Download Anxiety Disorders 2010

April 16, 2010, 2010
Elliott K. Lee MD, FRCP(C)
Staff Psychiatrist
Anxiety Disorders Clinic
Royal Ottawa Mental Health Centre
 Anxiety results from an unknown internal
stimulus, or is inappropriate or excessive when
compared to the existing external stimulus.
 It is an expected, normal and transient response
to stress; may be a necessary cue for
adaptation and coping (future event)
 Different from Fear:
sense of dread/foreboding that occurs in
response to external threatening event.
Pathologic anxiety
1. Autonomy: i.e. Minimal/no recognizable
environmental trigger
2. Intensity – exceeds tolerance capacity
3. Duration – persistent, not transient
4. Behaviour – impairs coping:
results in disabling behavioural strategies –
avoidance, withdrawal
 Physical symptoms:
- autonomic arousal – tachycardia, tachypnea,
diaphoresis, diarrhoea, light headedness
 Affective symptoms:
Mild
Severe
edginess
terror, feeling
loss of control,
dying
 Behaviour
Avoidance, or compulsions (“compensatory”)
 Cognitions – worry, apprehension, obsessions
Anxiety disorders are
Prevalent , real, serious, treatable
Anxiety disorders are not
Signs of personal weakness
Nutt et al. In: Handbook of Anxiety and Fear 2008
Neurophysiology
Psychodynamic
formulation
Cognitive
behavioural
formulation
 Central noradrenergic system (NE):
locus coeruleus (LC)– major source of brain’s
adrenergic innervation. E.g. – stimulate LC – get
panic attacks; block LC – decrease
 Gamma Amino Butyric Acid (GABA) system
Especially – septohippocampal areas – mediate
generalized anxiety, worry, vigilance
- BDZ bind to GABA receptors; reduce vigilance
 Serotonergic system (5-HT)
Modulate above 2 systems – explains efficacy of
multiple clinical interventions – SSRIs, SNRIs,
GABA agents, CBT
 Psychopharmaology for anxiety disorders is
based on those neurotransmitter systems:
1) Norepinephrine
TCAs, Prazosin
2) GABA
Benzodiazepines, anticonvulsants
3) Serotonergic (5-HT) modulation
- SSRIs, SNRIs, TCAs
Limbic cortex
Nucleus
accumbens
Periaqueductal
Gray matter
Orbitofrontal
cortex
Amygdala
Brain Stem
Hippocampus
Ventral
Tegmental Area
 State anxiety
An interruption of
one’s emotional state
- become restless,
agitated, and then
may react/overreact
to external stimuli
- high state anxiety is
unpleasant – pts may
seek out “adaptive”
behaviours to
alleviate this.
 Trait anxiety
“Stable aspect of
personality”
- may worry all the
time, even with
“normal stimuli”, then
when there’s a real
threatening stimuli –
may worry even more
Normal healthy pts
vs.
Healthy pts with high
trait anxiety
(Stait Trait Anxiety
Inventory (STAI))
 Shown
- fearful faces
- neutral faces
- fearful+neutral faces
- neutral+neutral faces
Etkin A. et al. Neuron, 2004
 Analyzed activation
of amygdala (fMRI)
 Conscious awareness
of fearful face
- dorsal region of
amygdala activated in
all subjects
 Unconscious (masked)
awareness fearful face
- basolateral amygdala
activated
(high trait anixety pts)
Etkin A. et al. Neuron, 2004
 Focus on information processing and
behavioural reactions
 Faulty cognitionse.g. Overprediction of likelihood/degree of
catastrophe
 Attempts to neutralize anxiety – e.g. With
avoidance, compulsive behaviour,
paradoxically “lock in” or reinforce anxiety
►chronic arousal and anticipatory anxiety
Single person sees attractive person
Automatic thoughts/Feelings:
I am foolish, I am incompetent, I
am not loveable
Automatic thoughts/Feelings:
that person is attractive, I am a
good person. Maybe we can be a
good match. Let’s find out
Behaviour: RUN!
