Transcript Anxiety Disorders

Anxiety Disorders
Mayyada Wazaify, Phd
Are You Anxious?
• Take the test
• Score?
5- mild
10- moderate
15- severe
Worry vs. Anxiety?
Worry
Anxiety
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• Our bodies
• Diffuse
• Verbal thought and Mental
imagery
• Not productive
• Severe emotional distress
• Mostly unrealistic
• Less controllable
• Can linger
• Does impact personal and
professional functionning
In our heads
More specific
Verbally focused
Triggers problem solving
Mild emotional distress
Caused by more realistic
concerns
• More Controllable
• Temporary state
• Doesn’t impact personal and
professional functioning
Winch G. Psychology Today. 2016
Anxiety
• an emotional state commonly caused by the
perception of real or perceived danger that
threatens the security of an individual.
• Anxiety Disorder: persistent, severe anxiety
symptoms with irrational fears that
significantly impair normal daily functioning
Epidemiology
• the most commonly occurring psychiatric
disorders.
• a group of heterogeneous illnesses that develop
before age 30 years
• more common in women, individuals with social
issues, and those with a family history of anxiety
and depression.
• Patients often develop another anxiety disorder,
major depression, or substance abuse.
• The clinical picture of mixed anxiety and
depression is much more common than an
isolated anxiety disorder.
Etiology
• Differentiate from“situational” anxiety
• The differential diagnosis: psychiatric and
medical illnesses and certain drugs
• Combination of factors:
1. Vulnerability (e.g. genes+ childhood adversity)
2. Stress (e.g. Occupational or traumatic)
Pathologic anxiety may be:
(1) primary anxiety disorder,
(2) secondary anxiety disorder due to medical
causes or substances,
(3) response to acute stress (e.g., loss of a loved
one, marital or family problems),
(4) symptom associated with other psychiatric
disorders.
Common Medical Illnesses Associated
with Anxiety Symptoms
Drugs Associated with Anxiety
Symptoms
Neurobiology of Anxiety
• Involves multiple regions of the brain and
abnormal function in several neurotransmitter
systems,
• norepinephrine (NE), γ-aminobutyric acid
(GABA), serotonin (5-HT), corticotropinreleasing factor (CRF), and cholecystokinin.
• Neuroanatomic models of fear- key brain
areas
Key Brain Areas
IMPORTANT: Watch the video
Key Brain Areas
1. The amygdala: a temporal lobe structure- assessment
of fear stimuli and learned response to fear.
2. The locus ceruleus (LC), located in the brain stem, is
the primary NE-containing site, with widespread
projections to areas responsible for implementing
fear responses (e.g., vagus, lateral and paraventricular
hypothalamus).
3. The hippocampus: integral in the consolidation of
traumatic memory and contextual fear conditioning
4. The hypothalamus: the principal area for integrating
neuroendocrine and autonomic responses to a threat.
CLINICAL PRESENTATION
DSM-IV classification of primary
anxiety disorders
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Generalized anxiety disorder (GAD),
Panic disorder (with or without agoraphobia),
Agoraphobia,
Social Anxiety Disorder (SAD),
Specific phobia,
Obsessive-compulsive disorder (OCD),
Posttraumatic stress disorder,
Acute stress disorder
Generalized Anxiety Disorder (GAD)
IMPORTANT: Watch the video
Generalized Anxiety Disorder (GAD)
• unrealistic , excessive, persistent anxiety and
worry about a number of events or activities.
• The patient usually has great difficulty
controlling the worry, which is accompanied
by at least three of the associated symptoms
• persistent symptoms for most days for at least
6 months.
Generalized anxiety disorder (GAD)
clinical presentation
Panic Attack
watch the video!
• Panic disorder begins as a series (at least 2) of
unexpected (spontaneous) panic attacks
involving an intense, terrifying fear similar to
that caused by life-threatening danger.
• The unexpected panic attacks are followed by
at least 1 month of:
a) persistent concern about having another panic attack,
b) worry about the possible consequences of the panic attack, or a
c) significant behavioral change related to the attacks.
