Anxiety disorder

1. Anxiety Disorders

2. Fear vs. Anxiety
Fear is a response to external threat.
Or otherwise is the emotional response for certain danger or threat.
Anxiety it is an internal state, focused very much on anticipation of
danger. It resembles fear but occurs in the absence of an identifiable
external threat, or it occurs in response to an internal threatening
stimulus.
Or otherwise is the emotional response for uncertain danger or threat.

3. Anxiety disorders in primary care settings
• Anxiety disorders are commonly encountered in clinical practice. In
most studies of primary care settings (e.g., Lowe et al. 2008), anxiety
disorders (10%-15% of patients) are more common than depressive
disorders (7%-10% of patients). In a general psychiatric outpatient
practice, anxiety disorders will comprise up to 40% of new referrals.
• Much of the treatment of anxiety disorders can be successfully carried
out by the primary care treatment provider (e.g., family doctor or
internist). The psychiatrist usually plays a consultative role or manages
the patients who are most difficult to treat.

4. Epidemiology
• Among the mental disorders, anxiety disorders are the most prevalent
conditions in any age category.
• They are associated with substantial cost to society due to disability
and loss of work productivity.
• Emerging evidence shows that anxiety disorders are associated with
increased risk of suicidal behavior (Sareen 2011).

5. Approximate lifetime and 12-month prevalence,
gender ratio, and median age at onset for anxiety
disorders in the U.S. general population
Disorder
Lifetime
prevalence
(%)
12-month
prevalence
(%)
Gender ratio
(F:M)
Median age
at onset
(years)
Panic disorderᵃ 3.8 2.4 1.8:1 23
Agoraphobiab 2.5 1.7 1.8:1 18
Social anxiety disorder 10.7 7,4 1.4:1 15
Generalized anxiety
disorder
4.3 2.0 1.8:1 30
Specific phobia 15.6 12.1 1.5:1
Separation anxiety disorder 6.7 1.2 1.6:1 16

6. Common risk factors for the most of the
anxiety disorders:
• Female sex,
• younger age,
• single or divorced marital status,
• low socioeconomic status,
• poor social supports,
• low education,
• Stressful life events and childhood maltreatment are strong
risk factors for anxiety disorders

7. Comorbidity
Comorbidity is the presence of one or more additional diseases or
disorders co-occurring with a primary disease or disorder
• Anxiety disorders are highly comorbid with other mental disorders,
personality disorders, and physical health conditions.
• Over 90% of persons with an anxiety disorder having lifetime
comorbidity with one or more of these disorders
• Comorbidity of anxiety disorders with other conditions often leads to
poorer outcomes and affects treatment.
• Mood and substance use (including nicotine and alcohol) disorders
also commonly co-occur with anxiety disorders.

8. Comorbidity
• Physical health conditions are also common among patients with anxiety
disorders (Sareen et al. 2006).
Among the comorbid physical health conditions, the most prevalent are
1. cardiovascular disease,
2. respiratory illness (e.g., asthma)
3. arthritis
4. migraines
• The onset of a serious physical illness might trigger the onset of an anxiety
disorder, or conversely, anxiety and avoidance might lead to physical
health problems.

9. Generalized Anxiety Disorder
Generalized anxiety disorder is characterized by
nervousness, somatic symptoms of anxiety, and worry. What
distinguishes GAD is the multifocal and pervasive nature of
the worries. Individuals with GAD have multiple domains of
worry; these might include:
finances,
health (their own and that of their loved ones),
safety,
and many others

10. DSM-5 Criteria for Generalized Anxiety
Disorder
A. Excessive anxiety and worry (apprehensive expectation),
occurring more days than not for at least 6 months,
about a number of events or activities (such as work or
school performance).
B. The individual finds it difficult to control the worry.

11. DSM-5 Criteria for Generalized Anxiety
Disorder
C. The anxiety and worry are associated with three (or
more) of the following six symptoms (with at least some
symptoms having been present for more days than not for the
past 6 months):
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).