Behaviour: Initiate conversation***
Reinforcement:
I have not dated; good people
don’t like me; I am foolish, I am
incompetent, I am not loveable
Reinforcement:
Attractive person seemed to
enjoy talking to me. Maybe I
have something to offer in a
relationship
 Cognitive Behavioural Therapy (CBT) is based on
these notions
 Replace anxiogenic thoughts and behaviours
with positive ones.
Anxiety Thought
World view
Self View
• World is dangerous
• I am not competent
• I can not cope
Coping Thought
• World is safe
• I am competent
• I can cope
 Anxiety = threat to the ego; signals are elicited
because current events have similarities
(symbolic or actual) to threatening
developmental experiences (traumatic anxiety)
 Object relations theorists emphasize the use of
internalized objects to maintain affective
stability under stress
 Ms. Anxietas – 23-year-old engaged grad
student complains of periodic episodes of
intense anxiety, and chronic fears about dying
 Ruminates about her own age, and subsequent
death, then to her parents.
 Fears impair her sleep, and ability to function in
her studies.
 In therapy – issues of death are explored – the
therapist comments concerns about living
contribute to fears of death; “could anything be
going on in her life that might contribute to her
anxiety?”
 “It’s not about my fiancee being stationed




overseas!”....she cries....therapist offers her a
tissue, but she declines
Therapist asks “Why did you decline tissue?”
She replies – she thought it would be a sign of
weakness.
They go on to explore, how everyone comes to
her for help, but she could not acknowledge
she needed help from others.
Revealed significant issues with anger – but
feared that her anger would explode and drive
others away.
 Further exploration – reveals she had a great




deal of anger towards her father, that she had
been unable to express
Unconscious concern – was that her anger
would be so explosive it would destroy him.
After 2 months of therapy – Ms. Anxietas gained
greater mastery over her fears
Began to understand the impact of her anger
and her fears of being abandoned and alone.
Defensive function of anxiety may be to distract
patient form more disturbing or underlying
Gabbard, GO. Psychodynamic Psychiatry in
concerns.
Clinical Practice, 2000
 Panic Disorder without Agoraphobia
 Panic Disorder with Agoraphobia
 Agoraphobia without history of Panic Disorder
 Specific Phobia
 Social Phobia
 Obsessive-Compulsive Disorder
 Acute Stress Disorder
 Posttraumatic Stress Disorder
 Generalized Anxiety Disorder
 Anxiety Disorder Due to General Medical
Condition or Substance-Induced Anxiety Disorder
 Anxiety Disorder NOS
Somers et al. Can J Psychiatry 2006
 9282 pts – english speaking
 12 month prevalence of numerous psychiatric
disorders
 Any psychiatric disorder 26.2%
 Any anxiety disorder 18.1%
10
Percentage (%)
Kessler et al. Arch Gen Psychiatry, 2005
5
Specific
phobia
(8.7%)
Social
phobia
(6.8%)
PTSD
(3.5%)
GAD
(3.1%)
Panic
(2.7%)
OCD
(1%)
 Persistent and irrational fear of certain
objects or situations
 Exposure provokes anxiety/panic response
 Recognized as excessive or unreasonable
 Phobic object/situation avoided or
endured with intense anxiety or distress
 Significant interference or marked distress
 Types: animals/insects, natural environment,
blood/injury, situational, other
 Most common anxiety disorder
 Marked and persistent fear of clearly discernible





circumscribed objects or situations
Exposure almost invariably provokes anxiety
Fear is recognized as excessive or unreasonable
(though children may not)
Phobic stimulus is avoided, or tolerated with
dread
Avoidance/fear leads to significant distress or
interference with social/occ functioning
In children – should persist >6 m
 Biopsychosocial
- Bio
- Medications – generally not helpful.
BDZs – may provide some temporary relief
(e.g. For flying etc.)
