2. Introduction
• Anxiety is a normal response to stressful or fearful circumstances
• Most people experience some degree of anxiety in reaction to
stressful situations, such as exams or giving a speech
• This allows an individual to adapt to or manage the
stressful/threatening situation
• Anxiety symptoms generally are short-lived and do not necessarily
impair function
• Anxiety that becomes excessive, causes irrational thinking or behavior,
and impairs a person’s functioning is considered an anxiety disorder.
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3. Introduction cont.…..
• Anxiety disorders often are missed or attributed incorrectly to other
medical illnesses, with most pts being treated inadequately
• Anxiety disorders are chronic in nature with low rates of
spontaneous symptom remission and high rates of relapse
• Untreated anxiety disorders are associated with
• Impairment in psychosocial functioning: impact marital, educational,
and employment status
• A decrease in quality of life: increased healthcare utilization, morbidity
and mortality.
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5. Etiology
• Genetic
• Create a vulnerable phenotype
• Psychosocial factors
• Play a role in the initiation and expression of anxiety disorders
• Individual’s life stressors and means of coping with the stress
• Diseases and drugs (anxiety from secondary causes can’t count as anxiety).
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8. Pathophysiology
• Thalamus and amygdala are important in the generation of a normal
fear response and play a central role in most anxiety disorders
• Thalamus passes information
• To amygdala for rapid assessment of highly charged emotional
information and
• To higher cortical centers for finer processing.
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11. Pathophysiology cont.…..
• Amygdala
• The integrative center for emotions, emotional behavior, and
motivation
• Provides the emotional importance of the information to help the
organism to act quickly on ambiguous but vital events
• Sends projections to the hypothalamus influencing the ANS to
affect HR, BP, and stress-associated changes
• Influences the HPA axis, leading to a cascade of stress hormones
• One such hormone is cortisol, which, if elevated for prolonged periods,
can have damaging effects on the brain and other organs.
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12. Pathophysiology cont.…..
• Cortex
• Performs a more detailed analysis, sending updates to the amygdala for
comparison and any needed course corrections
• There is a widespread direct and indirect connections to the reticular
activating system (RAS)
• Modulation of these connections relies on the neurotransmitters 5HT
and NE, which have their primary origins in the RAS.
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13. Reticular Formation
• Reticular Activating System (RAS)
• Is a region spanning the
medulla, pons, and midbrain
• Help to regulate arousal,
vigilance, and fear
• Maintains consciousness and
alertness
• Functions in sleep and arousal
from sleep.
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17. Generalized Anxiety Disorder (GAD)
• Epidemiology:
• Lifetime Prevalence: ~ 5%
• F:M= 2:1
• Age of onset: 15 – 25 years
• 50% start before age 20
• 25% drop out in anxiety clinics.
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18. Etiology
• Unknown
i. Genetics
• 50% concordance in monozygotic twins, 15% dizygotic twins
• 1st degree relative (25%???)
ii. Biological Factors
• Possibly occipital lobe, limbic system, basal ganglia or frontal cortex
• Speculation: Abnormal serotonin regulation; sub-sensitivity (↓) of alpha2
adrenergic receptors
• Brain imaging: Lower metabolic rate in basal ganglia and white matter.
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19. Etiology cont.…..
iii. Psychosocial
• Incorrect perception of dangers due to:
• Selective attention to negative details
• Distorted information processing
• Negative view of personal coping skills
• Anxiety is due to an unresolved and unconscious conflict.
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20. Clinical Symptoms
• Excessive, uncontrolled, irrational anxiety or worry about everyday
things (involving multiple events or activities) occurring more days
than not for at least 6 months
• Associated with at least three of the following symptoms:
i. Physical symptoms
ii. Psychological and cognitive symptoms
iii. Impairment.
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22. Clinical Presentation………….
