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ANXIETY DISORDERS
Dr. Manal Buabeid
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LIST OF DISORDERS
• MOST COMMON PSYCHIATRIC DISORDERS
• Generalized anxiety disorder (GAD)
• Panic disorder with or without agoraphobia
• Obsessive compulsive disorder (OCD)
• Post traumatic stress disorder (PTSD)
• Social phobia
• Specific phobia

• Substance induced anxiety disorder

• Anxiety disorder due to general medical condition
• Anxiety disorder not otherwise specified (NOS)
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DEFINITIONS
• Anxiety:
• A mixture of arousal, negative affects
• A sense of danger or lack of control over events
• Less clearly focused on a particular danger

• Panic attack:
• A discrete period, in which there is a sudden onset of intense fear
or terror accompanied by peripheral manifestations of anxiety

• Agoraphobia:
• Anxiety about, or avoidance of, places or situations from which
escape might be difficult
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DIFFERENTIAL DIAGNOSIS

• Anxiety disorder due to a general medical condition

• Substance induced anxiety disorder

• Anxiety associated with other psychiatric illnesses:

(depression or psychosis)
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SECONDARY CAUSES OF ANXIETY

• Medical conditions:
• Endocrine or metabolic disorders (electrolyte abnormalities,
hypoglycemia, hyperthyroidism)
• CV (CHF, MI, HTN)
• GI (PUD, IBS)
• Respiratory (COPD, asthma)
• Psychiatric:
• Depression, mania, schizophrenia, eating disorders
• Drugs:
• CNS stimulants, CNS depressants
• Excessive caffeine intake, nicotine withdrawal
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TREATMENT TARGETS
• GABA is a predominant inhibitory NT
• BZs potentiate the effects of endogenous GABA

• 5-HT hypofunction is associated with hypersensitivity to

environmental cues and increased responsiveness to
threat

• NE facilitates the physiologic and behavioral adaptation to

stress, alarm and fear
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TREATMENT
• Pharmacologic:
• Benzodiazepines (BDZs)
• Antidepressants
• SSRIs
• TCAs
• MAOIs

• Non-pharmacologic:
• Behavioral
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GAD – Definition
• Excessive and persistent worrying that is hard to control
• Causes significant distress or impairment
• Occurs on more days than not for at least six months
• Other features include:
• Psychological symptoms of anxiety, such as apprehensiveness and
irritability
• Physical (or somatic) symptoms of anxiety, such as increased
fatigue and muscular tension
One of the most common mental disorders in primary care settings and
is associated with increased use of health services 

Twice as common in women as it is in men

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GAD - Pathogenesis
• Biological factors  Genetics
• Neuropsychological factors  Brain metabolism of
glucose
• Developmental and personality factors  higher-than-
average number of traumatic experiences and other
undesirable life events in childhood
• Cognitive origins of excessive worrying
• Constantly scan the environment for cues of threat
• Develop worrying in an attempt to solve problems
• Use worrying to avoid the fear response
• Have intolerance of uncertainty or ambiguity
• Worry about the uncontrollability and presumed dangerous
consequences of worrying
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GAD – Clinical Presentation

• Hyperarousal
• Autonomic hyperactivity
• Motor tension
• Poor sleep
• Fatigue
• Difficulty relaxing
• Headaches and pain in the neck, shoulders, and back
• Having greater worry over minor matters
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GAD – Diagnosis (DSM V – TR) 

A. Excessive anxiety and worry (apprehensive expectation), occurring more days than
not for at least six months, about a number of events or activities (such as work or
school performance)
B. The individual finds it difficult to control the worry
C. The anxiety and worry are associated with three (or more) of the following six
symptoms (with at least some symptoms having been present for more days than not
for the past six months):
Note: Only one item is required in children.
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 (difficulty falling or staying asleep, or restless, unsatisfying sleep)
D. The anxiety, worry, or physical symptoms cause clinically significant distress or
impairment in social, occupational, or other important areas of functioning
E. The disturbance is not attributable to the physiological effects of a substance (eg, a
drug of abuse, a medication) or another medical condition (eg, hyperthyroidism)
F. The disturbance is not better explained by another mental disorder
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GAD – Differential diagnosis

