Definition, Epidemiology, Etiology, Aspects of anxiety, Classification/types of anxiety, Pathophysiology of anxiety disorders, Management of anxiety disorders along with treatment algorithms

1. ANXIETY
DISORDERS
T.SOUJANYA
PHARM.D

2. CONTENT:
• Definition
• Epidemiology
• Etiology
• Aspects of anxiety
• Classification/types of anxiety disorders
• Medical diseases associated with anxiety
• Pathophysiology of anxiety disorders
• Management of anxiety disorders
• Treatment algorithms

3. DEFINITION:
Anxiety can be defined as a subjective sense of unease, dread or
foreboding and can indicate a primary psychiatric condition. Anxiety
can produce uncomfortable and potentially debilitating psychological
(e.g. worry or feeling of threat) and physiological arousal (e.g.
tachycardia or shortness of breath).
Anxiety disorder is a chronic condition characterized by an
excessive and persistent sense of apprehension, with physical symptoms
such as sweating, palpitation and feeling of stress.

4. EPIDEMIOLOGY:
• In general, anxiety disorders are a group of heterogenous illness that
develop before age 30 and are more common in women, individuals
with social issues, and those with a family history of anxiety and
depression.
• In United States, the 1-yaer prevalence rate for anxiety disorders was
13.3% in persons aged 18 to 54 years and 10.6% in those over age 55
years.

5. ETIOLOGY:
1. Genetic factors.
2. Environmental factors (early childhood trauma, traumatic social
experience).
3. Known or unrecognized medical condition.
4. Substance-induced anxiety disorder (OTC medications, herbal
medications, substances of abuse).

6. ASPECTS OF ANXIETY:
Anxiety has three aspects.
1. Physical: It includes headache, nausea, trembling, sweating,
precipitation. Increase in heart rate etc., and may other physical
symptoms.
2. Behavioural: It may include avoidance behaviour, dependent
behaviour and agitated behaviour.
3. Cognitive: It may include worry, fear of losing control, apprehension
about future, confused thoughts, difficulty concentration, and thinking
about that things are getting out of control.

7. CLASSIFICATION/TYPES OF ANXIETY
DISORDERS:
Anxiety disorders are broadly divided into:
1. Generalized anxiety disorder (GAD).
2. Panic disorder.
3. Phobic disorder.
4. Post-traumatic stress disorder (PTSD).
5. Obsessive compulsive disorder (OCD).

8. 1. GENERALIZED ANXIETY DISORDER
(GAD):
It is the chronic anxiety state associated with uncontrollable
worry. Patients with GAD have persistent, excessive, unrealistic worry
associated with muscle tension, impaired concentration and insomnia.
Complaints of shortness of breath, palpitations and tachycardia are
relatively rare. Alcohol abuse and dependence are common in GAD
patients.

9. CONTD…
Risk factors:
Factors that may increase the risk of GAD include:
i) Family members with an anxiety disorder
ii) Increase in stress
iii) Exposure to physical or emotional trauma
iv) Unemployment, poverty
v) Drug abuse

10. CONTD…
Symptoms:
i. Psychological and cognitive symptoms:
• Excessive anxiety
• Worries that are difficult to control
• Feeling keyed up or on edge
• Poor concentration or mind going blank
ii. Physical symptoms:
• Restlessness
• Fatigue
• Muscle tension
• Sleep disturbance
• Irritability

11. 2. PANIC DISORDER:
Panic disorder is defined by the presence of recurrent and
unpredictable panic attacks, which are distinct episodes of intense fear
and discomfort with a variety of physical symptoms.
Symptoms: They include:
i. Psychological symptoms:
• Depersonalization
• Derealization
• Fear of losing control
• Fear of going crazy
• Fear of dying

12. CONTD…
ii. Physical symptoms:
• Abdominal distress
• Chest pain or discomfort
• Chills, dizziness or light-headedness
• Feeling of choking, hot flushes
• Palpitations
• Nausea, paresthesias, shortness of breath
• Sweating, tachycardia, trembling or shaking

13. 3. PHOBIC DISORDERS:
They are again classified into:
i) Specific phobia
ii) Social phobia/Social anxiety disorder (SAD)
iii) Agoraphobia

14. CONTD…
i. Specific phobia:
Specific phobia is marked and persistent fear of a circumscribed
object or situation (e.g., insects, heights, blood, or public
transportation). Apart from contact with the feared object or situation,
the patient is usually free of symptoms. Most persons simply avoid the
feared object and adjust to certain restrictions on their activities.
ii. Social phobia:
It is characterized by clinically significant anxiety provoked by
exposure to certain types of social or performance situations, often
leading to avoidance behaviours. Common physical symptoms include
blushing, diarrhea, sweating and tachycardia.

