Anxiety Disorders

DR. Lely Setyawati, dr. Sp.KJ(K).

Cemas dapat menjadi penyebab seseorang bunuh diri
 Prevalence of Anxiety Disorders
• Anxiety and related disorders are very common in clinical
practice, and frequently comorbid with other psychiatric and
medical conditions

Unfortunately, anxiety disorders are under-diagnosed and

under-treated
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Katzman et al. BMC Psychiatry 2014, 14(Suppl 1):S1
 Prevalence estimates of anxiety and related disorders
among youths in the NCS-A (age 13-18 years)

Anxiety and related disorder Estimated prevalence (%)

12-month Lifetime

Any anxiety disorder 24.9 31.9

Separation anxiety disorder 1.6 7.6

Specific phobia 15.8 19.3

Social anxiety disorder 8.2 9.1

Posttraumatic stress disorder 3.9 5.0

Panic disorder 1.9 2.3

Generalized anxiety disorder 1.1 2.2

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Katzman et al. BMC Psychiatry 2014, 14(Suppl 1):S1

Anxiety Disorders Can Impact Everyday Life
▪For many patients, anxiety disorders are a significant cause of disability

Work
Productivity
Impairment

Social
Impairment

A review of current research findings on generalized anxiety disorder and its associated burden, cost, and resulting disability.
Significant impairment in work productivity defined as ≥10% reduction. Significant social impairment defined as “marked
impairment” based on clinician ratings.

▪88% of the per capita cost of employees with anxiety disorders is due to
lost productivity while at work and 12% is due to the cost of missed work
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Importance of Proper Diagnosis of Anxiety
Disorders

▪About 1 in 5 to 1 in 12 patients presenting to

primary care will have symptoms of an anxiety
disorder
▪Anxiety disorders are often misdiagnosed because
the patient presents with somatic complaints
▪87% of patients with generalized anxiety disorder show
primary symptoms that are not considered “anxiety”

▪In patients with depression, a coexisting anxiety

disorder is often missed and therefore not treated

▪The goal of treatment is for the patient to recover the

ability to interact normally with his/her environment
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 Primary Care Setting

Proper Diagnosis

Failure to Recognize
as Anxiety Ds.

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 Mental Disorders vs. Chronic Physical Conditions

Type of mental disorder

Type of physical
condition Non-comorbid Non-comorbid Comorbid
depressive anxiety disorder depression-anxiet
disorder y
Obesity 1.1 (0.9, 1.2) 1.2 (1.1, 1.4) ⁎ 1.2 (1.0, 1.4) ⁎
Diabetes 1.3 (1.1, 1.6) ⁎ 1.3 (1.1, 1.5) ⁎ 1.4 (1.1, 1.8) ⁎
Asthma 1.7 (1.4, 2.0) ⁎ 1.6 (1.4, 1.8) ⁎ 1.6 (1.4, 1.9) ⁎
Hypertension 1.5 (1.4, 1.8) ⁎ 1.7 (1.5, 1.9) ⁎ 1.8 (1.5, 2.1) ⁎
Arthritis 1.6 (1.4, 1.8) ⁎ 1.7 (1.5, 1.9) ⁎ 2.5 (2.2, 2.9) ⁎
Ulcer 1.8 (1.6, 2.2) ⁎ 1.9 (1.7, 2.3) ⁎ 2.7 (2.3, 3.2) ⁎
Heart disease 2.0 (1.7, 2.3) ⁎ 1.9 (1.6, 2.3) ⁎ 2.8 (2.3, 3.4) ⁎

Back/neck problems 2.2 (1.9, 2.4) ⁎ 2.0 (1.8, 2.3) ⁎ 2.9 (2.5, 3.3) ⁎
Chronic headache 2.5 (2.2, 2.8) ⁎ 2.3 (2.1, 2.5) ⁎ 4.0 (3.5, 4.7) ⁎
Multiple pains 2.5 (2.2, 2.9) ⁎ 2.3 (2.1, 2.6) ⁎ 4.5 (4.0, 5.1) ⁎

* p<0.05
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K.M. Scott et al. / Journal of Affective Disorders 103 (2007) 113–120
1. Both anxiety and depressive disorders
are independently associated with
chronic physical conditions

2. Having both depression and anxiety

further increases the risk of a number
of physical conditions co-occurring.