Panic Attack
clinical presentation
DSM-V
4 or more
For Dx of panic disorder:
A. 2 or more,
B. persistent/recurrent
attacks,
C. followed by persistent
worry or change in
behavior,
D. not an effect of
substance abuse
E. Not part of other Dx*
Depersonalization
• Individuals who experience depersonalization
feel divorced from their own personal self by
sensing their body sensations, feelings,
emotions, behaviors etc. as not belonging to
the same person or identity.
• Often a person who has experienced
depersonalization claims that things seem
unreal or hazy.
Depersonalization
• “When you talk you feel like someone else has written your
lines for you. Everything around you feels like it is an illusion.”
• “I will be driving and somehow detach from my actions and
someone else is guiding the way,I can see the road,and know
the way,but somewhere along the way have drifted and a
street later you become aware of the road again”
Derealization
• Depersonalization is a subjective experience
of unreality in one's self, while derealization is
unreality of the outside world.
Agoraphobia
Agoraphobia
• Up to 70% develop Agoraphobia secondary to
panic attacks
• Agoraphobia is anxiety about being in places
or situations in which escape might be difficult
or where help might not be available in the
event of a panic attack Avoidance
• Complications of panic attack also include:
depression 10-65% MDD, alcohol abuse, risk of
suicide, high use of health services and ERs
Assessment of anxiety
• Hamilton Anxiety Rating Scale (HAM-A): useful
assessment tool to evaluate clinical anxiety
• HAM-A score of >18 is generally correlated with
significant anxiety & score of ≤7-10 is associated with
remission.
• Sheehan Disability Scale is a patient-rated
instrument, which is commonly used to assess
functional impairment due to anxiety disorders. A
score of ≤1 reflects mild disability.
Social Anxiety Disorder (SAD)
Social Anxiety Disorder (SAD)
• intense, irrational, and persistent fear of being
negatively evaluated or scrutinized in at least
one social or performance situation
• Exposure to the feared circumstance usually
provokes an immediate situation-related panic
attack.
• Differentiating SAD and panic disorder (?)
Specific Phobia
watch the video!
• Specific phobia is marked and persistent fear
of a circumscribed object or situation (e.g.,
insects or heights).
TREATMENT
Non-Pharmacological Treatment of GAD
Nondrug treatments:
1. Psycho-education (stress management, sleep hygiene
etc),
2. Short-term counseling,
3. Psychotherapy (most commonly Cognitive Behavioral
Therapy; CBT),
4. Meditation,
5. Exercise
Pharmacologic Therapy of GAD
• Benzodiazepines (BZD): most effective/most
prescribed. Somatic and Autonomic symptoms
• First line : antidepressants
• All benzodiazepines are equally effective
anxiolytics,
• pharmacokinetic properties + patient’s clinical
situation will assist in the selection
Pharmacotherapy
Treatment Algorithm of GAD
Antidepressants
• are considered first-line agents in GAD.
• venlafaxine XR, duloxetine, paroxetine, & escitalopram
are FDA-approved antidepressants for GAD.
• imipramine is considered when patients fail to respond
to SSRIs or venlafaxine
• antianxiety response of antidepressants is delayed by 2
to 4 weeks or >
• HW: which anticonvulsants & antihistamines are used in
GAD?
Non-benzodiazepines for GAD
IMPORTANT!
Tardive Dyskinesia
watch the video!
• Tardive dyskinesias (TD) are involuntary
movements of the tongue, lips, face, trunk,
and extremities that occur in patients treated
with long-term dopaminergic antagonist
medications.
Benzodiazepines (BDZ)
• Estazolam, flurazepam, temazepam, quazepam, &
triazolam are marketed as sedative-hypnotic agents.
• Midazolam, short-acting, water-soluble BDZ, is
indicated only for induction of sedation before
surgery or for short diagnostic or endoscopic
procedures.
• Clonazepam, anticonvulsant, is now also indicated
for treatment of panic disorder.
• HW: which subtype of GABA receptors is involved in
antianxiety effect of BDZs???