• Depression
• Hypochondriasis
• Panic disorder
• Adjustment disorder
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GAD – Treatment
• First line
• SSRIs
• SNRIs
• Second line
• TCAs
• BDZs
• Buspirone
• Pregabalin
• Other medications
• Other antidepressants
• Antipsychotics
• Hydroxyzine
• Duration of treatment
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GAD – First Line

• SSRIs
• Recommended
• Paroxetine 
• Sertraline  
• Citalopram
• Escitalopram
• Alternative
• Fluoxetine
• Fluvoxamine
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GAD – First Line

• SSRIs
• Choose SSRI based on side effects and tolerability
• Sexual dysfunction
• Gastrointestinal abnormalities (nausea and diarrhea)
• Insomnia
• Withdrawal on discontinuation
• Drug interactions
• WEIGHT GAIN
• Agitation and/or hyperactivation

• Same dosing and tapering up as in depression

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GAD – First Line

• SSRIs
• Time to effect is ~ 4 weeks
• Concomitantly administered benzodiazepine (eg,lorazepam1 to
2 mg/day in divided doses)  Treat agitation and anxiety during this
time
• If partial response  Increase dose
• If no improvement after 6 – 8 weeks on a therapeutic dose 
Taper off and switch to a different SSRI
• If no response to 2nd SSRI  Go to 2nd line or augment SSRI
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GAD – First Line

• SNRIs
• Venlafaxine
• Duloxetine

• Side effects
• Nausea, dizziness, insomnia, sedation, constipation, and sweating
• Venlafaxine  may increase blood pressure

Tricyclic antidepressants
Imipramine

Increase risk of cardiotoxicity in overdose and less acceptable

tolerability profiles
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GAD – Second Line

• Benzodiazepines 
• Reduction of emotional and somatic symptoms within minutes to
hours
• Given during acute, maintenance, or long-term treatment of GAD
• Monotherapy (if no comorbid depression)
Or
• More common  Adjunct to antidepressant
• Acute management of anxiety and worry during the period before SSRIs
or SNRIs take effect
• Counteract the initial agitation often caused by the SSRI
• When patient responds to the SSRI  Taper off benzodiazepine
gradually
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GAD – Second Line

• Benzodiazepines 
• Chronic GAD
+
• Minimal depressive symptoms
+
• No history of substance abuse

GIVE long-term, low-dose benzodiazepine treatment (if

antidepressants are ineffective or poorly tolerated)
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GAD – Second Line

• Benzodiazepines – Pharmacology 
• Potentiate the effects of endogenous GABA (main inhibitory
neurotransmitter)
• GABAA receptors  Mediates neuronal excitability (seizures),
rapid mood changes, clinical anxiety, and sleep
• GABAB receptors  Mediate memory, mood, and analgesia
• GABAC receptors  Role remains unclear

• Flumazenil  BDZ antagonist to GABAA

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GAD – Second Line

• Benzodiazepines – Drug Interactions
• Increased with  Alprazolam, diazepam, midazolam, triazolam
• Decreased with  Oxazepam, lorazepam, and temazepam

• Benzodiazepines – Side effects

• Impairment of psychomotor performance, amnesia, dependence
• Withdrawal symptoms after long-term treatment
• Rebound anxiety after short-term treatment

• Short t1/2  Rapid withdrawal  alprazolam,lorazepam, and oxazepam

• Long t1/2  delayed withdrawal  clorazepate, diazepam, flurazepam,
prazepam, and clonazepam

• Taper down slowly  Decrease by 10% of dose q 1 – 2 weeks

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GAD – Second Line

• Buspirone 
• Pharmacology  blocks 5HT1A autoreceptors

• Time to onset  4 weeks

• Use as monotherapy (if no comorbid depression) or augmentation

• SE: dizziness, chest pain, headache

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GAD – Second Line

• Pregabalin 
• Pharmacology   inhibits calcium currents via high-voltage-
activated channels containing the α2d-1 subunit

• Not approved by USA (only Europe)