12. DSM-5 Criteria for Generalized Anxiety
Disorder
•The anxiety, worry, or physical symptoms cause clinically
significant distress or impairment in social, occupational,
or other important areas of functioning.
•The disturbance is not attributable to the physiological
effects of a substance (e.g., a drug of abuse, a medication)
or another medical condition (e.g., hyperthyroidism).

13. DSM-5 Criteria for Generalized Anxiety
Disorder
The disturbance is not better explained by another mental disorder
-e.g., anxiety or worry about having panic attacks in panic disorder,
- negative evaluation in social anxiety disorder [social phobia],
- contamination or other obsessions in obsessive-compulsive disorder,
- separation from attachment figures in separation anxiety disorder,
- reminders of traumatic events in posttraumatic stress disorder,
- gaining weight in anorexia nervosa,
- physical complaints in somatic symptom disorder,
- perceived appearance flaws in body dysmorphic disorder,
- having a serious illness in illness anxiety disorder, or
- the content of delusional beliefs in schizophrenia or delusional disorder).

14. GAD is encountered much more frequently by primary
care physicians and other medical practitioners than by
psychiatrists (Kroenke et al. 2007)
GAD typically presents with somatic symptoms for which sufferers seek help
in the primary care setting:
- headache
- back pain and other muscle aches
- gastrointestinal distress
- Insomnia is another common complaint in GAD for which patients may
seek help in primary care. Here more common initial insomnia (difficulty
falling or staying asleep)
- GAD-like symptoms can be caused by some physical ailments (e.g.,
hyperthyroidism) and substances (e.g., excess caffeine use; stimulants)

15. Etiology
• Twin studies suggest that GAD is influenced by genetic factors that
overlap extensively with those for the personality trait neuroticism
(Hettema et al. 2004)
1. Individuals who score high on neuroticism are more likely than
average to be moody and to experience such feelings as anxiety,
worry, fear, anger, frustration, envy, jealousy, guilt, depressed
mood, and loneliness.
2. People who are neurotic respond worse to stressors and are more
likely to interpret ordinary situations as threatening and minor
frustrations as hopelessly difficult.

16. Neuroimaging studies in GAD:
There is some evidence of failure of anterior cingulate activation and
connectivity with the amygdala during implicit regulation of emotional
processing in GAD (Etkin et al. 2009).

17. Panic Disorder
(soldier's heart; neurocirculatory asthenia)
• Panic disorder is mainly consisting of a panic attacks.
• Panic attacks are sudden, at least sometimes unexpected episodes of
severe anxiety, accompanied by an array of physical (e.g.,
cardiorespiratory, motoneurological, gastrointestinal, and/or autonomic)
symptoms
• These attacks are extremely frightening, particularly because they seem
to occur out of the blue and without explanation.
• Patients with panic disorder often report extreme fatigue after
experiencing an attack (not included as part of current diagnostic
criteria)

18. DSM-5 Criteria for Panic Disorder
Recurrent unexpected panic attacks. A panic attack is an
abrupt surge of intense fear or intense discomfort that reaches a
peak within minutes, and during which time four (or more) of the
following symptoms occur:
Note: The abrupt surge can occur from a calm state or an
anxious state.
1. Palpitations, pounding heart, or accelerated heart rate.
2. Sweating.
3. Trembling or shaking,
4. Sensations of shortness of breath or smothering.
5. Feelings of choking.
6. Chest pain or discomfort.

19. DSM-5 Criteria for Panic Disorder
7. Nausea or abdominal distress.
8. Feeling dizzy, unsteady, light-headed, or faint.
9. Chills or heat sensations.
10. Paresthesias (numbness or tingling sensations).
11. Derealization (feelings of unreality) or
depersonalization (being detached from oneself).
12. Fear of losing control or “going crazy.”
13. Fear of dying.

20. DSM-5 Criteria for Panic Disorder
B. At least one of the attacks has been followed by 1 month (or
more) of one or both of the following:
1. Persistent concern or worry about additional panic attacks or
their consequences (e.g., losing control, having a heart attack, “going
crazy”).
2. A significant maladaptive change in behavior related to the
attacks (e.g., behaviors designed to avoid having panic attacks, such as
avoidance of exercise or unfamiliar situations).
C. The disturbance is not attributable to the physiological effects of
a substance (e.g., a drug of abuse, a medication) or another medical
condition (e.g., hyperthyroidism, cardiopulmonary disorders).

