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Anxiety Disorders Back to Basics. April 9 , 2014 Elliott K. Lee MD, FRCP(C) Staff Psychiatrist Anxiety Disorders Clinic Royal Ottawa Mental Health Centre. Anxiety.

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anxiety disorders back to basics

Anxiety DisordersBack to Basics

April 9, 2014

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
Pathologic Anxiety

Pathologic anxiety

  • Autonomy: i.e. Minimal/no recognizable environmental trigger
  • Intensity – exceeds tolerance capacity
  • Duration – persistent, not transient
  • Behaviour – impairs coping:results in disabling behavioural strategies – avoidance, withdrawal
manifestations of anxiety
Manifestations of anxiety
  • 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
essential education
Essential education

Anxiety disordersare

Prevalent , real, serious, treatable

Anxiety disordersare notSigns of personal weakness

shared and specific features of ad
Shared and specific features of AD

Nutt et al. In: Handbook of Anxiety and Fear 2008

neurophysiology prototypic panic disorder generalized anxiety disorder
Neurophysiology(prototypic – panic disorder, generalized anxiety disorder)
  • 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
  • Psychopharmaology for anxiety disorders is based on those neurotransmitter systems:1) Norepinephrine TCAs, Prazosin2) GABA Benzodiazepines, anticonvulsants3) Serotonergic (5-HT) modulation - SSRIs, SNRIs, TCAs
neurobiology of anxiety
Neurobiology of anxiety

Limbic cortex

Nucleus accumbens

Periaqueductal Gray matter

Orbitofrontal cortex


Brain Stem

Ventral Tegmental Area


neurobiology of anxiety1
Neurobiology of anxiety
  • 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
alternative strategies
Alternative Strategies
  • SwitchDrug- Another SSRI/SNRI- Clomipramine - OCD - Panic Disorder
  • NB NEVER COMBINE SSRI/SNRI with MAOI SSRI + MAOI = DOA(Serotonin Syndrome)
  • Augment:- Clonazepam- Buspirone (OCD)- Gabapentin - Panic Disorder - Social phobia - PTSD - Pain- Atypical Antipsychotic - GAD, OCD, PTSD
  • SSRIs- Fluoxetine (Prozac)- Paroxetine (Paxil)- Sertraline (Zoloft)- Fluvoxamine (Luvox)- Citalopram (Celexa)- Escitalopram (Cipralex)
  • SNRIs- Venlafaxine (Effexor)- Desvenlafaxine (Pristiq)- Cymbalta (Duloxetine) -Pain
  • NDRI- Bupropion (Wellbutrin, Zyban) (Anxiety worse)
  • NRI- Atomexetine (Strattera) - Indicated for ADHD
cognitive behavioural
Cognitive Behavioural
  • 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
cognitive behavioural model of anxiety
Cognitive-behavioural model of anxiety


Cognitive restructuring

Perception of



Beliefs &







- Escape

- Avoidance

- Safety behaviours

Exposure therapy


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.

World view

Self View

psychodynamic developmental
  • 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
anxiety disorders in dsm iv
Anxiety Disorders in DSM-IV
  • 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
pooled prevalence rates for ad
Pooled prevalence rates for AD

Somers et al. Can J Psychiatry 2006

national comorbidity survey replication study
National Comorbidity Survey – Replication study
  • 9282 pts – english speaking
  • 12 month prevalence of numerous psychiatric disorders
  • Any psychiatric disorder 26.2%
  • Any anxiety disorder 18.1%
national comorbidity study r
National Comorbidity Study- R


Kessler et al. Arch Gen Psychiatry, 2005

Percentage (%)


Specific phobia (8.7%)

Social phobia (6.8%)

PTSD (3.5%)

Panic (2.7%)

GAD (3.1%)

OCD (1%)

specific phobia
Specific Phobia
  • 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
specific phobia1
Specific Phobia
  • 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
social phobia social anxiety disorder
Social PhobiaSocial Anxiety Disorder
  • 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
social phobia
Social Phobia
  • Epidemiology:- 6.8% of the population- Onset - by age 11, 50% have symptoms; - by age 20, 80% have symptoms - I.E.- CHILDHOOD ONSET- Children – may refuse to go to school; - Associated with early drop out from school - Selective mutism – highly likely becomes social anxiety disorder (severe variant)
social phobia1
Social Phobia
  • Etiology-Familial, with recurrence risk ratio 2<x<6 i.e. Moderate heritability (chromosome 16 implicated –NE transporter)
  • 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
social phobia comorbidities
Social Phobia - comorbidities
  • 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
social phobia treatment
Social Phobia - Treatment
  • Biopsychosocial approach
  • Bio –

