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

for Cost Effective

Pharmacologic Treatment

Funded by NC Community Care

NC Academic Consortium

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

for Cost Effective

There are no disclosures to be made for this program. This program did not receive any commercial support.

for Cost Effective

Anxiety Disorders

• Goals:• Emphasize the prevalence of anxiety disorders in primary

• Review diagnosis and treatment of anxiety disorders

• Review first-line treatments for anxiety and cost-effective treatments

• Examine common medical causes of anxiety

for Cost Effective

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

for Cost Effective

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

for Cost Effective

Antipsychotic Medications and Anxiety

Comer 2011

for Cost Effective

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

for Cost Effective

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

for Cost Effective

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

for Cost Effective

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

for Cost Effective

OCD First-Line Treatments

• Obsessions:• FDA approved:

• Fluvoxamine, paroxetine, sertraline

• Clomipramine

• Compulsions:• CBT

for Cost Effective

OCD Treatment

• Other SSRIs/SNRIs

• Antipsychotics – useful in augmentation of refractory OCD (haldol, risperidone), especially those with comorbid tics

• Odansetron – insufficent evidence

Bloch 2006

for Cost Effective

PTSDAmygdala, prefrontal cortex, hypothalamus

for Cost Effective

Posttraumatic Stress Disorder

• Lifetime prevalence: 6.8% (non-combat)

Kessler 2005

for Cost Effective

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

for Cost Effective

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 ---

for Cost Effective

Social Phobia

amygdala, striatum, prefrontal cortex, hippocampus

for Cost Effective

Social Phobia

• Prevalence 7-12%

• F:M 2:1

• Trigger: social situation

• Fear of embarrassment

for Cost Effective

Social Phobia Screening

Copyright Davidson 2012 (david001.mc.duke.edu)

for Cost Effective

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

for Cost Effective

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

for Cost Effective

Benzodiazepines

• Short acting (alprazolam, midazolam)

• Intermediate acting (lorazepam)

• Long-acting (clonazepam)

for Cost Effective

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

for Cost Effective

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

for Cost Effective

Benzodiazepine Conversion

for Cost Effective

CBT vs Placebo for Treatment of Anxiety Disorders

Otte 2011

for Cost Effective

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

for Cost Effective

Anxiety Due to A General Medical Condition

Cardiac – SVT, MAT, CHF, CAD, afib

Endocrine – hyperthyroidism, hypoglycemia, hyperparathyroidism, pheochromocytoma

Pulmonary – asthma, COPD, PE

for Cost Effective

Anxiety Due to Substance Use

Substance abuse – cocaine, amphetamines

Substance withdrawal – alcohol, benzodiazepines

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Mixed Anxiety Disorders

Lowe 2008

for Cost Effective

Bystritsky 2004

for Cost Effective

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

for Cost Effective

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

for Cost Effective

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

for Cost Effective

Primary Care PTSD Screen

for Cost Effective

PC-PTSD Screen

Prins, Ouimette, and Kimerling 2003

for Cost Effective

Zung Anxiety Self Rating Scale

Zung 1971

for Cost Effective

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

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

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