Mechanism of Action of BNZ
What reduces GABA levels in the
body?
1.high amount of caffeine
2.chronic stress
3.alcohol withdrawal (hangover anyone?)
4.chronic pain
5.not enough sleep
6.low levels progesterone
7.too much loud noise (phonic pollution)
8.too much electromagnetic radiation
9.lack of minerals like zinc, iron, manganese
10.low levels of vitamin B1 & B6
GABA and Yoga!
Case Scenario:
• The physician decides to treat N.K.’s GAD with
venlafaxine XRand alsowants to prescribe a
benzodiazepine for quick control of her
anxiety during the first several weeks until the
onset of venlafaxine’s anxiolytic effects. What
factors are important in the selection of a
particular benzodiazepine agent for N.K.?
BZD Pharmacokinetics
• Lorazepam & oxazepam:free of active metabolites.
• Lorazepam, alprazolam & oxazepam: unlikely to
accumulate with chronic administration→
preferred in patients with liver disease & in elderly
• Unlike phase I oxidative metabolism, phase II
glucuronidation processes do not appear to
decline with age.
BZD Pharmacokinetics
• readily absorbed within 2 to 3 hours after oral
administration.
• widely distributed in the body
• accumulate preferentially in lipid-rich areas
such as the CNS and fat tissue.
• Lipid solubility varies among the agents,
resulting in differences in rates of absorption
and speed of onset, as well as duration of
clinical effects
BZD Pharmacokinetics
• Diazepam & clorazepate have:
1. the highest lipid solubilities & the quickest onsets
of action, but both can produce unpleasant
“drugged” or “high” feeling in some patients.
2. they are also > quickly redistributed out of brain
→↓duration of action (no correlation with halflife).
IV and IM dosage
• Diazepam, lorazepam, chlordiazepoxide, and
midazolam are also available for IV or IM
administration.
• These routes are usually reserved for treatment
of severe agitation or seizures or for induction of
preoperative sedation and anxiolysis.
• IM injection of both chlordiazepoxide and
diazepam can be very painful.
• Lorazepam: preferred
Side Effects of BZD
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Overall, very safe and well tolerated
D/C due to S.E: very rare
Most common S.E: sedation and tiredness
Sedation can be beneficial in anxiety
Tolerance within 2 weeks- to sedation
Fortunately, tolerance does not appear to
develop to the anxiolytic or muscle relaxant
effects
• can cause cognitive impairment and anterograde
amnesia- Tolerance!
Side Effects of BZD
• Respiratory depression (only if resp. disease,
OD or in combination with alcohol)
• Also if comb: olanzapine, loxapine or clozapine
• IV administration  slow! (over 2-3 min)
• Elderly are very sensitive to ADRs
• Problems with balance/coordination, delayed
reaction time – may be improved with time
• Use before driving ↑ risk of RTA 1.5-6.5 fold
• ↑ risk of falls in elderly→hip fractures!
• ↑ anxiety, irritability, agitation, mainly in
elderly
Common Question!
• What potential for abuse and dependence is
associated with benzodiazepines? How should
N.K. be counseled regarding “becoming
addicted” to lorazepam?
BZD and Abuse Potential
• Abuse vs. Misuse
• Dependence vs. Addiction
• Abuse is characterized by drug use outside the
therapeutic setting and implies recreational
use combined with
• Addiction: Continued use despite negative
consequences, dose escalation, and loss of
control over use. (The 5 C’s)
BZD and Abuse Potential
• Diazepam, alprazolam, & lorazepam:more likely
to be abused than are oxazepam &
chlordiazepoxide (quicker onset of effects → subjective euphoria)
• XR alprazolam formulation: less abuse potential
• Misuse & abuse of BDZ is limited primarily to
those with a current or past history of abusing
other substances, including alcohol
Justify…
Cancer patients are dependent on morphine
NOT addicted
CONTEXT!
How to avoid or minimize problems with BZD
abuse?
