Anxiety Disorders Back to Basics

1. Anxiety DisordersBack to Basics April 16, 2010, 2010 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. Neurobiology of anxiety 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

13. Neurobiology of anxiety • 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) Etkin A. et al. Neuron, 2004

14. 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

15. 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

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

17. 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

18. Implications • 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?”

19. Implications • “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.

20. Implications • 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

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. Normative anxiety in children

29. Separation Anxiety Disorder • 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.

30. 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

31. Social Phobia • 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)

32. Social Phobia • 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

34. 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

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

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

37. 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

38. 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

39. 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” Kessler RC et al. Arch Gen Psychiatry, 2005

40. GAD 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

41. 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

42. 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 • 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

43. GAD Clinical features • 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

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

45. 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

46. 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

47. 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

48. Panic disorder +/- Agoraphobia • 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

49. Etiology • Panic attacks – may come from a dysfunction of the fear circuitry • Amygdala – central involvement- Consists of several distinct nuclei in the brain

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