Anxiety and PTSD

Dr. Joseph Polimeni Psychiatrist University of Manitoba

1 Disclosure: Joseph Polimeni

Financial Interest or Affiliation Commercial Enterprise(s)

Ownership or partnership Employment Investments (mutual funds excluded) Advisory board or similar committee Clinical trials or studies Honoraria or other fees (e.g., travel support) Research grants Patents

Other (specify) Speaker’s Bureau

2 Learning Objectives

At the end of this symposium the learner will be able to:

• List the main pharmacotherapeutic and psychotherapeutic treatment options for Panic Disorder/Agoraphobia.

• List the main pharmacotherapeutic and psychotherapeutic treatment options for Generalized Anxiety Disorder.

• List the main pharmacotherapeutic and psychotherapeutic treatment options for Social Anxiety Disorder.

• List the main pharmacotherapeutic and psychotherapeutic treatment options for PTSD.

3 Forward, Stop, Backwards

4 It is better to run away 100 times than be eaten once

5 Mismatch Theory Radiation, Divorce, Unemployment

6 Anxious Emotions Alert to Danger (They are only a warning light and not the actual danger)

- Suffering is evolutionarily adaptive - Environmental Mismatch -Genetic variation -Disease

7 Depression and anxiety are mostly due to threats to social standing (and attachments)

8 Threats to Social Standing (as well as attachments and our reputation as cooperators) were very dangerous in the ancestral environment.

9 Anxiety Disorders

• Physical Threats • Social Threats

• Hierarchal status • Attachments

6. Generalized Anxiety Disorder (GAD) 10 Emotions

• Love, comradery, sexual attraction, mirth and laughter, happiness, anger, jealousy, revenge, dysphoria, sadness, anxiety, fear, boredom, adoration, pride, spirituality. • Emotions place the organism in a state that makes certain evolutionarily desirable behaviors more probable. • Emotions reflect a complex stimulus-response paradigm • All emotions are irrational (because they are unthinking reflexes) • Frontal cortex modulates the intensity of emotions

11 Why drugs and talk therapy compliment each other

12 Anxiety presents in a few common ways

• Depression is contending with loss • Anxiety is contending with threat of loss • Life is complicated and therefore we are often dealing with stresses with both elements. • Brains are complicated and therefore anxiety (or depression) can manifest in different ways.

• Normal anxiety, • GAD • Panic Disorder (agoraphobia) • Social Anxiety Disorder (Social phobia) • PTSD

13 Causes of Depression and Anxiety

• Hierarchal status (job loss, flunking exams) • Attachments (divorce, break-up) • Physical threats • Genetic variation (Bipolar II Disorder) • Early childhood trauma (borderline personality disorder) • Disease (hypothyroidism, hyperthyroidism)

14 Panic Disorder (Agoraphobia alone is uncommon)

TABLE 1. DSM-IV criteria for panic attack A discrete period of intense fear or discomfort, in which four (or more) of the following symptoms developed abruptly and reached a peak within 10 min

1. Palpitations, pounding heart, or accelerated heart rate 2. Sweating 3. Trembling or shaking 4. Sensations of shortness of breath or smothering 5. Feeling of choking 6. Chest pain or discomfort 7. Nausea or abdominal distress 8. Feeling dizzy, unsteady, lightheaded, or faint 9. Derealization (feelings of unreality) or depersonalization (being detached from oneself) 10. Fear of losing control or going crazy 11. Fear of dying 12. Paresthesias (numbness or tingling sensations) 13. Chills or hot flushes

15 Social Anxiety Disorder

• Marked fear or anxiety about one or more social situations in which the individual is exposed to possible scrutiny by others. Examples include social interactions (e.g., having a conversation), being observed (e.g., eating or drinking), or performing in front of others (e.g., giving a speech). • The individual fears that he or she will act in a way or show anxiety symptoms that will be negatively evaluated (e.g., be humiliated, embarrassed, or rejected) or will offend others. • The social situation(s) almost always provoke fear or anxiety. (Note: in children, the fear or anxiety may be expressed by crying, tantrums, freezing, clinging, shrinking, or failure to speak in social situations.) • The social situation(s) are actively avoided or endured with marked fear or anxiety. • The fear or anxiety is out of proportion to the actual threat posed by the social situation. (Note: “Out of proportion” refers to the sociocultural context.) • The fear, anxiety, or avoidance is persistent, typically lasting six or more months • The fear, anxiety, and avoidance cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

16 Generalized Anxiety Disorder – core symptoms

• Uncontrollable and excessive worry about day-to- day matters such as finances, family, work, or health

• Worry about the impact of worrying • i.e. they may be concerned that worry will damage their health or they may think that negative things will occur if they do not worry enough.

