Anxiety disorder, types, pathophysiology, pharmacologic and non pharmacologic therapy, management, GAD, Panic disorder,

1. Anxiety Disorder
Presented by: Usha Pokharel and Manij Joshi
Masters in Pharmaceutical Care
Kathmandu University, Dhulikhel, Kavre, Nepal.

2. Anxiety Disorder
• As defined by American Psychological Association; Anxiety is an
emotion characterized by feelings of tension, worried thoughts and
physical changes like increased blood pressure.

3. Pathophysiology
• The pathophysiologic mechanisms of anxiety disorders
have yet to be fully elucidated.
• Several neurotransmitters mediate anxiety. These include
inhibitory amino acids such as:
1. γ- amino butyric acid (GABA)
2. Noradrenergic model
3. 5HT model

4. γ-Aminobutyric acid (GABA) receptor model:
• GABA is the major inhibitory neurotransmitter in the
central nervous system (CNS).
• Considerable evidence links GABAA receptor dysfunction
and the pathophysiology of anxiety disorders.GABAA
receptors act as gatekeepers for chloride channels and
have multiple modulatory sites such as benzodiazepine
(BZD) receptors.
• In normal individuals GABAA binds to the GABA
receptors and opens up the chloride ion channels
causing hyper polarization and thus decreasing cellular
excitability.
• Anxiety symptoms may be linked to under activity of
GABA system.

6. • In generalized SAD(Social Anxiety Disorder) may occur
due to abnormal central GABA(B) receptor function .
• Abnormalities of GABA(A) inhibition leads to increased
( ) response to stress in Post Traumatic Stress
Disorder(PTSD).

7. Noradrenergic model
• This model suggests that the autonomic nervous system of
anxious patients is hypersensitive and overreacts to various
stimuli.
• The locus ceruleus may have a role in regulating anxiety, as
it activates nor epinephrine release and stimulates the
sympathetic and parasympathetic nervous systems.
• Chronic noradrenergic over activity down regulates α2-
adrenoreceptors in patients with generalized anxiety
disorder (GAD) and posttraumatic stress disorder (PTSD).
• Patients with social anxiety disorder (SAD) appear to have a
hyper responsive adrenocortical response to psychological
stress.

10. 5HT MODEL
• The major serotonergic systems
originate in the raphe nuclei(in
brain stem) and project to the
areas throughout the brain.
• These projections appear to have
primarily inhibitory function
acting in opposition to
cholinergic, noradrenergic and
dopaminergic projections.
• Increased serotonergic activity is
associated with reduced levels of
behavioral activation and arousal,
serotonin plays an important role
in sleep, mood , appetite,
temperature regulation and pain
perception.
Moderate sized cluster
found in brain stem , they
have 5HT1 receptors in brain
which functions as
autoreceptors in brain.

11. TYPES OF ANXIETY DISORDERS
1. GENERALIZED ANXIETY DISORDER
2. PANIC DISORDER
3. Social Anxiety Disorder
4. Post Traumatic Stress Disorder

12. GENERALIZED ANXIETY DISORDER
The diagnosis of GAD requires excessive anxiety and worry
most days about a number of matters for at least 6
months. Symptoms are at least three of the following:
PHYSICAL PSYCHOLOGICAL
RESTLESSNESS EXCESSIVE ANXIETY
FATIGUE WORRIES that are difficult to
control
MUSCLE WEAKNESS Feeling keyed up
SLEEP DISTURBANCES Poor concentration or mind
going blank
IRRITABILITY

13. • Persons with GAD may have endured their symptoms for
many years, without recognizing that such symptoms are
out of the ordinary.
• The pattern of onset of GAD differs from that of other
anxiety disorders. Most anxiety disorders have their onset
before the age of 20 years, rates of GAD in the young are
usually low, with substantially increasing prevalence
observed with advancing age.
• Women are approximately twice as likely as men to have
GAD.