• Generally better tolerated than benzodiazepines

• SE: sedation and dizziness

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GAD – Other medications

• Other antidepressants
•  Mirtazapine
• Single agent or augmentation to SSRI
• May be useful in the treatment of refractory anxiety with insomnia
• SE: Weight gain and sedation
• Not FDA Approved
• Antipsychotic medications
• Quetiapine
• Adjunct to SSRI or SNRI
• Not FDA Approved
• Hydroxyzine 
• Efficacious for GAD
• More sedating than benzodiazepines and buspirone  Good for
insomnia
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GAD – Duration Of Pharmacotherapy 

•  If effective antidepressant
 Continue AD for at least 12 months

• If relapse following termination of an effective medication

 Extend length of treatment

• After two relapses when tapering off the medication

 Ongoing maintenance treatment should be considered
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PD – Definition
• Patients experience:
• Recurrent, unexpected panic attacks
And
• One month or more of either worry about future
attacks/consequences, or a significant maladaptive change in
behavior related to the attacks, such as avoidance of the
precipitating circumstances
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PD – Epidemiology
• 12-month prevalence in the United States (age 15 to 54
years)  2.7 %
• Lifetime prevalence in the United States (US) population
(age 15 to 54 years)  4.7 %

• Twice as common in women as among men

• Frequently accompanied by comorbid psychiatric

disorders
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PD – Pathophysiology
• Genetic factors
• First degree relatives
• Twin studies
• Childhood adversity
• History of physical or sexual abuse
• Several personality traits
• Anxiety sensitivity  measure of fear of anxiety symptoms and catastrophic cognitions
regarding bodily sensations (rapid heartbeat may be misinterpreted as a heart attack)
• Neuroticism  personality trait that is associated with poor stress resilience and often
manifests in greater reactivity to life stressors
• Uncontrollable or undesirable events causing severely reduced self-esteem
• An accident, trauma, rape, assault, or physical illness (including endocrinologic
changes, eg, hyperthyroidism)
• Severe illness or death in a friend or relative
• Neurobiology 
• Serotonin, norepinephrine, and GABA
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PD – Clinical Presentation
• Panic disorder 
• Panic attacks  sudden onset of intense apprehension, fear or
terror, and by the abrupt development of specific somatic,
cognitive, and affective symptoms
• Somatic features 
• Cardiac / Neurologic / Gastrointestinal
• Agoraphobia (independent of panic disorder)
• Anxiety about and avoidance of situations where help may not be
available or where it may be difficult to leave the situation in the
event of developing panic-like symptoms or other incapacitating or
embarrassing symptoms
• Utilization of medical services 
• Substance use 
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PD – Diagnosis
• History and physical examination

• Testing  thyroid function tests, complete blood count,

and a chemistry panel

• DSM 5
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• An abrupt surge* of intense fear or intense discomfort that

reaches a peak within minutes, and during which time four
or more of the following 13 symptoms occur:
1.Palpitations, pounding heart, or accelerated heart rate
2.Sweating
DSM 5 3.Trembling or shaking

Panic Attacks 4.Sensations of shortness of breath or smothering

5.Feelings of choking
6.Chest pain or discomfort
7.Nausea or abdominal distress
8.Feeling dizzy, unsteady, light-headed, or faint
9.Chills or heat sensations
Paresthesias (numbness or tingling sensations)
10.
Derealization (feelings of unreality) or depersonalization (being
11.
detached from oneself)
Fear of losing control or "going crazy"
12.
Fear of dying
13.
• The abrupt surge can occur from a calm state or an
anxious state
• Note: Culture-specific symptoms (eg, tinnitus, neck
soreness, headache, uncontrollable screaming or crying)
may be seen. Such symptoms should not count as one of
the four required symptoms
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A. Recurrent unexpected panic attacks