1. Identify patients who are susceptible to (past or present
alcoholism or other substance abuse)  using nonBDZ
treatments
2. Counsel about duration of BDZ use (How long?), the
possibility of withdrawal symptoms (What?), and
importance of gradual drug tapering when (How?)
3. Distinguish “addiction” and appropriate therapeutic
use, which may be accompanied by some degree of
physical dependence, also should be explained.
When does BZD withdrawal begin?
• Short t1/2: Onset within 24-48 hrs of D/C
• long t1/2 : Onset within 3-8 days after D/C
• High doses & long duration of therapy, usually 3
months are risk factors for increased severity of BZs
withdrawal.
Duration of BDZ therapy
• when BDZ are used for acute anxiolytic effects during
initiation of antidepressant treatment, they are
commonly limited to short-term (2 to 4 weeks)
therapy.
• dose should be gradually decreased over several
weeks
• effective medication (e.i. antidepressants) treatment
should be continued for at least 6-12 months after
response.
How to taper BZD?
• Recommendation: 25% per week reduction, until 50%
of dose is reached, then↓ by 1/8 every 4-7 days.
• If therapy > 8 weeks: a slow dosage taper over 2-3
weeks is recommended;
• If therapy is 6 months: taper over 4-8 weeks.
• Long-term use of BDZ (i.e., 1 year or >) requires 2-4
month slow taper.
• Adjunctive use of imipramine, valproic acid, or
buspirone or CBT can help to ↓ withdrawal symptoms
during BDZ taper.
Exercise
• How would you taper the 40 mg of Diazepam
dose of Mr. Ahmad, who has been on this
drug for the past 6 weeks?
BDZ use during pregnancy & lactation
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Pregnancy can be planned or not
Recommended to taper before pregnancy
Generally: Avoid
Non-drug treatments
1st trimester: ↑ risk for oral clefts by <1%→should
be avoided in this period
• The lowest dosage for the shortest period of time,
• Alprazolam and lorazepam are the preferred
agents.
• Total daily dosage should be divided into 2-3 doses
to prevent high peak plasma
BDZ use during pregnancy & lactation
• Withdrawal symptoms in newborns:
sedation, muscle weakness, hypotonia, apnea,
poor feeding, impaired to regulation, possible
long-term neurobehavioral effects
• BDZ are readily excreted in breast milk →
Generally recommended that they be avoided
by nursing mothers
BDZ Overdose and Treatment
• Koda-Kimble, Applied Therapeutics 9th Edition
2014. PP. 76-18- Question 11
• www.emedicine.com
Case Scenario
• B.G., a 68-year-old man, is brought to the emergency department (ED) by his
wife after being involved as the driver in a minor car accident. He has no
physical injuries except for several small abrasions caused by the car airbag
deployment. However, B.G. appears drowsy, is mildly confused, and has an
unsteady gait. A toxicology screen reveals no alcohol or other substances,
except for diazepam, which his physician prescribed several months ago.
B.G.’s wife states that he has been taking 1 tablet (5 mg) BID or TID and that
it has been remarkably effective in improving his mood and anxiety. B.G.,
who is 5 feet 8 inch tall and weighs 250 lb, is a recovering alcoholic with
moderate liver disease caused by years of heavy drinking. He has
successfully maintained his sobriety for nearly 2 years. In addition to
diazepam, B.G. also occasionally takesOTComeprazole (Prilosec) and
cimetidine (Tagamet) for heartburn. It is determined that B.G. is suffering
from adverse effects of diazepam, probably caused by drug accumulation.
What factors could be influencing disposition of diazepam in this patient?
Physiological Variables Influencing
Benzodiazepines
Buspirone
• A selective nonbenzodiazepine anxiolytic
• lacks anticonvulsant, muscle relaxant, hypnotic, motor or
cognitive/memory impairment, and dependence properties.
• Exact mechanism: Unknown
• partial agonist of 5HTIA receptor → increases serotonin
neurotransmission.
• Lacks general CNS depressant effects & is relatively free of
potential for abuse & dependence.
