Beruflich Dokumente
Kultur Dokumente
By
Dr Ejaz Gul
Heidi Combs, MD
Assistant Professor
University of Washington/HMC
Paul Zarkowski
Assistant Professor
A
Few medical conditions
associated with Anxiety
• Tourette Syndrome
• Stiff-person syndrome
• Delirium
• Joint hypermobility
• Diabetes
• Takotsubo Cardiomyopathy
• IBS
• Fahr's Disease
• Asthma
• Pregnancy
• Epilepsy
• Chronic renal failure
• Parkinson’s disease
• Pheochromocytoma
• SLE
• Stroke
• COPD
• Hypertension
• Eating disorders
• Myocardial Infarction
• Head injury
• Hyperthyroidism
• Hypothyroid
Different aspects of Anxiety
• Phenomenological
– Affective: dread, tension, worry
– Cognitive: expectations of an inability to
cope, impaired cognitive ability
• Behavioural
– Impaired motor functioning and avoidance
• Physiological
– increased blood pressure, heart rate,
breathing; disruptions in GI functioning and
dizziness
Types of Anxiety Disorders
• Panic Disorder
• Generalized Anxiety Disorder
• Phobias
• Posttraumatic Stress Disorder
• Obsessive-Compulsive Disorder
General considerations for anxiety
disorders
• Often have an early onset- teens or early
twenties
• Show 2:1 female predominance
• Have a waxing and waning course over
lifetime
• Similar to major depression and chronic
diseases such as diabetes in functional
impairment and decreased quality of life
Normal versus Pathologic Anxiety
Specific Phobia
– fear of circumscribed objects or situations
Phobias
• Algophobia -pain
• Astraphobia -thunderstorms
• Pathophobia -disease
• Monophobia -being alone
• Mysophobia -contamination
• Nyctophobia -darkness
• Ochlophobia -crowds
Phobias: Social Phobia
• Fear of social embarrassment or
humiliation
– public speaking
– eating in public
– using public bathrooms
• Impact on self confidence and restricts
social activity
Posttraumatic Stress Disorder
• Intense fear and helplessness in response
to events involving actual or threatened
death or serious injury.
• Acute Stress Disorder
– symptoms last for 2 days - 4 weeks
• Posttraumatic Stress Disorder
– symptoms last at least 1 month
Obsessive-Compulsive Disorder
• Obsession
– unwanted thought or image that keeps
intruding into awareness
• Compulsion
– an action that a person feels compelled to
repeat again and again despite a lack of
desire to do so
Comorbid diagnoses
• Once an anxiety disorder is diagnoses it is
critical to screen for other psychiatric
diagnoses since it is very common for
other diagnoses to be present and this can
impact both treatment and prognosis.
Specify If:
Generalized or Specific
The Life Cycle of Anxiety
Behavioral Stable Childhood Social Panic
Inhibition behavioral anxiety phobia Disorder
inhibition
Inhibited Toddler
Retreat from the unfamiliar Social Fears
Shy, tearful Social phobia
Age yrs
.3 2 5 8 13 14-18 20 30
Adapted from: Pollack, et al., Psych Clin NA, 1995;18(4):785-801
Social Anxiety Disorder
• Lifetime prevalence rate: 7 – 13%
• Onset usually in adolescence: mean 15.5 y/o
• Male to female ratio - 2:3
• Chronic course with mean duration of 25 years
with low rates of recovery
• Lifetime rates of comorbid depression near 60%
• Rates of comorbid alcohol dependence near
40%
• Severe educational, occupational and
interpersonal functional impairments
Medication Choice
• Blanco C, Schneier FR, Schmidt A, et al. Pharmacologic
Treatment of Social Anxiety Disorder: A Meta-Analysis
Depression and Anxiety 18 (2003) 29-40
• Medication effect size:
– Phenelzine: 1.02 [0.52-1.52]
– Clonazepam: .97 [0.49-1.45]
– Gabapentin: .78 [0.29-1.27]
– SSRIs: .65 [0.50-0.81]
• No statistical difference between medication groups
• Venlafaxine XR not included due to unpublished data
Social Anxiety Disorder
Social Anxiety Disorder (SAD)
• Marked fear of one or more social or performance
situations in which the person is exposed to the possible
scrutiny of others and fears he will act in a way that will
be humiliating
• Exposure to the feared situation almost invariably
provokes anxiety
• Anxiety is out of proportion to the actual threat posed by
the situation
• The anxiety lasts more than 6 months
• The feared situation is avoided or endured with distress
• The avoidance, fear or distress significantly interferes
with their routine or function
SAD epidemiology
• 7% of general population
• Age of onset teens; more common in
women. Stein found half of SAD patients
had onset of sx by age 13 and 90% by age
23.