14. PANIC DISORDER
In panic disorder, the attacks are triggered randomly and are
followed by:
• At least 1 month of persistent concern about the possibility of
additional panic attacks.
• Worry about the consequences of the attacks
• Significant behavioral changes related to the attacks.
The frequency and severity of panic attacks vary widely, with
some persons having
• Moderately frequent attacks (e.g., once weekly for months at
a time)
• Others reporting short bursts of attacks (e.g., daily for a
week)
• and still others reporting infrequent attacks (e.g., two per
month over many years

15. CLINICAL PRESENTATION OF PANIC ATTACKS
Depersonalization: It is
described as a feeling
disconnected or detached
from one’s self

16. Derealization: It is a feeling that
one’s surroundings are not real,
especially as a symptom of mental
disturbance.

17. PHYSICAL SYMPTOMS
1. Abdominal distress
2. Chest pain or discomfort
3. Trembling or shaking

18. • During an attack, there must be at least four physical
symptoms in addition to intense fear or discomfort.
• Symptoms reach a peak within 10 minutes and usually
last no more than 20 or 30 minutes.
• Up to 70% of patients eventually develop agoraphobia,
which is avoidance of specific situations (e g, being in
crowded places or crossing bridges) where they fear a
panic attack might occur. Patients may become
homebound

19. SOCIAL ANXIETY DISORDER
• SAD is a chronic disorder with an intense fear or anxiety
about one or more social situations in which there is
scrutiny by others which may result in negative
evaluation and rejection.
• Exposure to the feared situation(s) almost always
provokes fear or anxiety, and the situations are avoided
or endured with intense anxiety.

20. Fears Of Being
• Scrutinized by others
• Embarrassed
• Humiliated
Some Feared Situations
• Eating or writing in front of others
• Interacting with authority figures
• Speaking in public
• Talking with strangers

21. PHYSICAL SYMPTOMS
• Blushing
• Butterflies in stomach
• Diarrhea
• Sweating

22. POST TRAUMATIC STRESS DISORDER
• PTSD is characterized by the development of symptoms after
a person experiences or witnesses a traumatic event in which
actual or threatened death or serious injury occurs.
• Core symptoms of PTSD are grouped into three domains:
1. Experiencing the traumatic event (e.g., nightmares or
flashbacks)
2. Avoidance of associated stimuli or an emotional numbing
of general responsiveness
3. Hyper arousal (e.g., sleep difficulties, hyper vigilance,
exaggerated startle response, irritability or anger
outbursts).
 For the diagnosis of PTSD to be made, symptoms must be
present for at least 1 month and must cause significant
functional impairment.

23. • For example: A traumatic event was experienced in which
the individual witnessed, experienced, or was confronted
with actual or threatened death or serious injury and to
which the person responded with intense fear, helplessness,
or horror.
• Traumatic event is re-experienced persistently in some way
(e.g., nightmares, flashbacks), or intense distress is
experienced on exposure to stimuli associated with the
traumatic event.

24. The individual persistently avoids stimuli associated with the
event and numbing of general responsiveness occurs,
involving at least three of the following:
1. Efforts to avoid thoughts, feelings, or conversations
associated with the trauma.
2. Efforts to avoid activities, places, or people that are
reminders of the trauma.
3. Inability to recall an important aspect of the trauma
4. Markedly diminished interest in significant activities.
5. Feeling of detachment or estrangement from others
6. Restricted range of affect
7. Sense of foreshortened future

25. Persistent symptoms of increased arousal occur, involving at
least two of the following:
1. Difficulty falling or staying asleep
2. Irritability or angry outbursts
3. Difficulty concentrating
4. Hyper vigilance( a person experiencing it will have an
enhanced state of sensory sensitivity accompanied by
exaggerated behavior).
5. Exaggerated startle response
Above symptoms endure for at least 1 month
Symptoms cause clinically significant impairment in social,
occupational, or other important area of functioning.

26. Treatment
• Treatment for anxiety disorders often requires multiple approaches.
The patient may need short-term treatment with an anxiolytic, such
as a benzodiazepine, to help reduce the immediate symptoms
combined with psychological therapies and an antidepressant for
longer term treatment and prevention of symptoms returning.

