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Anxiety Disorders


Title: Overview Author: Hughes Melton Last modified by: ETSU Created Date: 12/29/2006 9:40:09 PM Document presentation format: On-screen Show (4:3) Company – PowerPoint PPT presentation

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Title: Anxiety Disorders

Anxiety Disorders
Sarah Melton, PharmD,BCPP,CGP Director of
Addiction Outreach Associate Professor of
Pharmacy Practice Appalachian College of
Pharmacy Oakwood, VA
  • Given a case example, evaluate whether the
    patient meets DSM-IV-TR criteria for an anxiety
    disorder generalized anxiety disorder (GAD),
    panic disorder, obsessive compulsive disorder
    (OCD), social anxiety disorder (SAD), and
    post-traumatic stress disorder (PTSD).
  • Interpret common rating scales in the evaluation
    and management of anxiety disorders.
  • Distinguish differences in pharmacology,
    kinetics, efficacy, dosing, adverse effects, and
    drug interactions of benzodiazepines in the
    management of anxiety disorders.
  • Compare the efficacy, dosing, and adverse effects
    of the serotonergic antidepressants, and the role
    of antipsychotics in the management of anxiety

  • Evaluate whether patient and professional
    education is optimal to facilitate safe and
    effective drug therapy for anxiety disorders.
  • Using practice guidelines, develop a
    pharmacotherapy plan, including dosing and
    duration of therapy, and nonpharmacologic
    treatments, for a patient with anxiety disorders.
  • Discuss the role of pharmacotherapy in the
    management of anxiety disorders in special
    populations (e.g., children, elderly patients and
  • Resolve potential drug-related problems in
    patients with anxiety disorders.

Epidemiology of Anxiety Disorders
  • As a group - most frequently occurring
    psychiatric disorders
  • Over the past decade, prevalence has not
    changed, but rate of treatment has increased.
  • Patients are frequent users of emergency medical
    services, at high risk for suicide attempts, and
    substance abuse.
  • Costs for anxiety disorders represent one-third
    of total expenditures for mental illness.
  • In primary care, often underdiagnosed or
    recognized years after onset.
  • Median age of onset
  • GAD 31 years
  • SAD 13 years
  • OCD 19 years
  • PTSD 23 years
  • PD 24 years
  • Lifetime prevalence
  • GAD 5.7
  • SAD 12.1
  • OCD 1.6
  • PTSD 6.8
  • PD 4.7

WFSBP Guidelines for the Pharmacological
Treatment of Anxiety, Obsessive Compulsive , and
Post-Traumatic Stress Disorders- First Revision
(2008), Data from the National Comorbidity
Survey Replication(2005)
Treatment Plan
  • Patient preference
  • Severity of illness
  • Comorbidity
  • Concomitant medical illness
  • Complications like substance abuse or suicide
  • History of previous treatments
  • Cost issues
  • Availability of treatments in given area

Patient Education
  • Mechanisms underlying psychic and somatic anxiety
    should be explained.
  • Describe typical features of the disorder,
    treatment options, adverse drug effects.
  • Explain advantages and disadvantages of the drug
  • Delayed onset of effect
  • Activation syndrome or initial jitteriness with

Duration of Drug Treatment
  • Anxiety disorders typically have a waxing and
    waning course.
  • After treatment response, which often occurs much
    later in PTSD and OCD, treatment should continue
    for at least 12 months to reduce the risk of

  • In RCTs, SSRIs and SNRIs have a flat response
    curve with the exception of OCD
  • 75 of patients respond to the initial (low) dose
  • In OCD, the dose must usually be pushed to
    maximally tolerated dosages
  • In elderly patients, treatment should be started
    with half the recommended dose or less to
    minimize adverse effects
  • Patients with panic disorder are very sensitive
    to serotonergic stimulation and often discontinue
    treatment because of initial jitteriness
  • Antidepressant doses should be increased to the
    highest recommended level if the initial low or
    medium dose fails

  • Controlled data on maintenance treatment are
  • Continue the same dose as in the acute phase
  • For improved compliance, administer medications
    in a single dose if supported by half-life data
  • Benzodiazepine doses should be as low as
    possible, but as high as necessary
  • In hepatic impairment, dose should be adjusted

Monitoring Treatment Efficacy
  • Use of symptom rating scales
  • Panic and Agoraphobia Scale (PAS)
  • Hamilton Anxiety Scale (HAM-A)
  • Liebowitz Social Anxiety Scale (LSAS)
  • Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)
  • Clinician-Administered PTSD Scale (CAPS)
  • Scales are time-consuming and require training
  • Clinical Global Impression (CGI) or specific
    self-report measures may suffice in busy settings