21. DSM-5 Criteria for Panic Disorder
D. The disturbance is not better explained by another mental
disorder
• the panic attacks do not occur only in response to feared social
situations, as in social anxiety disorder;
• in response to circumscribed phobic objects or situations, as in
specific phobia;
• in response to obsessions, as in obsessive-compulsive disorder;
• in response to reminders of traumatic events, as in posttraumatic
stress disorder;
• in response to separation from attachment figures, as in separation
anxiety disorder).

22. Over time the individual may curtail many
activities to prevent panic attacks from occurring in
such situations.
It is this pervasive phobic avoidance—which
carries the diagnostic label agoraphobia—that often
leads to the extensive disability seen with panic
disorder.

23. Panic disorder and general medical
conditions
Because panic disorder mimics numerous medical conditions,
patients often have increased utilization of health care, including
physician visits, procedures, and laboratory tests (Kroenke et al. 2007).
Persons with panic disorder frequently have the belief that their
intense somatic symptoms are indicative of a serious physical illness
(e.g., cardiac or neurological).
This is particularly true early on in the course of their illness and
in situations where they fail to get good care that includes appropriate
diagnosis and education about their condition.

24. Panic disorder and comorbid medical
problems
Panic attacks (and, when recurrent, panic disorder) can occur as a direct
result of common conditions such as hyperthyroidism and caffeine and
other stimulant (e.g., cocaine, methamphetamine) use/abuse, and more
rarely with disorders such as pheochromocytoma or partial complex
seizures. To "rule out" for such conditions :
• A thorough medical history,
• physical examination,
• routine electrocardiogram,
• thyroid-stimulating hormone blood level,
• urine or blood drug screen are sufficient as a first-pass "rule out" for such
conditions.

25. Panic disorder and comorbid medical
problems
Additional tests may be indicated if:
1. frequent palpitations indicating the need for a Holter monitor,
echocardiogram, and/ or cardiology consultation;
2. profound confusion during or after attacks indicating the need for an
electroencephalogram and/or neurology consultation).
The physician have to revisit the medical differential diagnosis if:
1. the course of illness changes,
2. if symptoms become atypical,
3. the patient does not respond well to standard treatments

26. Etiology
Genetics.
Twin studies suggest that panic disorder is moderately heritable (~
40%) (Gelernter and Stein 2009). F
Panic disorder, like other psychiatric disorders, is a complex disorder
with multiple genes conferring vulnerability through as-yet largely
undetermined pathways (Manolio et al. 2009; Smoller et al. 2009).

27. Etiology
Neurobiology.
Beginning in 1967 with Pitt's observation that hyperosmolar sodium lactate
provoked panic attacks in patients with panic disorder but not in control
subjects (Pitts and McClure 1967),
Agents with disparate mechanisms of action such as caffeine, isoproterenol,
yohimbine, carbon dioxide, and cholecystokinin (CCK) had similar abilities to
provoke panic in patients with panic disorder but not in control subjects (Roy-
Byme et al. 2006).
Many of these neurobiological "challenge" agents have been thought to have
specific effects on the brain's fear circuits, which are believed to function
aberrantly in patients with panic disorder.

28. The amygdala has a
crucial role as an anxiety
way-station that mediates
incoming stimuli from the
environment (thalamus
and sensory cortex) and
stored experience (frontal
cortex and hippocampus),
thereby affecting the
anxiety and panic
response by stimulating
various brain areas
responsible for key panic
symptoms.

29. Etiology
Psychology
Learning theory postulates that factors that increase the salience of bodily
sensations are central to the onset and maintenance of panic disorder.
The heightened state of interoceptive attention (attention to internal
sensations) that primes the individual to experience panic attacks and to
be intensely frightened by them when they occur.
"Fear of fear" develops after the initial panic attacks and is believed to be
the result of interoceptive conditioning (conditioned fear of internal cues
such as pounding heart) and the subsequent misappraisal of these internal
cues as indicating something threatening or dangerous (e.g., loss of
control; heart attack or stroke) (Bouton et al. 2001).