• Causes significant disability
• Increased depressive disorders
Incidence of social anxiety disorders and the consistent risk for secondary depression in the first
three decades of life. Arch Gen Psychiatry 2007 Mar(4):221-232
Functional imaging studies in
SAD
• Several studies have found hyperactivity
of the amygdala even with a weak form of
symptom provocation namely presentation
of human faces.
• Successful treatment with either CBT or
citalopram showed reduction in activation
of amygdala and hippocampus
Furmark T et al. Common changes in cerebral blood flow in patients with social phobia treated with
citalpram or cognitive behavior therapy. Arch Gen Psychiatry 2002; 59:425-433
Social Anxiety Disorder treatment
Amygdala Central
Lateral Nucleus Nucleus of Sensory
the Thalamus
Hippocampus Amygdala
Basal
Parabrachial
Hypothalamus Nucleus
Paraventricular Lateral
Nucleus Nucleus
Periaquaductal
Gray Region Nucleus of the
Locus Solitary Tract
Pituitary Autonomic
Ceruleus
Pathways
Adrenal
Pathways Adapted from: Gorman J, et al. AJP 2000;157:493-505 Visceral Pathways
Panic Neurotransmitters
Norepinephrine Serotonin
GABA GABA
• Depression: 40 – 80 %
• Substance abuse: 20 – 40 %
Treatment
• SSRIs
• Benzodiazepines
• Cognitive Behavioral Therapy
– TCAs
– MAOIs
– Other agents
• Anticonvulsants
• Buspirone
• Atypical neuroleptics
Panic Disorder
• Panic Attack
• Panic Disorder
Panic Disorder: Agoraphobia
• Fear of being in a situation where having a
panic attack would be dangerous or where
escape would be impossible
Panic Disorder
• Recurrent unexpected panic attacks and
for a one month period or more of:
– Persistent worry about having additional
attacks
– Worry about the implications of the attacks
– Significant change in behavior because of the
attacks
A Panic Attack is:
A discrete period of intense fear in which 4 of the following
Symptoms abruptly develop and peak within 10 minutes:
4-7% of general
population
Median onset=30
years but large range
Female:Male 2:1
GAD Comorbidity
• 90% have at least one other lifetime Axis I
Disorder
• 66% have another current Axis I disorder
• Worse prognosis over 5 years than panic
disorder
GAD Treatment
• PET studies
– Activation of paralimbic circuits, posterior medial orbitalfrontal cortex,
anterior cingulate and temporal limbic regions associated with all
anxiety conditions
– Activation of anterior orbitalfrontal cortex and caudate nucleus specific
for OCD
• Cortico-strato-thalamo-cortico network
– Probable involvement of glutamate, GABA, DA and 5-HT
OCD Treatment
• Clomipramine and SSRIs
– 40% have no clinical improvement
– 60% with 25 – 35% decrease in symptoms
• (considered a response on Yale-Brown Obsessive
Compulsive Scale {Y-BOCS})
• FDA approved in adults:
– Clomipramine, Fluoxetine, Fluvoxamine, Sertraline,
Paroxetine
• FDA approved in pediatrics:
– Clomipramine, Fluvoxamine, Sertraline
OCD Treatment
• Augmentation:
– Li (?)
– Buspirone (?)
– rTMS (?)