15. CONTD…
iii. Agoraphobia:
It is anxiety or avoidance of places or situations from which
escape might be difficult (or embarrassing) or in which help may not be
available in the event of having a panic attack or panic-like symptoms.
Phobic disorders are common, affecting 10% of population. The
patients avoid phobic stimulus and this avoidance usually impairs
occupational or social functioning.
Common phobias include fear of closed spaces (claustrophobia),
fear of blood, fear of flying. Patient with social phobia, in particular,
have a high rate of co-morbid alcohol abuse, as well as of other
psychiatric conditions (e.g. eating disorder).

16. 4. POST TRAUMATIC STRESS
DISORDER (PTSD):
Patients with stress disorders are at risk for the development of
other disorders related to anxiety, mood and substance abuse (especially
alcohol).
Symptoms:
i. Re-experiencing symptoms:
• Recurrent, intrusive distressing memories of the trauma
• Recurrent, disturbing dreams of the event
• Feeling that the traumatic event is recurring (e.g., dissociative
flashbacks)
• Physiologic reaction to reminders of the trauma

17. CONTD..
ii. Avoidance symptoms:
• Avoidance of conversations about the trauma
• Avoidance of thoughts or feelings about the trauma
• Avoidance of activities that are reminders of the event
• Avoidance of people or places that arouse recollections of the trauma
• Inability to recall an important aspect of the trauma
• Anhedonia
• Estrangement from others
• Restricted affect
• Sense of a foreshortened future (e.g., does not expect to have a career,
marriage)

18. CONTD…
iii. Hyperarousal symptoms:
• Decreased concentration
• Easily startled
• Hypervigilance
• Insomnia
• Irritability or angry outbursts
• Symptoms usually begin early, within 3 months of the traumatic
incident, but sometimes that begin years afterward. Symptoms must
last more than a month.

19. 5. OBSESSIVE COMPULSIVE
DISORDER (OCD):
OCD is characterized by obsessive thoughts and compulsive
behaviours that impair everyday functioning. Fears of contamination
and germs are common as are hand washing, counting behaviours and
having check and recheck the actions like whether a door is closed.

20. CONTD…
Symptoms:
i. Obsessions:
• Repetitive thoughts (e.g., feeling contaminated after touching an
object, doubting whether the stove was turned off).
• Repetitive images (e.g., recurrent sexually explicit pictures).
• Repetitive impulses (e.g., need for symmetry or putting things in
specific order, impulse to shout out obscenities in a church).
ii. Compulsions:
• Repetitive activities (e.g., hand washing, checking, ordering, need to
ask, need to confess).
• Repetitive mental acts (e.g., counting, repeating words silently,
praying).

21. PATHOPHYSIOLOGY:
Data from biochemical and neuroimaging studies indicate that the
modulation of normal and pathologic anxiety states is associated with
multiple regions of the brain and abnormal function in several
neurotransmitter systems, including norepinephrine (NE), γ-amino
butyric acid (GABA) and serotonin (5-HT).

22. 1. GABA RECEPTOR MODEL:
GABA is the major inhibitory neurotransmitter in the CNS. Many
antianxiety drugs target the GABAA receptor. Benzodiazepines (BZs) enhance
the inhibitory effects of GABA, which has a strong regulatory or inhibitory
effect on serotonin (5-HT), norepinephrine and dopamine systems.
The role of GABA-benzodiazepine receptor complex in anxiety
disorders has not been successfully characterized. However, a potential role
has been implicating in panic disorders, GAD and PTSD.
• In GAD, reduced temporal lobe benzodiazepine receptors are observed.
• In PTSD, cortical benzodiazepine receptors are reduced.
• In panic disorder, decreased GABAA binding is noted.

23. CONTD…
Anxiogenic agents
(having the property of altering the binding of benzodiazepines to the
GABA receptor)
Leads to
Nerve cell excitability
Anxiety
Abnormalities of GABA inhibition may lead to increased
response to stress in PTSD patients.

24. 2. NON-ADRENERGIC SYSTEM:
The locus coeruleus (LC), located in the brain stem, is the
primary NE-containing site in the brain, with widespread projections to
areas responsible for implementing fear responses (e.g., vagus, lateral
and paraventricular hypothalamus).
In response to threat or fearful situations, the LC serves as an
alarm centre, activating NE release and stimulating the sympathetic and
parasympathetic nervous systems. Drugs with anxiogenic effects (e.g.,
yohimbine, an α2-adrenergic receptor antagonist) stimulate LC firing
and increase noradrenergic activity. NE in turn increases glutamate
release (an excitatory neurotransmitter). This produces subjective
feelings of anxiety and can precipitate a panic attack in those with panic
disorder.