• is preferred over BDZ in patients with history of substance
abuse or dependence, & those who are elderly or medically ill
Buspirone
• It is considered to be a second-line agent for
GAD because of:
1. inconsistent reports of efficacy (particularly long
term),
2. delayed onset of effect (i.e., 2 weeks or longer), and
3. lack of efficacy for other potential concurrent
depressive and anxiety disorders.
• Unlike benzodiazepines, buspirone is effective
for the psychic symptoms of anxiety
Buspirone
Kava Kava?
TREATMENT OF PANIC DISORDER
Panic Disorder
Desired Outcomes
• The goal of therapy in panic disorder is
remission
• Patients should be free of panic attacks,
• No or minimal anticipatory anxiety and
• No or minimal agoraphobic avoidance, and
• No functional impairment
Panic Disorder
General Approach
• Either Pharmacotherapy + Non• Most patients without agoraphobic avoidance
will improve with pharmacotherapy alone;
• However, if avoidance is present, CBT typically
is initiated concurrently.
Pharmacotherapy
Nonpharmacologic Therapy
• Avoid caffeine, nicotine, alcohol, drugs of abuse,
and nonprescription stimulants.
• Avoid smoking
• Aerobic exercise (e.g., walking for 60 minutes or running
for 20 to 30 minutes 4 days/wk)
• CBT is associated with short-term improvement
in 80% to 90% of patients and 6-month
improvement in 75% of patients.
• Bibliotherapy (the use of self-help books), exercise, and
Internet-based CBT
Drugs used in the treatment of panic disorder-1
All
Drugs used in the treatment of panic disorder-2
Last resort
Panic Disorder
• Alternative Drug Treatments
• Buspirone, trazodone, bupropion,
antipsychotics, antihistamines, and β-blockers
are ineffective in panic disorder
• MAOIs are reserved for the most refractory or
difficult patients
An algorithm for the pharmacologic therapy of panic
disorder
TREATMENT OF SAD
Desired Outcomes
• Acute Phase: 4-12 weeks, depending on the
drug therapy
•  reduce physiologic symptoms of anxiety
(e.g., tachycardia, flushing, and sweating), social anxiety,
and phobic avoidance.
Continuation phase (3 to 6 months):
•  to extend the therapeutic benefits, especially
the patient’s ability to participate in social
activities, and improve QOL
• At least a 1-year medication maintenance period
is recommended to maintain improvement and
decrease the rate of relapse
• Patients with SAD often respond more slowly and
less completely than patients with other anxiety
disorders.
SAD- Pharmacotherapy
• SSRIs and venlafaxine are beneficial for
concurrent depression, and are safe when
used in patients with substance abuse.
• Paroxetine, sertraline, venlafaxine XR, and
fluvoxamine CR are approved for the
treatment of generalized SAD
• TCAs are not effective in SAD
Algorithm for treatment of
generalized SAD
β-Blockers
• For specific SAD only
• Propranolol (Inderal): very effective in reducing certain
physical symptoms of anxiety (tremor, flushing, tachycardia)
that result from activation of sympathetic nervous
• especially effective in preventing performance anxiety
or “stage fright”
• does not modify cognitive symptoms of anxiety
• Dose: 10-80 mg one hour before the stressful event
• Also, 25-100 mg atenolol
• A test dose at home
Special Populations
Children/Adolescents
• SAD can present in children of preschool to
elementary school age.
• If not treated  adulthood and increase the risk
of depression and substance abuse.
• CBT and social skills training are effective
nonpharmacologic therapies in children
• If SSRIs or SNRIs monitor for suicidality
• BZD: Last line in this age group
Special Populations
SAD+ Alcohol use disorder (1/5th)
• SSRIs: drugs of choice
• Avoid: MOAI and BZD
Specific Phobias
Treatment of Specific Phobias
• Management: mere avoidance of the stimuli.
• Medications generally are not considered
beneficial.
• CBTs involving repeated exposure to feared
situation & systemic desensitization are very
effective.
• Computer-generated, virtual environment
desensitization has been used successfully to
reduce fears associated with flying & heights.
The End of Part-1