ANXIETY DISORDERS

 Anxiety is an emotional state commonly caused by the perception of real or perceived danger
that threatens the security of an individual
 Anxiety can produce uncomfortable and potentially debilitating psychologic (e.g., worry or
feeling of threat) and physiologic arousal (e.g., tachycardia or shortness of breath) if it
becomes excessive.
 Some individuals experience persistent, severe anxiety symptoms and possess irrational fears
that significantly impair normal daily functioning.
 These persons often suffer from an anxiety disorder.
 Anxiety disorders are among the most frequent mental disorders
EPIDEMIOLOGY

 In general, anxiety disorders are a group of heterogeneous illnesses that develop before age 30
years and are 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
ETIOLOGY

 The differential diagnosis of anxiety disorders includes medical and psychiatric illnesses and
certain drugs.2 Family studies show that SAD can be inherited
 10 times greater among first–degree relatives of patients
 Parental dysfunction and abuse are potential risk factors for developing SAD
 DRUG-INDUCED ANXIETY Drugs are a common cause of anxiety symptoms
 Anxiety can be a presenting feature of several major psychiatric illnesses. Anxiety symptoms
are extremely common in patients with mood disorders, schizophrenia, delirium, dementia,
and substanceuse disorder
 Symptoms of anxiety frequently present in medical disorders include palpitations,
tachycardia, chest pain or tightness, shortness of breath, and hyperventilation
 Anticonvulsants: carbamazepine
 Antidepressants: selective serotonin reuptake inhibitors, tricyclic antidepressants
 Antihypertensives: felodipine Antibiotics: quinolones, isoniazid
 Bronchodilators: albuterol, theophylline
 Corticosteroids: prednisone
 Dopa agonists: levodopa Herbals: ma huang, ginseng, ephedra
 Nonsteroidal anti-inflammatory drugs: ibuprofen
 Stimulants: amphetamines, methylphenidate, caffeine, cocaine
 Sympathomimetics: pseudoephedrine
 Thyroid hormones: levothyroxine
 Toxicity: anticholinergics, antihistamines
PATHOPHYSIOLOGY

 several neurotransmitter systems, including norepinephrine (NE), γ-aminobutyric acid

(GABA), serotonin (5-HT), corticotrophin-releasing factor (CRF), and cholesystokinin
 NEUROCHEMICAL THEORIES
Noradrenergic Model
 The basic premise of the noradrenergic theory is that the autonomic nervous system of
anxious patients is hypersensitive and overreacts to various stimuli. Many anxious patients
clearly display symptoms of peripheral autonomic hyperactivity.
  activating NE release and stimulating the sympathetic and parasympathetic nervous systems.
 Chronic central noradrenergic overactivity downregulates α2-adrenoreceptors in patients with
GAD
 Drugs with anxiolytic or antipanic effects (e.g., benzodiazepines, antidepressants, and
clonidine) inhibit LC firing, decrease noradrenergic activity, and block the effects of
anxiogenic drugs
 GABA Receptor Model There are two superfamilies of GABA protein receptors: GABAA
and GABAB. Drugs to reduce anxiety and produce sedation target the GABAA receptor. The
GABAB receptor is a G-protein coupled receptor postulated to be involved in the presynaptic
inhibition of GABA release.
 GABA, the major inhibitory neurotransmitter in the CNS, has a strong regulatory or
inhibitory effect on the 5-HT, NE, and dopamine (DA) systems.
 When GABA binds to the GABAA receptor, neuronal excitability is reduced
 Serotonin Model Although there are data suggesting that the 5-HT system is dysregulated in
patients with anxiety disorders, definitive evidence that shows a clear abnormality in 5-HT
function is lacking. 5-HT is primarily an inhibitory neurotransmitter
 The selective serotonin reuptake inhibitors (SSRIs) acutely increase 5-HT levels by blocking
the SERT to increase the amount of 5-HT available postsynaptically, and are efficacious in
blocking the manifestations of panic and anxiety
 GAD symptoms may reflect excessive 5-HT transmission or overactivity of the stimulatory 5-
HT pathways
NEUROIMAGING STUDIES
 Functional neuroimaging studies suggest that frontal and occipital brain areas are integral to
the anxiety response.
 In GAD there is an abnormal increase in cortical activity and a decrease in basal ganglia
activity.
 After benzodiazepine treatment, basal ganglia activity increases, and cortical activity is
reduced.
 Patients with panic disorder have abnormal activation of the parahippocampal region and
prefrontal cortex at rest, and reduced GABA concentrations in the occipital region.
 Panic anxiety is associated with activation of brain stem and basal ganglia area
CLINICAL PRESENTATION