• Psychological and cognitive symptoms
• Excessive anxiety /worry
• Worries that are difficult to control
• Feeling keyed-up or on edge
• Blank mind or Difficulty concentrating or Poor concentration
• Impairment
• Social, occupational, or other important functional areas
• Poor coping abilities.
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23. Differential Diagnosis
• Rule out underlying medical or psychiatric disorders and medications
that may cause anxiety
• Laboratory Evaluation for medical illnesses considered at differential
diagnosis
• Basic metabolic panel
• TSH
• Polysomnogram.
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24. Management of GAD
• Desired Outcomes
• Acute: to reduce the severity and duration of anxiety symptoms and
restore overall functioning
• Long-term: to achieve and maintain remission
• Management
• Nonpharmacologic, pharmacotherapy, or Both
• Treatment should be individualized based on symptom severity
(medical status), comordid illnesses, age, and preference.
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25. Nonpharmacologic Therapy
• Patient education: Pts should be instructed to avoid stimulating
agents such as caffeine, decongestants, diet pills, and excessive
alcohol
• Regular exercise is also recommended.
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26. Nonpharmacologic cont.…..
• Psychotherapy [Cognitive-behavioral therapy (CBT)]
• Most effective therapy with benefits comparable to antidepressants
• Good individually or in group setting
• Benefits are maintained for 6 month – 2 years
• CBT Activities
• Psychoeducation on stress management, pertinent information on GAD and
its management
• Supportive therapy: Reassurance and comfort
• Helps pts to recognize and alter patterns of distorted thinking and dysfunctional
behavior.
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27. Pharmacologic Therapy
• Drug classes
1. Drugs for acute treatment
• Benzodiazepines
2. Drugs for chronic treatment
• Antidepressants: 5-HT reuptake inhibitors, TCAs, Venlafaxine
• 5-HT1A agonists.
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28. Pharmacologic cont.…..
• Antidepressants
• First-line agents for chronic GAD
• Reduce the psychic symptoms (e.g., worry and apprehension)
• Modest effect on autonomic or somatic symptoms (e.g., tremor, rapid HR,
and/or sweating)
• The onset of antianxiety effect is delayed (2 to 4 weeks)
• Venlafaxine and SSRIs usually are preferred over TCAs (imipramine) owing to
improved safety and tolerability
• Selection of a particular antidepressant generally is based on history of prior
response, side effect profile, DDIs, cost, or formulary availability.
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30. Pharmacologic cont.…..
• Benzodiazepines
• For acute treatment [short-term relief or to improve sleep]
• Usually given for 2 – 6 weeks with 1 – 2 weeks of tapering
• More effective in reducing somatic symptoms than psychic symptoms
• Some pts also may be disinhibited with BZDs treatment and experience
confusion, irritability, aggression, and excitement
• Disadvantage: lack of effectiveness in treating depression (anxiety???)
• ADR: Anterograde amnesia (from high-potency BZDs like lorazepam).
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31. Pharmacologic cont.……Benzodiazepines
• Abrupt or rapid discontinuation
• Associated with withdrawal symptom, risk of seizures, rebound anxiety, and
high rate of relapse
• Relapse or recurrence ~50%
• Higher doses and longer duration of therapy increase the severity
• Pts should be tapered rather than discontinued abruptly
• 2 to 6 months use: should be tapered over 2 to 8 weeks,
• 12 months of use: should be tapered over 2 to 4 months
• Reduce dose by 25% every 5 to 7 days until reaching half the original dose
and then decreasing by 10% to 12% per wk until discontinued.
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33. Pharmacologic cont.……
• Buspirone
• 5-HT1A partial agonist and takes 2 – 3 weeks to have an effect
• As effective as BZDs but may not be as good in pts who previously used BZDs
• No abuse potential, withdrawal reactions, or potentiate alcohol and sedative-
hypnotic effects
• May start by combining the two and tapering off BZDs
• Especially helpful for “chronic psychological anxiety”
• Less effective than venlafaxine ➔ Second-line agent for GAD
• Initial dose of 7.5 mg BID and titrated in 5 mg/day increments (every 2 – 3
days) to a usual target dose of 20 to 30 mg/day
• Maximum dose is 60 mg/day.
