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April 16, 2010, 2010
Elliott K. Lee MD, FRCP(C)
Staff Psychiatrist
Anxiety Disorders Clinic
Royal Ottawa Mental Health Centre
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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.
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Pathologic anxiety1.Autonomy: i.e. Minimal/no recognizable
environmental trigger2.Intensity – exceeds tolerance capacity3.Duration – persistent, not transient4.Behaviour – impairs coping:
results in disabling behavioural strategies – avoidance, withdrawal
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Physical symptoms:- autonomic arousal – tachycardia, tachypnea, diaphoresis, diarrhoea, light headedness
Affective symptoms:Mild Severeedginess terror, feeling
loss of control, dying
BehaviourAvoidance, or compulsions (“compensatory”)
Cognitions – worry, apprehension, obsessions
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Anxiety disorders arePrevalent , real, serious, treatable
Anxiety disorders are not
Signs of personal weakness
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Nutt et al. In: Handbook of Anxiety and Fear 2008
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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) systemEspecially – 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
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Psychopharmaology for anxiety disorders is based on those neurotransmitter systems:1) Norepinephrine
TCAs, Prazosin2) GABA
Benzodiazepines, anticonvulsants3) Serotonergic (5-HT) modulation
- SSRIs, SNRIs, TCAs
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Limbic cortex
Periaqueductal Gray matter
Brain Stem
Ventral Tegmental Area
Hippocampus
Amygdala
Nucleus accumbens
Orbitofrontal cortex
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State anxietyAn 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
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Normal healthy ptsvs.
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
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Etkin A. et al. Neuron, 2004
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)
Analyzed activation of amygdala (fMRI)
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Focus on information processing and behavioural reactions
Faulty cognitions-e.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
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Automatic thoughts/Feelings:I am foolish, I am incompetent, I am not loveable
Behaviour: RUN!
Reinforcement: I have not dated; good people don’t like me; I am foolish, I am incompetent, I am not loveable
Single person sees attractive person
Automatic thoughts/Feelings: that person is attractive, I am a good person. Maybe we can be a good match. Let’s find out
Behaviour: Initiate conversation***
Reinforcement: Attractive person seemed to enjoy talking to me. Maybe I have something to offer in a relationship
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Cognitive Behavioural Therapy (CBT) is based on these notions
Replace anxiogenic thoughts and behaviours with positive ones.
World viewSelf View
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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
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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?”
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“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.
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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 concerns.
Gabbard, GO. Psychodynamic Psychiatry in Clinical Practice, 2000
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Panic Disorder without AgoraphobiaPanic Disorder with AgoraphobiaAgoraphobia without history of Panic DisorderSpecific PhobiaSocial PhobiaObsessive-Compulsive DisorderAcute Stress DisorderPosttraumatic Stress DisorderGeneralized Anxiety DisorderAnxiety Disorder Due to General Medical
Condition or Substance-Induced Anxiety DisorderAnxiety Disorder NOS
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Somers et al. Can J Psychiatry 2006
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9282 pts – english speaking12 month prevalence of numerous psychiatric
disordersAny psychiatric disorder 26.2%Any anxiety disorder 18.1%
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Specific phobia (8.7%)
Social phobia (6.8%)
PTSD (3.5%)
GAD (3.1%)
Panic (2.7%)
OCD (1%)
5
10
Per
cent
age
(%)
Kessler et al. Arch Gen Psychiatry, 2005
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Persistent and irrational fear of certain objects or situations
Exposure provokes anxiety/panic responseRecognized as excessive or unreasonablePhobic object/situation avoided or endured
with intense anxiety or distressSignificant interference or marked distress
Types: animals/insects, natural environment, blood/injury, situational, other
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Most common anxiety disorderMarked and persistent fear of clearly discernible
circumscribed objects or situationsExposure almost invariably provokes anxietyFear is recognized as excessive or unreasonable
(though children may not)Phobic stimulus is avoided, or tolerated with
dreadAvoidance/fear leads to significant distress or
interference with social/occ functioningIn children – should persist >6 m
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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
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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 Separation anxiety disorder
8m-3yrs Separation anxiety, fear of lightening, thunder, animals, nightmares
Crying, clinging, withdrawal, freezing
4-5 yrs Fear of death, dead people
GAD, Panic disorder
5-12yrs Nightmares,Fear of fantasy objects, animals, physical things- natural 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
Panic disorder, agoraphobia
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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.