Treatment Resistance
  • Many patients do not fulfill response criteria
    after initial treatment
  • Commonly used threshold for response is 50
    improvement in total score of commonly used
    rating scale
  • Review diagnosis, assess for adherence, maximally
    tolerated dosages, sufficient trial period,
    assess for comorbidities
  • Change the dose or switch to another medication?
  • If no response after 4-6 weeks (8-12 weeks in OCD
    or PTSD), then switch medication
  • If partial response, reassess in 4-6 weeks
  • Issue of switching vs. augmentation is debated by
    experts and not clearly defined in the literature

Non-pharmacological Treatment
  • Psychoeducation is essential
  • Disease state, etiology, and treatment options
  • Effect sizes with psychological therapies are as
    high as the effect sizes with medications
  • Exposure therapy and response prevention
  • Agoraphobia, social anxiety, OCD, PTSD
  • Cognitive Behavioral Therapy most evidence to
    support in all disorders
  • Response is delayed, usually later than
  • Prolonged courses are needed to maintain
    treatment response
  • Some evidence to show that treatment gains are
    maintained over time longer than medications
  • Expensive, not readily available in rural or
    remote areas

Selective Serotonin Reuptake Inhibitors (SSRIs)
  • First-line drugs for all anxiety disorders
  • Dose and education at initiation of therapy is
  • Restlessness, jitteriness, insomnia, headache in
    the first few days/weeks of treatment may
    jeopardize compliance
  • Lower starting doses reduces overstimulation
  • Adverse effects include headache, fatigue,
    dizziness, nausea, anorexia
  • Weight gain and sexual dysfunction are long-term
  • Discontinuation syndrome paroxetine
  • Anxiolytic effect is delayed 2-4 weeks (6-8 weeks
    in PTSD, OCD)

Selective Serotonin Norepinephrine Reuptake
Inhibitors (SNRIs)
  • Efficacy of venlafaxine and duloxetine in certain
    anxiety disorders has been shown in controlled
  • Early adverse effects such as nausea,
    restlessness, insomnia and headache may limit
  • Sexual dysfunction long-term
  • Modest, sustained increase in blood pressure may
    be problematic
  • Significant discontinuation syndrome with
    venlafaxine occurs, even with a missed dose
  • Antianxiety effects have latency of 2-4 weeks

Tricyclic Antidepressants (TCAs)
  • Efficacy in all anxiety disorders is well-proven,
    except in SAD
  • Imipramine, clomipramine have most evidence
  • Adverse effects initially increased anxiety,
    anticholinergic, cardiovascular, sedation,
    impaired cognition, decreased seizure threshold,
    elevated LFTs (clomipramine)
  • Weight gain, sexual dysfunction are problematic
  • Discontinuation syndrome
  • Avoid in elderly, patients with cardiovascular
    disease, seizure disorders, and suicidal thoughts
  • Second-line agents because of adverse
  • Dosage should be titrated up slowly onset of
    effect is 2-6 weeks, longer in OCD

Monamine Oxidase Inhibitors (MAOIs)
  • Efficacy of phenelzine established in panic, SAD
    and PTSD
  • Last-line agent for treatment resistance used by
    experienced psychiatrists
  • Risk of adverse effects
  • Life threatening drug and food interactions
  • Patient education on dietary restrictions and
    drug interactions imperative
  • Give doses in the morning and mid-day to avoid
    overstimulation and insomnia

  • Anxiolysis begins in 30-60 minutes after oral or
    parenteral administration
  • Safe and effective for short-term use
    maintenance requires evaluation of risks vs.
  • Avoid in patients with history of substance or
    alcohol abuse
  • Most commonly used in combination with SSRI/SNRI
    during first few weeks of therapy
  • Guideline recommendations Prescribe on
    scheduled, not prn basis
  • Not effective in depression

  • Commonly used in community setting anxiolytic
    effects that may be beneficial in treating GAD
  • There are controlled data supporting efficacy,
    but up to 40 of patients report adverse effects
  • This agent was similar to buspirone in anxiolytic
    effects in a short-term trial
  • Hydroxyzine is not associated with dependence

Other Agents
  • Not FDA- approved for anxiety, but used commonly
    in Europe
  • Effective in acute/long-term GAD and a few trials
    of SAD
  • Typical doses of 300-600 mg/day
  • Onset of activity was evident after 1 week
  • Adverse effects dizziness, sedation, dry mouth,
    psychomotor impairment
  • Pregabalin was not associated with clinically
    significant withdrawal symptoms when tapered over
    1 week
  • Not used in routine treatment of anxiety
    disorders, but may some utility as adjunctive
    agents in some disorders
  • Carbamazepine, valproate, lamotrigine, and
    gabapentin have shown efficacy in preliminary
    studies for PTSD