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10
 Anxiety Disorders

• Features: excessive fear, anxiety ~

behavioral disturbances
• Develop in childhood and tend to persist
if
not treated
• Females > males (2 : 1)

• Increased risk of suicide attempts (1.7 - 2.5 X)

• Comorbid mood disorder  suicidal behavior
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1. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; 2. Katzman et al. BMC Psychiatry 2014, 14(Suppl 1):S1
 Overview of the management of anxiety
and related disorders

• Screen for anxiety and related symptoms

• Conduct DD/
• Identify specific anxiety or related disorder
• Psychological and/or pharmacological
treatment
• Perform follow-up

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Katzman et al. BMC Psychiatry 2014, 14(Suppl 1):S1
 General screening questions

• During the past two weeks how much

have you been bothered by the following
problems?
– Feeling nervous, anxious, frightened, worried,
or on edge
– Feeling panic or being frightened
– Avoiding situations that make you anxious

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Katzman et al. BMC Psychiatry 2014, 14(Suppl 1):S1
 Risk Factors
1. Family history of anxiety (or other mental
disorder)
2. Personal history of anxiety in childhood or
adolescence, including marked shyness
3. Stressful life event and (or) traumatic event,
including abuse
4. Being female
5. Comorbid psychiatric disorder (particularly
depression)
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Can J Psychiatry, Vol 51, Suppl 2, July 2006
 When does anxiety become a disorder?

• Intensity and (or) duration >

• Impairment or disability in occupational, social,
or interpersonal functioning
• Daily activities are disrupted by the avoidance of
certain situations or objects in an attempt to
diminish the anxiety
• Clinically significant, unexplained physical
symptoms and (or) obsessions, compulsions,
and intrusive recollections or memories of
trauma
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Can J Psychiatry, Vol 51, Suppl 2, July 2006
Vegetative Somatic Psychic Motor
▪ Increased heart ▪ Excessive
▪ Pain ▪ Tremor
rate
worry/fear
▪ Diaphoresis ▪ Hot or cold flashes ▪ Insomnia ▪ Dizziness

▪ Dry mouth ▪ Muscle tension ▪ Irritability/agitation

▪ Difficulty ▪ Difficulty
▪ Muscle aches
swallowing concentrating

▪ Abdominal ▪ High startle

▪ Diarrhea
response
discomfort
▪ Palpitations ▪ Restlessne
▪ Paresthesi ss
▪ Respiratory a ▪ Fatigue
symptoms

▪ Foreign-body
sensation

▪ Derealization 16
 Type of Anxiety Disorders

• Separation Anxiety Disorder

• Selective Mutism
• Specific Phobia
• Social Anxiety Disorder (Social Phobia)
• Panic disorder
• Agoraphobia
• Generalized anxiety disorder.
• Substance/Medication-Induced Anxiety
Disorder
 GENERALISED ANXIETY DISORDER

Neurobiology
Aspect
of Anxiety Disorder

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Amigdala Pusat Pengolahan Rasa Takut

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Ke bentuk simptom

Ansietas : Fenotipe

Ansietas

si
Circuit CSTC

dro truk
amygdala

sin kons
-centered

m
circuit

De
Takut Khawatir
• Panik • Kecemasan
• Fobia • Obsesi

Stahl SM. Stahl’s Essential Psychopharmacology. 4th. Ed. 2013; 390-391 *CSTC =Cortico-striato-thalamo cortical
 Fear response ~ Fight or flight

ACC=anterior cingulate cortex. OFC=occipital frontal cortex

Stahl 393 21
PAG= periaqueductal gray □ respons motorik (fight, flight, freezing)
Endocrine ~ Fear

Stahl 394
 Breathing Output ~ Fear response

PBN= parabrachial nucleus (brain stem) 23

Otonomic output ~ Fear

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Hipocampus and Re-experiencing

25
 Worry or Obsessions

CSTC = cortico-striato- thalamo -cortical □DLPFC= dorsolateral PFC 26

 Brain circuit & Symptoms

Khawatir
Korteks frontal/singulat
(kognisi khawatir)
Keterjagaan

Talamus
Insula lobus
(keterjaga temporalis
an)
(aktivasi simpatis)

Perubahan
Ketegangan
otonom
motorik
Ganglia basalis
(ketegangan motorik) 27
Neurotransmiter in Anxiety disorder

• GABA

• Dopamine (DA)

• Serotonine (5-HT1A)

• Nor-epinephrine

• Glutamat

• Cholesitocinin

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 GABA & Anxiety

Obat yang bekerja meningkatkan akivitas

reseptor GABAA
Stresor
Ikatan reseptor
BDZ turun di Ketakutan
korteks frontal, dan
hipokampus, kecemasan
hipotalamus

1. Ninian PT. J Clin Psychiatry 1999; 60 (Suppl 22): 12-17 1999.

2. Nutt DJ, dkk. J Clin Psychiatry. 2001; 62 (Suppl 11): 22-27 2001
3. Kalueff A, dkk. Depress Anxiety 1997; 4: 100-10 1997.
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Management of Anxiety Disorders
 Treatment options for anxiety disorders
Psychological treatment Pharmacological treatment
• Consider treatments that have been most • Refer to section for diagnosed disorder for specific
thoroughly evaluated first medication choices
• If response inadequate, adapt treatment • Consider short-term benzodiazepines if severe
to the anxiety or
individual agitation or acute functional impairment