 Psychosocial
- Exposure therapy – has shown the most benefit
Novel methods
- internet based
- virtual reality
Age
Development conditioned
fears
Psychological Sx
DSM-IV
Corresponding d/o
0-6 months
Fear of loss of caregiver
-
-
6-8 months
Shyness with stranger
8m-3yrs
Separation anxiety, fear of
lightening, thunder,
animals, nightmares
4-5 yrs
Fear of death, dead
people
5-12yrs
Nightmares,
Fear of fantasy objects,
animals, physical thingsnatural disasters, germs,
getting a serious illness
Shyness, timidity
Avoidant PD,
Specific phobias.
OCD
13-17 yrs
Fear of inadequacy,
performance, rejection by
peers
Fear of negative
evaluation
Overanxious
disorder, social
phobia
17-21 yrs
Fear of personal loss, failing
personal standards
Separation anxiety
disorder
Crying, clinging,
withdrawal, freezing
GAD, Panic disorder
Panic disorder,
agoraphobia
 Classified as “Other disorder of infancy and
childhood” in DSM-IV-TR
 Excessive anxiety beyond that expected for the
child’s developmental level related to:
- Separation
- Impending separation from attachment
figure
 NB Must be in children <18 yrs old, and lasting at
least 4 wks.
 Fear of social or performance situations
due to anticipated scrutiny, humiliation or
embarrassment
 Exposure provokes anxiety/panic
 Considered excessive or unreasonable
 Situations avoided or endured with anxiety
 Significant interference or suffering
 Duration > 6 months if age < 18
 Generalized or circumscribed
 Epidemiology:
- 6.8% of the population
- Onset - by age 11, 50% have symptoms;
- by age 20, 80% have symptoms
- Children – may refuse to go to school;
- Associated with early drop out from school
- Selective mutism – highly likely becomes
social anxiety disorder (severe variant)
 Etiology
-Familial, with recurrence risk ratio 2<x<6
i.e. Moderate heritability
(chromosome 16 implicated –NE transporter)
- Heritable behavioural trait
= behavioural inhibition (strong association)
 Consequences:
- Reduced work productivity
- Financial costs
- Reduced quality of life
 Despite these issues – only half seek treatment,
and usually after 15-20 years of suffering
 ALCOHOL /SUBSTANCE ABUSE/DEPENDENCE
- Strongly consider underlying social phobia in
pts with a history of alcohol abuse/dependence
» ¼ of pts may have comorbid abuse
 Parkinsons pts – may frequently develop social
anxiety – suggesting striatal involvement
 Biopsychosocial approach
 Bio –
SSRIs*
SNRIs*
RIMAs+MAOIs
AntiCon
BDZs
Escitalopram
Venlafaxine
Moclobemide
Gabapentin
Clonazepam
Phenelzine
Pregabalin
Alprazolam
Sertraline
Divalproex
Bromazepam
Paroxetine
Topiramate
Fluvoxamine
Citalopram
Fluoxetine
1st line: SSRI, SNRI
2nd line: BDZ, AntiCon, MAOIs
 Other alternatives with evidence of benefit
Antidepressants
Bupropion (NDRI)
Mirtazapine (NaSSa)
Clomipramine (TCA)
Antipsychotics
Olanzapine
Risperidone
Quetiapine
Aripiprazole
Cognitive restructuring
Trigger
Perception of
Danger
Reduced
Anxiety
Beliefs &
Assumptions
- Escape
- Avoidance
- Safety
behaviours
Increased
Anxiety
Exposure therapy
 CBT - 12-15 sessions – lasting 50-90 minutes
(individual or group therapy)
Correcting distorted cognitions – e.g.
