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© 2010 NC Center of Excellence for Integrated Care icarenc.org
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Virginia O’Brien, MD
Duke University Medical Center
The Anxiety Disorders
A Presentation from NC-ACCEPT: The NC Academic Consortium for Cost Effective
Psychopharmacologic Treatment
Supported by Community Care of NC and the NC AHEC Program
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There are no disclosures to be made for this program. This program did not receive any commercial support.
© 2010 NC Center of Excellence for Integrated Care icarenc.org
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Anxiety Disorders
• Goals:• Emphasize the prevalence of anxiety disorders in primary
care
• Review diagnosis and treatment of anxiety disorders
• Review first-line treatments for anxiety and cost-effective treatments
• Examine common medical causes of anxiety
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Anxiety Disorders
• Panic disorder, with or without agoraphobia
• Generalized anxiety disorder (GAD)
• Obsessive compulsive disorder (OCD)
• Post traumatic stress disorder (PTSD)
• Social phobia
• Specific phobia
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Anxiety
• Everyday anxiety
• Due to a general medical condition
• Due to substance abuse/withdrawal
• Common with depression
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Anxiety Disorders
• Lifetime prevalence 28.8%
• Most common class of psychiatric disorders
• Increase in disability, worse functional status, and more physician visits than those without anxiety
Kessler 2005, Kroenke 2007
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Kroenke 2007
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Anxiety
• Affect 40 million American adults per year
• Recognition in primary care settings:• 23% of primary anxiety disorders
• 56% depression
Kessler 2005, Roy-Byrne 2004, Ormel 1991
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Anti-anxiety Medication Use in US
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Comparative Cost of Antidepressants
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Cost of Drugs Used to Treat Anxiety
• $4 plans (Target, Wal-Mart, CVS, etc.)• Amitriptyline 10mg-100mg
• Citalopram 20mg-40mg
• Buspirone 10mg (BID dosing)
• Fluoxetine 10mg-40mg
• Paroxetine 10mg-20mg
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Antipsychotic Medications and Anxiety
Comer 2011
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Panic Disorder
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Panic Disorder
• Lifetime prevalence: 4.7%
• Women:Men 2-3:1
• 80% have onset before they are 30
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Panic Disorder Diagnosis
• Criteria• rapid crescendo of anxiety or fear
• Occurs out of the blue
• Recurrent
• at least 4 of 12 somatic symptoms
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Panic Disorder Diagnosis
• Agoraphobia• Anxiety related to being in places where it is hard to
escape
• Individual avoids these places or endures them with great distress
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Panic Disorder Treatment
• First line:• SSRIs/SNRIs – start at ½ beginning dose
• FDA approved: sertraline, paroxetine, fluoxetine, venlafaxine
• Cognitive behavioral therapy (CBT)
• FDA approved benzodiazepines: clonazepam, alprazolam
• Tricyclics (imipramine, clomipramine)
• MAOIs (primarily phenelzine)
Furukawa 2007, van Apeldoorn 2010
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Panic Disorder: Non-FDA Approved Treatments
Drug Effectiveness Pros Cons
hydroxyzine none generic No evidence; sedation
gabapentin mixed generic Mixed evidence
mirtazepine open-label, no placebo or small n
generic weight gain, sedation
duloxetine one open-label -- cost
Beta-blockers
one pos RCT (pindolol) generic orthostasis
olanzapine effective augmentor -- cost, metabolic side effects
risperidone effective in one small study compared to
paroxetine
-- metabolic side effects
Prosser 2009; Perna 2011
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20GAD
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Generalized Anxiety Disorder (GAD)
• Lifetime prevalence: 2.8-6.6%
• Female to male 2:1
• Can have later onset
Kessler 2005
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GAD Diagnosis
• Criteria• Excessive “free-floating” worry occurring more days than
not for at least 6 months
• Difficult to control the worry• Worry associated with >3:
Restlessness, on edgeDifficulty concentratingIrritabilityFatigueMuscle tensionSleep disturbance
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GAD Treatment
• First Line • FDA approved:
• sertraline, escitalopram, paroxetine• venlafaxine, duloxetine• buspirone
• Benzodiazepines may be used, but are not preferred
• Treat for one year
Kessler 2005, Rickels 2010
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GAD Treatment Comparison
• SSRIs
• Effexor IR all generic, all
• Buspirone efficacious
• Benzodiazepines
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GAD Treatment
Davidson 2010
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Pregabalin vs. Alprazolam vs. Placebo for GAD
Rickles 2005
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Off Label GAD TreatmentsDrug Pros Cons
pregabalin positive evidence, but all funded by pharma
optimal dose unknown, no studies longer than 8 wks;
dizziness; cost
gabapentin generic conflicting evidence
hydroxyzine positive evidence; generic sedation
quetiapine positive evidence metabolic side effects; cost; monitoring
tiagabine ---- not effective
Montgomery 2006, Rickles 2005
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OCD
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Obsessive Compulsive Disorder
• Lifetime prevalence – 1.6%
• Prior to age 15, M>F (3:1)
• By 20’s, F>M
Kessler 2005
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Obsessive Compulsive Disorder
• Obsessions:• Intrusive recurrent thoughts, impulses, or images which