B. At least one of the attacks has been followed by a
month or more of one or both of the following:
1. Persistent concern or worry about additional panic attacks or
DSM 5 their consequences (eg, losing control, having a heart attack,
"going crazy")
Panic disorder
2. A significant maladaptive change in behavior related to the
attacks (eg, behaviors designed to avoid having panic attacks,
such as avoidance of exercise or unfamiliar situations)
C. The disturbance is not attributable to the physiological
effects of a substance (eg, medication or illicit drug) or
another medical condition (eg, hyperthyroidism,
cardiopulmonary disorders).
D. The disturbance is not better explained by another
mental disorder. As examples, the panic attacks do not
occur only in response to:
• Feared social situations, as in social anxiety disorder
• Circumscribed phobic objects or situations, as in specific
phobia;
• Obsessions, as in obsessive-compulsive disorder
• Reminders of traumatic events, as in posttraumatic stress
disorder
• Separation from attachment figures, as in separation anxiety
disorder
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PD – Differential Diagnosis
• Somatic symptom disorder
• Antisocial personality disorder or substance abuse problems,
chaotic family histories, childhood sexual or physical abuse or
emotional neglect
• Illness anxiety disorder 
• Other mental disorders 
• Schizophrenia, bipolar disorder …
• Stimulant abuse
• Caffeine / cocaine / amphetamines
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PD – Treatment
• SSRIs
• SNRIs
• Benzodiazepines  we usually starts with it
• TCAs
• MAOIs
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PD – SSRIs
• No evidence for superior efficacy in panic disorder among
the SSRIs
• Fluoxetine  longer half-life / more stimulating / DDI
• Paroxetine  short half-life (given qd) / has some anticholinergic
effects / may be more sedating (bedtime)
• Sertraline  diarrhea
• Fluvoxamine uncommonly used because short t ½ (bid or tid)
• Citalopram  qd and low DDI
• Escitalopram  qd and low DDI

• Reduce the frequency of panic attacks, severity of

anticipatory anxiety, and degree of phobic avoidance
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PD – SSRIs
• Dosing
• Same as depression
• Start low and taper up very slowly
• PD patients are sensitive to overstimulation effects with antidepressants

• Side effects
• Headaches, irritability, gastrointestinal distress (nausea or
diarrhea), insomnia and sexual dysfunction
• Serotonin syndrome
• Withdrawal syndrome
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PD – SNRIs
• Venlafaxine extended release (ER)

• Second choice for use if SSRIs are ineffective

• May cause hypertension, particularly at higher dose + may be
lethal in overdose

• Reduces all three core components of panic disorder

(attack frequency, anticipatory anxiety and phobic
avoidance)
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PD – SNRIs
• Dosing
• ER  start 37.5 mg, taken orally in the morning
• Increase up to 225 mg in six weeks

• Side effects
• Nausea, dry mouth, constipation, anorexia, sweating, somnolence
and sexual dysfunction

PD – Benzodiazepines 
Alprazolam & clonazepam  FDA
Approved
• Clonazepam > alprazolam
• Clonazepam
• Longer t ½  qd or bid
• Less intensive symptoms on
discontinuation
• Alprazolam
• Shorter t ½  tid or qid
• Alprazolam XR  bid
• More inter-dose anxiety
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Lorazepam & diazepam  Effective
• When alprazolam’s faster
onset of action (greater lipid
solubility and brain
penetration), is combined
with its short half-life
Strongly reinforce pill-taking to
alleviate anxiety
Can enhance potential for
abuse, and may reduce self-
efficacy (ie, patients’ confidence
that they can manage their
anxiety on their own)
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PD – Benzodiazepines 
• Dosing 
• Clonazepam  0.5 mg/day taken orally at bedtime up to 1 to 3
mg/day
• Divide dose if breakthrough anxiety
• Alprazolam  0.25 mg tid or qid up to 10 mg/day (most patients
respond to 2- 6 mg/day)

• Taper and D/C over 6 months

• Not more than 10 % of the dose reduced every 2 weeks
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PD – Benzodiazepines 
• Side effects
• Abuse and addiction especially for the short acting
• Risk of abuse confined to individuals with a substance abuse history
or problem (family history ?)
• Withdrawal if stopped abruptly
• Sedation, fatigue, psychomotor impairment and reduced memory
and concentration
• Caution against operating motor vehicles or heavy machinery

