Anxiety Disorders
Sarah Melton, PharmD,BCPP,CGP
Director of Addiction Outreach
Associate Professor of Pharmacy Practice
Appalachian College of Pharmacy
Oakwood, VA
Objectives
• Given a case example, evaluate whether the patient meets DSMIV-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 disorders.
Objectives
• Evaluate whether patient and professional education is
optimal to facilitate safe and effective drug therapy for anxiety
disorders. (DII)
• 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 pregnancy).
• 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 risk
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
SSRIs/SNRIs
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 relapse.
Dosing
• 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
Dosing
• Controlled data on maintenance treatment are
scarce
– Continue the same dose as in the acute phase
• For improved compliance, administer
medications in a single dose if supported by halflife 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 selfreport 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 medications
– 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
important
– 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
concerns
• 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 studies
• Early adverse effects such as nausea, restlessness,
insomnia and headache may limit compliance
• 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 long-term
• Discontinuation syndrome
• Avoid in elderly, patients with cardiovascular disease, seizure
disorders, and suicidal thoughts
• Second-line agents because of adverse effects/toxicity
• 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
Benzodiazepines
• Anxiolysis begins in 30-60 minutes after oral or parenteral
administration
• Safe and effective for short-term use; maintenance
requires evaluation of risks vs. benefits
• 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
Hydrozyzine
• 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
PREGABALIN
• 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
ANTICONVULSANTS
• 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
Buspirone
– Beneficial only in GAD
– Adverse Effects
• Nausea, headache,
dizziness, jitteriness
and dysphoria (initial)
– Dosing
• Initial 5 mg tid up to
maximum 60 mg/day
– 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??
Other Agents
ATYPICAL ANTIPSYCOTICS
• 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
BETA-ADRENERGIC BLOCKERS
• β - 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 worries
• Anxiety may also be induced by medications or
medical conditions
CASE 1
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 patient’s anxiety?
Substance-Induced Anxiety
•
•
•
•
•
CNS Stimulants
CNS depressant withdrawal
Psychotropic medications
Cardiovascular medications
Heavy metals and toxins
Anxiety Secondary to Medical
Conditions
• Endocrine
– Addison’s 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 Sadock’s Comprehensive
Textbook of Psychiatry (9th ed, pp. 1844-1855). Philadelphia, PA: Lippincott,
Williams and Wilkins.
CASE 1 (continued)
• Factors that need further investigation before
a diagnosis of an anxiety disorder can be
made include:
– Medical illness (COPD, angina)
– Possible depression, adjustment to stressors
– Medications/substances
•
•
•
•
Pseudoepehdrine
Theophylline
Caffeine
Nicotine
CASE 2
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 (2008)
CASE 3
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 attack.
What do you recommend at this point in his therapy?
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 attack
• 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 abuse
– 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 100–300 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 (2008)
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 longterm use or high dose
Benzodiazepines – Pharmacokinetics
• Onset of Action
• Metabolic Pathway
– High lipophilicity – fastest
– Hepatic microsomal oxidation
absorption = faster onset but also
(Phase I metabolism)
“euporic rush”
• Impaired by aging, liver
• Diazepam, clorazepate,
disease, or meds that inhibit
alprazolam
oxidative process
– Lower lipophilicity = longer onset,
– Prolonged half-life,
less euphoria
accumulation
• Chlordiazepoxide,
– Alprazolam, clonazepam,
clonazepam, oxazepam
chlordiazepoxide,
clorazepate, diazepam
• Duration of Action (t1/2)
• Long: diazepam,
chlordiazepoxide,
clonazepam
• Short: alprazolam, lorazepam,
oxazepam
– 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 halflife, 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 > 8 weeks: taper over 2-3 weeks
– Therapy > 6 months: taper over 4-8 weeks
– Therapy > 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 >3 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 distress
• 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 24 weeks
• Treatment resistance
– Addition of buspirone to an SSRI effective in one open
study; buspirone not effective as monotherapy.
– Phenelzine
WFSBP Guidelines for the Pharmacological Treatment of Anxiety, Obsessive Compulsive , and Post-Traumatic Stress Disorders- First Revision (2008)
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 baby’s 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
Case 4
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
patient’s mind
• Compulsions
– Repetitive behaviors that the person feels “compelled” to perform in
response to an obsession, or according to rigid self-imposed rules
– 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 Tourette’s syndrome
• PANDAS (pediatric autoimmune neuropsychiatric
disorders)
• OCD spectrum disorders
– Somatoform disorders (body dysmorphic disorder)
– Eating disorders (anorexia, bulimia, binge-eating)
– Impulse control disorders (trichotillomania, compulsive
nail biting, kleptomania, compulsive buying)
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 patients
• 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 alone
WFSBP Guidelines for the Pharmacological Treatment of Anxiety, Obsessive Compulsive , and Post-Traumatic Stress Disorders- First Revision (2008)
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 commitment.
• She prefers therapy with medication as she
had positive experience when her depression
was treated.
• 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 remission
• Decrease symptom frequency and severity, improve the patient’s
functioning, and help the patient improve QOL
• Enhance the patient’s ability to cooperate with care
• 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 treatment.
• 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 4–6 weeks after starting medication,
for some 10–12 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 25%–35% from
baseline
– Rated much improved or very much improved on
the Clinical Global Impressions–Improvement
scale (CGI-I).
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 others.
• 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 < 3 months
• Chronic – symptom duration of > 3 months
• Delayed onset – symptoms begin > 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 self-talk
• 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 PTSD
• 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 mg/day)
– 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 (2008)
PTSD Treatment: Augmenting Agents
Medications
PTSD Symptoms
Antiadrenergics
Hyperarousal, flashbacks and
impulsivity – monitor BP, PR
Prazosin – nightmares and sleep
disruption
Startle response, nightmares
Psychosis or flashbacks with
hallucinations, dissociation
Nightmares
Irritability, mood swings
Anticonvulsants
Antipsychotics
Cyproheptadine
Lithium
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 outcome. Foa E. Effective treatments for PTSD, Chapter 6. 2 edition, 2009. The Guilford Press, New York, NY.
nd
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 Conditions
• 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 malformations
• Avoid paroxetine due to risk of cardiac malformations
– 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 Conditions
• Children and Adolescents
– Many experts feel drug therapy should be reserved for
patients who do not respond to psychological therapy
– SSRIs are first-line drug treatment
– Careful monitoring required for activation syndrome and
increased suicidal thoughts or behaviors
• Elderly
– Increased sensitivity for anticholinergic properties
– Increased risk of EPS, orthostasis, EKG changes
– Increased risk of paradoxical reactions to benzodiazepines
– 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
CONCLUSION