April 9, 2014

Elliott K. Lee MD, FRCP(C)

Staff Psychiatrist

Anxiety Disorders Clinic

Royal Ottawa Mental Health Centre

Anxiety DisordersBack to Basics

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.

Anxiety

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

Pathologic 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

Manifestations of anxiety

Essential education

Anxiety disorders arePrevalent , real, serious, treatable

Anxiety disorders are not

Signs of personal weakness

Shared and specific features of AD

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

Neurophysiology

Cognitive behavioural formulation

Psychodynamic formulation

Etiology

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

Neurophysiology (prototypic – panic disorder, generalized anxiety disorder)

Psychopharmaology for anxiety disorders is based on those neurotransmitter systems:1) Norepinephrine

TCAs, Prazosin2) GABA

Benzodiazepines, anticonvulsants3) Serotonergic (5-HT) modulation

- SSRIs, SNRIs, TCAs

Implications

Neurobiology of anxietyLimbic cortex

Periaqueductal Gray matter

Brain Stem

Ventral Tegmental Area

Hippocampus

Amygdala

Nucleus accumbens

Orbitofrontal cortex

Neurobiology of anxietyState 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

Pharmacotherapy

SSRI or

SNRI(8-12 wks)

GAD

Panic Disorder

OCD

PTSD

Social Anxiety disorder

Alternative StrategiesSwitch Drug

- 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

MedicationsSSRIs

- Fluoxetine (Prozac)- Paroxetine (Paxil)- Sertraline (Zoloft)- Fluvoxamine (Luvox)- Citalopram (Celexa)- Escitalopram (Cipralex)

SNRIs- Venlafaxine (Effexor)- Desvenlafaxine (Pristiq)- Cymbalta (Duloxetine)

-PainNDRI

- Bupropion (Wellbutrin, Zyban) (Anxiety worse)

NRI- Atomexetine (Strattera)

- Indicated for ADHD

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

Cognitive-behavioural model of anxiety

Trigger

Perception of Danger

Increased Anxiety

- Escape- Avoidance- Safety behaviours

Reinforc

ement

Reduced Anxiety

Cognitive restructuring

Exposure therapy

Reinforcement

Beliefs & Assumptions

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

Cognitive Behavioural Therapy (CBT) is based on these notions

Replace anxiogenic thoughts and behaviours with positive ones.

Implications

Anxiety Thought

• World is dangerous• I am not competent• I can not cope

Coping Thought

• World is safe• I am competent• I can cope

World viewSelf View

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

Psychodynamic/Developmental

Anxiety Disorders in DSM-IV 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 Disorder

Anxiety Disorder NOS

Pooled prevalence rates for AD

Somers et al. Can J Psychiatry 2006

9282 pts – english speaking12 month prevalence of numerous psychiatric

disordersAny psychiatric disorder 26.2%Any anxiety disorder 18.1%

National Comorbidity Survey – Replication study

National Comorbidity Study- R

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

Specific PhobiaPersistent and irrational fear of certain

objects or situationsExposure 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

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

Specific Phobia

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

Treatment

Social Phobia Social 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

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 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

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 - comorbidities

Biopsychosocial approachBio –

Social Phobia - Treatment

SSRIs* SNRIs* RIMAs+MAOIs

AntiCon BDZs

Escitalopram Venlafaxine Moclobemide Gabapentin Clonazepam

Fluvoxamine Phenelzine Pregabalin Alprazolam

Sertraline Divalproex Bromazepam

Paroxetine Topiramate

Citalopram

Fluoxetine1st line: SSRI, SNRI2nd line: BDZ, AntiCon, MAOIs

Other alternatives with evidence of benefitAntidepressants AntipsychoticsBupropion (NDRI) OlanzapineMirtazapine (NaSSa) RisperidoneClomipramine (TCA) Quetiapine

Aripiprazole

Social Phobia

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

Psychosocial treatments

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

Generalized Anxiety Disorder (GAD)

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

GAD in elderly (most common anxiety disorder in elderly)

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

GAD Clinical FeaturesExcessive, 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 impairmentNot due to the effects of substance of GMC

Often – do not present with anxiety initially - May be (somatic)

PainFatigueSleep disturbancesPoor concentrationDepression

- Frequently associated with disabilities in work, education, and/or social interactions

Comorbidities common (>90%) – mood disorders, anxiety disorders, substance abuse

GAD Clinical features

Biopsychosocial approach- Bio

GAD Treatment

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

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

GAD Treatment

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

Psychosocial Treatment

Panic disorder +/- AgoraphobiaPanic attacks (PA)

Recurrent and unexpected, acute, time-limited symptoms (at least 4/13)

Not caused by substance or GMCNB 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

Etiology

YohimbineLactateCO2CaffeineIsoproterenol5HT agonists (fenfluramine, m-CPP)Choleocystokinin (CCK-4, CCK-5)Stimulants – nicotine, amphetamines

Substances that elicit panic

Biopsychosocial approach- Bio

Panic Disorder Treatment

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

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.

Panic Disorder Treatment

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)

Psychosocial Treatment

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 (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

Obsessive Compulsive Disorder (OCD)

Obsessions +/- compulsionsObsessions

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

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

OCD

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)

OCD

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)

OCD

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

Biopsychosocial (NB lowest response rate to placebo among anxiety disorders)

- Bio

OCD treatment

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

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)

Pharmacology issues

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

Another option...

CBT with Exposure Response Prevention (ERP)- the most evidence for efficacy for treatment

Individual may be better than group (individualization of treatment)

Psychosocial treatment

Anxiety in 5 4 slides….

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)

Anxiety Disorders

*Childhood onset

*

Comorbidity: MAJOR DEPRESSIVE DISORDER (all)- Social Phobia – Alcohol dependence- OCD – Depressing BODY TAASTE

Neurotransmitters involved:5-HT (esp OCD) NE GABA

Structures: Amygdala

Anxiety Disorders

Amygdala

Bio (Pharmacotherapy)

SSRI or

SNRIHigher doses(8-12 wks);

(BDZ short termexcept OCD)

GAD

Panic Disorder

OCD

PTSD

Social Anxiety disorder

OCD – Can also do neurosurgery

Psychosocial

CBT(ERP with OCD)

GAD

Panic Disorder

OCD

PTSD

Social Anxiety disorder

EMDR – Used with PTSD

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.

Summary

Questions?