Everyone laughing at me – come up with
alternative explanations
 Exposure therapy – may be integrated in CBT
- e.g. Returning item, going to crowded mall
 Social skills training
- making small talk, looking at tone, posture,
active listening, assertiveness
 Epidemiology
- 3.1% of the population affected (F:M = 2:1)
- Onset
(median US age=31 yrs, but often childhood)
- 25% have onset by 20 yrs old
- 50% have onset b/w 20-47 yrs old
- Children
- may be “overanxious disorder of childhood”
Kessler RC et al. Arch Gen Psychiatry, 2005
 Elderly –
- may be associated with social isolation,
trauma, migration, illness in spouse,
bereavement
- left untreated – may be associated with
medical/psychiatric complications
- Cardio/cerebrovascular disease
- COPD
- Malnutrition
- Depression
- Dementia
- Alcohol abuse
Weisberg R.B. J Clin Psychiatry, 2009
 Etiology
- Multiple neurotransmitters likely involved
- 5-HT, NE, CCK
- Genetic factors likely involved
- Some twin studies – show 50%
concordance rate in monozygotic twins,
and 15% in dizygotic twins
- Behavioural, psychosocial factors involved
 Excessive, wide-spread and uncontrollable
anxiety and worry ( 6 months)
 Symptoms of tension and exhaustion (3/6)
 restlessness, muscle tension, tiredness, irritability,
insomnia, difficulty concentrating
 NB – children only need ≥1
 Worry not confined to another Axis I disorder
 Significant distress or impairment
 Not due to the effects of substance of GMC
 Often – do not present with anxiety initially
- May be
Pain
Fatigue
Sleep disturbances
Poor concentration
Depression
- Frequently associated with disabilities in work,
education, and/or social interactions
 Comorbidities common – mood disorders,
anxiety disorders, substance abuse
 Biopsychosocial approach
- Bio
SSRIs*
SNRIs*
TCAs
AntiCon
BDZs
Escitalopram*
Venlafaxine*
Imipramine
Pregabalin
Lorazepam
Alprazolam
Sertraline*
Bromazepam
Paroxetine*
Diazepam
Citalopram
1st line: SSRI, SNRI x 8-12 wks
2nd line: BDZ, NDRI, Buspar, Pregabalin, TCA
 Other alternatives with evidence of benefit
Antidepressants
Bupropion (NDRI)
Mirtazapine (NaSSa)
Antipsychotics
Olanzapine
Risperidone
Other
Buspirone (Buspar)
 With discontinuation of treatment
- 20-40% relapse within 6-12 m, suggesting long
term treatment is necessary
 CBT – most evidence for efficacy
 Efficacy is comparable to pharmacologic
therapy, but may have higher remission rates
 Other therapies that may be effective:
- Short term psychodynamic therapy
- Interpersonal therapy
Cognitive restructuring
Trigger
Perception of
Danger
Reduced
Anxiety
Beliefs &
Assumptions
- Escape
- Avoidance
- Safety
behaviours
Increased
Anxiety
Exposure therapy
 Panic attacks (PA)
 Recurrent and unexpected, acute, time-limited
symptoms (at least 4/13)
 Not caused by substance or GMC
 Anticipatory anxiety
 Concern about additional attacks, their implications
and consequences or change in behaviour  1 month
 Agoraphobia

Avoidance/distress/anxiety in places or situations
difficult to escape or get help in case of PA
 Panic attacks – may come from a dysfunction of
the fear circuitry
 Amygdala – central involvement
- Consists of several distinct nuclei in the brain
 Yohimbine
 Lactate
 CO2
 Caffeine
 Isoproterenol
 5HT agonists (fenfluramine, m-CPP)
 Choleocystokinin (CCK-4, CCK-5)
 Stimulants – nicotine, amphetamines
 Biopsychosocial approach
- Bio
SSRIs*
SNRIs*
TCAs
AntiCon
BDZs
Escitalopram
Venlafaxine
Imipramine
Gabapentin
Lorazepam
Clomipramine
Divalproex
Alprazolam
Fluoxetine
Sertraline
Paroxetine
Diazepam
Citalopram
Clonazepam
Fluvoxamine
1st line: SSRI, SNRI
2nd line: BDZ, NaSSA, TCA
3rd line: Anticon, MAOI, Atypical Antipsych, RIMA, pindolol
 Other alternatives with evidence of benefit
Antidepressants
Bupropion (NDRI)
Mirtazapine (NaSSa)
Other: Pindolol
Antipsychotics
Olanzapine
Risperidone
Quetiapine
 SSRI Benefits – may be seen within 1 wk;
- up to 6-8 wks
 Continued benefits may be seen after 12 m
 Treatment time of 8 -12 m is suggested, to
prevent relapse risk.