25. Locus coeruleus (located in the brain stem)
According to noradrenergic theory of anxiety
(in the presence of perceived threat)
The locus coeruleus serves as an alarm centre
Increases glutamate release (an excitatory neurotransmitter)
Leads to anxiety

26. 3. SEROTONIN SYSTEM (5-HT MODEL):
GAD symptoms may reflect excessive 5-HT transmission or
overactivity of the stimulatory 5-HT pathways. Patients with SAD have
greater prolactin response to buspirone challenge, indicating an
enhanced central serotonergic response.
The role of 5-HT in panic disorder is unclear, but it may have a
role in development of anticipatory anxiety. Preliminary data suggest
that the 5-HT and 5-HT2 antagonist, metachlorophenylpiperazine causes
increased anxiety in PTSD patients.
In patients with SAD, there may be abnormalities in the
amygdala, hippocampus and various cortical regions. Lower
hippocampal volumes in patients with PTSD may be a precursor for
subsequent development of PTSD.

27. MANAGEMENT OF ANXIETY
DISORDERS:
Treatment for anxiety disorders often requires multiple
approaches. The patient may need short-term treatment with an
anxiolytic, such as benzodiazepine, to help reduce the immediate
symptoms combined with psychological therapies and an antidepressant
for long term treatment and prevention of symptoms returning.

28. NON-PHARMACOLOGICAL TREATMENT:
Psychotherapy:
1. The specific psychotherapy with the most supporting evidence in anxiety
disorders is cognitive behavioural therapy (CBT). Cognitive behavioural
therapy focuses on the ‘here and now’ and explores how the individual
feels about themselves and others and how behaviour is related to those
thoughts.
2. Through individual therapy or group work the patient and therapist
identify and question maladaptive thoughts and help develop an
alternative perspective. Individual goals and strategies are developed and
evaluated with patients encouraged to practice what they have learned
between sessions.
3. Therapy usually lasts for around 60-90 minutes every week for 8-16
weeks or longer in more resistant cases.
4. Specific phobias are also almost exclusively treated using exposure
techniques and most patients will respond to this treatment. Only a very
few will require additional drug therapy.

29. PHARMACOLOGICAL TREATMENT:
Classification of anti-anxiety drugs:
1. Benzodiazepines: Diazepam, oxazepam, lorazepam
2. Azapirones: Buspirone, ispapirone
3. Sedative antihistaminic: Hydroxyzine – 200-400 mg/day
4. β-adrenergic blocker: Propranolol
5. Selective serotonin reuptake inhibitors (SSRIs): Fluoxetine,
paroxetine, fluvoxamine, sertraline
6. Tricyclic antidepressants (TCAs): Clomipramine

30. 1. BENZODIAZEPINES:
MOA:
Benzodiazepines work by increasing the efficiency of a natural brain
chemical, GABA, to decrease the excitability of neurons.
Binding of benzodiazepines to GABAA receptor complex promotes
binding of GABA, which in turn increases of chloride ions across the
neuronal cell membrane, resulting in inhibition of neuronal firing.
ADRs: Blood disorders, respiratory depression, hypotension, jaundice etc.
Dose:
• Diazepam- 2-40mg/day PO or 5-10mg IV
• Oxazepam- 30-120mg/day
• lorazepam- 0.5-10mg/day

31. 2. AZAPIRONES:
MOA:
They stimulate presynaptic 5-HT1A autoreceptors and the activity
of dorsal raphe serotonergic neurons decreases. They agonist action on
5-HT1A receptors.
ADRs:
They mainly include dizziness, nausea, headache, light
headedness, excitement (rarely).
Dose:
• Buspirone – 15-60mg/day

32. 3. SSRIs & TCAs:
MOA:
SSRIs and clomipramine inhibit 5-HT reuptake into the presynaptic neuron and
makes more 5-HT available to post synaptic receptors and reduces the formation of
5-HT metabolite 5-hydroxy indole acetic acid and reduces symptoms of anxiety.
ADRs:
Nausea, vomiting, dyspepsia, sedation, postural hypotension, sexual dysfunction,
constipation
Dose:
• Fluoxetine: 20-60mg/day
• Paroxetine: 20-60mg/day
• Fluvoxamine: 100-300mg/day
• Sertraline: 75-200mg/day
• Clomipramine: 100-150mg/day

33. Treatment algorithm for post traumatic stress disorder

34. Treatment algorithm for generalized anxiety disorder

35. Treatment algorithm for generalized social anxiety disorder

36. Treatment algorithm for panic disorder

37. REFERENCE/BIBLIOGRAPHY:
Textbook of Pharmacotherapy: A
Pathophysiologic approach by
Joseph T. Dipiro.