  • Advantages
  • Non-sedating
  • No abuse potential
  • Disadvantages
  • No antidepressant effect for comorbid conditions
  • Initial therapeutic effect delayed by 1-2 weeks,
    full effects occurring over several weeks
  • Ineffective in patients who previously responded
    to benzodiazepines??
  • Beneficial only in GAD
  • Adverse Effects
  • Nausea, headache, dizziness, jitteriness and
    dysphoria (initial)
  • Dosing
  • Initial 5 mg tid up to maximum 60 mg/day

Other Agents
  • Quetiapine was effective as monotherapy for GAD
  • Atypical antipsychotics have been used as
    adjunctive agents for non-responsive cases of
    anxiety associate with OCD and PTSD
  • ß - blockers reduce autonomic anxiety symptoms
    such as palpitations, tremor, blushing
  • However, double-blind studies have not shown
    efficacy in any disorder
  • Recommended for use in nongeneralized SAD given
    before a performance situation

Differentiating Anxiety Disorders
  • Many anxiety disorders present similarly
  • Key to differentiation is rationale behind fear
  • Panic attacks occur in both social anxiety and
    panic disorder
  • Fear of anxiety symptoms is characteristic of
    panic disorder
  • Fear of embarrassment is from social interactions
    typifies SAD
  • GAD is likely diagnosis if anxiety about social
    situations are part of a pattern of multiple
  • Anxiety may also be induced by medications or
    medical conditions

  • A 70-year-old man presents to his physician
    complaining of having trouble sleeping, being
    nervous all the time, and feeling like he is
    going to lose control. His wife died 2 years
    ago and the symptoms have been getting worse
    since that time. He is retired as an accountant,
    but lately cannot even concentrate to pay his own
    bills. He has seasonal allergies, COPD, angina,
    and Type II diabetes. Medications include
    albuterol/ipratropium inhaler, theophylline,
    enalapril, aspirin, metformin, and loratatadine
    with pseudoephedrine. He smokes 2 ppd (100 pack
    years). He drinks 8-10 drinks/day that are
    caffeinated and also drinks 2-3 beers nightly to
    help him fall asleep and relieve his stress.
  • What factors should be considered in the
    assessment and differential diagnosis of this
    patients anxiety?

Substance-Induced Anxiety
  • CNS Stimulants
  • CNS depressant withdrawal
  • Psychotropic medications
  • Cardiovascular medications
  • Heavy metals and toxins

Anxiety Secondary to Medical Conditions
  • Endocrine
  • Addisons disease
  • Cushing disease
  • Hyperthyroidism
  • Hypoglycemia
  • Pheochromocytoma
  • Cardiovascular
  • Angina, MI
  • CHF, MVP
  • Respiratory
  • Asthma, COPD
  • Hyperventilation, PE
  • Metabolic
  • Porphyria, Vitamin B12 deficiency
  • Neurologic
  • CNS neoplasms, chronic pain
  • Encephalitis, PD, epilepsy
  • Gastrointestinal
  • Crohns Disease, PUD
  • IBS, Ulcerative Colitis
  • Inflammatory
  • RA, SLE
  • Other
  • HIV, Malignancy

McClure EB, Pine DS. (2009). Clinical Features of
the Anxiety Disorders. In BJ Sadock, VA Sadock ,
P Ruiz (Eds.). Kaplan and Sadocks Comprehensive
Textbook of Psychiatry (9th ed, pp. 1844-1855).
Philadelphia, PA Lippincott, Williams and
CASE 1 (continued)
  • Factors that need further investigation before a
    diagnosis of an anxiety disorder can be made
  • Medical illness (COPD, angina)
  • Possible depression, adjustment to stressors
  • Medications/substances
  • Pseudoepehdrine
  • Theophylline
  • Caffeine
  • Nicotine

  • A 30-year-old woman presents to her PCP c/o of
    daily headaches, muscle tension, diarrhea and
    difficulty sleeping. She states that her husband
    says she is a worry wart and she admits that
    she has difficulty controlling her anxiety over
    her financial situation, job security, and the
    safety of her children. She has become irritable
    because she always feels on the edge. The
    symptoms started 7 months ago, following the
    death of her sister but she recalls her mother
    telling her that she worried too much, just like
    her father during her adolescent years.
  • She is employed as an office manager, but has
    missed several days of work in the past month
    because of her anxiety, physical symptoms, and
    inability to concentrate.
  • No significant past medical history and only
    medications include a multivitamin.
  • PPH Major Depression 2 years ago treated with
    fluoxetine 20 mg for 6 months.
  • She is married with 2 children (ages 3 and 6),
    denies tobacco or alcohol use. Drinks 1 cup of
    coffee in the morning and an occasional soda in
    the afternoon.