 The characteristic features of these illnesses are anxiety and avoidance behavior. Anxiety
symptoms must cause significant distress, and impairment in social, occupational, or other
areas of functioning and should not be secondary to a drug or illicit substance or a general
medical disorder
 Presentation of Generalized Anxiety Disorder
 Psychologic and cognitive symptoms- Excessive anxiety • Worries that are difficult to control
• Feeling keyed up or on edge • Poor concentration or mind going blank
 Physical symptoms- Restlessness • Fatigue • Muscle tension • Sleep disturbance • Irritability
 Impairment -Social, occupational, or other important functional areas

 Presentation of Social Anxiety Disorder

 Fears -Being scrutinized by others • Being embarrassed • Being humiliated
 Some feared situations -Addressing a group of people • Eating or writing in front of others •
Interacting with authority figures • Speaking in public • Talking with strangers • Use of public
toilets
 Physical symptoms -Blushing • “Butterflies in the stomach” • Diarrhea • Sweating •
Tachycardia • Trembling
 Types • Generalized type: fear and avoidance extend to a wide range of social situations •
Nongeneralized type: fear is limited to one or two situations
 Symptoms of a Panic Attack
 Psychological symptoms •-Depersonalization • Derealization • Fear of losing control • Fear
of going crazy • Fear of dying
 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
 Specific phobia is marked and persistent fear of a circumscribed object or situation, symptom
free
TREATMENT
GENERALISED ANXIETY DISORDER

 Nonpharmacologic treatment
 Non pharmacological treatment GAD include psychoeducation, short-term counseling, stress
management, psychotherapy, meditation, or exercise. Psychoeducation includes information
on the etiology and management of GAD. Anxious patients should be instructed to avoid
caffeine, nonprescription stimulants, diet pills, and excessive use of alcohol
 Cognitive behavioral therapy (CBT) is the most effective psychologic therapy in GAD
patients.
PHARMACOLOGICAL TREATMENT
 BZD antianxiety drugs

Non-BZD antianxiety drugs

 Alternative Drug Treatments Hydroxyzine, kava kava, and pregabalin are alternatives.
Patients with GAD demonstrated continued efficacy for 3 months with hydroxyzine or
bromazepam
 Because of reports of hepatotoxicity, kava kava is not recommended as an anxiolytic
 Antidepressants are considered first-line agents in the management of GAD. Venlafaxine
extended-release, duloxetine, paroxetine, and escitalopram are FDA-approved antidepressants
for GAD. Imipramine is considered when patients fail to respond to SSRIs or venlafaxine
 MOA: antidepressants modulate receptor activation of neuronal signal transduction pathways
connected to the neurotransmitters 5- HT, DA, and NE.
 Adverse Effects Paroxetine was associated with a high rate of somnolence, nausea, abnormal
ejaculation, dry mouth, decreased libido, and asthenia compared with placebo.
 Escitalopram caused nausea, insomnia, fatigue, decreased libido, ejaculation disorders, and
decreased libido at a higher rate than placebo in patients with GAD
 The most common adverse events of venlafaxine in patients with GAD were nausea,
somnolence, and dry mouth.30 The package insert warns of toxicity in venlafaxine overdose
 Benzodiazepine Therapy
 The benzodiazepines are the most frequently prescribed drugs for the acute treatment of
anxiety
 Alprazolam is indicated for the treatment of panic disorder with or without agoraphobia, as
well as GAD
  Mechanism of Action The GABA receptor model of anxiety theorizes that benzodiazepines
ameliorate anxiety through potentiation of the inhibitory activity of GABA
 Adverse Effects The most common adverse events associated with benzodiazepine therapy
involve CNS depression. This is manifested clinically as drowsiness, sedation, psychomotor
impairment, and ataxia
 Two serious complications of benzodiazepine therapy are the potential for abuse and
development of physical dependence
 Common symptoms of benzodiazepine withdrawal include anxiety, insomnia, restlessness,
muscle tension, and irritability. Less frequently occurring symptoms are nausea, malaise,
coryza, blurred vision, diaphoresis, nightmares, depression, hyperreflexia, and ataxia.
Tinnitus, confusion, paranoid delusions, hallucinations, seizures, and psychosis occur rarely.
Seizures can occur with both therapeutic and high doses of benzodiazepines
 Buspirone Therapy
 Buspirone is a nonbenzodiazepine anxiolytic that lacks anticonvulsant, muscle relaxant,
hypnotic, motor impairment, and dependence properties. It is considered to be a second-line
agent for GAD
 Mechanism of Action Buspirone’s anxiolytic mechanism of action is unknown. It is thought
to exert its anxiolytic effect through 5-HT1A partial agonist activity at the presynaptic 5-HT
receptors by reducing the firing of 5-HT neurons
 Adverse Effects Adverse events include dizziness, nausea, and headaches
 The dose of buspirone can be titrated in increments of 5 mg/day every 2 to 3 days as needed
Panic Disorder