27. 1. Psychotherapy
• Psychological therapies (talking therapies) are generally considered first-
line treatments in all anxiety disorders because they may provide a longer
lasting response and lower relapse rates than pharmacotherapy.
Psychotherapy, however, is less available, more demanding and takes
longer time to work than pharmacotherapy. If the patient is unable to
tolerate the anxiety or associated distress, then medicines are often used
before psychotherapy or while awaiting psychotherapy.
• The specific psychotherapy with the most supporting evidence in anxiety
disorders is cognitive behavioural therapy (CBT). Cognitive behaviour
therapy focuses on the ‘here and now’ and explores how the individual
feels about themselves and others and how behaviour is related to these
thoughts.

28. 2. Pharmacotherapy
A. Benzodiazepines
• Benzodiazepines are commonly prescribed to provide
immediate relief of the symptoms of severe anxiety.
These drugs differ considerably in potency (equivalent
dosage) and in rate of elimination but only slightly in
clinical effects.
Mechanism of Action
• The effects of benzodiazepines result from their
interaction with specific binding sites associated with
postsynaptic GABA (A) receptors in the brain and
potentiation of influx of chlorine ion.
• GABA is the most important inhibitory neurotransmitter
in the central nervous system (CNS). Neuronal activity in
the CNS is regulated by the balance between GABA
inhibitory activity and excitatory neurotransmitters such
as glutamate. If the balance swings towards more GABA
activity, sedation, ataxia and amnesia occur. Conversely,
when GABA is reduced arousal, anxiety and restlessness
occur.

29. Pharmacokinetics
• Most benzodiazepines are well absorbed and rapidly penetrate the brain, producing an effect
within half an hour after oral administration.
• The drugs undergo hepatic metabolism via oxidation or conjugation and some form
pharmacologically active metabolites with even longer elimination half-lives. Oxidation of
benzodiazepines is decreased in the elderly, in patients with hepatic impairment and in the
presence of some drugs, including alcohol.
• Benzodiazepines are metabolized through the cytochrome P450 3A4/3 enzyme system in the liver,
so significant enzyme inducers (such as carbamazepine) may reduce levels while enzyme
inhibitors (e.g. erythromycin) may increase levels.
• Lorazepam and oxazepam are less lipophilic, have a slower onset, but a longer duration of action.
They are not recommended for immediate relief of anxiety.
Picture obtained from “Essentials of Medical pharmacology” by KD Tripathi, 7th edition.

30. Adverse effects:
1. Psychomotor and cognitive impairment.
• Although over sedation is not usually a problem in anxious patients,
there is evidence that long-term use of benzodiazepines results in
psychomotor impairment and has adverse effects on memory.
• Many patients on long-term benzodiazepines complain of poor
memory. In elderly patients, the amnesic effects may falsely suggest
the development of dementia.
2. Paradoxical effects
• Occasionally, benzodiazepines produce paradoxical stimulant effects.
These effects are most marked in anxious subjects and include
excitement, increased anxiety, irritability and outbursts of rage.

31. 3. Affective reactions
• Chronic use of benzodiazepines can aggravate depression, may sometimes
provoke suicide attempts in impulsive patients, and can cause depression
in patients with no previous history of depressive disorder. Aggravation of
depression is a particular risk in anxious patients who often have mixed
anxiety/depression. Benzodiazepines are taken alone or in combination
with other drugs in 40% of self-poisoning incidents.
4. Dependence
• The greatest drawback of chronic benzodiazepine use is the development
of drug dependence. It is generally agreed that the regular use of
therapeutic doses of benzodiazepines as hypnotics or anxiolytics for more
than a few weeks (2–4 weeks) can give rise to dependence, with
withdrawal symptoms on cessation of drug use in over 40% of patients.

