Treatment of

Anxiety
Disorders
CHERRYRICH M. CHENG, MD, DSBPP
OBJECTIVES

 At the end of this lecture the participants should

be able to
 Identify the different DSM 5 diagnosis under Anxiety
Disorders
 Explain the principles of psychopharmacologic
treatment for anxiety disorders
Overview of Anxiety
Disorders
Both anxiety and fear can involve arousal, or sympathetic nervous
system activity

Anxiety Fear
• Apprehension over an • Reaction to immediate danger
anticipated problem • Fight or flight
• Helping us plan for future threats
Overview of Anxiety
Disorders
 Associated with significant morbidity and often are chronic
and resistant to treatment

DSM 5

• Panic disorder
• Agoraphobia
• Specific phobias
• Social anxiety disorder
• Generalized anxiety
disorder
Overview of Anxiety
Disorders
Burden of Anxiety Disorders

• Associated with twice the average rate of

medical costs
• Higher risk of cardiovascular diseases
• Twice the risk of suicidal ideation and attempts
compared to people without a psychiatric
diagnosis
• Difficulties in employment
• Serious interpersonal concerns
• Decrease quality of life
Symptoms in Anxiety
disorders
fatigue
concentration arousal

Panic attacks
anxiety Worry
sleep
Phobic
avoidance
irritability Muscle Compulsions
tension
Panic Disorder

 An acute attack of anxiety

accompanied by feelings of
impending doom
 All diagnoses under anxiety
disorders may have episode/s of
panic attacks
Panic Disorder
 Criterion A  Palpitations
 Recurrent unexpected  Chest pain
panic attacks
 SOB/DOB
 Reaches peak within
 Feelings of choking
minutes
 Sweating
 Accompanied by 4 or
more the following  Chills
symptoms:
 Paresthesias
 Trembling
 Nausea/ abdominal distress
 Dizzy/faintiness
 Derealization/depersonalizations
 Loosing control
 Fear of dying
Panic Disorder

 Criterion B
 At least one of the attacks has been followed by 1
month or more of one or both
 Persistent concern or worry about additional panic
attacks
 Significant maladaptive change in behavior such as
avoidance

 Criterion C
 Not due to substance
 Criterion D
 Not better accounted for by other disorder
Agoraphobia
 From the Greek word “agora” or marketplace
 Anxiety about inability to flee anxiety- provoking situations
 Causes significant impairment
 In DSM-IV-TR, was a subtype of Panic Disorder
 Al least half of agoraphobics do not suffer panic attacks
Agoraphobia
 Criterion A
 Marked fear or anxiety on 2 or more of the following 5
situations:
Specific Phobias
 The single most common mental disorder in
the US, affecting approximately 10-25
percent of the population.
 A phobia is defined as a disrupting, fear-
mediated avoidance that is out of
proportion to the danger posed by a
particular situation or object.
 Moreover, the patient recognizes this as a
groundless and irrational fear.
Specific Phobias
 The term phobia implies also that a person suffers intense
distress and social or occupational impairment because of the
anxiety.
 Lasts for 6 months
Social Anxiety Disorder
 Persistent, irrational fears generally
linked to the presence of other people
 Lifetime prevalence: 3 to 13 percent
 Onset usually during adolescence
 More debilitating than specific
phobias: suicide rates are increased
among persons with social phobias as
compared to other anxiety disorders
Social Anxiety Disorder
 The person with social phobia usually tries to avoid situations in
which he might be evaluated.
 Can either be generalized or specific, depending on the range
of situations feared or avoided
 Persons with generalized social phobias have an earlier age of
onset, more comorbidity with other disorders, and more severe
impairment.
Generalized Anxiety
Disorder
Excessive anxiety and worry at least 50 percent of days about
at least two life domains (e.g., family, health, finances, work,
and school)
 The worry is sustained for at least 3 months AND is associated
with at least three of the following:
 1. restlessness or feeling keyed up or on edge
 2. being easily fatigued
 3. difficulty concentrating or mind going blank
 4. irritability
 5. muscle tension
 6. sleep disturbance
Generalized Anxiety
Disorder
Generalized anxiety disorder is the disorder that most often
coexists with another mental disorder!
 80% of those with anxiety disorder meet criteria for another
anxiety disorder, usually phobias or panic disorder.
 75% of those with anxiety disorder meet criteria for another
psychological disorder.
Psychotherapies

 Psychotherapies are based on several theories

 Psychodynamic/Psychoanalytic
 Behavioral
 Cognitive
Pharmacologic treatment
of anxiety Disorders
Relationship between
Anxiety and Depression
Anxiety Phenotype
Anxiety Phenotype

Amygdala Centered
Circuit

Cortico-striato-thalamo-
cortical Circuit
Connections of the
Amygdala
Prefrontal cortex • regulates emotions

Periaqueductal gray
• Regulate the motor responses to fear
area of the brain stem

Hypothalamus • Endocrine reactions brought about by fear

Parabrachial Nucleus • Regulates breathing

Locus Ceruleus • Noradrenergic responses

Hippocampus • Stored memory like trauma

Cortico-striato-thalamo-
cortical Circuit
 CSTC loop in the Prefrontal Cortex is linked to the
“worry” symptoms of anxiety disorders
Neurobiological Modulators
of Amygdala and CSTC Loop
 Serotonin
 Innervates the amygdala as well as elements of the CSTC loop
 Acute stress results in increased serotonin turn over in the
prefrontal cortex
 Norepinephrine
 Chronic symptoms experienced by patients with anxiety disorder
are characteristic of increased noradrenergic function
 Patients with anxiety disorders have poorly regulated
noradrenergic activity
 GABA
 Most strongly supported by undisputed efficacy of
benzodiazepines
The Use of Antidepressants
 Antidepressants play a role in the treatment of anxiety due to
their close relationship in symptomatology and
neurophysiology with depression
 Currently, many clinicians consider SSRIs the first-line treatment
choice
 Relapse is common upon discontinuation; hence,
combination therapy with psychological treatment is
recommended.
The Use of Antidepressants