• These individuals report more worry about the future than patients with other anxiety problems

• GAD worry is chronic, exaggerated and impairs functioning

17 Generalized Anxiety Disorder (GAD): DSM-5 Diagnostic Criteria • Excessive anxiety and worry present most of the time for > 6 months • Difficult to control worry • Associated with (at least 3 items – adults; 1 item - children): • Restlessness • Being easily fatigued • Concentration difficulties • Irritability • Muscle tension • Sleep disturbance • Anxiety, worry or physical symptoms cause clincially significant distress or functional impairment • Not due to medication or substance or medical condition • Disturbance not better explained another mental disorder

18 Generalized Anxiety Disorder (GAD)

• Prevalence: • Frequently under-recognized • 1-year: 1%-4% • Lifetime: approx. 6% • <1/3 of patients adequately • Children: 3% treated • Adolescents: 10.8% • Diagnosis and treatment in • More frequent in Caucasians, children complicated by elderly, and women previous designation of (2-3x more likely) Overanxious Disorder of Childhood and its possible • Age of onset: variable and may differentiation of childhood be bimodal: GAD from GAD in adults • Children and adolescents: ages 10-14 • Painful physical symptoms in • Adults: 31 (median), 32.7 (mean) 60%-94% of patients (initial reason for presentation to • Substantial economic costs physician in 72% of cases)

6. Generalized Anxiety Disorder (GAD) 19 Most Patients with GAD do NOT Present with Anxiety as the Primary Complaint

Only 13% had anxiety as primary complaint

20 Actual Presentation May not be Worry

• Physical symptoms can be the main avenue through which GAD patients express their distress (known as somatization) • Common presenting physical complaints include: - Insomnia - Muscle tension, trembling, twitching, aching, soreness - Cold, clammy hands - Dry mouth - Sweating - Nausea or diarrhoea - Urinary frequency - Tachycardia, palpitations - Dizziness, light-headedness - Breathing difficulties - Numbness, tingling - Hot or cold flushes

21 GAD: A Common Comorbid Condition

• GAD is one of the most common conditions that occurs comorbidly with other disorders – 91% of patients with GAD have ≥1 additional diagnosis1

• GAD occurs comorbidly with many medical and psychiatric conditions, including: — Major depression1-4 — Chronic fatigue syndrome2 — Panic disorder1-3 — Gastrointestinal disease5 — Social phobia1 — Irritable bowel syndrome2,5 — Specific phobia1 — Hypertension2 — Post-traumatic stress disorder2 — Heart disease2 — Chronic pain conditions4

• Comorbid psychiatric disorders are related to a poorer prognosis

22 Work Impairment in GAD and Other Chronic Conditions

Days Work Impairment in Past Month

23 GAD Course of Illness

• Chronic • Waxing and waning of symptoms1 • Low rates of remission over long term1,2

• Intermittent exacerbations • Exaggerated response to stress1,3

• Symptom overlap with medical and psychiatric disorders3 • Many are undiagnosed4

• Episodes may be more persistent with age5

• Duration: Mean 6.5 – 10.4 yrs (ECA)

• Poorer outcomes in patients with psychiatric comorbidities6

24 GAD-7: Generalized Anxiety Disorder 7-item Scale

25 Main Points of Treating GAD

1. Treat based on comorbidity 2. SSRI’s/SNRIs are first line 3. Benzodiazepines are not evil 4. Buspirone and Pregabalin can be considered 5. Antipsychotics are not the cure for everything but have a place in treating GAD 6. In cases of treatment resistance, carefully review the diagnosis

26 Medications approved by Health Canada for GAD • Venlafaxine • Paroxetine • E-citalopram • Duloxetine • Buspirone

• Note: Benzodiazepines have been approved for treatment of anxiety disorders not specifically GAD

• All other Meds are Off-label use in the treatment of GAD

Katzman et al. BMC Psychiatry 2014 27 Katzman et al. Canadian Clinical Practice Guidelines for Anxiety…. BMC Psychiatry 2014

28 SSRI’s/SNRIs Are First Line

• Ecitalopram, Venlafaxine have strong evidence in treating GAD • Gelenberg JAMA 2000 – 6month RCT with Venlalfaxine • Lenze JAMA 2009- 12-week RCT in older adults with ecitalopram

• But, pick your favorite based on patient’s side effect profile.

• Start low, go slow, aim high.

29 Can J Psychiatry 2009

30 Antidepressants vs. Benzodiazepines in Treating GAD

• Berney et al 2008 reviewed the literature and found that there were 22 RCTs comparing ADs to BZDs.

• None of them showed superiority of ADs over BZDs in the treatment of GAD. They concluded that there has been a shift in prescribing ADs instead of BZDs for GAD without any evidence to support this shift.

31 Risk of Fractures Not Just With Benzodiazepines

1. Bolton JM, Metge C, Lix L, et al. Fracture risk from psychotropic medications: a population-based analysis. J Clin Psychopharmacol. 2008;28(4):384 –391.

2. Woolcott JC, Richardson KJ, Wiens MO, et al. Meta-analysis of the impact of 9 medication classes on falls in elderly persons. Arch Intern Med. 2009;169(21):1952–1960.

3. Wagner AK, Ross-Degnan D, Gurwitz JH, et al. Effect of New York State regulatory action on benzodiazepine prescribing and hip fracture rates. Ann Intern Med. 2007;146(2):96 –103.