 CBT – most evidence for efficacy
 Efficacy is comparable to pharmacologic
therapy, but may have higher remission rates
 Other therapies that may be effective:
(BUT – INSUFFICIENT evidence to recommend)
- Psychodynamic therapy
- Eye Movement Desensitization and
Reprocessing (EMDR)
 Epidemiology
- 1% of population (F:M= 3:2)
- Onset – median age 19 yrs old, though can be
childhood onset (NB – in childhood, F:M= 1:2)
- Children
 Etiology:
- Dysregulation of 5-HT*
- Genetics – significant
35% of 1st degree relatives of OCD also have
OCD
- Neuroimaging studies
- show increased metabolism of frontal
lobes, caudate and cingulum
- Behavioural, psychosocial factors involved
 Obsessions
 recurrent, persistent thoughts, urges or images
experienced as intrusive and anxiety-provoking,
distinct from excessive worry, attempted to be
suppressed, ignored or neutralized
 contamination, harm/aggression, somatic, religious, sexual
 Compulsions
 repetitive, excessive behaviours or mental acts and
rituals aimed to prevent or decrease anxiety/distress
 cleaning, checking, counting, repeating, arranging, hoarding
 Obsessions or compulsions are time consuming
(>1 hr/day) or cause clinically significant distress
 At some point – obsessions/compulsions are
recognized as excessive or unreasonable
(may not occur in childhood)
 Not due to medical condition/substance
 Obsessions – are distressing –
e.g. Repeated thoughts about contamination
Usual response – compulsion – a behaviour
aimed at reducing the anxiety associated with
obsession – e.g. wash hands – temporary relief
from anxiety of obsession, but then obsession
returns.
 Egodystonic: i.e. “alien”, not within his/her
control BUT – recognized as product of the mind
(i.e. Not thought insertion)
 Children - clinical features:
- Most frequent compulsion children
- Handwashing (75%)
- Checking
- Sorting
 May not be egodystonic – often brought by
parents
 Small subset (<5%) – ass with Gp A β-hemolytic
streptococcal infection (scarlet fever, “strep
throat”) abrupt onset, with motor abnormalities
= PANDAS
(Paediatric Autoimmune Neuropsychiatric Disorder Ass with Streptococcal infection)
 Elderly onset – more concerns about morality
and washing rituals.
 Comorbid issues with OCD
“Depressing BODY TAASTE”:
- Depressive disorder
- Body dysmorphic disorder
- Trichotillomania and other impulse control d/o
- Anxiety Disorders
- Autism
- Schizophrenia
- Tourette’s/Tic disorders
- Eating Disorders e.g. Anorexia nervosa
 Biopsychosocial
- Bio
SSRIs*
SNRIs*
Escitalopram
Venlafaxine
TCAs
Fluoxetine
Clomipramine
Sertraline
IV Clomipramine
AntiCon
AntiPsych
Gabapentin
Risperidone
Topiramate
Olanzapine
Paroxetine
Citalopram
Fluvoxamine
1st line: SSRI
2nd line: Clomipramine, SNRI, NaSSA, Risperidone
3rd line: Something else....antipsych, anticon, MAOI
Quetiapine
Haloperidol
 Dosages of meds e.g. SSRIs may need to be
higher
 Response may take 6 wks or longer
 Most recommendations – suggest staying on
treatment for 1-2 yrs (reduce relapse risk)
 Neurosurgical options
- deep brain stimulation
- anterior cingulotomy
- anterior capsulotomy,
- subcaudate tractotomy
- limbic leucotomy
 Indicated for severe OCD, refractory to
therapy/medications
 40-60% of refractory pts may benefit
 CBT with Exposure Response Prevention (ERP)
- the most evidence for efficacy for treatment
 Individual may be better than gp
(individualization of treatment)
 Anxiety is common – we all experience this
 Pathological anxiety can also be common, and





is not a sign of personal weakness.
Important, but sometimes difficult to recognize.
There are significant biological underpinnings to
anxiety disorders.
Psychological approaches are very effective.
Treatment can be very effective, but should be
tailored to individual patients.
Use BIOPSYCHOSOCIAL approach.