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36. Panic Disorder (PD)
• Epidemiology:
• Life-time Prevalence:
• Panic Attacks: 15%
• Panic Disorder: ~ 5%
• Agoraphobia: ~ 5% (2 – 6%) [35 - 50% of PD pts have agoraphobia]
• F:M = 2 – 3:1
• Onset usually among teen/young adults
• Mean age of onset 25 (17 – 35)
• Onset after 40 more likely secondary to medical /substances.
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37. Etiology
• Genetics:
• Twin studies suggest 40% heritability
• First degree relative will get PD: 8x more likely
• Social and other factors:
• 50 – 75 % have no relative affected
• Recent divorce /separation
• 60% of women with PD had sexual abuse
• 80% first seen at primary care/ER.
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38. Etiology cont.……
• Biological Theories
• Neurotransmitter abnormalities: Dysregulation of 5HT, NE, GABA
• Postsynaptic 5 – HT hypersensitivity in median raphe nuclei
• Abnormal brain autonomic nervous (noradrenergic) systems
• Increased sympathetic tone (NE at the locus ceruleus)
• Slow adaptation to repeated stimuli
• Excessive response to moderate stimuli
• ↓ inhibitory GABA – nergic transmission in amygdala, midbrain, hypothalamus
• Limbic system: anticipatory anxiety (responds to relaxation, breathing and
benzodiazepines)
• Cortex: prefrontal cortex in phobic avoidance.
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39. Clinical Features
• Panic Attacks:
• Recurrent, discrete episodes that typically develop rapidly and
peak within 10 minutes involving at least 4 of the ff symptoms:
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41. Clinical Features cont.………..
• Panic Disorder
• Recurrent panic attacks – at least 2 attacks
• One or more attacks has been followed by 1 month or more:
• Persistent concern of a future attack
• Worry about consequence of the attack
• Significant change in behavior related to the attack
• Presence or absence of agoraphobia.
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42. Clinical Features cont.………..
• Other Features:
• Increased use of health – care visits
• Increased cardiopulmonary co-morbidity
• Its course tends to be a chronic that fluctuates
• Common agoraphobic situations: Crossing a bridge, vehicles, leaving home
• Can decrease if with trusted person
• Patients seek help more often than those with other disorders.
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43. Differential Diagnosis
• Rule out underlying medical or psychiatric disorders and medications that may
cause anxiety
• Hyperthyroidism, Hyperparathyroidism, Pheochromocytoma, Hypoglycemia
• CNS illness (neoplasm, vestibular dysfunction)
• Arrhythmia
• Asthma
• Laboratory Evaluation for medical illnesses considered at differential diagnosis
• Urine drug screen, Urine vanillylmandelic acid (VMA)
• Basic metabolic panel, TSH
• Electrocardiogram, Electroencephalogram.
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44. Management of PD
• Desired Outcomes
• Acute phase:
• Reduce severity and frequency of panic attacks
• Reduce anticipatory anxiety and agoraphobic behavior
• Minimize symptoms of depression or other comorbid disorders
• Long – term: to achieve and sustain remission.
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45. General Consideration on Management
• Acute phase of treatment
• Lasts about 12 weeks (3 months)
• Should result in marked reduction (ideally total elimination) in panic attacks
• Should result in minimal reduction in anticipatory anxiety and phobic avoidance
• Maintenance phase of treatment
• 12 to 18 months before discontinuation
• Treatment to prevent relapse
• Pts who relapse following discontinuation of medication should have therapy
resumed.
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46. Nonpharmacologic Therapy
• Patient education: Pts should be instructed to avoid stimulating
agents such as caffeine, decongestants, diet pills, and excessive
alcohol that may precipitate a panic attack.
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47. Nonpharmacologic cont.…..