– Trazodone
– Psychosurgery
– Atypicals
– IV clomipramine
– Clonazepam
OCD Treatment
• Cognitive Behavioral
Therapy
• OCFoundation
Obsessive-Compulsive and Related
Disorders
• Obsessive-
Compulsive Disorder
• Body Dysmorphic
Disorder
• Hoarding Disorder
• Trichotillomania
• Excoriation Disorder
Prevalence of Obsessive-
Compulsive Related Disorders
• Body Dysmorphic Disorder-2.4%
– 9-15% of dermatologic pts
– 7% of cosmetic surgery pts
– 10% of pts presenting for oral or maxillofacial
surgery!
• Hoarding Disorder- est. 2-6% F<M
• Trichotillomania 1-2% F:M 10:1!
• Excoriation Disorder 1.4% F>M
Obsessive-Compulsive Disorder
Obsessive-Compulsive Disorder
(OCD)
Obsessions or compulsions or both defined by:
• Obsessions defined by:
– recurrent and persistent thoughts, impulses or
images that are intrusive and unwanted that cause
marked anxiety or distress
– The person attempts to ignore or suppress such
thoughts, urges or images, or to neutralize them
with some other thought or action (i.e. compulsion)
OCD continued
• Compulsions as defined by:
– Repetitive behaviors or mental acts that the
person feels driven to perform in response to
an obsession or according to rigidly applied
rules.
– The behaviors or acts are aimed at reducing
distress or preventing some dreaded situation
however these acts or behaviors are not
connected in a realistic way with what they
are designed to neutralize or prevent.
OCD continued
• The obsessions or compulsions cause
marked distress, take > 1 hour/day or
cause clinically significant distress or
impairment in function
• Specify if:
– With good or fair insight- recognizes beliefs are
definitely or most likely not true
– With poor insight- thinks are probably true
– With absent insight- is completely convinced the
COCD beliefs are true
– Tic- related
OCD Epidemiology
• 2% of general
population
• Mean onset 19.5
years, 25% start by
age 14! Males have
earlier onset than
females
• Female: Male 1:1
OCD Comorbidities
• >70% have lifetime dx • 12% of persons with
of an anxiety disorder schizophrenia/
such as PD, SAD, schizoaffective
GAD, phobia disorder
• >60% have lifetime dx
of a mood disorder
MDD being the most
common
• Up to 30% have a
lifetime Tic disorder
OCD Etiology
• Genetics
• Serotonergic
dysfunction
• Cortico-striato-
thalamo-cortical loop
• Autoimmune-
PANDAS
Treatment
• 40-60% treatment response
• Serotonergic antidepressants
• Behavior therapy
• Adjunctive antipsychotics, psychosurgery
• PANDAS – penicillin, plasmapharesis, IV
immunoglobulin
Functional imaging studies
• Increased activity in the right caudate is
found in pts with OCD and Cognitive
behavior therapy reduces resting state
glucose metabolism or blood flow in the
right caudate in treatment responders.
• Similar results have been obtained with
pharmacotherapy
Baxter L. et al. Caudate glucose metabolic rate changes with both drug and behavioral therapy for
obessive-compulsive disorder. Arch Gen Psych 1992;49:681-689
Trauma- and Stressor-Related
Disorders
Fani N. et al. Increased neural response to trauma scripts in posttraumatic stress disorder
following paroxetine treatment: A pilot study. Neurosci Letters 2011;491:196-201
DSM-IV-TR
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 2. The person’s response
confronted with an event involved intense fear,
that involved actual or helplessness, or horror. Note:
threatened death or In children, this may be
serious injury, or a threat expressed instead by
to the physical integrity of disorganized or agitated
self or others behavior.