32. B. Anti-depressants
Antidepressants can provide a long-term treatment option for those with an anxiety disorder. They are generally recommended
for those who are unable to commit to or have not responded to psychological therapies.
I. Reversible inhibitors of MAO-A (RIMAs)
Moclobemide, Clorgyline
II. Tricyclic antidepressants (TCAs)
A. NA + 5-HT reuptake inhibitors
Imipramine, Amitriptyline, Trimipramine, Doxepin, Dothiepin, Clomipramine
B. Predominantly NA reuptake inhibitors
Desipramine, Nortriptyline, Amoxapine, Reboxetine
III. Selective serotonin reuptake inhibitors (SSRIs)
Fluoxetine, Fluvoxamine, Paroxetine, Sertraline, Citalopram, Escitalopram, Dapoxetine
IV. Serotonin and noradrenaline reuptake inhibitors (SNRIs)
Venlafaxine, Duloxetine
V. Atypical antidepressants
Mirtazapine, Bupropion

33. I. Reversible inhibitors of MAO-A (RIMAs)
• MAO is a mitochondrial enzyme involved in the oxidative deamination of biogenic
amines (Adr, NA, DA, 5-HT). Two isoenzyme forms of MAO have been identified.
• MAO-A: Preferentially deaminates 5-HT and NA, and is inhibited by clorgyline,
moclobemide.
• MAO-B: Preferentially deaminates phenylethylamine and is inhibited by
selegiline.
• Moclobemide : It is a reversible and selective MAO-A inhibitor with short
duration of action; full MAO activity is restored within 1–2 days of stopping the
drug. Because of competitive enzyme inhibition, tyramine is able to displace it
from the enzyme, so that potentiation of pressor response to ingested amines is
minor, and dietary restrictions are not required.
• Adverse effects are nausea, dizziness, headache, insomnia, rarely excitement and
liver damage.
• Dose: 150mg BD or TDS

34. II. Tricyclic antidepressants (TCAs)
MOA: The TCAs and related drugs inhibit NET and SERT which mediate active
reuptake of biogenic amines NA and 5-HT into their respective neurons and
thus potentiate them. Reuptake inhibition results in increased concentration
of the amines in the synaptic cleft in both CNS and periphery.
Pharmacokinetics: The oral absorption of TCAs is good, though often slow.
They are highly bound to plasma and tissue proteins, therefore have large
volumes of distribution (~20 L/kg). They are extensively metabolized in liver;
the major route for imipramine and amitriptyline is demethylation whereby
active metabolites—desipramine and nortriptyline respectively are formed.
Both these metabolites predominantly block NA reuptake. The plasma t½ of
amitriptyline, imipramine and doxepin range between 16–24 hours. The t½ is
longer for some of their active metabolites. Because of relatively long t½s,
once daily dosing (at bed time) is practicable in the maintenance phase.

35. • Adverse effects: Side effects are common with TCAs because of which SSRIs, SNRIs and atypical antidepressants are more preferred these days.
1. Anticholinergic: dry mouth, bad taste, constipation, epigastric distress, urinary retention (especially in males with enlarged prostate), blurred vision,
palpitation.
2. Sedation, mental confusion and weakness, especially with amitriptyline and more sedative congeners.
3. Increased appetite and weight gain is noted with most TCAs.
4. Some patients receiving any antidepressant may abruptly ‘switch over’ to a dysphoric agitated state or to mania.
5. Sweating (despite antimuscarinic action) and fine tremors are relatively common.
6. Seizure threshold is lowered—fits may be precipitated, especially in children.
7. Postural hypotension, especially in older patients.
8. Sexual distress: especially delay or interference with erection and ejaculation.
9. Cardiac arrhythmias, especially in patients with ischaemic heart disease.
10. Rashes and jaundice due to hypersensitivity are rare.

36. Drug Interactions:
1. TCAs potentiate directly acting sympathomimetic amines (present in cold/asthma remedies). Adrenaline containing local anaesthetic
should be avoided. However, TCAs attenuate the action of indirect sympathomimetics (ephedrine, tyramine).
2. TCAs abolish the antihypertensive action of guanethidine and clonidine by preventing their transport into adrenergic neurones.
3. TCAs potentiate CNS depressants, including alcohol and antihistaminics.
4. Phenytoin, phenylbutazone, aspirin and CPZ can displace TCAs from protein binding sites and cause transient overdose symptoms.
5. Phenobarbitone competitively inhibits as well as induces imipramine metabolism. Carbamazepine and other enzyme inducers enhance
metabolism of TCAs.
6. SSRIs inhibit metabolism of several drugs including TCAs—dangerous toxicity can occur if the two are given concurrently.
7. By their anticholinergic property, TCAs delay gastric emptying and retard their own as well as other drug’s absorption. However, digoxin
and tetracyclines may be more completely absorbed. When used together, the anticholinergic action of neuroleptics and TCAs may add
up.
8. MAO inhibitors—dangerous hypertensive crisis with excitement and hallucinations has occurred when given with TCAs.