Problem Identification
  • What symptoms does the patient exhibit that are
    consistent with Generalized Anxiety Disorder?
  • What risk factors are present in her history?
  • What are treatment options?

Diagnostic Criteria for GAD
  • The patient reports having excessive anxiety and
    worry occurring more days than not for at least 6
    months about a number of events of activities
    (such as work or school performance).
  • The patient has difficulty in controlling worry.
  • The anxiety and worry are associated with 3 or
    more of the following 6 symptoms
  • Restlessness or feeling keyed up and on edge
  • Easily fatigued
  • Difficulty concentrating, or mind going blank
  • Irritability
  • Sleep disturbance (difficulty falling asleep or
    staying asleep, or restless, unsatisfying sleep)

Diagnostic and Statistical Manual of Mental
Disorders-IV-TR, 2000.
CASE 2 (continued)
  • Risk Factors for GAD present in case
  • Gender (female)
  • Genetic factors (father)
  • Medication/substance induced (stimulant)
  • Stressful event (death of sister)
  • Treatment options
  • Nonpharmacologic - Psychoeducation, CBT
  • Pharmacologic (antidepressants, benzodiazepines,
    buspirone, others)

Pharmacological Treatment of GAD
  • First-line
  • Recommended daily doses
  • Escitalopram 10-20mg Venlafaxine 75-225 mg
  • Paroxetine 20-50 mg Duloxetine 60-120 mg
  • Sertraline 50-150 mg
  • Second-line
  • Benzodiazepines when patient has no history of
    dependency may combine with antidepressants for
    first 2-4 weeks
  • Pregabalin 150-600 mg Imipramine 75-200 mg
  • Others
  • Hydroxyzine 37.5-75 mg effective in trials for
    acute anxiety, but ADRs limit use
  • Buspirone 15- 60 mg indicated for GAD, but
    efficacy results were inconsistent
  • Treatment resistance
  • Augmentation of SSRI with atypical antipsychotic
    (quetiapine, risperidone or olanzapine)
  • Quetiapine effective as monotherapy, but not FDA
    approved for anxiety because of metabolic and
    cardiac risks associated with chronic use

WFSBP Guidelines for the Pharmacological
Treatment of Anxiety, Obsessive Compulsive , and
Post-Traumatic Stress Disorders- First Revision
  • A 24-year old college student presents to the
    student mental health facility for follow-up for
    treatment of panic disorder with agoraphobia. He
    presented 5 months ago complaining of attacks of
    chest pain, SOB, tingling fingers, dizziness,
    nausea. During the attacks, he felt like he was
    outside his body and everything was crashing
    in on him. He began staying in his apartment
    nearly all the time and was on the verge of being
    dismissed from college for not attending classes.
  • He was started on paroxetine 5 mg daily and
    alprazolam 0.5 mg three times daily. His current
    doses are paroxetine 40 mg po daily and
    alprazolam 1 mg in the morning, 1 mg at lunch,
    and 2 mg at bedtime.
  • He was doing so well that he decided to
    discontinue the alprazolam yesterday because his
    mother told him she thought he was hooked on
    it. Today, he feels quite anxious, his heart is
    racing, and his hands are tremulous. He wonders
    if he is getting ready to have a full-blown panic
  • What do you recommend at this point in his

Diagnostic Criteria for Panic Disorder
  • Presence of at least 2 unexpected panic attacks
    characterized by at least 4 of the following
    somatic or cognitive symptoms, which develop
    abruptly and peak within 10 minutes
  • Cardiac, sweating, shaking, SOB or choking,
    nausea, dizziness, depersonalization, fear of
    loss of control, fear of dying, paresthesias,
    chills or hot flashes
  • The attacks are followed by one of the following
    for 1 month
  • Persistent concern about having another attack
  • Worry about consequences of the attack
  • Significant change in behavior because of the
  • May occur with or without agoraphobia

Diagnostic and Statistical Manual of Mental
Disorders-IV-TR, 2000.
Panic Attack/Agoraphobia
  • Panic Attack
  • About 7 of the population will experience at
    least one panic attack
  • Types
  • Unexpected (uncued)
  • Situationally bound (cued)
  • Situationally predisposed
  • Can occur in the context of another anxiety or
    mental disorder
  • Agoraphobia
  • Anxiety about being in a situation where escape
    is difficult or help is unavailable in the event
    of a panic attack
  • Examples of feared situations open spaces,
    trains, tunnels, bridges, crowded rooms
  • Situations are avoided or endured with
    significant anxiety about having a panic attack
    or symptoms
  • Can persist even after panic attacks abate