31. Agoraphobia
Agoraphobia literally, in Greek, means "fear of the marketplace."
Agoraphobia refers to marked fear or anxiety of the situations in which
patient can stay alone without possibility to get help from companion
or from other close person. Patient afraid that certain symptoms, like
dizziness, heart racing, trouble concentrating, occur in these situations.
The agoraphobic situations are actively avoided, require the presence
of a companion, or are endured with intense fear or anxiety.:

32. DSM-5 Criteria for Agoraphobia
A. Marked fear or anxiety about two (or more) of the following five
situations:
1. Using public transportation (e.g., automobiles, buses, trains,
ships, planes).
2. Being in open spaces (e.g., parking lots, marketplaces, bridges).
3. Being in enclosed places (e.g., shops, theaters, cinemas).
4. Standing in line or being in a crowd.
5. Being outside of the home alone.

33. DSM-5 Criteria for Agoraphobia
B. The individual fears or avoids these situations because of thoughts
that escape might be difficult or help might not be available in the event of
developing panic-like symptoms or other incapacitating or embarrassing
symptoms (e.g., fear of falling in the elderly; fear of incontinence).
C. The agoraphobic situations almost always provoke fear or anxiety.
D. The agoraphobic situations are actively avoided, require the presence
of a companion, or are endured with intense fear or anxiety.
E. The fear or anxiety is out of proportion to the actual danger posed by
the agoraphobic situations and to the sociocultural context.
F. The fear, anxiety, or avoidance is persistent, typically lasting for 6
months or more.

34. DSM-5 Criteria for Agoraphobia
G. The fear, anxiety, or avoidance causes clinically significant distress or
impairment in social, occupational, or other important areas of functioning.
H. If another medical condition (e.g., inflammatory bowel disease,
Parkinson’s disease) is present, the fear, anxiety, or avoidance is clearly
excessive.
I. The fear, anxiety, or avoidance is not better explained by the symptoms
of another mental disorder—for example:
• the symptoms are not confined to specific phobia, situational type;
• do not involve only social situations (as in social anxiety disorder);
• and are not related exclusively to obsessions (as in obsessive-compulsive
disorder),
• perceived defects or flaws in physical appearance (as in body dysmorphic
disorder),
• reminders of traumatic events (as in posttraumatic stress disorder), or fear
of separation (as in separation anxiety disorder).

35. Social Anxiety Disorder
Social anxiety disorder, also known as social phobia, is characterized
by a marked fear of social and performance situations that often results in
avoidance. The concern in such situations is that the individual will say or do
something that will result in embarrassment or humiliation.
The core fear in SAD is fear of negative evaluation—that is, the belief
that when in situations where evaluation is possible, the individual will not
measure up and will be judged negatively (Hofmann et al. 2009).
Despite the extent of suffering and impairment associated with social
phobia, few individuals with the disorder seek treatment, and often only
after decades of suffering.

36. DSM-5 Criteria for Social Anxiety Disorder
(Social Phobia)
A. Marked fear or anxiety about one or more social situations in
which the individual is exposed to possible scrutiny by others. Examples
include social interactions (e.g., havng a conversation, meeting
unfamiliar people), being observed (e.g., eating or drinking), and
performing in front of others (e.g., giving a speech).
Note: In children, the anxiety must occur in peer settings and not just
during interactions with adults.
B. The individual fears that he or she will act in a way or show
anxiety symptoms that will be negatively evaluated (i.e., will be
humiliating or embarrassing; will lead to rejection or offend others).

37. DSM-5 Criteria for Social Anxiety Disorder
(Social Phobia)
C. The social situations almost always provoke fear or anxiety.
Note: In children, the fear or anxiety may be expressed by crying, tantrums,
freezing, clinging, shrinking, or failing to speak in social situations.
D. The social situations are avoided or endured with intense fear or
anxiety.
E. The fear or anxiety is out of proportion to the actual threat posed by
the social situation and to the sociocultural context.
F. The fear, anxiety, or avoidance is persistent, typically lasting for 6
months or more.
G. The fear, anxiety, or avoidance causes clinically significant distress or
impairment in social, occupational, or other important areas of functioning.