37. III. Selective serotonin reuptake inhibitors (SSRIs)
• The relative safety and better acceptability of SSRIs has made them 1st line
drugs in depression and allowed their extensive use in anxiety, phobias,
OCD and related disorders.
• The SSRIs produce little or no sedation, do not interfere with cognitive and
psychomotor function or produce anticholinergic side effects.
• They are devoid of α adrenergic blocking action—postural hypotension
does not occur, making them suitable for elderly patients.
• They have practically no seizure precipitating propensity and do not inhibit
cardiac conduction—overdose arrhythmias are not a problem.
• Prominent side effects are gastrointestinal; all SSRIs frequently produce
nausea (due to 5-HT3 receptor stimulation), but tolerance develops over
time.
• Loose motions are due to 5-HT uptake blockade in the gut and activation of
5-HT receptors on enteric plexus neurons. Weight gain is not a problem
with SSRIs, but they more commonly interfere with ejaculation.

38. • They should be used cautiously in children and teenagers, because
about 1 out of 50 children report suicidal ideation as a result of SSRI
treatment.
• The SSRIs inhibit drug metabolizing isoenzymes CYP2D6 and CYP3A4:
elevate plasma levels of TCAs, haloperidol, clozapine, terfenadine,
astemizole, warfarin, β blockers, some BZDs and carbamazepine.
• ‘Serotonin syndrome’ manifesting as agitation, restlessness, rigidity,
hyperthermia, delirium, sweating, twitchings followed by convulsions
can be precipitated when any serotonergic drug (e.g. MAOIs,
tramadol, pethidine) is taken by a patient receiving SSRIs.

39. IV. Serotonin and noradrenaline reuptake inhibitors (SNRIs)
• These agents, may be effective in treating depression in
patients in whom SSRIs are ineffective.
• Furthermore, depression is often accompanied by chronic
painful symptoms, such as backache and muscle aches,
against which SSRIs are also relatively ineffective. This pain is,
in part, modulated by serotonin and norepinephrine
pathways in the CNS.
• Venlafaxine is a potent inhibitor of serotonin reuptake and,
at medium to higher doses, is an inhibitor of norepinephrine
reuptake. It is also a mild inhibitor of dopamine reuptake at
high doses. Doesn’t decrease BP, rather increases the BP.
• Duloxetine is used in panic attack.
• Half life of both antidepressants is around 12 hours. The
metabolites of duloxetine are excreted through kidney, and
should not be used in ERD.
• They don’t decrease BP, rather increase the BP slightly.
• The most common side effects are nausea, head ache, sexual
dysfunction, dizziness, insomnia, sedation, and constipation.
Picture : Lipincott’s
“Pharmacology”, 5th edition.

40. V. Atypical Antidepressants
• The atypical antidepressants are a mixed group of
agents that have actions at several different sites.
They are not any more efficacious than the TCAs or
SSRIs, but their side effect profiles are different.
• Mirtazapine acts by a novel mechanism, viz. blocks α2
auto- (on NA neurons) and hetero- (on 5-HT neurons)
receptors enhancing both NA and 5-HT release.
• It is a sedative because of its potent antihistaminic
activity, but it does not cause the antimuscarinic side
effects of the TCAs, or interfere with sexual
functioning, as do the SSRIs. Increased appetite and
weight gain frequently occur. It is markedly sedating,
which may be an advantage in depressed patients
having difficulty sleeping.