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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
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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)
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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
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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
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Biopsychosocial approachBio – SSRIs* SNRIs* RIMAs+MAOI
sAntiCon BDZs
Escitalopram Venlafaxine Moclobemide Gabapentin Clonazepam
Fluvoxamine Phenelzine Pregabalin Alprazolam
Sertraline Divalproex Bromazepam
Paroxetine Topiramate
Citalopram
Fluoxetine
1st line: SSRI, SNRI2nd line: BDZ, AntiCon, MAOIs
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Other alternatives with evidence of benefitAntidepressants AntipsychoticsBupropion (NDRI) OlanzapineMirtazapine (NaSSa) RisperidoneClomipramine (TCA) Quetiapine
Aripiprazole
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Trigger
Perception of Danger
Increased Anxiety
- Escape- Avoidance- Safety behaviours
Reinforc
ement
Reduced Anxiety
Cognitive restructuring
Exposure therapy
Reinforcement
Beliefs & Assumptions
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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
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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
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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
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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
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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 impairmentNot due to the effects of substance of GMC
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Often – do not present with anxiety initially - May be
PainFatigueSleep disturbancesPoor concentrationDepression
- Frequently associated with disabilities in work, education, and/or social interactions
Comorbidities common – mood disorders, anxiety disorders, substance abuse
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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 wks2nd line: BDZ, NDRI, Buspar, Pregabalin, TCA
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Other alternatives with evidence of benefitAntidepressants AntipsychoticsBupropion (NDRI) OlanzapineMirtazapine (NaSSa) Risperidone
OtherBuspirone (Buspar)
With discontinuation of treatment- 20-40% relapse within 6-12 m, suggesting long term treatment is necessary
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CBT – most evidence for efficacyEfficacy is comparable to pharmacologic
therapy, but may have higher remission ratesOther therapies that may be effective:
- Short term psychodynamic therapy- Interpersonal therapy
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Trigger
Perception of Danger
Increased Anxiety
- Escape- Avoidance- Safety behaviours
Reinforc
ement
Reduced Anxiety
Cognitive restructuring
Exposure therapy
Reinforcement
Beliefs & Assumptions
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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
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Panic attacks – may come from a dysfunction of the fear circuitry
Amygdala – central involvement- Consists of several distinct nuclei in the brain
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YohimbineLactateCO2CaffeineIsoproterenol5HT agonists (fenfluramine, m-CPP)Choleocystokinin (CCK-4, CCK-5)Stimulants – nicotine, amphetamines
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Biopsychosocial approach- Bio
SSRIs* SNRIs* TCAs AntiCon BDZs
Escitalopram Venlafaxine Imipramine Gabapentin Lorazepam
Fluoxetine Clomipramine Divalproex Alprazolam
Sertraline
Paroxetine Diazepam
Citalopram Clonazepam
Fluvoxamine
1st line: SSRI, SNRI2nd line: BDZ, NaSSA, TCA3rd line: Anticon, MAOI, Atypical Antipsych, RIMA, pindolol
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Other alternatives with evidence of benefitAntidepressants AntipsychoticsBupropion (NDRI) OlanzapineMirtazapine (NaSSa) Risperidone
QuetiapineOther: Pindolol
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.
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CBT – most evidence for efficacyEfficacy is comparable to pharmacologic
therapy, but may have higher remission ratesOther therapies that may be effective:
(BUT – INSUFFICIENT evidence to recommend)- Psychodynamic therapy- Eye Movement Desensitization and Reprocessing (EMDR)
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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
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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
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Obsessions recurrent, persistent thoughts, urges or images
experienced as intrusive and anxiety-provoking, distinct from excessive worry, attempted to be suppressed, ignored or neutralizedcontamination, harm/aggression, somatic, religious, sexual
Compulsions repetitive, excessive behaviours or mental acts and
rituals aimed to prevent or decrease anxiety/distresscleaning, checking, counting, repeating, arranging, hoarding
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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
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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)
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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)
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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
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Biopsychosocial- Bio
SSRIs* SNRIs* TCAs AntiCon AntiPsych
Escitalopram Venlafaxine Gabapentin Risperidone
Fluoxetine Clomipramine Topiramate Olanzapine
Sertraline IV Clomipramine
Quetiapine
Paroxetine Haloperidol
Citalopram
Fluvoxamine
1st line: SSRI2nd line: Clomipramine, SNRI, NaSSA, Risperidone3rd line: Something else....antipsych, anticon, MAOI
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Dosages of meds e.g. SSRIs may need to be higher
Response may take 6 wks or longerMost recommendations – suggest staying on
treatment for 1-2 yrs (reduce relapse risk)
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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
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CBT with Exposure Response Prevention (ERP)- the most evidence for efficacy for treatment
Individual may be better than gp (individualization of treatment)
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Anxiety is common – we all experience thisPathological 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.
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