• Treatment lasting months or more  physiological dependence

and consequent withdrawal symptoms if discontinued too quickly
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PD – TCAs and MAOI

TCAs MAOIs

• Imipramine / Clomipramine • Phenelzine 

• Dosing
• 10 mg/day and increase up to 200
mg/day in 25 mg increments/week
infrequently used due to
dietary restrictions and
side effects

• Side effects 
• Anticholinergic effects, sweating,
sleep disturbance, orthostatic
hypotension, fatigue and weakness,
weight gain, modest blood pressure
increases, and sexual dysfunction
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PD – Onset and Duration of treatment

• Onset of therapeutic effect  2 to 4 weeks
• Clinical response  can take up to 8 to 12 weeks

• PD  Continue for at least one year after symptom

control has been attained

• Severe PD  Treatment for more than one to two year

range
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PD – Treatment Selection
• Treat on the basis of patient preference and treatment availability
• Medication
• Psychotherapy (CBT)
• Combined treatment  Meds + Psychotherapy (CBT)

• First line  SSRIs

• Second line  different SSRI
• Third line  Not responded to one or more trials of SSRIs  venlafaxine ER

• Severe symptoms and associated disability that has either not responded to an
SSRI or SNRI, or who cannot wait for the time required for them to work  Give
long acting BDZ
• Augment in the first weeks of treatment before antidepressant takes effect
• Caution for history of drug abuse

• Serotonergic antidepressant + CBT  panic disorder + other psychiatric disorders

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OCD – Definition
• Recurrent intrusive thoughts, images, or urges
(obsessions)
• Typically cause anxiety or distress, and by repetitive
mental or behavioral acts (compulsions)
• Individual feels driven to perform, either in response to an
obsession or according to rules that he or she believes
must be applied rigidly
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OCD – Epidemiology
• Childhood or adolescence
• Persists throughout a person’s life
• Produces substantial impairment in functioning due to the
severe and chronic nature of the illness

• 12-month prevalence in United States  1.2 %

• Lifetime prevalence in United States  2.3 %

• Mean age  19.5 years

• May appear at 14 years
• Males have an earlier age of onset than females
• < 10 years
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OCD – Pathophysiology
• Genetic factors 
• Environmental factors
• Group A streptococcal infection in childhood
• Neurobiology 
• Abnormalities in serotonergic or dopaminergic signaling

OCD – Clinical Presentation
Obsessions
• Repetitive and persistent
• Thoughts (eg, of contamination)
• Images (eg, of violent or horrific
scenes)
• Urges (eg, to stab someone)
• Obsessions are not
pleasurable or experienced
as voluntary
• Intrusive, unwanted, and
cause marked distress or
anxiety in most individuals
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Compulsions
• Rituals
• Repetitive behaviors (eg,
washing, checking) or
mental acts (eg, counting,
repeating words silently)
• Individual feels driven to
perform in response to an
obsession or according to
rules that must be applied
rigidly
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OCD – Differential Diagnosis

• Anxiety disorder
• Major depression
• Tic disorder
• Psychotic disorder
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OCD – Treatment
• Exposure and response prevention (a type of CBT) is more effective
than medication as first-line treatment of non-comorbid OCD

• Medications  patients who prefer medication to psychotherapy, or

when CBT is not available
• SSRIs: GOOD EVIDENCE
• Fluoxetine, fluvoxamine, sertraline, paroxetine  FDA APPROVED
• Citalopram and escitalopram  Not FDA approved by effective

• Clomipramine: GOOD EVIDENCE

• FDA approved

• Venlafaxine: NO GOOD EVIDENCE

• Less data and Not FDA approved
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OCD – Medication selection

• First-line treatment  SSRIs
• Choice among the SSRIs on the basis of prior treatment response,
drug side effects and their acceptability to the patient, and the
potential for drug interactions
• Second line treatment  Another SSRI or Clomipramine
or Venlafaxine

• If partial response  Augmentation

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OCD – Medication Dosing

• Higher doses than depression

Class Drug Dose

Fluoxetine 40 to 80 mg/day
Fluvoxamine 200 to 300 mg/day

Paroxetine 40 to 60 mg/day
SSRI
Sertraline 200 mg/day
Citalopram up to 40 mg/day
Escitalopram 20 to 40 mg/day