Step 1: First-line agent

Optimize dosage and duration

Step 2: If inadequate response or side effects, switch to alternate first-line agent. If partial
response, adding another agent may be preferred over switching

Step 3: Consider referral to specialist, or consider combination treatment, or switch to

second- or third-line agents

Potential combinations
• Psychological treatment + pharmacological treatment Contraindicated combinations
• SSRI-SNRI + benzodiazepines (short-term) • SSRI-SNRI-TCA + MAOI
• SSRI-SNRI + anticonvulsant or atypical antipsychotic • Buspirone + MAOI
• Refer to section for disorder for augmenting agents

Follow up
• Response may take 8-12 weeks
• Pharmacotherapy may be needed for 1-2 years or longer 31

Can J Psychiatry, Vol 51, Suppl 2, July 2006

 Medications with Health Canada-approved indications
for the treatment of anxiety disorders
Anx PD SAD OCD GAD PTSD
ds
Antidepressants
SSRIs
Fluoxetine
Fluvoxamine V
Paroxetine V V V
Paroxetine CR V
Sertraline V
V V V
Other antidepressants V
Venlafaxine XR V

V
V V V
Azapirones: Buspirone V
Benzodiazepines* V V 32
Can J Psychiatry, Vol 51, Suppl 2, July 2006
 Medications to avoid during pregnancy

Phase of pregnancy Medication to avoid

First trimester • Carbamazepine
• Divalproex
• Lithium
• Conventional antipsychotics
• Paroxetine
• Benzodiazepines can be
used with caution
Third trimester and High dose benzodiazepines
labour-delivery should be used with
caution
All trimesters MAOIs
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Can J Psychiatry, Vol 51, Suppl 2, July 2006
 Alprazolam Speed of Action
▪ According to several measures, alprazolam demonstrated a rapid onset of action in
the majority of patients

64%

Percent (%)

Magnitude
Hours

Average Time to Patients Achieving Peak Average Benefit Observed 1 Hour

Peak Benefit Benefit Within 1 Hour After Morning Dose

Results from a 9-week, open-label, switch-over study in 30 patients with DSM-IV panic disorder. Patients stable on alprazolam compressed tablet for 3 weeks were
switched to alprazolam extended release. Analysis of profile data derived from the clinician and patient from daily diary records was used to determine magnitude
of benefit.

▪ In patients treated with alprazolam, 90% of the peak benefit occurred within the first hour
post-dose
DSM=Diagnostic and Statistical Manual of Mental Disorders.
3
4
 Improvements in Anxiety and Panic Attacks
▪ After 6 weeks of treatment, alprazolam was found to be significantly more effective than
placebo, according to HAM-A scores and the percentage of patients experiencing freedom
from panic attacks

HAM-A Score Freedom From Panic Attacks

P<0.01
Change From Baseline

P=0.03 P<0.04

Patients (%)
(%)

Data from a double-blind, placebo-controlled, flexible-dose (1-10 mg/d), multicenter, 6-week study (n=209) comparing regular alprazolam given four times per
day with placebo in adult patients, evaluated with the Structured Clinical Interview for DSM-III-R in order to establish a diagnosis of panic disorder
and extensive phobic avoidance (agoraphobia with panic attacks) or limited phobic avoidance. Results are calculated using LOCF.

LOCF=last observation carried forward; HAM-A=Hamilton Rating Scale for Anxiety; DSM=Diagnostic and Statistical Manual of Mental Disorders.
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 Key Decision Points
A. Identify anxiety
symptoms
• Determine whether anxiety causing distress or functional impairment
• Assess suicidality

B. Differential diagnosis
• Is anxiety due to another medical or psychiatric condition?
• Is anxiety comorbid with another medical or psychiatric condition?
• Is anxiety medication-induced or drug-related?
• Perform physical examination and baseline laboratory assessment?

C. Identify specific anxiety disorder

• PD, specific phobia, SAD, OCD, GAD, PTSD

Comorbid medical conditions Comorbid mental disorders

• If medical, assess benefits and risks of • If substance abuse, use caution if prescribing benzodiazepines
medication for the anxiety disorder, • If another anxiety disorder, consider therapies that are first line for both
but disorder impact of untreated disorders
anxiety • If mood disorder, consider therapies that are effective for both
disorders;
also, refer to depression or bipolar disorder guidelines

D. Consider psychological and pharmacological treatment

• Patient preference and motivation extremely important when choosing treatment modality
• If formal psychological treatment not applied, all patients should receive education and support to encourage them to
face their fears
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Can J Psychiatry, Vol 51, Suppl 2, July 2006
THANK YOU

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