© 2010 NC Center of Excellence for Integrated Care icarenc.org for Cost Effective Pharmacologic Treatment Funded by NC Community Care NC Academic Consortium

© 2010 NC Center of Excellence for Integrated Care icarenc.org

for Cost Effective

Pharmacologic Treatment

Funded by NC Community Care

NC Academic Consortium

1

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.


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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

Documents

© 2010 NC Center of Excellence for Integrated Care icarenc.org for Cost Effective Pharmacologic Treatment Funded by NC Community Care NC Academic Consortium