cause marked anxiety• Person attempts to ignore or suppress thoughts with
another thought or action• Person knows thoughts are a product of own mind
• Compulsions• Repetitive behaviors or mental acts that the personal
feels driven to perform in response to an obsession• Behaviors/mental acts are aimed at preventing or
reducing stress or preventing a dreaded event
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OCD First-Line Treatments
• Obsessions:• FDA approved:
• Fluvoxamine, paroxetine, sertraline
• Clomipramine
• Compulsions:• CBT
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OCD Treatment
• Other SSRIs/SNRIs
• Antipsychotics – useful in augmentation of refractory OCD (haldol, risperidone), especially those with comorbid tics
• Odansetron – insufficent evidence
Bloch 2006
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PTSDAmygdala, prefrontal cortex, hypothalamus
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Posttraumatic Stress Disorder
• Lifetime prevalence: 6.8% (non-combat)
Kessler 2005
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PTSD Diagnosis
• Criteria:Intense fear, helplessness or horror triggered by an event involving actual or threatened death or serious injury to self or others
• Reexperience >1/5 symptoms
• Avoidance > 3/7 symptoms
• Increased arousal >2/5 symptoms
• Lasts more than one month
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PTSD Screening: PC-PTSD
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PTSD Treatment
• First Line• FDA approved: sertraline, paroxetine
• Other SSRIs/venlafaxine
• Individual trauma-focused CBT
• Second line• TCAs (imipramine)
• Eye movement desensitization and reprocessing (EMDR)
APA practice guidelines 2006
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Off-Label Treatments for PTSDDrug Pros Cons
prazosin positive evidence in RCTs for nightmares; generic
orthostasis
pregabalin case reports cost
anticonvulsants --- poor evidence
atypical antipsychotics
some evidence as adjunct to SSRIs
cost; metabolic side effects
beta-blockers poor evidence ---
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Social Phobia
amygdala, striatum, prefrontal cortex, hippocampus
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Social Phobia
• Prevalence 7-12%
• F:M 2:1
• Trigger: social situation
• Fear of embarrassment
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Social Phobia Screening
Copyright Davidson 2012 (david001.mc.duke.edu)
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Social Phobia Treatment• First line
• FDA approved – paroxetine, sertraline, venlafaxine
• Escitalopram, fluvoxamine, fluoxetine (all have good evidence)
• CBT
• Second line• Benzodiazepines (alprazolam, clonazepam)
• Third line • Phenelzine (MAOI), gabapentin, pregabalin, olanzapine
Davidson 2006
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SSRI Side Effects
• Nausea/loose stool
• Increased anxiety
• Anorgasmia, decreased libido
• Weight gain/Sedation (paroxetine)
• Increased risk of bleeding
• Hyponatremia
• Serotonin syndrome
• Mania
• Increased risk of suicidal thoughts in those age 18-24 44
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Benzodiazepines
• Short acting (alprazolam, midazolam)
• Intermediate acting (lorazepam)
• Long-acting (clonazepam)
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Benzodiazepine Side Effects
• Sedation
• Tolerance, dependence, abuse
• Withdrawal
• Decreased respiratory rate
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When to Use Benzodiazepines
• Start for patients with severe anxiety symptoms
• Limit use to several weeks
• Educate patient about side effects, dependence, temporary treatment
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How to Taper Benzodiazepines
• For longer-term users, taper no more that 25% per week in outpatient setting
• Decrease to 10% per week at lower doses or if tapering alprazolam
• May switch to long-acting benzodiazepine for smoother taper
• Scheduled, not prn dosing
• Follow up every 1-4 weeks depending on severity
• Warn long term users about the risks of sudden discontinuation and withdrawal symptoms
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Benzodiazepine Conversion
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CBT vs Placebo for Treatment of Anxiety Disorders
Otte 2011
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Brief CBT for Anxiety in Primary Care
Cape 2010
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Other Anxiety
• Due to a general medical condition
• Substance-induced
• Acute stress disorder
• Mixed anxiety-depressive disorder
• Adjustment disorder with anxious mood
• NOS
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Anxiety Due to A General Medical Condition
Cardiac – SVT, MAT, CHF, CAD, afib
Endocrine – hyperthyroidism, hypoglycemia, hyperparathyroidism, pheochromocytoma
Pulmonary – asthma, COPD, PE
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Anxiety Due to Substance Use
Substance abuse – cocaine, amphetamines
Substance withdrawal – alcohol, benzodiazepines
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Mixed Anxiety Disorders
Lowe 2008
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Bystritsky 2004
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Additional Considerations
• Consider medication interactions (CYP450)
• Consider patient drug use
• Bupropion should not be used to treat anxiety
• Educate patient about medication side effects before initiating therapy
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Summary
• Anxiety disorders are common and debilitating
• We can do a better job diagnosing anxiety
• Choose a screening/monitoring tool that works for your setting
• Start treatment with CBT or low dose SSRI
• Remember to ask about patient substance use
• Consider other medical causes of anxiety
• Consider cost
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References• Adams SM, Miller KE, Zylstra RG. Pharmacologic management of adult depression. American Family Physician
2008;77(6):789.