• Psychological: Cognitive Behavior Therapy (CBT)
• First-line treatment with efficacy similar to that of pharmacotherapy
• Less likely to relapse during the 6 months after discontinuation
• CBT Activities
• Exposure: exposure to fear cues and continuous panic monitoring
• Supportive therapy: reassurance and comfort
• Relaxation training: breathing retraining
• Cognitive restructuring: psychoeducation.
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48. Pharmacologic Therapy
1. Drugs for acute treatment
• Benzodiazepines: Alprazolam or clonazepam
2. Drugs for chronic treatment
• First Line
• Any SSRI: Fluoxetine, Paroxetine and Sertraline
• SNRIs: Venlafaxine
• Second Line:
• TCAs: Clomipramine > Imipramine
• Third Line:
• MAOI: Phenelzine.
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49. Pharmacologic cont.……
• SSRIs are the treatment of choice
• PD pts more likely experience stimulant-like side effects than pts with
depression. So,
• They should be initiated on lower doses of antidepressant than those that
are used for depression or other anxiety disorders
• Target doses are similar to those used in depression
• Antidepressants should be tapered when treatment is discontinued to avoid
withdrawal symptoms
• Dose of BZD required is higher than that used in other anxiety disorders.
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53. Social Anxiety Disorder (SAD)
• Often occurs in context of other anxiety disorders
• The feared social or performance situation can be limited to a specific
social interaction (e.g., public speaking) or generalized to most any
social interaction.
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54. Types of Social Phobia
• Generalized type
• Chronic and disabling condition characterized by a fear and phobic
avoidance of most social situations
• Non-generalized type
• Fear is limited to one or two situations
• Differs from specific phobia,
• In phobias, the fear and anxiety are limited to a particular object or
situation (e.g., insects, heights, public transportation)
• In phobias, attenuation of the response to stimulus does not occur.
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55. Epidemiology
• Incidence: 3% of population
• Lifetime prevalence: 8 – 12%
• F: M = 3:2
• Onset rare after age 25
• Usually seek help for MDD, substance abuse
• Patients are often less educated, low socioeconomic status (SES),
Unmarried.
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56. Etiology
• Behavioural Factors:
• Anxiety arouses with naturally frightening stimuli along with a
second neutral stimulus
• When the frightening and neutral stimuli occur together
frequently → the neutral stimuli can then provoke anxiety by itself
• Operant conditioning: the person learns to avoid the anxiety
provoking stimulus
• Biological Factors: Dysregulation of serotonin.
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57. Clinical Symptoms
• Persistent fear of social interactions, during which time the individual
is concerned about being embarrassed or being under scrutiny
• Example: speaking in public, urinating in a public rest room “shy
bladder”, and speaking to a date
• Engaging in the feared activities can lead to
• Extreme anxiety and panic
• Distress or avoidance of the situation sufficient enough to cause trouble
in the patient’s life.
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59. Differential Diagnosis
• Rule out underlying medical or psychiatric disorders and medications
that may cause anxiety
• Laboratory Evaluation for DDx
• Laboratory investigation is of limited value and should be pursued only
in context of other history or physical examination findings.
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60. Management of SAD
• Desired Outcomes
• Acute
• To reduce physiologic symptoms of anxiety, fear of social situations, and
phobic behaviors
• Pts with comordid depression should have a significant reduction in
depressive symptoms
• Long – term: to restore social functioning and improve quality of life
• Pharmacotherapy is the first choice owing to relative greater access and
reduced cost compared with psychotherapy.
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61. Non-pharmacologic Therapy
• Patient Education: Pt education on disease course, treatment
options, and expectations is essential given the chronic nature and
functional impairment of SAD.
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62. Nonpharmacologic cont.…..
• Psychological: Cognitive Behavior Therapy (CBT)
• Effective for reducing anxiety and phobic behaviors
• Greater likelihood of maintaining response after treatment discontinuation
than does pharmacotherapy
• CBT Activities
• Exposure: exposure to a feared situation and continuous monitoring
• Target avoidance-learning and negative-thinking patterns associated with
social anxiety will be improved
• Social skills training with supportive therapy: Reassurance and comfort
• Relaxation training: breathing retraining.