Panic Disorder - Treatment
  • Non-pharmacologic Treatment
  • Avoid trigger substances
  • Caffeine, OTC stimulants, nicotine, drugs of
  • CBT
  • Correct avoidance behavior
  • Train individual to identify and control signals
    associated with panic attacks
  • Efficacy 80-90 short term

Pharmacological Treatment of Panic Disorder
  • First-line
  • Recommended daily doses
  • Citalopram 20-60 mg Paroxetine 20-60 mg
  • Escitalopram 10-20 mg Sertraline 50-150 mg
  • Fluoxetine 20-40 mg Venlafaxine 75-225 mg
  • Fluvoxamine 100300 mg
  • Second-line
  • Imipramine 75-250 mg , clomipramine 75-250 mg
  • Benzodiazepines when no history of dependency
    may combine with antidepressants for first 2-4
    weeks for more rapid response and to limit ADRs
  • Alprazolam 1.5-8 mg/day Diazepam 5-20 mg/day
  • Clonazepam 1-4 mg/day Lorazepam 2-8 mg/day
  • Treatment-resistance phenelzine

WFSBP Guidelines for the Pharmacological
Treatment of Anxiety, Obsessive Compulsive , and
Post-Traumatic Stress Disorders- First Revision
Panic Disorder Therapeutic Use of Benzodiazepines
  • Antipanic effect begins within the first week
  • Effective in 55-75 of panic disorder patients
  • Effective in patients needing rapid relief of
    anticipatory anxiety
  • Breakthrough (interdose rebound) anxiety may
    occur 3-5 hours after a dose of shorter acting
    benzodiazepines such as alprazolam
  • Dependence/withdrawal are associated with
    long-term use or high dose

Benzodiazepines Pharmacokinetics
  • Onset of Action
  • High lipophilicity fastest absorption faster
    onset but also euporic rush
  • Diazepam, clorazepate, alprazolam
  • Lower lipophilicity longer onset, less euphoria
  • Chlordiazepoxide, clonazepam, oxazepam
  • Duration of Action (t1/2)
  • Long diazepam, chlordiazepoxide, clonazepam
  • Short alprazolam, lorazepam, oxazepam
  • Metabolic Pathway
  • Hepatic microsomal oxidation (Phase I metabolism)
  • Impaired by aging, liver disease, or meds that
    inhibit oxidative process
  • Prolonged half-life, accumulation
  • Alprazolam, clonazepam, chlordiazepoxide,
    clorazepate, diazepam
  • Glucuronide conjugation (Phase II metabolism)
  • Lorazepam, oxazepam

Benzodiazepines Drug Interactions
  • Pharmacodynamic
  • CNS depressants alcohol, barbiturates, opiates
  • Pharmacokinetic
  • Inhibitors cimetidine, nefazodone, fluoxetine,
    fluvoxamine, erythromycin, ketoconazole, oral
    contraceptives, protease inhibitors, grapefruit
    juice, isoniazid
  • Inducers phenytoin, carbamazepine,
    phenobarbital, rifampin

Benzodiazepines Dependence and Abuse
  • Physical dependence
  • Within 3-4 months, can lead to down-regulation of
    endogenous GABA production
  • Withdrawal symptoms common
  • Rebound anxiety, insomnia, jitteriness, muscle
    aches, depression, ataxia, blurred vision
  • Do not stop therapy abruptly TAPER
  • Abuse
  • High risk in patients with substance or alcohol
    abuse history
  • Alprazolam, lorazepam, and diazepam

Benzodiazepine Withdrawal
  • Onset, duration and severity varies according to
    dosage, duration of treatment, and half-life, and
    speed of discontinuation
  • Short half-life, withdrawal begins in 1-2 days,
    shorter duration, more intense
  • Long half-life, withdrawal begins in 5-10 days,
    lasts a few weeks
  • Common symptoms anxiety, insomnia, irritability,
    nausea, diaphoresis, systolic hypertension,
    tachycardia, tremor
  • Possible consequences delirium, confusion,
    psychosis, seizures

CASE 3 (Continued)
  • The patient has had excellent response to
    pharmacotherapy however, he has only been
    treated for 5 months.
  • Treatment guidelines recommend therapy for at
    least 1 year after resolutions of symptoms before
    considering discontinuation
  • Benzodiazepines are typically used in the first
    2-4 weeks as acute therapy, so it is reasonable
    to consider slowly tapering the alprazolam at
    this point.
  • Abrupt discontinuation is not appropriate he now
    has withdrawal symptoms that must be addressed,
    as well as his concern about addiction.

