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

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Presentation on theme: "April 9, 2014 Elliott K. Lee MD, FRCP(C) Staff Psychiatrist Anxiety Disorders Clinic Royal Ottawa Mental Health Centre."— Presentation transcript:

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

2 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 1. Autonomy: i.e. Minimal/no recognizable environmental trigger 2. Intensity – exceeds tolerance capacity 3. Duration – persistent, not transient 4. Behaviour – impairs coping: results in disabling behavioural strategies – avoidance, withdrawal

4 Physical symptoms: - autonomic arousal – tachycardia, tachypnea, diaphoresis, diarrhoea, light headedness Affective symptoms: MildSevere edginessterror, feeling loss of control, dying Behaviour Avoidance, or compulsions (“compensatory”) Cognitions – worry, apprehension, obsessions

5 Anxiety disorders are Prevalent, real, serious, treatable Anxiety disorders are not Signs of personal weakness

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

7 Neurophysiology Cognitive behavioural formulation Psychodynamic formulation

8 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) system Especially – 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 Psychopharmaology for anxiety disorders is based on those neurotransmitter systems: 1) Norepinephrine TCAs, Prazosin 2) GABA Benzodiazepines, anticonvulsants 3) Serotonergic (5-HT) modulation - SSRIs, SNRIs, TCAs

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

11 State 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

12 SSRI or SNRI (8-12 wks) GAD Panic Disorder OCDPTSD Social Anxiety disorder

13 Switch 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

14 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 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 Trigger Perception of Danger Increased Anxiety - Escape - Avoidance - Safety behaviours Reinforcement Reduced Anxiety Cognitive restructuring Exposure therapy Reinforcement Beliefs & Assumptions

17 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

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


20 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 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 Somers et al. Can J Psychiatry 2006

23 9282 pts – english speaking 12 month prevalence of numerous psychiatric disorders Any psychiatric disorder 26.2% Any anxiety disorder 18.1%

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

25 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 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 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 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 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 Etiology -Familial, with recurrence risk ratio 2 { "@context": "", "@type": "ImageObject", "contentUrl": "", "name": "Etiology -Familial, with recurrence risk ratio 2


32 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 Biopsychosocial approach Bio – SSRIs*SNRIs*RIMAs+MAOIsAntiConBDZs EscitalopramVenlafaxineMoclobemideGabapentinClonazepam FluvoxaminePhenelzinePregabalinAlprazolam SertralineDivalproexBromazepam ParoxetineTopiramate Citalopram Fluoxetine 1 st line: SSRI, SNRI 2 nd line: BDZ, AntiCon, MAOIs

34 Other alternatives with evidence of benefit AntidepressantsAntipsychotics Bupropion (NDRI)Olanzapine Mirtazapine (NaSSa)Risperidone Clomipramine (TCA)Quetiapine Aripiprazole

35 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 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 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 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 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 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 Biopsychosocial approach - Bio SSRIs*SNRIs*TCAsAntiConBDZs Escitalopram*Venlafaxine* Imipramine PregabalinLorazepam Alprazolam Sertraline*Bromazepam Paroxetine* Diazepam Citalopram 1 st line: SSRI, SNRI x 8-12 wks 2 nd line: BDZ, NDRI, Buspar, Pregabalin, TCA

42 Other alternatives with evidence of benefit AntidepressantsAntipsychotics Bupropion (NDRI)Olanzapine Mirtazapine (NaSSa)Risperidone Other Buspirone (Buspar) With discontinuation of treatment - 20-40% relapse within 6-12 m, suggesting long term treatment is necessary

43 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 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 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 Yohimbine Lactate CO2 Caffeine Isoproterenol 5HT agonists (fenfluramine, m-CPP) Choleocystokinin (CCK-4, CCK-5) Stimulants – nicotine, amphetamines

47 Biopsychosocial approach - Bio SSRIs*SNRIs*TCAsAntiConBDZs EscitalopramVenlafaxineImipramineGabapentinLorazepam FluoxetineClomipramineDivalproexAlprazolam Sertraline ParoxetineDiazepam CitalopramClonazepam Fluvoxamine 1 st line: SSRI, SNRI 2 nd line: BDZ, NaSSA, TCA 3 rd line: Anticon, MAOI, Atypical Antipsych, RIMA, pindolol

48 Other alternatives with evidence of benefit AntidepressantsAntipsychotics Bupropion (NDRI)Olanzapine Mirtazapine (NaSSa)Risperidone Quetiapine Other: 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 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 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

51 Etiology: - Dysregulation of 5-HT* - Genetics – significant 35% of 1 st degree relatives of OCD also have OCD - Neuroimaging studies - show increased metabolism of frontal lobes, caudate and cingulum - Behavioural, psychosocial factors involved

52 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

53 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

54 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)

55 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)

56 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

57 Biopsychosocial (NB lowest response rate to placebo among anxiety disorders) - Bio SSRIs*SNRIs*TCAsAntiConAntiPsych EscitalopramVenlafaxineGabapentinRisperidone FluoxetineClomipramineTopiramateOlanzapine SertralineIV ClomipramineQuetiapine ParoxetineHaloperidol Citalopram Fluvoxamine 1 st line: SSRI 2 nd line: Clomipramine, SNRI, NaSSA, Risperidone 3 rd line: Something else....antipsych, anticon, MAOI

58 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)

59 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

60 CBT with Exposure Response Prevention (ERP) - the most evidence for efficacy for treatment Individual may be better than group (individualization of treatment)


62 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 – Separation 4) Objects/animals – phobia*** commonest 5) 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 *

63 Comorbidity: MAJOR DEPRESSIVE DISORDER (all) - Social Phobia – Alcohol dependence - OCD – Depressing BODY TAASTE Neurotransmitters involved: 5-HT (esp OCD) NE GABA Structures: Amygdala Amygdala

64 SSRI or SNRI Higher doses (8-12 wks); (BDZ short term except OCD) GAD Panic Disorder OCDPTSD Social Anxiety disorder OCD – Can also do neurosurgery

65 CBT (ERP with OCD) GAD Panic Disorder OCDPTSD Social Anxiety disorder EMDR – Used with PTSD

66 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.


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