41. • Bupropion: This inhibitor of DA and NA uptake has excitant rather than
sedative property. It is metabolized into an amphetamine like compound
which can cause presynaptic release of DA and NA. Its short half-life may
require more than once-a-day dosing or the administration of an extended-
release formulation. Side effects may include dry mouth, sweating,
nervousness, tremor, a very low incidence of sexual dysfunction, and an
increased risk for seizures at high doses.
• Nefazodone and trazodone: These drugs are weak inhibitors of serotonin
reuptake. Their therapeutic benefit appears to be related to their ability to
block postsynaptic 5-HT2A receptors. With chronic use, these agents may
desensitize 5-HT1A presynaptic autoreceptors and, thereby, increase
serotonin release. Both agents are sedating, probably because of their
potent H1-blocking activity. Trazodone has been associated with causing
priapism, and nefazodone has been associated with the risk for
hepatotoxicity. Both agents also have mild to moderate α1-receptor
antagonism contributing to orthostasis and dizziness.

42. C. β Blockers
• Many symptoms of anxiety (palpitation, rise in BP, shaking, tremor,
gastrointestinal hurrying, etc.) are due to sympathetic overactivity,
and these symptoms reinforce anxiety. Propranolol and other
nonselective β blockers help anxious patients troubled by these
symptoms, by cutting the vicious cycle and provide symptomatic
relief.
• They do not affect the psychological symptoms such as worry, tension
and fear, but are valuable in acutely stressful situations (examination
fear, unaccustomed public appearance, etc.). They may be used for
performance/situational anxiety or as adjuvant to BZDs. The role of β
blockers in anxiety disorders is quite limited.

43. D. Other medications occasionally used in anxiety
• Hydroxyzine, a sedating antihistamine, is licensed for the short term
treatment of anxiety in adults at a dose of 50–100 mg four times a day. The
clinical evidence only supports its use in GAD (for up to 4 weeks) if sedation
is required. NICE supports the use of a sedating antihistamine in the
immediate management of GAD but state they should not be used in panic
disorders (NICE, 2007).
• Usual adult dose: Oral 50-100mg four times a day.
• IM: 50 to 100mg immediately, then every 4-6 hours as needed.
• Pregabalin is licensed for GAD and has shown an anxiolytic effect over
placebo after 1 week in adults or 2 weeks in the elderly (Montgomery et
al., 2008). Two short-term studies (4 and 6 weeks) suggest that pregabalin
400–600 mg/day is as effective but better tolerated than venlafaxine 75
mg/day XL or lorazepam 6 mg/day. Pregabalin, however, commonly causes
dizziness, somnolence and nausea and is more expensive than other
medication options in GAD and should be limited to specialist use only
after other treatments have failed.

44. Management
1. Generalized anxiety disorder
• Goals of Treatment: The goals are to reduce severity, duration, and
frequency of symptoms and improve functioning. The long-term goal
is minimal or no anxiety symptoms, no functional impairment,
prevention of recurrence, and improved quality of life.
• Nonpharmacologic modalities include psychotherapy, short-term
counseling, stress management, cognitive therapy, meditation,
supportive therapy, and exercise. Ideally, patients with GAD should
have psychological therapy, alone or in combination with antianxiety
drugs. Cognitive behavioral therapy (CBT), though not widely available,
is the most effective psychological therapy. Patients should avoid
caffeine, stimulants, excessive alcohol, and diet pills.

45. * Pictures obtained from “Pharmacotherapy, a pathophysiologic approach” by Dipiro, 9th edition.

46. Source: http://www.guiasalud.es/egpc/traduccion/ingles/ansiedad/completa/apartado08/estrategias.html

47. 2. Panic disorder
• Goals of Treatment: The goals are complete resolution of panic
attacks, marked reduction in anticipatory anxiety, elimination of phobic
avoidance, and resumption of normal activities.
General Approach
• SSRIs are first-line agents for panic disorder. Most patients without
agoraphobia improve with pharmacotherapy alone, but if
agoraphobia is present, CBT typically is initiated concurrently. Patients
treated with CBT are less likely to relapse than those treated with
imipramine alone. For patients who cannot or will not take
medications, CBT alone is indicated.
• Educate patient to avoid caffeine, nicotine, alcohol, drugs of abuse,
and stimulants.