Benzodiazepine Discontinuation
  • Typical tapering schedule for benzodiazepines
  • 25 per week reduction in dosage until 50 of
    dose then reduce by one eighth every 4-7 days
  • Therapy gt 8 weeks taper over 2-3 weeks
  • Therapy gt 6 months taper over 4-8 weeks
  • Therapy gt 1 year taper over 2-4 months
  • For patients on high potency benzodiazepines for
    monotherapy of panic disorder, a very gradual
    discontinuation is recommended
  • Discontinue benzodiazepines slowly over 3-4
    months to prevent relapse and emergence of
    withdrawal symptoms
  • Alprazolam doses gt3 mg/d ? by 0.5 mg every 2
    weeks until 3 mg, then ? by 0.25 mg every 2 weeks
    until 1 mg, then ? by 0.125 mg every 2 weeks
  • Clonazepam ? by 0.125 mg every 2 weeks
  • Diazepam ? by 2.5 mg every 2 weeks
  • Lorazepam ? by 0.5 mg every 2 weeks

Diagnostic Criteria for SAD
  • A marked and persistent fear of one or more
    social or performance situations involving
    exposure to unfamiliar people or possible
    scrutiny by others. The person fears that he or
    she will act in a way (or show symptoms of
    anxiety) that will be humiliating or embarrassing
  • Exposure to the feared social situation provokes
    anxiety or even a panic attack
  • The person recognizes that the fear is excessive
    or unreasonable
  • Feared social or performance situations are
    avoided or endured with intense anxiety or
  • The condition interferes significantly with the
    person's normal routine, occupational (or
    academic) functioning, or social activities or
    relationships, or there is marked distress about
    having the phobia
  • Specify the disorder as generalized if fears
    include most situations

Diagnostic and Statistical Manual of Mental
Disorders-IV-TR, 2000.
Social Anxiety Disorder Treatment
  • Early detection and treatment is important
  • Because of the nature of the illness, patients
    are reluctant to to seek treatment
  • Pharmacological and nonpharmacological therapy
    both effective

Social Anxiety Disorder Nonpharmacologic Treatment
  • CBT
  • Change negative thoughts patterns
  • Repeated exposure to feared situation
  • Social skills training
  • 12-16 weekly sessions, each 60-90 minutes
  • Workbook with homework exercise
  • Clinical improvement within 6-12 weeks
  • Long term gains

Pharmacological Treatment of SAD
  • First-line
  • Recommended doses
  • Escitalopram 10-20 mg Fluoxetine 20-40 mg
  • Fluvoxamine 100-300 mg Sertraline 50-150 mg
  • Paroxetine 20-50 mg Venlfaxine 75-225 mg
  • Second-line
  • Imipramine 75-200 mg
  • Clonazepam 1.5-8 mg/day, when patient has no
    history of dependency may combine with
    antidepressants for first 2-4 weeks
  • Treatment resistance
  • Addition of buspirone to an SSRI effective in one
    open study buspirone not effective as
  • Phenelzine

WFSBP Guidelines for the Pharmacological
Treatment of Anxiety, Obsessive Compulsive , and
Post-Traumatic Stress Disorders- First Revision
Case 4
  • A 28-year old woman presents to the Anxiety
    Disorders Clinic after being referred by her PCP.
    The patient recently gave birth to a son 2
    months ago. Within 2 weeks after delivery, she
    started having intrusive thoughts of harming her
    baby. Over and over again, she imagined herself
    dropping the baby, cutting or burning him. She
    checks the appliances in the house multiple times
    to make sure they are cut off because she fears
    starting a fire that will harm the baby. She
    will not use the kitchen knives or scissors.
  • She spends 40 minutes every time she goes
    out checking and re-checking the babys car seat,
    so now she just stays at home. She reports some
    relief during the day when she knocks on hard
    objects in 3 sets of 5 knocks. She is so
    concerned about hurting her baby that she has
    started avoiding holding him except when nursing.
    She says that half of her days are consumed with
    her checking behavior. Past psychiatric history
    is positive for depression when she was in
    college that responded well to sertraline. YBOCS
    score 32

Diagnostic Criteria for OCD
  • Obsessions
  • Recurrent and persistent thoughts, impulses or
    images that are intrusive and cause a great
    amount of anxiety
  • These thoughts, impulses, or images are not
    worries about daily life issues
  • Patient attempts to ignore or suppress the
    thoughts, impulses, images, or to neutralize them
    by applying special thoughts or actions
  • The thoughts, impulses, or images are recognized
    as a product of the patients mind
  • Compulsions
  • Repetitive behaviors that the person feels
    compelled to perform in response to an
    obsession, or according to rigid self-imposed
  • The behaviors or mental acts are aimed at
    preventing or reducing distress or preventing
    some dreaded event or situation but are not
    connected in a realistic or logical way with what
    they are designed to neutralize or prevent
  • The person has recognized that the obsessions or
    compulsions are excessive or unreasonable (this
    does not apply to children).