DSM-IV-TR
B. The traumatic event is C. Persistent avoidance of stimuli
persistently reexperienced in associated with the trauma and
one or more of the following numbing of general
ways: responsiveness, as indicated by
1. Recurrent and intrusive three or more of the following:
distressing recollections of the 1. Efforts to avoid thoughts, feelings
event or conversations associated with
2. Recurrent distressing dreams of the trauma
the event 2. Efforts to avoid activities, places
3. Acting or feeling as if the or people that arouse
traumatic event were recurring recollections of the trauma
4. Intense psychological distress at 3. Inability to recall important aspect
exposure to internal or external of the trauma
cues that symbolize or resemble 4. Markedly diminished interest in
an aspect of the event significant activities
5. Physiologic reactivity on 5. Feelings of detachment or
exposure to internal or external estrangement from others
cues that symbolize or resemble 6. Restricted range of affect
an aspect of the event
7. Sense of a foreshortened future
DSM-IV-TR
D. Persistent symptoms of E. Duration of the
increased arousal, as disturbance is more than
indicated by two or one month
more of the following: F. Disturbance causes
1. Difficulty falling or staying clinically significant
asleep distress or impairment in
2. Irritability or outbursts of social, occupational, or
anger
other important areas of
3. Difficulty concentrating
functioning
4. Hypervigilance
5. Exaggerated startle
response
PTSD
• Lifetime prevalence
– Approximately 8%
• 10 – 12% women, 5 – 6% men
– Additional 5 – 15% may experience subclinical form
of disorder
• Predisposing vulnerability factors
– Childhood trauma, cluster B personality disorder
traits, inadequate support system, being female,
genetic vulnerability to psych illness, recent stressful
life changes, perception of external locus of control
PTSD
• Biologic considerations
– Noradrenergic system
• Increased 24 hr urine epinephrine concentrations
• Platelet α2 receptors downregulated
– chronically elevated catecholamine
– HPA axis
• Hyperregulation of HPA axis in PTSD
– Low plasma and urinary free cortisol
– Exogenous CRF yields blunted ACTH response
– Suppression of cortisol with dexamethasone is enhanced
in PTSD
PTSD
• Biologic
considerations
– MRI, PET studies
implicate reduced
volume and function of
hippocampus in PTSD
PTSD
• Treatment
– SSRIs
– Atypicals, benzos
– CBT
– (EMDR – eye movement desensitization and
reprocessing)
Acute Stress Disorder
• Similar exposure as in PTSD
• Presence of >9 of 5 categories of
intrusion, negative mood, dissociation,
avoidance, and arousal related to the
trauma.
• Duration of disturbance is 3 days to 1
month after trauma
• Causes significant impairment
Screening questions
• How ever experienced a panic attack? (Panic)
• Do you consider yourself a worrier? (GAD)
• Have you ever had anything happen that still haunts
you? (PTSD)
• Do you get thoughts stuck in your head that really bother
you or need to do things over and over like washing your
hands, checking things or count? (OCD)
• When you are in a situation where people can observe
you do you feel nervous and worry that they will judge
you? (SAD)
Treatment
General treatment approaches
• Pharmacotherapy
– Antidepresssants
– Anxiolytics
– Antipsychotics
– Mood stabilizers
• Psychotherapy- Cognitive Behavior
Therapy
Crank up the serotonin
• Cornerstone of treatment for anxiety
disorders is increasing serotonin
• Any of the SSRIs or SNRIs can be used
How to use them
• Start at ½ the usual dose used for
antidepressant benefit i.e citalopram at
10mg rather than the usual 20mg
• WARN THEM THEIR ANXIETY MAY GET
WORSE BEFORE IT GETS BETTER!!
• May need to use an anxiolytic while
initiating and titrating the antidepressant
Other options
• Hydroxyzine- usually 50mg prn. Helpful for
some patients but has prominent
anticholinergic SEs
• Buspirone-For GAD- 60mg daily
• Propranolol-Effective for discrete social
phobia i.e. performance anxiety
• Atypical antipsychotics at low doses for
augmentation in difficult to treat OCD pts
Anticonvulsants
• Valproic acid 500-750 mg bid (ending
dose)
• carbamazepine 200-600 mg bid (ending
dose)
• Gabapentin 900-2700 mg daily in 3
divided doses (ending dose)
• Atypical antipsychotics at low doses for
augmentation in difficult to treat OCD pts
Psychotherapy
• Please refer to psychotherapy lecture!