TCA Clomipramine 100 to 250 mg/day

SNRI Venlafaxine 225 to 350 mg/day

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OCD– Onset and Duration of treatment

• Adequate trial  maximum tolerated dose for a minimum
of 6 weeks

• Duration of treatment  at least one to two years

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OCD – Augmentation
• Add:
• Risperidone or another antipsychotic medication (haloperidol,
quetiapine, olanzapine)
• Added only after the patient has not responded following a trial of at
least 12-weeks at the maximal antidepressant dose tolerated
• Cognitive-behavioral therapy (CBT)
• A low dose of clomipramine 10 – 50 mg/day (to an SSRI or SNRI)
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PTSD – Definition
• Complex somatic, cognitive, affective, and behavioral
effects of psychological trauma
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PTSD – Epidemiology
• Military combat
• Violent personal assault
• Natural and man-made
disasters
• Severe motor vehicle accidents
• Rape
• Incest
• Childhood sexual abuse
• Diagnosis of a life-threatening
illness
• Severe physical injury
• Hospitalization in an intensive
care unit (ICU)
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PTSD – Pathophysiology
• Increased central norepinephrine levels with down-
regulated central adrenergic receptors

• Chronically decreased glucocorticoid levels with up-

regulation of their receptors
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PTSD – Clinical Presentation

• Most individuals who experience trauma react to some
degree when experiencing reminders of the trauma

• Marked cognitive, affective, and behavioral responses to

stimuli, leading to flashbacks, severe anxiety, and fleeing
or combative behavior
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PTSD – Treatment
• Trauma-focused cognitive-
behavioral therapy (CBT)

• Medication  First line:

SSRI or SNRI
• Patients who prefer
medication to psychotherapy,
or when CBT is not available

• Or combination of both
modalities
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PTSD – Other Treatment and Adequate Trial

• Atypical antipsychotics
• Risperidone and olanzapine
• If no response after 2 – 3 weeks  D/C gradually
• Alpha-adrenergic receptor blockers
• For sleep disruption or nightmares  Prazocin
• Benzodiazepines
• Treat symptoms of anxiety and hyperarousal

• Medication should be continued for at least 6 months to a

year to prevent relapse or recurrence
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Social Phobia (SP)

• Definition
• Social anxiety disorder (SAD), also known as social phobia, is
characterized by excessive fears of scrutiny, embarrassment and
humiliation in social or performance situations, leading to significant
distress and/or impairment in functioning
• Epidemiology
• SAD is one of the most common psychiatric disorders with a lifetime
prevalence in the US estimated to be 5 to 12 %
• Its prevalence may be lower in developing countries
• Mean age of onset in the mid-teens, although it can occur as early as
age five years. New onset of SAD after age 30 is uncommon, but can
occur in the context of new social demands (eg, promotion to a job that
requires public speaking)
• Pathophysiology
• Genetic and environmental factors contribute to the development of SAD
 62

SP
• Treatment
• Antidepressant or cognitive behavioral therapy
• Partial response to CBT  SSRI
• Partial response to SSRI  CBT

• First-line treatment  SSRI or SNRI

• Prefer medications or no CBT

• After a therapeutic trial of 8 to 12 weeks with an SSRI or SNRI at a

maximally tolerated dose  augmentation with a long-acting
benzodiazepine
• Others: gabapentin or pregabalin
 63

Specific Phobias (SPS)

• Definition
• Anxiety characterized by clinically significant anxiety associated
with anticipation of, or exposure to, a circumscribed situation or
object that often leads to avoidant behavior and results in
considerable distress and impairment in functioning
• Types
• Animal, natural environment, blood-injection-injury, situational, and
other
• Assess for significant impairment and disability that may
be associated with the disorder
 64

SPS
• Treatment
• First-line treatment with CBT over other psychotherapeutic or
pharmacologic interventions

• Benzodiazepine
• Lorazepam  infrequently encountered phobic stimulus

• SSRI
• CBT unavailable or patient prefers medications