Diagnostic and Statistical Manual of Mental
Disorders-IV-TR, 2000.
OCD Comorbidities
  • Depression (75)
  • Anxiety disorders
  • Tic Disorders (20-30)
  • 5-7 have full Tourettes syndrome
  • PANDAS (pediatric autoimmune neuropsychiatric
  • OCD spectrum disorders
  • Somatoform disorders (body dysmorphic disorder)
  • Eating disorders (anorexia, bulimia,
  • Impulse control disorders (trichotillomania,
    compulsive nail biting, kleptomania, compulsive

OCD Non-Pharmacologic Treatment
  • CBT
  • Exposure therapy with response prevention
  • High rate of discontinuation
  • Effective in 66-75 of patients if continued
  • Neurosurgery
  • Intervention to hyperreactive portions of brain
  • Effective in 40-90 of treatment resistant
  • Deep brain stimulation

Pharmacotherapy of OCD
  • First-line
  • Recommended doses/day
  • Escitalopram 10-20 mg Fluoxetine 40-60 mg
  • Fluvoxamine 100-300 mg Paroxetine 40-60 mg
  • Sertraline 50-200 mg
  • Second-line- typically reserved until after
    failure with 2 SSRIs
  • Clomipramine 75-250 mg equally effective as
    SSRIs but less well-tolerated
  • Treatment resistance
  • Intravenous clomipramine (not FDA approved) was
    more effective than oral clomipramine
  • SSRI antipsychotic (haloperiodol, quetiapine,
    olanzapine, risperidone) more effective than SSRI

WFSBP Guidelines for the Pharmacological
Treatment of Anxiety, Obsessive Compulsive , and
Post-Traumatic Stress Disorders- First Revision
CASE 4 (continued)
  • What is the most appropriate therapy for this
    patient what do we know?
  • YBOCS 32 (extremely severe OCD)
  • She is breastfeeding
  • Previous response to sertraline for depression
  • Treatment algorithm developed by the American
    Psychiatric Association considers CBT or SSRI to
    be first-line treatments

Case 4 (continued)
  • The patient declines CBT because of cost and time
  • She prefers therapy with medication as she had
    positive experience when her depression was
  • Sertraline 25 mg po every AM is prescribed with
    decision to increase dose to 50 mg by the end of
    the week. She will follow-up for assessment in
    one week.

Goals of Therapy in OCD
  • Marked clinical improvement, recovery, and full
  • Decrease symptom frequency and severity, improve
    the patients functioning, and help the patient
    improve QOL
  • Enhance the patients ability to cooperate with
  • Anticipate stressors likely to exacerbate OCD and
    help the patient develop coping strategies
  • Minimize any adverse effects
  • Educate the patient and family about OCD and its
  • Reasonable treatment outcome targets include
  • less than 1 hour per day spent obsessing and
    performing compulsive behaviors no more than
    mild OCD-related anxiety an ability to live with
    uncertainty and little or no interference of OCD
    with the tasks of ordinary living

Assessment of Response in OCD
  • Most patients will not experience substantial
    improvement until 46 weeks after starting
    medication, for some 1012 weeks.
  • Higher SSRI doses produce higher response rates
    and greater magnitude of symptom relief
  • Doses can be titrated more rapidly in OCD (in
    weekly increments to maximum dosage), rather than
    waiting for treatment response for 1-2 months.
  • Example (Case 4), the patient would go from 50 mg
    at the end of week 1 to 100 mg at the end of week
    2, with subsequent increases of 50 mg/day at
    weekly intervals up to 200 mg/day.

Assessment of Response in OCD
  • The Y-BOCS rating scale is helpful to document
    treatment response over time
  • In clinical trials, OCD responders
  • Y-BOCS scores decrease by at least 2535 from
  • Rated much improved or very much improved on the
    Clinical Global ImpressionsImprovement scale

OCD Duration of Therapy
  • After response, patient should remain on
    pharmacotherapy for at least 1-2 years
  • Medication should be tapered over an extended
    period of time
  • Decrease dose by 25 every 2 months
  • Life-long prophylaxis recommended after 2-4
    severe relapses or 3-4 mild relapses

Diagnostic Criteria for PTSD
  • Criterion A stressor
  • The person has been exposed to a traumatic event
    in which both of the following have been present
  • The person has experienced, witnessed, or been
    confronted with an event or events that involve
    actual or threatened death or serious injury, or
    a threat to the physical integrity of oneself or
  • The person's response involved intense fear,
    helplessness, or horror. Note in children, it
    may be expressed instead by disorganized or
    agitated behavior.
  • Criterion B intrusive recollection
  • Criterion C avoidance/numbing
  • Criterion D hyper-arousal
  • Criterion E duration
  • Duration of the disturbance (symptoms in B, C,
    and D) is more than one month.