 Panic disorder is treated effectively with several drugs including the SSRIs, the TCA
imipramine, and the benzodiazepines alprazolam and clonazepam
 SSRIs are the first-line agents because of their tolerability and efficacy
 the benzodiazepines are the most commonly used drug for panic disorder
 Alternative Drug Treatments Buspirone, trazodone, bupropion, antipsychotics, antihistamines,
and β-blockers are ineffective in panic disorder
Antidepressant Therapy
 Tricyclic Antidepressants Efficacy.
 Imipramine is the most studied TCA, alleviating panic attacks in 75% of patients with panic
disorder
 Adverse Effects. Up to 40% of patients experience stimulant-like side effects, including
anxiety, insomnia, and jitteriness
 Dosing and Administration. When using imipramine, treatment should be slowly increased by
10 mg every 2 to 4 days as tolerated
Selective Serotonin Reuptake Inhibitors Efficacy.
 Clinical studies indicate that all SSRIs are effective in panic disorder
 Adverse Effects. Typical antidepressant doses of SSRIs can cause side effects of insomnia,
jitteriness, restlessness, and agitation
Serotonin Norepinephrine Reuptake Inhibitors Efficacy.
 Approximately 54% to 60% of patients were panic-free on venlafaxine-extended release 75
mg or 150 mg daily
 Adverse Effects. The most common adverse effects of venlafaxine extended-release in panic
trials were nausea, somnolence, tremors, sweating, and abnormal sexual functioning
 Benzodiazepines Efficacy.
 The high-potency benzodiazepines clonazepam and alprazolam are the preferred agents.
 Diazepam and lorazepam are possibly effective in treating panic disorder when taken in
sufficiently high doses
 Alprazolam is an ideal agent for patients who need rapid relief
 sedation, side effects are reported
 Dosing and Administration. Doses of clonazepam can be increased by 0.25 or 0.5 mg every 3
days to 4 mg/day if needed

Phases of Therapy
 Acute Phase- The main goal of therapy in the acute phase is reduction of symptoms (e.g.,
resolution of panic attacks, reduction in anxiety and phobic fears, resumption of the patient’s
usual activities).The duration of this phase is generally 1 to 3 months depending on the choice
of drug. The duration of the acute phase with antidepressants is about 12 weeks. Therapy
should be altered if there is no response after 6 to 8 weeks of an adequate dose
 Maintenance Phase and Discontinuation. The optimal length of therapy is unknown; however,
the total duration of therapy appears to be 12 to 24 months before drug discontinuation over 4
to 6 months is attempted. The dose used in the acute phase is continued into the maintenance
phase. Citalopram, clomipramine, fluoxetine, sertraline, and imipramine have been shown to
maintain clinical effects for up to 1 year of treatment
 When drugs are discontinued too early, a high rate of relapse occurs
Social Anxiety Disorder

 SAD is a chronic, long-term illness. At least a 1-year maintenance period is recommended to

maintain improvement and decrease the rate of relapse
 Children and adolescents prescribed an SSRI or SNRI for social anxiety
 Benzodiazepines should be reserved as the last-line agents in children with SAD
Antidepressant Therapy
 The SSRIs and venlafaxine have the benefits of antidepressant activity for concurrent
depression and safety when used in patients with substance abuse. Paroxetine, sertraline, and
venlafaxine extended-release are approved for the treatment of generalized SAD and are
considered first-line agents because of their efficacy and tolerability
Selective Serotonin Reuptake Inhibitors
 Daily doses up to 60 mg of paroxetine, 200 mg of sertraline, 20 mg of escitalopram, and 300
mg of fluvoxamine were well tolerated
Venlafaxine
 Adverse Effects. Adverse effects included anorexia, dry mouth, nausea, insomnia, and sexual
dysfunction. Dosing and Administration. Additional therapeutic benefits of venlafaxine above
75 mg/day, should be tapered slowly
Mirtazapine
 Mirtazapine reduced social anxiety
 dose was 30 mg/day
Alternate Agents
 Benzodiazepines are commonly used in the treatment of patients who cannot tolerate or fail to
respond to antidepressant
 Anticonvulsants Anticonvulsants are another therapeutic option in SAD. Gabapentin, a
nonbenzodiazepine GABA analog, was effective for SAD
 For patients with specific SAD, 10 to 80 mg of propranolol or 25 to 100 mg of atenolol
 Patients who have an incomplete response to a first-line agent can benefit from augmentation
with buspirone.
 The MAOIs are reserved for treatment-resistant patients
 Specific Phobia
 Specific phobia is considered unresponsive to drug therapy, although highly responsive to
CBT. The use of benzodiazepines or paroxetine in patients who failed CBT is supported by
limited data. Benzodiazepines can be detrimental in patients with specific phobias treated
with CBT