Anxiety Disorders Back to Basics

1. Anxiety DisordersBack to Basics April 2, 2013 Elliott K. Lee MD, FRCP(C) Staff Psychiatrist Anxiety Disorders Clinic Royal Ottawa Mental Health Centre

2. Anxiety • 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.

3. 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

4. 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

5. Essential education Anxiety disordersare Prevalent , real, serious, treatable Anxiety disordersare notSigns of personal weakness

6. Shared and specific features of AD Nutt et al. In: Handbook of Anxiety and Fear 2008

7. Etiology

8. 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

9. Implications • Psychopharmaology for anxiety disorders is based on those neurotransmitter systems:1) Norepinephrine TCAs, Prazosin2) GABA Benzodiazepines, anticonvulsants3) Serotonergic (5-HT) modulation - SSRIs, SNRIs, TCAs

10. Neurobiology of anxiety Limbic cortex Nucleus accumbens Periaqueductal Gray matter Orbitofrontal cortex Amygdala Brain Stem Ventral Tegmental Area Hippocampus

11. 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

12. Pharmacotherapy

13. 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

14. Medications • 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

15. 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

16. Cognitive-behavioural model of anxiety Trigger Cognitive restructuring Perception of Danger Reinforcement Beliefs & Assumptions Increased Anxiety Reduced Anxiety Reinforcement - Escape - Avoidance - Safety behaviours Exposure therapy

17. 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

18. Implications • Cognitive Behavioural Therapy (CBT) is based on these notions • Replace anxiogenic thoughts and behaviours with positive ones. World view Self View

20. 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

21. 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

22. Pooled prevalence rates for AD Somers et al. Can J Psychiatry 2006

23. 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%

24. National Comorbidity Study- R 10 Kessler et al. Arch Gen Psychiatry, 2005 Percentage (%) 5 Specific phobia (8.7%) Social phobia (6.8%) PTSD (3.5%) Panic (2.7%) GAD (3.1%) OCD (1%)

25. 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

26. 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

27. Treatment • 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

28. 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

29. 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)

30. 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

32. 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

33. Social Phobia - Treatment • Biopsychosocial approach • Bio – 1st line: SSRI, SNRI2nd line: BDZ, AntiCon, MAOIs

34. Social Phobia • Other alternatives with evidence of benefitAntidepressantsAntipsychoticsBupropion (NDRI) OlanzapineMirtazapine (NaSSa) RisperidoneClomipramine (TCA) Quetiapine Aripiprazole

35. 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

36. 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

37. 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

38. GAD • 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

39. 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

40. 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

41. GAD Treatment • Biopsychosocial approach- Bio 1st line: SSRI, SNRI x 8-12 wks2nd line: BDZ, NDRI, Buspar, Pregabalin, TCA

42. 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

43. 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

44. 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

45. Etiology • 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

46. Substances that elicit panic • Yohimbine • Lactate • CO2 • Caffeine • Isoproterenol • 5HT agonists (fenfluramine, m-CPP) • Choleocystokinin (CCK-4, CCK-5) • Stimulants – nicotine, amphetamines

47. Panic Disorder Treatment • Biopsychosocial approach- Bio 1st line: SSRI, SNRI2nd line: BDZ, NaSSA, TCA 3rd line: Anticon, MAOI, Atypical Antipsych, RIMA, pindolol

48. 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.

49. 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)

50. 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