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63. Pharmacologic Therapy
1. Drugs for acute treatment goals
1. Benzodiazepines
2. Beta adrenergic receptor blockers
2. Drugs for chronic treatment goals
• First Line: Antidepressants
• SSRI: Paroxetine (IR or CR), Sertraline, Fluvoxamine, Escitalopram
• Venlafaxine
• Second Line:
• 5-HT1A agonists, clonazepam
• MOA inhibitors: phenelzine
• Anticonvulsants [GABA receptor activators]: Gabapentin and pregabalin.
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64. Drugs For Acute Treatment Goals
• Benzodiazepines: Clonazepam, alprazolam or Bromazepam
• Efficacy reported similar to SSRI or CBT and superior to placebo
• Useful for acute relief of physiologic symptoms of anxiety when used
concomitantly with antidepressants or psychotherapy
• Long-term treatment is not desirable for many SAD pts owing to the risk of
withdrawal and difficulty with discontinuation, cognitive side effects, and lack
of effect on depressive symptoms
• Contraindicated in SAD pts with alcohol or substance abuse.
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65. Drugs For Acute Goals cont……..
• β-Blockers
• Decrease physiologic symptoms of anxiety and are useful for
reducing performance anxiety
• Propranolol or atenolol should be administered 1 hour before a
performance situation
• β-Blockers are not useful in generalized SAD.
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66. Drugs For Chronic Treatment Goals
• Response is slow to pharmacotherapy
• Antidepressants have delayed onset of response as long as 8 to 12 weeks
• Many will not achieve a full response
• Many will relapse on discontinuation
• Relapse is common on discontinuation of effective short-term
pharmacotherapy
• Pts responding to medication should continue treatment for at least 1 year
• There are no clear predictive factors of who will maintain response
• Some pts may elect more long-term treatment owing to fear of relapse.
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67. Drugs For Chronic Goals cont.……..
• First Line: SSRIs and Venlafaxine
• SSRIs
• Are the drugs of choice based on their tolerability and efficacy
• Paroxetine, sertraline, and escitalopram;
• Fluoxetine is not effective
• SSRIs doses should be tapered slowly when discontinuing therapy.
• Venlafaxine
• Venlafaxine may be effective in SSRI non-responders
• Extended release in doses of 75 to 225 mg/day.
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68. Drugs For Chronic Goals cont.……..
• Second Line:
• Citalopram
• Phenelzine: reserved for treatment-refractory pts owing to dietary
restrictions, DDIs, and side effects
• Anticonvulsants: Gabapentin, Pregabalin
• Gabapentin: most pts were titrated to a maximal dose of 3600 mg/day
• Pregabalin: 600 mg/day was effective for social anxiety, fear, and
avoidance behavior.
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69. Fig: Algorithm for the pharmacotherapy of generalized social anxiety disorder
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71. Post – traumatic Stress Disorder (PTSD)
• Occurs in people who have experienced a severely distressing traumatic
event
• Characterized by symptoms of intrusive re-experiencing, avoidance
features, emotional numbing, and symptoms of autonomic hyperarousal
• The trauma does not have to involve physical injury to the PTSD victim
• Witnessing someone else being injured or killed, being diagnosed with a
life-threatening illness, and experiencing the unexpected death of a loved
one are common types of trauma that may lead to PTSD.
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72. Etiology
• PTSD has been recognized most commonly in
• War veterans
• Natural disasters
• Serious accidents
• Criminal assault
• Rape, physical or sexual abuse, and
• Political victimization (refugees, concentration camp survivors,
hostages).