Take home points
• Anxiety, Obsessive-Compulsive and Related,
and Trauma and Stressor-related disorders are
common, common, common!
• There are significant comorbid psychiatric
conditions associated with anxiety disorders!
• Screening questions can help identify or rule out
diagnoses
• There are many effective treatments including
psychotherapy and psychopharmacology
• There is a huge amount of suffering associated
with these disorders!
The Psychodynamic Approach
to Anxiety
• Anxiety is a signal that the ego is having a
hard time mediating between reality, id
and superego.
• Different anxiety disorders are the result of
different defense mechanisms used to
cope.
The Psychodynamic Approach
to Anxiety: Attachment Theories
• Bowlby
– disturbances in parent-child bond leads to
“anxious attachment” and a vulnerability to
anxiety disorders later in life
The Behavioural Approach to
Anxiety
• Mowrer (1948) Avoidance learning
– 1) classical (respondent) conditioning
– 2) negative reinforcement
The Behavioural Approach to
Anxiety
• Barlow (1988) Anxiety Sensitivity or “Fear
of Fear”
The Behavioural Approach to
Anxiety
• Treatment:
– systematic desensitization
– exposure
– flooding
The Biological Approach to
Anxiety
• Genetic Component
– family and twin studies suggest a genetic
component in most anxiety disorders
– panic disorder shows the strongest genetic
component and generalized anxiety disorder
the least
The Biological Approach to
Anxiety
• “Suffocation false alarm hypothesis” of
panic disorder
• serotonin and basal ganglia abnormalities
in OCD
• hormonal theory of PTSD
• State-dependent learning
The Cognitive Approach to
Anxiety
• Individuals misperceive and misinterpret
internal and external stimuli
Cognitive Appraisal
• Stimulus--->Appraisal---> Response
– evaluation of stimulus based on memories,
beliefs, and expectations
Information Processing
• Schema
– how we understand the information we take in
from the environment
• Selective Attention
– what information we take in
Cognitive Approach to Panic
Disorder
• Catastrophic interpretations of bodily
sensations
• Feeling of control
• Some Problems:
– panic attacks during sleep
– why do catastrophic interpretations develop
Anxiety and Selective Attention
Phobias
Chapter 4- anxiety disorders
What is a phobia?
• A specific phobia is an
_________________________________
_________________________________
________________________________
• _________________________________
_______________
RUN!!!
• _________________________________
__________is necessary to meet the
criteria for a phobia.
4. _________________________________
________________
_________________________________
________________
3. ________________________________
_______________ can sometimes
It’s all in the breeding…
• _________________________________
_________________________________
________________________________
– 31% of first-degree relatives of people with
specific phobias also had a phobia,
compared to only 11% of first relatives of
normal controls.
5. A 30-year-old patient has been treated for unreasonable fear of eating in public places,
feeling embarrassment in public places, and anger over the possibility of being
scrutinized. The patient has responded to high doses of paroxetine, citalopram,
buspirone, and alprazolam, each of them administered for 4 to 6 weeks. Which of the
following medications would be appropriate for the psychiatrist to consider prescribing
next?
a. Bupropion
b. Fluoxetine
c. Mirtazapine
d. Phenelzine
Review Questions
6. Which of the following benzodiazepines has an active metabolite?
a. Lorazepam
b. Temazepam
c. Oxazepam
d. Chlordiazepoxide
8. Which of the following symptoms would be most commonly associated with Tourette’s
Syndrome?
a. Somatization
b. Panic attacks
c. Violent behavior
d. Psychotic thinking
e. Obsessions and Compulsions
Review Questions
9. Which of the following medications has the least protein binding?
a. Fluoxetine
b. Sertraline
c. Paroxetine
d. Venlafaxine
e. Clomipramine
11. Which of the following is a principal goal of the CBT of panic disorder?
a. Learning to use biofeedback techniques
b. Mastering relaxation in the face of flooding
c. Learning more adaptive defenses
d. Using restructured interpretation of disturbing sensations
THANX