48. Starting dose of clonazepam = 0.25 mg twice daily, with a dose increase to 1 mg by the third day. Increases by 0.25 to 0.5 mg every 3 days to 4 mg/day
can be made
if needed.
Starting dose of alprazolam = 0.25 to 0.5 mg three times daily (or 0.5 mg once daily of extended-release alprazolam), slowly increasing over several
weeks as needed. Most patients require 3 to 6 mg/day.
* Pictures obtained from “Pharmacotherapy, a pathophysiologic approach” by Dipiro, 9th edition.

49. 3. Social anxiety disorder
• Goals of Treatment: The goals are to reduce the physiologic symptoms and
phobic avoidance, increase participation in desired social activities, and
improve quality of life.
• Patients with SAD often respond more slowly and less completely than
patients with other anxiety disorders. After improvement, at least 1 year of
maintenance treatment is recommended. Long term treatment may be
needed for patients with unresolved symptoms, comorbidity, an early
onset of disease, or a prior history of relapse.
• CBT (exposure therapy, cognitive restructuring, relaxation training, and
social skills training) and pharmacotherapy are considered equally effective
in SAD, but CBT can lead to a greater likelihood of maintaining response
after treatment termination. Even after response, most patients continue
to experience more than minimal residual symptoms. CBT and social skills
training are effective in children with SAD.
• SSRIs and serotonin norepinephrine reuptake inhibitors are effective in
children 6 to 17 years of age. Individuals up to 24 years of age should be
closely monitored for increased risk of suicide.

50. * Pictures obtained from “Pharmacotherapy, a pathophysiologic approach” by Dipiro, 9th edition.

51. *Paroxetine, sertraline, extended-release fluvoxamine, and extended-release venlafaxine
are first-line agents
* Pictures obtained from “Pharmacotherapy, a pathophysiologic approach” by Dipiro, 9th edition.

52. 4. Post traumatic stress disorder
• Goals of Treatment: The goals are to decrease core symptoms,
disability, and comorbidity and improve quality of life.
• Immediately after the trauma, patients should receive treatment
individualized to their presenting symptoms (eg, nonbenzodiazepine
hypnotic or short courses of CBT). Brief courses of CBT in close
proximity to the trauma can help prevent PTSD.
• If symptoms persist for 3 to 4 weeks, and there is social or
occupational impairment, patients should receive pharmacotherapy
or psychotherapy, or both.
• Psychotherapies for PTSD include stress management, eye movement
desensitization and reprocessing (EMDP), and psychoeducation.
Trauma-focused CBT (TFCBT) and EMDP are more effective than stress
management or group therapy to reduce PTSD symptoms.

53. • Prazosin, in daily doses of 1 to 4 mg, can be useful in some patients with PTSD.
• See patients frequently for the first 3 months, then monthly for 3 months. In months 6 to 12, patients can be
seen every 2 months. Monitor for symptom response, suicidal ideation, disability, side effects, and treatment
adherence.
* Pictures obtained from “Pharmacotherapy, a pathophysiologic approach” by Dipiro, 9th edition.

54. References:
• KD Tripathi (2013) Essentials of Medical Pharmacology, 7th edn., :
Jaypee Brothers Medical Publishers Private Limited.
• Michelle A. Clark, Richard Finkel, Jose A. Rey, Karen Whalen
(2012) Pharmacology, 5th edn., : Lipincott's Illustrated Reviews.
• Barbara G. Wells, Joseph T. DiPiro, Terry L. Schwinghammer and Cecily
V. DiPiro (2012) Pharmacotherapy Handbook, 9th edn., : Mc Graw Hill
Education.
• Roger Walker and Cate Whittlesea (2012) Clinical Pharmacy and
Therapeutics, 5th edn., London, UK: ChurchHill Livingstone.
• http://www.guiasalud.es/egpc/traduccion/ingles/ansiedad/completa/
apartado08/estrategias.html