Diagnostic and Statistical Manual of Mental
Disorders-IV-TR, 2000.
Subtypes of PTSD
  • Acute symptom duration of lt 3 months
  • Chronic symptom duration of gt 3 months
  • Delayed onset symptoms begin gt 6 months after
    the traumatic event

Acute Treatment After Traumatic Event
  • Symptoms should diminish over the first few weeks
  • Social support is critical
  • 4-5 sessions of time-limited psychotherapy during
    the first month reduces the rates of PTSD by at
    least 50

PTSD Treatment Psychotherapy
  • Education
  • Nature of the condition
  • Process of recovery
  • Understanding that symptoms are a psychobiologic
    response to overwhelming stress
  • Goals of Psychotherapy
  • Reduce the level of distress associated with
    memories of the event
  • Reduce the physiological reaction to memories

Types of Psychotherapy
  • Cognitive therapy
  • Exposure therapy
  • Imaginal or in vivo exposure
  • Anxiety management
  • Relaxation training
  • Stress inoculation training
  • Breathing retraining
  • Assertiveness and positive thinking and
  • Interpersonal or group therapy
  • Play (children) and drama (adults) therapy

Pharmacotherapy of PTSD
  • First-line
  • Recommended doses/day
  • Fluoxetine 20-40 mg Paroxetine 20-40 mg
  • Sertraline 50-100 mg Venlafaxine 75-300 mg
  • Prazosin may be more effective in combat-related
  • Second-line therapies
  • TCAs amitriptyline, imipramine 75-200 mg
  • Mirtazapine 30-60 mg
  • Risperidone 0.5-6 mg
  • Lamotrigine (study doses ranged from 50-500
  • Nefazodone (effective in small, controlled trial
    in male combat veterans)
  • Treatment resistance
  • Venlafaxine, prazosin, quetiapine venlafaxine,
    gabapentin SSRI

WFSBP Guidelines for the Pharmacological
Treatment of Anxiety, Obsessive Compulsive , and
Post-Traumatic Stress Disorders- First Revision
PTSD Treatment Augmenting Agents
Medications PTSD Symptoms
Antiadrenergics Hyperarousal, flashbacks and impulsivity monitor BP, PR Prazosin nightmares and sleep disruption
Anticonvulsants Startle response, nightmares
Antipsychotics Psychosis or flashbacks with hallucinations, dissociation
Cyproheptadine Nightmares
Lithium Irritability, mood swings
Acute administration of propranolol superior to
placebo in reducing subsequent PTSD symptoms and
physiological hyperactivity, but not the
emergence of PTSD. Benzodiazepines are not
recommended in patients with PTSD early
administration does not prevent emergence of PTSD
and may be associated with a less favorable
Foa E. Effective treatments for PTSD, Chapter 6.
2nd edition, 2009. The Guilford Press, New York,
Goals of Pharmacotherapy for PTSD
  • Reduce core PTSD symptoms
  • Reduce disability
  • Improve QOL
  • Improve resilience to stress
  • Reduce co-morbidity

Treatment of Anxiety Disorders Under Special
  • Pregnancy
  • Risks of drug treatment must be weighed against
    risk of withholding treatment
  • Majority of studies indicate that use of most
    SSRIs and TCAs imposed no increased risk for
  • Avoid paroxetine due to risk of cardiac
  • Benzodiazepines are typically avoided in
    pregnancy because of reports of congenital
    malformations however, there is no consistent
    evidence that benzodiazepines are hazardous
  • Literature suggests safety with diazepam and
    chlordiazepoxide alprazolam should be avoided
  • Breast feeding paroxetine, sertraline,
    nortriptyline are safer avoid benzodiazepines
    and fluoxetine

Treatment of Anxiety Disorders Under Special
  • Children and Adolescents
  • Many experts feel drug therapy should be reserved
    for patients who do not respond to psychological
  • SSRIs are first-line drug treatment
  • Careful monitoring required for activation
    syndrome and increased suicidal thoughts or
  • Elderly
  • Increased sensitivity for anticholinergic
  • Increased risk of EPS, orthostasis, EKG changes
  • Increased risk of paradoxical reactions to
  • Few trials evaluate anxiety in the elderly
  • Venlafaxine efficacious in elderly with GAD
  • Citalopram effective in patients older than 60
    with anxiety disorders

Anxiety Disorders