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73. Diagnostic Criteria for PTSD
1. Person has experienced a traumatic event in which the individual
witnessed, experienced, or was confronted with actual or threatened
death, or serious injury to self or others, and to which the person
responded with intense fear, helplessness, or horror
2. Traumatic event is re-experienced persistently in some way (e.g., dreams,
nightmares, flashbacks, recurrent thoughts or images), or intense distress
is experienced on exposure to stimuli associated with the traumatic event.
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74. Diagnostic Criteria cont.……
3. Persistent avoidance of stimuli associated with the event and numbing
of general responsiveness involving at least three of the following:
a. Efforts to avoid thoughts, feelings, or conversations related to the trauma
b. Efforts to avoid people, places, or activities that are reminders of the
trauma
c. Impaired recall of the traumatic event
d. Decreased interest or participation in activities
e. Feelings of detachment
f. Restricted range of affect
g. Sense of foreshortened future.
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75. Diagnostic Criteria cont.……
4. Persistent symptoms of increased arousal (not present before the event)
that include at least two of the following:
a. Sleep disturbances
b. Irritability or anger outbursts
c. Difficulty concentrating
d. Hypervigilance
e. Exaggerated startle response
5. Duration of the disturbance (2 – 4) of at least 1 month
6. Disturbance causes significant impairment in some aspect of daily
functioning.
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76. Treatment of PTSD
• Both medications and CBTs are useful
• The preferred first-line medications are SSRIs (Sertraline, Paroxetine), but various
other antidepressants may also be useful.
• Response to pharmacotherapy occurs very gradually, over 8 to 12 wks or longer.
• Partial response at 12 wks of treatment may be followed by full remission after several more
months of therapy
• Lack of improvement after 4 wks of therapy is unlikely to be effective with medication
continuation, so alternate treatment strategies should be tried in these cases
• Early treatment during the first 3 months that follow a trauma may prevent the
development of chronic PTSD.
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78. Obsessive Compulsive Disorder (OCD)
• OCD is characterized by recurrent obsessions or compulsions, which are
severe enough to be distressing, consume at least 1 hour a day, or significantly
interfere with some aspect of functioning
• An obsession is an intrusive or recurrent thought, image, or impulse that
incites anxiety in the person and that cannot be ignored or suppressed
voluntarily
• A compulsion is a behavior or ritual that is performed in a repetitive or
stereotypic way that is designed to reduce anxiety associated with obsessions
or to prevent some future event or situation
• The obsessions and compulsions are unpleasant and disturbing to the sufferer.
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80. Diagnostic Criteria
1. Presence of either obsessions or compulsions:
• Obsessions:
i. Recurrent and persistent ideas or thoughts are experienced, at some time during the
disturbance, as intrusive and senseless
ii. Thoughts, impulses, or images are not simply excessive worries about real life
problems
iii. Person attempts to ignore or neutralize the ideas or thoughts with some other
thought or action
iv. Person realizes the obsessions are the product of his or her own mind
• Compulsions:
i. Repetitive and intentional behaviors or mental acts are performed in response to the
obsession or according to rigid rules
ii. Behavior is designed to prevent or reduce distress or to prevent some dreaded event;
however, the activity is clearly excessive and unrealistic to neutralize the situation.
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81. Diagnostic Criteria cont.…….
2. At some point during the disturbance, the person realizes that the
obsessions and compulsions are excessive or unreasonable (not
necessary in children)
3. Obsessions or compulsions cause marked distress, are time
consuming (>1 hr/day), or significantly interfere with some aspect
of daily functioning
4. Content of the symptoms is not related to another psychiatric
disorder, and the disturbance is not due to the direct effects of a
substance, medication, or general medical illness.
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82. Treatment of OCD
• Behavioral therapy is vitally important for OCD, and the combination of
drugs plus behavioral therapy provides optimal treatment
• All medications consistently effective in the treatment of OCD are potent
inhibitors of serotonin reuptake
• SSRIs: Fluvoxamine, Fluoxetine, Paroxetine, Sertraline
• Clomipramine
• Venlafaxine.
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