32 Antipsychotics Are Not the Cure for Everything, But Have a Place • Atypical Antipsychotics- may have utility in people • GAD + Bipolar disorder • GAD + borderline personality disorder

• Zahreddenni et al. Current Clinical Pharmacotherapy Opinion 2013

33 Generalized Anxiety Disorder Overview of Psychological Strategies • CBT (preventing worry behaviors, problem solving, allaying guilt and anger, imagery exposure, psycheducation) • Mindfulness-based strategies (meditation, acceptance of emotions, focus on here and now, Buddhist principles ) • Relaxation Therapies (progressive muscle relaxation) • Psychodynamic psychotherapy • Motivational Interviewing

34 CBT vs. Medication for GAD

• Only three controlled studies were found that examined the relative and combined effects of CBT vs. medication (buspirone, diazepam, venlafaxine), with mixed results

• In a recent meta-analysis, CBT plus medication was generally more effective than CBT plus placebo at posttreatment, but not at follow-up for the treatment of GAD (Hofmann et al., 2009)

35 PTSD – Haunted by an Experience 37 38 39 40 Which criterion of DSM-IV ACUTE stress Disorder and PTSD was removed in DSM-5?

• A. Persistent avoidance of places that remind the person of the traumatic event. • B. The person's response involved intense fear, helplessness, or horror. • C. Persistent symptoms of increased arousal (not present before the trauma). • D. Persistent re-experiencing of the trauma (e.g., nightmares, intrusive thoughts) PTSD Criteria (DSM-5)

• A. Exposure to actual or threatened a) death, b) serious injury, or c) sexual violation, in one or more of the following ways: • 1. directly experiencing the traumatic event(s) • 2. witnessing, in person, the traumatic event(s) as they occurred to others • 3. learning that the traumatic event(s) occurred to a close family member or close friend; cases of actual or threatened death must have been violent or accidental • 4. experiencing repeated or extreme exposure to aversive details of the traumatic event(s) (e.g., first responders collecting human remains; police officers repeatedly exposed to details of child abuse); this does not apply to exposure through electronic media, television, movies, or pictures, unless this exposure is work-related.

American Psychiatric Association, DSM-5 PTSD core symptoms

• Re-experiencing the trauma – “Intrusion Symptoms” (distressing memories, flashbacks, nightmares) • Hyperarousal (panic attacks, anxiety, poor concentration, startle reflex, irritable, insomnia) • Active Avoidance • Negative mood and Cognitions (depressed mood, emotional numbing, anger, guilt, pessimism) • Greater than 1 month DSM-5 Acute Stress Disorder

• PTSD Criteria • Greater than 3 days and less than 1 month. Prevalence of traumatic events in US General Population

Husarewycz N, El-Gabalawy R, Logsetty S, Sareen J. Gen Hosp Psych, 2014 Pre-Trauma Post-Trauma Factors Factors Trauma Factors High heart rate Low Social support Female sex Perceived fear of Financial stress Low IQ death Pain severity Prior trauma Assaultive trauma Intensive care unit stay exposure Severity of trauma PTSD Traumatic brain injury Prior mental Physical injury disorder Peritraumatic dissociation Personality factors Acute stress disorder Genetics Disability

Sareen J. Can J Psychiatry 2014 Sareen et al. Depression and Anxiety 2013 Bryant et al. JAMAPsychiatry 2013 Brewin et. Al JCCP 2000 DSM-IV PTSD Prevalence

• Canadian general Population • Lifetime 9.2% • US general population • Lifetime 6.8% (se 0.4) in NCS-R • Female:Male ~ 2:1 • Prevalence higher in some US subpopulations • 2 to 3X in American Indians on reservations2 • Most prevalent disorder in women is PTSD (~20%) • Cambodian refugees in US, 20 years later3 • 12-month prevalence 62% • Combat veterans 30-50%

Van Ameringen et al. 2003 NCS-R, National Comorbidity Survey Replication; 1Kessler RC et al. Arch Gen Psychiatry. 2005;62:617-627; 2Beals J et al. Arch Gen Psychiatry. 2005;62:99-108; 3Marshall G et al. JAMA. 2005:294:571-579. Prevention and Treatment

• 1. Pharmacological interventions in the acute stage of injury have not shown efficacy in reducing PTSD (but being drunk during the trauma helps!). • 2. Group based Critical Incident Stress Debriefing does not have evidence of reducing PTSD. • 3. Cognitive-behavioral therapy (CBT), and Exposure therapy (systematic desensitization) are more efficacious than citalopram or waiting list in preventing PTSD (however, access for CBT is difficult). • 4. Treatment approach for a person with PTSD should consider comorbidity • 5. EMDR - Eye Movement Desensitization Reprocessing • “What is effective in EMDR is not new, and what is new is not effective” • 6. SSRIs and SNRIs are the first line treatment. • 7. Management of insomnia is crucial with zopiclone, trazodone, quetiapine, prazosin. (minimize benzodiazepines) Questions