1st line: SSRI, SNRI2nd line: BDZ, AntiCon, MAOIs

social phobia2
Social Phobia
  • Other alternatives with evidence of benefitAntidepressantsAntipsychoticsBupropion (NDRI) OlanzapineMirtazapine (NaSSa) RisperidoneClomipramine (TCA) Quetiapine Aripiprazole
psychosocial treatments
Psychosocial treatments
  • 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
generalized anxiety disorder gad
Generalized Anxiety Disorder (GAD)
  • 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”- >90% comorbidity

Kessler RC et al. Arch Gen Psychiatry, 2005

gad in elderly most common anxiety disorder in elderly
GAD in elderly(most common anxiety disorder in elderly)
  • 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
gad clinical features
GAD Clinical Features
  • 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(SICKEM – sleep, irritability, conc, keyed up/restless, energy, muscle tension)
    • 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
gad clinical features1
GAD Clinical features
  • Often – do not present with anxiety initially - May be (somatic) Pain Fatigue Sleep disturbances Poor concentration Depression- Frequently associated with disabilities in work, education, and/or social interactions
  • Comorbidities common (>90%) – mood disorders, anxiety disorders, substance abuse
gad treatment
GAD Treatment
  • Biopsychosocial approach- Bio

1st line: SSRI, SNRI x 8-12 wks2nd line: BDZ, NDRI, Buspar, Pregabalin, TCA

gad treatment1
GAD Treatment
  • Other alternatives with evidence of benefitAntidepressantsAntipsychoticsBupropion (NDRI) OlanzapineMirtazapine (NaSSa) RisperidoneOtherBuspirone (Buspar)
  • With discontinuation of treatment- 20-40% relapse within 6-12 m, suggesting long term treatment is necessary
psychosocial treatment
Psychosocial Treatment
  • 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
panic disorder agoraphobia
Panic disorder +/- Agoraphobia
  • Panic attacks (PA)
    • Recurrent and unexpected, acute, time-limited symptoms (at least 4/13)
    • Not caused by substance or GMC
    • NB Panic attack ≠ Panic disorder (yet)
  • 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
  • Very high comorbidity- 50-60% may have comorbid major depressive disorder
substances that elicit panic
Substances that elicit panic
  • Yohimbine
  • Lactate
  • CO2
  • Caffeine
  • Isoproterenol
  • 5HT agonists (fenfluramine, m-CPP)
  • Choleocystokinin (CCK-4, CCK-5)
  • Stimulants – nicotine, amphetamines
panic disorder treatment
Panic Disorder Treatment
  • Biopsychosocial approach- Bio

1st line: SSRI, SNRI2nd line: BDZ, NaSSA, TCA

3rd line: Anticon, MAOI, Atypical Antipsych, RIMA, pindolol

panic disorder treatment1
Panic Disorder Treatment
  • Other alternatives with evidence of benefitAntidepressantsAntipsychoticsBupropion (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.
psychosocial treatment1
Psychosocial Treatment
  • 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)
obsessive compulsive disorder ocd
Obsessive Compulsive Disorder (OCD)
  • 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
obsessive compulsive disorder ocd1
Obsessive Compulsive Disorder (OCD)
  • 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
obsessi ons compulsi ons
Obsessions +/- compulsions
  • 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 contaminationUsual 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
ocd treatment
OCD treatment
  • Biopsychosocial(NB lowest response rate to placebo among anxiety disorders)- Bio

1st line: SSRI2nd line: Clomipramine, SNRI, NaSSA, Risperidone

3rd line: Something else....antipsych, anticon, MAOI

pharmacology issues
Pharmacology issues
  • 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)
another option
Another option...
  • 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
psychosocial treatment2
Psychosocial treatment
  • CBT with Exposure Response Prevention (ERP)- the most evidence for efficacy for treatment
  • Individual may be better than group (individualization of treatment)
anxiety disorders
Anxiety Disorders
  • Epidemiology – genetics, environment♀>♂, usually 2:1. OCD the exception (1:1)
  • Look at Trigger:1) Constant- GAD (6 months)2) Groups of People – Social Phobia (6 months) 3) Parents – Separation4) Objects/animals – phobia*** commonest5) Trauma – PTSD (>1 month)6) “Out of the Blue” – Panic (>1 month)7) Contamination, “bad things happening”– OCD NB: Egodystonic Streptococcus possibility(PANDAs)

*Childhood onset


anxiety disorders1
Anxiety Disorders
  • Comorbidity: MAJOR DEPRESSIVE DISORDER (all)- Social Phobia – Alcohol dependence- OCD – Depressing BODY TAASTE
  • Neurotransmitters involved:5-HT (espOCD) NE GABA
  • Structures: Amygdala


bio pharmacotherapy
Bio (Pharmacotherapy)

OCD – Can also do neurosurgery


EMDR – Used with PTSD

  • 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.