mild. The main side effects are sedation and dizziness, which usually go away with time
or with dosage adjustment. Caution must be exercised when using heavy or dangerous machinery
or when driving, especially when first starting the medication or when the dosage is changed.
Benzodiazepines should not be used in combination with alcohol, as they can intensify its
effects.
Medications for Chronic Recurrent or Unpredictable Anxiety
Most anxiety disorders are characterized by chronic recurrent anxiety (e.g., generalized anxiety
disorder, posttraumatic stress disorder [PTSD], generalized social anxiety disorder, or obsessive-
compulsive disorder [OCD]) or unpredictable
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attacks of anxiety (e.g., panic disorder with or without agoraphobia). Given the nature of these
illnesses, the use of as-needed medication is almost always insufficient, and the regular use of
medication to control or prevent the occurrence of symptoms is strongly preferred. The
aforementioned anxiety disorders—as well as major depression and dysthymia, with which they
are frequently comorbid—share responsiveness to medications that have presynaptic serotonin
reuptake blockade as one of their properties. This grouping includes all of the SSRIs, the
serotonin–norepinephrine reuptake inhibitors (SNRIs) (also known as dual reuptake inhibitors),
and several cyclic antidepressants (e.g., clomipramine [Anafranil]). The evidence base is
stronger for particular compounds used for particular disorders, but this is almost certainly a
reflection of how decisions were made to test and market particular compounds, rather than real
differences in utility. Rather than repeat nearly identical prescribing information on a disorder-
by-disorder basis, the next section of this chapter describes the use of these compounds to treat
the aforementioned set of disorders as a group. Where applicable, differences among disorders
are described.
Table 14.9-1 lists some of the commonly used medications for treating chronic or unpredictable
anxiety syndromes.
Table 14.9-1 Commonly Used Medications for Treating Chronic or Unpredictable Anxiety
Syndromes
Medication Brand Name Daily Dosagea
Antidepressantsb
Fluoxetine Prozac 20–80 mg/day
Fluvoxamine Luvox 100–300 mg/day
Paroxetine Paxil 20–50 mg/day
Paxil CR 25–75 mg/day
Sertraline Zoloft 50–200 mg/day
Citalopram Celexa 20–60 mg/day
Escitalopram Lexapro 10–30 mg/day
Venlafaxine Effexor XR 75–225 mg/day
Phenelzine Nardil 45–90 mg/day
Benzodiazepinesc
Alprazolam Xanax 2–6 mg/daye
Clonazepam Klonopin 1–4 mg/day
Lorazepam Ativan 1–3 mg/daye
Azapironed
Buspirone BuSpar 30–60 mg/day
a
Some individuals will require higher or lower dosages than those listed here.
b
Useful as a primary treatment for panic disorder (where lower starting doses are usually used)
with or without agoraphobia, generalized anxiety disorder, generalized social anxiety disorder,
and posttraumatic stress disorder. All except phenelzine are useful as a primary treatment for
obsessive-compulsive disorder.
c
Useful as a primary treatment for panic disorder with or without agoraphobia, generalized
anxiety disorder, and generalized social anxiety disorder. May be a useful adjunct to
antidepressants in the treatment of posttraumatic stress disorder or obsessive-compulsive
disorder.
d
Useful as a primary treatment for generalized anxiety disorder.
e
Total daily dosage that is divided across 3–4 doses/day.
Antidepressants for Anxiety Disorders
Antidepressants are among the most effective antianxiety agents available. Many nonpsychiatrist
physicians have experience using these medications with their depressed patients, so they are
familiar with them and comfortable prescribing them. Although nonpsychiatrist physicians may
be relatively unfamiliar with some of the anxiety disorders, they can readily translate their
knowledge of how to treat depression with medications to the treatment of most of the anxiety
disorders. Increasingly, the treatment of the most common anxiety disorders (i.e., panic disorder,
social anxiety disorder, generalized anxiety disorder, and, to a lesser extent, PTSD) is falling into
the hands of primary care practitioners. The role of the psychiatrist is to support the appropriate
use of these medications (along with adequate counseling and education) by their primary care
physician colleagues, to make recommendations in difficult-to-treat cases, and, in some cases, to
assume direct care of patients who require more specialized psychotherapeutic or
pharmacotherapeutic management.
SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIS)
The SSRIs are a class of antidepressant medication that came to the market in the United States
and Canada in the mid-1980s. The first medication of this class to be marketed in the United
States was fluoxetine, soon to be followed by sertraline (Zoloft), paroxetine (Paxil), fluvoxamine
(Luvox), citalopram (Celexa), and the S-enantiomer of citalopram, escitalopram (Lexapro).
These medications, as a group, have been shown to help reduce or prevent various forms of
anxiety, including panic anxiety, obsessive-compulsive symptoms, generalized anxiety,
posttraumatic stress symptoms, and social anxiety. Most treatment algorithms begin treatment of
each of these disorders with an SSRI. Effective dosages are essentially the same as for the
treatment of depression, although it is customary to start with lower initial doses than in
depression (to minimize an initial anxiolytic effect, which is almost always short-lived) and to
titrate upward somewhat more slowly toward a therapeutic dosage. Typical duration of a
therapeutic trial (i.e., before the decision is made to switch to another medication due to lack of
efficacy) is 8 to 12 weeks, and perhaps even longer for OCD, in which it is believed that the time
course of response is somewhat slower than for the other disorders. Although this practice is not
strongly supported by randomized, controlled trials, it is the author's experience that patients will
very often do better at higher doses, and that medication dose should generally be titrated upward
to achieve an optimal balance between efficacy and adverse effects. A common error on the part
of practitioners is to settle for partial response, which can often be easily achieved at a starting
dose of an SSRI, rather than to aim for a more complete response. Patients who are only partially
treated are at greater risk for recurrence of symptoms and for persistent psychosocial
dysfunction. It is therefore incumbent on treating physicians to aim for as complete a response
(i.e., remission) as possible.
Although certain of these medications have been tested more extensively for one indication or
another within this spectrum of anxiety problems, and some have indications for the treatment of
certain disorders with the U.S. Food and Drug Administration (FDA), they are all more or less
effective for each condition. If the first SSRI tried is ineffective or results in intolerable adverse
effects, it is possible to switch to a different SSRI and have a reasonable expectation of a better
outcome. Although this strategy of switching between SSRIs (or, alternatively, from an SSRI to
an antidepressant in another class) is better substantiated in the case of major depression, clinical
experience supports this strategy for the anxiety disorders as well.
The SSRIs are generally very well tolerated. Although there are some differences between the
SSRIs in their adverse event profiles, in general they can cause sleep problems, drowsiness,
lightheadedness, nausea, diarrhea, and sexual dysfunction. Many of these adverse effects
improve with continued use, but sexual dysfunction, consisting mainly of delayed ejaculation for
men and difficulty in reaching orgasm for women (although diminished sexual desire and
erectile problems are also seen) often do not diminish with time and are among the most
common causes for noncompliance or medication discontinuation. If an individual is having
problems with side
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