• American Psychiatric Association (APA). Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: APA; 2000.
• Anxiety disorders. In: Sadock BJ, et al., eds. Kaplan and Sadock’s Comprehensive Textbook of Psychiatry. 9th ed. Vol. 1. Philadelphia: Lippincott Williams & Wilkins; 2009:1839-926.
• Baldwin D, Lawson R, and Taylor D. Efficacy of drug treatments for generalised anxiety disorder: systematic review and meta-analysis. British Medical Journal 2011;d1199.
• Bloch MH, Landeros-Weisenberger A, Kelmendi B, Coric V, Bracken MB, Leckman JF. A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder. Molecular Pscyhiatry 2006;11:622-632.
• Bystritsky A. Diagnosis and treatment of anxiety. Focus 2004;2(3):333-342.
• Cape J, Whittington C, Buszewicz M, Wallace P, Underwood L. Brief psychological therapies for anxiety and depression in primary care: a meta-analysis and metaregression. BMC Medicine 2010;8(38):1-15.
• Comer JS, Mojtabai R, Olfson M. National trends in the antipsychotic treatment of psychiatric outpatients with anxiety disorders. American Journal of Psychiatry 2011;168:1057-1065.
• Davidson JR, et al. A psychopharmacological treatment algorithm for generalised anxiety disorder (GAD). J Psychopharmacol 2010;24(1):3-26.
• Davidson J. Pharmacotherapy of social anxiety disorder: what does the evidence tell us? J Clin Psychiatry 2006;67(supp 12):20-26.
• Foa EB. Social anxiety disorder treatments: psychosocial therapies. J Clin Psychiatry 2006;67(supp 12):27-30.
• Furukawa TA, et al. Combined psychotherapy plus antidepressants for panic disorder with or without agoraphobia. Cochrane Database Syst Rev 20071:CD004364.
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References• Kessler RC, et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the national
comorbidity survey replication. Arch Gen Psychiatry 2005;62:593-602.
• Kroenke K, et al. Anxiety disorders in primary care: prevalence, impairment, comorbidity, and detection Ann Intern Med 2007;146:317-25.
• Lowe B, et al. Depression, anxiety and somatization in primary care: syndrome overlap and functional impairment. Gen Hosp Psychiatry 2008;30:191-9.
• Montgomery SA, Tobias K, Zornberg GL, Kasper S, Pande AC. Efficacy and safety of pregabalin in the treatment of generalized anxiety disorder.:a 6-week, multicenter, randomized, double-blind, placebo-controlled comparison of pregabalin and venlafaxine. Journal of Clinical Psychiatry 2006;67:771-782.
• Ormel J, Koeter MW, van den Brink W, van de Willige G. Recognition, management, and course of anxiety and depression in general practice. Arch Gen Psychiatry 1991 Aug;48(8):700-6.
Perna G, Guerruero G, Caldirola D. Emerging drugs for panic disorder. Expert Opinion Emerging Drugs 2011;16(4):631-645.
Prosser JM, Yard S, Steele A, Cohen LJ, Galynker II. A comparison of low-dose risperidone to paroxetine in the treatment of panic attacks: a randomized, single-blind study. BMC Psychiatry 2009; 9(25):pages not listed.
Rickles K, et al. Pregabalin for treatment of generalized anxiety disorder. Archives of General Psychiatry 2005;62:1022-1030.
• Rickels K, et al. Time to relapse after 6 and 12 months’ treatment of generalized anxiety disorder with venlafaxine extended release. Arch Gen Psych 2010;67(12):1274-81.
• Roy-Byrne PP, et al. Primary care perspectives on generalized anxiety disorder. J Clin Psychiatry 2004;65(suppl 13):20-6.
van Apeldoorn FJ, et al. A randomized trial of cognitive-behavioral therapy or selective serotonin reuptake inhibitor or both combined for panic disorder with or without agoraphobia: treatment results through 1-year follow-up. J Clin Psychiatry 2010;71(5):574-86.
Zung W. A rating instrument for anxiety disorders. Pscyhosomatics 1971;12(6):371-379.60
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Primary Care PTSD Screen
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PC-PTSD Screen
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Prins, Ouimette, and Kimerling 2003
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Zung Anxiety Self Rating Scale
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Zung 1971
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Zung Anxiety Self Rating Scale Scoring
• 20-44 Normal Range
• 45-59 Mild to Moderate
• 60-74 Marked to Severe
• 75-80 Extreme
Zung 1971