38. DSM-5 Criteria for Social Anxiety Disorder
(Social Phobia)
H. The fear, anxiety, or avoidance is not attributable to the physiological
effects of a substance (e.g., a drug of abuse, a medication) or another
medical condition.
I. The fear, anxiety, or avoidance is not better explained by the
symptoms of another mental disorder, such as panic disorder, body
dysmorphic disorder, or autism spectrum disorder.
J. If another medical condition (e.g., Parkinson’s disease, obesity,
disfigurement from burns or injury) is present, the fear, anxiety, or avoidance
is clearly unrelated or is excessive.
Specify if:
Performance only

39. Specific Phobia
A key feature of specific phobia is that the fear or anxiety is
limited to the phobic stimulus, which is a specific situation or object.
DSM-5 has codes for specifying the various types of situations or
objects that may be involved: animal, natural environment, blood-
injection-injury situational, and other.

40. DSM-5 Criteria for Specific Phobia
A. Marked fear or anxiety about a specific object or situation (e.g., flying,
heights, animals, receiving an injection, seeing blood).
Note: In children, the fear or anxiety may be expressed by crying, tantrums,
freezing, or clinging.
B. The phobic object or situation almost always provokes immediate fear
or anxiety.
C. The phobic object or situation is actively avoided or endured with
intense fear or anxiety.
D. The fear or anxiety is out of proportion to the actual danger posed by
the specific object or situation and to the sociocultural context.
E. The fear, anxiety, or avoidance is persistent, typically lasting for 6
months or more.
F. The fear, anxiety, or avoidance causes clinically significant distress or
impairment in social, occupational, or other important areas of functioning.

41. DSM-5 Criteria for Specific Phobia
G. The disturbance is not better explained by the symptoms of
another mental disorder, including:
• fear, anxiety, and avoidance of situations associated with panic-like
symptoms or other incapacitating symptoms (as in agoraphobia);
• objects or situations related to obsessions (as in obsessive-
compulsive disorder);
• reminders of traumatic events (as in posttraumatic stress disorder);
• separation from home or attachment figures (as in separation anxiety
disorder);
• or social situations (as in social anxiety disorder).

42. DSM-5 Criteria for Specific Phobia
Specify if:
Code based on the phobic stimulus:
300.29 (F40.218) Animal Natural environment
300.30 (F40.228) Natural environment
300.29 (F40.23x) Blood-injection-injury
300.29 (F40.248) Situational
300.29 (F40.298) Other

43. Specific phobias vs. Normal fears
• Specific phobias must be persistent (though this characteristic, of
course, depends on the opportunity for exposure to the situation or
object),
• the fear or anxiety must be intense or severe (sometimes taking the
form of a panic attack),
• the individual must either be routinely taking steps to actively avoid
the situation or object or be intensely distressed in its presence.
• the fear and/or avoidance in specific phobias must be
disproportionate to the actual danger posed by the situation (Craske
et al. 2009).

44. Treatment of Anxiety Disorders
General Approach
• Treatment of anxiety disorders can be extremely gratifying for
clinicians because anxiety disorders tend to respond well to
psychological and pharmacological treatments.
• Most patients with anxiety disorders can be well managed in the
primary care setting, with only the more difficult-to-treat cases
necessitating care in the mental health specialty setting.

45. • Most patients prefer treatment of anxiety with psychotherapy alone
or in combination with medications (Roy-Byrne et al. 2010). However,
evidence based psychotherapies administered by therapists well
trained and experienced in those psychotherapies may not be readily
accessible by all patients in all settings.
• Thus, medication treatment, which is more often available and
covered by insurance, frequently becomes the de facto treatment of
anxiety disorders.

46. Algorithm for the treatment and management of anxiety disorders

47. Cognitive-Behavior Therapy
Among the psychosocial interventions for anxiety disorders, CBT has
the most robust evidence for efficacy and has been delivered in a
variety of formats.
CBT strategies for the various anxiety disorders differ somewhat in
their focus and content, but despite this disorder-specific tailoring they
are similar in their underlying principles and approaches (Craske et al.
2011).
All CBT strategies have the following core components:
psychoeducation, relaxation training, cognitive restructuring, and
exposure therapy.