Monoamine
Neurotransmitt
ers

Degradatio Storage Reuptake

n / Inhibition Inhibition inhibitors

Stimulant
s (Methyl
MAOIs phenidat TCA SSRI SNRI
e)
The Use of Antidepressants
SSRI Additional General Indications
Receptor Binding Effects
Fluoxetine With 5HT 2c Generally Depressed patients
(Prozac) Antagonist activating with reduced positive
properties affect, hypersomnia,
psychomotor
retardation, apathy
and fatigue
Sertraline Dopamine Mildly More advantageous in
(Zoloft) transporter activating use for Psychotic and
inhibition and δ1 Anxiolytic delusional depression
receptor binding effects
Paroxetine Muscarinic More calming For patients with
(Seroxat) anticholinergic & / sedating anxiety symptoms
noerepinephrine however causes sexual
transporter dysfunctions and
inhibitory withdrawal with
The Use of Antidepressants
SSRI Additional General Indications
Receptor Binding Effects
Fluvoxamin Sigma- 1 receptor More potent For psychotic and
e binding properties δ1 receptor delusional depression
(Voxamine binding than Obsessive-compulsive
) sertraline D/O
Escitalopra Removed Best tolerated SSRI,
m unwanted R used in elderly patients
(Lexapro) enantiomer of and has fewest CYP-
citalopram mediated drug
interaction
Use of Antidepressants

 SNRI
 are a newer form of antidepressant that work on
both NE and 5HT
 they typically have similar side effects to the SSRIs
 there may be a withdrawal syndrome on
discontinuation that may necessitate dosage
tapering

 desvenlafaxine, duloxetine,
venlafaxine
Benzodiazepines

 These medications are sometimes classified as

sedative-hypnotics , although other drugs can
also be classified under this group.
 A sedative drug is used primarily to reduce
daytime anxiety, tamper excessive excitement,
and to calm persons.
 A hypnotic drug on the other hand produces
drowsiness and facilitates the onset and
maintenance of sleep.
Benzodiazepines

 In general, benzodiazepines act as hypnotics in

high doses and as anxiolytics or sedatives in low
doses.
 Benzodiazepines are the drugs of choice for
management of acute anxiety and agitation.
 There is however a risk for psychological
dependence.
 Mechanism of Action
Positive Allosteric Modulator: Cl Ions
a drug, eg BZD, acts as an agonist at the
allosteric (ie, ‘other site’) modulatory binding site
GABA
of a neurotransmitter, eg GABA. BZD

Bilipid Layer Cell Membrane

Receptor Complex
Benzodiazepines

 Pharmacokinetics
 The rapid onset benzodiazepines are desirable for
persons who take a single dose to calm an episodic
burst of anxiety or to fall asleep rapidly.
 Only lorazepam and midazolam have rapid and
reliable absorption following IM administration.
Benzodiazepines
 Choosing a benzodiazepine – onset of action

Fast-acting Medium-acting Slow-acting

benzodiazepines benzodiazepines benzodiazepines
w/in 15 mins 15 – 30 mins 30 – 60 mins
• Clonazepam • Alprazolam • Oxazepam
• Diazepam • Lorazepam • Prazepam
• Flurazepam • Chlordiazepoxide
• Triazolam
• Midazolam
• Zolpidem
Benzodiazepines

• Choosing a benzodiazepine- duration

of effects
Intermediate half-
Long half-lives Short half-lives
lives
18 – 50 hours 1 – 6 hours
3 – 40 hours
• Clonazepam • Alprazolam • Flurazepam
• Diazepam • Lorazepam • Midazolam
• Oxazepam • Zolpidem (2.6
• Temazepam hours)
• Chlordiazepoxide
Benzodiazepines

Choosing a benzodiazepine- duration of

effects
 The advantages of long half-life drugs over short
half-life drugs include:
 Less frequent dosing
 Less variation in plasma concentration
 Less severe withdrawal phenomena
 The disadvantages of long half-life drugs over short
half-life drugs include:
 Drug accumulation
 Increased daytime psychomotor impairment
 Increased daytime sedation
Benzodiazepines
 Adverse effects
 The most common adverse effect is drowsiness.
 This occurs in about 10 percent of all patients.
 Commonly, drowsiness can occur the day after its use, in so-called
daytime sedation.
 The most serious adverse effects occur when other sedative
substances such as alcohol is taken concurrently.
 This can lead to marked drowsiness, disinhibition, or marked
respiratory depression.
 Anterograde amnesia may also occur.
Benzodiazepines VS.
Antidepressants
 Antidepressants
 Maintained usually for 6 months or more
 Effects are seen after 2-3weeks
 Use Benzodiazepines for short term treatment

INITIATION OF TREATMENT
Antidepressants + Benzodiazepine
Beta Blockers
 Propanolol
 may be given to patients with performance only type of social
anxiety
 20 – 40 mg an hour prior to public speaking
Starting Pharmacological
Treatment
Rule out other comorbid medical condition
• Cushing’s
• Pheochromocytoma
• DM etc...
Start low and go slow

Psychoeducation is very important

• Efficacy
• Explain adverse effects
Often Asked Questions

 Would I get addicted to the medications?

 How soon would I notice improvements?
 How long do I have to take the medications?
 What are the possible side effects?