48. • Psychoeducation involves having the patient read material about the
normal and abnormal nature of anxiety that enhances their
understanding of the sources and meanings of anxiety.
• Relaxation training involves systematic desensitization, patients
gradually but in increasingly more challenging situations face the
phobic stimuli that make them feel anxious. Other techniques in CBT
include relaxation training through deep muscle relaxation and/or
breathing management.
• Exposure therapy. Over the course of the therapy the patient would
slowly face the anxiety-provoking situations and learn that if she stays
in the situation long enough, the anxiety resolves.

49. • Cognitive restructuring. The cognitive model of anxiety disorders proposes
that people with these disorders overestimate the danger in a particular
situation and underestimate their own capacity to handle the situation.
• People with anxiety disorders often have catastrophic automatic thoughts
in triggering situations.
• Patients are taught to become aware of these thoughts that precede or co-
occur with their anxiety symptoms, and they learn to challenge these
thoughts and change them.

50. Pharmacotherapy (general issues)
• Pharmacotherapy is a good option for many patients with anxiety
disorders, either in combination with CBT or as a stand-alone treatment
(Ravindran and Stein 2010)
• Providing patients with material that describes their symptoms, discusses
at an appropriate level of depth the theoretical underpinnings of their
disorder(s), and begins to make them aware of treatment options can be
the most important therapeutic intervention the clinician makes (see
psychoeducation).
• Exposure instructions and practice can be readily incorporated into
everyday pharmacotherapy of anxiety disorders. Patients should be
instructed that whereas their antianxiety medication(s) are intended to
reduce their spontaneous and anticipatory anxiety, it is important that they
begin to face situations that have made them fearful in the past in order to
learn that they are safe and that they can be successfully negotiated.

51. Pharmacotherapy (general issues)
• The medication classes with the best evidence of efficacy and (when
used properly) safety for the anxiety disorders are the
antidepressants and the benzodiazepine anxiolytics.
• The antidepressants include selective serotonin reuptake inhibitors
(SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs)
• There are currently six different SSRIs available for clinical use in the
United States: fluoxetine, sertraline, paroxetine, fluvoxamine,
citalopram, and escitalopram.
• There are currently four SNRIs available for clinical use in the United
States: venlafaxine ER, desvenlafaxine, duloxetine, and milnacipran.

52. • Experts usually recommend an initial trial of an SSRI beginning with
the lowest available dose, given that patients with anxiety disorders—
particularly those with panic disorder, who attend to and fear
physiological sensations—tend to be sensitive to medication side
effects. The dose is then increased gradually, in weekly or biweekly
increments, until therapeutic doses are reached.
• Time course of response is similar to that in major depression, that is,
taking 4–6 weeks to see a clinically meaningful response (though this
may occur sooner) and as long as 12–16 weeks to achieve an optimal
response.

53. Pharmacotherapy
• Benzodiazepines are the best-established pharmacotherapy for
treating anxiety that is predictable and limited to particular situations
(e.g., specific phobia such as flying phobia; social phobia such as
public speaking or other performance anxiety), for which they can be
prescribed on an “as needed” basis (el-Guebaly et al. 2010).
• Prescription of benzodiazepines on an as-needed basis for
unpredictable anxiety (e.g., panic disorder) or chronic anxiety (e.g.,
GAD) is not recommended.

54. Pharmacotherapy
• Nonbenzodiazepine Anxiolytics
• Buspirone is a nonbenzodiazepine anxiolytic with efficacy limited to
the treatment of GAD.
• Gabapentin and pregabalin have somewhat limited evidence for
efficacy in treating anxiety disorders, though they are sometimes
used as an alternative to benzodiazepines, often as an adjunct to
antidepressants.

55. Combining CBT and Pharmacotherapy
Although the evidence is limited, several studies suggest that
combining CBT and pharmacotherapy for anxiety disorders is superior
to either alone (Blanco et al. 2010), particularly in children (Walkup et
al. 2008).