Anxiety Disorders

Jawza F. AlSabhan PHCL 430

Overview

• Anxiety disorders are among the most prevalent mental disorders in the general population.

• Nearly 30 million persons are affected in the United States, with women affected nearly twice as frequently as men.

• Anxiety disorders are associated with significant morbidity and often are chronic and resistant to treatment.

Anxiety Disorders

Generalized Anxiety Disorder 3.1%

Panic disorder 2.7%

Agoraphobia

obsessive-compulsive disorder (OCD)

Post-traumatic stress disorder

Social phobia6.8%

Specific phobia 8.7%

Pathophysiology

• Neurochemical Theories– Noradrenergic Model– GABA Receptor Model– Serotonin Model

• Neuroimaging Studies

Diagnostic criteria for generalized anxiety disorder GAD

1. Excessive anxiety and worry about a number of events or activities, occurring more days than not for at least six months, that are out of proportion to the likelihood or impact of feared events.

2. The worry is pervasive and difficult to control. 3. The anxiety and worry are associated with three (or more) of the following

six symptoms (with at least some symptoms present for more days than not for the past six months):

A. Restlessness B. Being easily fatiguedC. Difficulty concentrating D. IrritabilityE. Muscle tension F. Sleep disturbance

4. The anxiety, worry, or physical symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Epidemiology

• GAD is twice as common in females. • criteria found a 12 month prevalence of GAD

in a community sample of 3.8%. • The lifetime prevalence has been estimated as

5-7%• Prevalence rates as high as 11.5% have been

reported.

Comorbidity

• Over 2/3 (68%) of individuals with GAD have an additional Axis I diagnosis – most commonly, other anxiety disorders and depression.

• One study found personality disorder in 49% of people with GAD

• It is associated with substance abuse and suicidality.

Genetic factors

• Genetic factors appear to play a modest role in the aetiology of GAD. It is five times more common in the first-degree relatives of index cases than among the first-degree relatives of controls

Neurobiological mechanisms

• The locus coeruleus and the sympathetic nervous system (SNS) are involved in fear and arousal, but their role in anxiety is yet to be fully elucidated.

• The hypothalamic-pituitary-adrenal (HPA) axis, and the release of cortisol are involved in response to stress.

• The amygdala and the bed nucleus of the stria terminalis appear to be important. The amygdala plays a central role in the mediation of fear reactions

Clinical Presentation Psychologic and cognitive symptoms 

  Excessive anxiety

Worries that are difficult to control

  Feeling keyed up or on edge

  Poor concentration or mind going blankPhysical symptoms 

  Restlessness

  FatigueMuscle tension

  Sleep disturbance

  Irritability

Impairment    Social, occupational, or other

important functional areas   Poor coping abilities

DIAGNOSIS

Score: 5-9 = mild anxiety; 10-14 = moderate anxiety; 15-21 = severe anxiety

General Approach to Treatment

• Nondrug treatment– Psychotherapy is cornerstone of treatment– CBT =Cognitive Behavioral Therapy

Drug therapy 

• Benzodiazepines• TCA• SSRIs• Venlafaxine• Buspirone

Indication for treatment• Treatment is indicated in most patients who fulfill the ICD-10

or DSM-IV criteria for an anxiety disorder.

• The treatment plan is based on the patient’s preference, severity of illness, co-morbidity, concomitant medical illnesses, complications like substance abuse or suicide risk and the history of previous treatments.

• In some health systems, costs may be a factor.

Drug Treatment

• Benzodiazepine: remain one mainstay of drug treatment.– Binding to BZD binding site located on GABAA

receptor- complex– used for the short-term (£ 6 wk)

• Lorazepam – a short onset of effect and a relatively long half-life

• Dosing – 0.5-6 mg PO/IV/IM in divided doses

Duration of drug treatment • Mostly, anxiety disorders have a waxing and waning course.

• After remission, which may occur later in OCD and PTSD than in the other anxiety disorders, treatment should continue for at least several months in order to prevent relapses.

• Expert consensus conferences generally recommend a duration of pharmacotherapy of at least 12-24 months (Table ).

Recent guidelines for anxiety disorders

Dosing

• SSRIs have a flat response curve, i.e., approximately 75% of patients respond to the initial (low) dose.

• For tricyclic antidepressants, it is recommended that the drug at a low dose and the initiated dose increased every 3-5 days.

Dosing

• Benzodiazepine doses should be as low as possible but as high as necessary to achieve a complete treatment result.

• The antidepressant dose should be increased to the highest recommended level when initial treatment with a low or medium dosage fails.

Dosing

Panic Disorder• Recurrent unexpected panic attacks characterized by four or more of the following developed abruptly

and reached a peak within 10 minutes: Palpitations Sweating Trembling or shaking Shortness of breath Feeling of choking (also known as air hunger) Chest pain or discomfort Nausea or abdominal distress Feeling dizzy, lightheaded, or faint Derealization or depersonalization Fear of losing control or going crazy Fear of dying Numbness or tingling Chills or hot flashes

• Persistent concern of future attacks Worry about the meaning of or consequences of the attacks (e.g., heart attack or stroke) Significant change in behavior related to the attacks (e.g., avoiding places at which panic attacks have occurred)

Pharmacotherapy• Alprazolam and paroxetine are the two drugs approved by the US

Food and Drug Administration (FDA) for the treatment of panic disorder.

• In general, experience is showing superiority of the selective serotonin reuptake inhibitors (SSRIs) and clomipramine over the benzodiazepines, monoamine oxidase inhibitors (MAOIs), and tricyclic and tetracyclic drugs in terms of effectiveness and tolerance of adverse effects.

• A few reports have suggested a role for venlafaxine ,and buspironehas been suggested as an additive medication in some cases.

Recommended Dosages for Antipanic Drugs

Maintenance (mg) Starting (mg) SSRIs

20-60 5-10  Paroxetine

62.5 12.5-25 Paroxetine CR

20-60 2-5 Fluoxetine

50-200 12.5-25 Sertraline

100-150 12.5 Fluvoxamine

20-40 10 Citalopram

20 10 Escitalopram

Maintenance (mg) Starting (mg) TCA

50-125 5-12.5 Clomipramine

150-500 10-25 Imipramine

150-200 10-25 Desipramine

Maintenance (mg) Starting (mg) Atypical Antidepressants

150-225 37.5 Venlafaxine XR

Selective Serotonin Reuptake Inhibitors

• All SSRIs are effective for panic disorder. Paroxetine and paroxetine CR have sedative effects and tend to calm patients immediately, which leads to greater compliance and less discontinuation.

• Citalopram, escitalopram ,fluvoxamine, and sertraline are the next best tolerated.

• One approach for patients with panic disorder is to give 5 or 10 mg a day of paroxetine or 12.5 to 25 mg of paroxetine CR for 1 to 2 weeks, then increase the dosage by 10 mg of paroxetine or 12.5 mg of paroxetine CR a day every 1 to 2 weeks to a maximum of 60 mg of paroxetine or 62.5 mg of paroxetine CR.

• If sedation becomes intolerable, then taper the paroxetine dosage down to 10 mg a day of paroxetine or 12.5 mg of paroxetine CR and switch to fluoxetine at 10 mg a day and titrate upward slowly.

Benzodiazepines• Benzodiazepines can reasonably be used as the first agent for treatment

of panic disorder, while a serotonergic drug is being slowly titrated to a therapeutic dose.

• After 4 to 12 weeks, benzodiazepine use can be slowly tapered (over 4 to 10 weeks) while the serotonergic drug is continued.

• The major reservation among clinicians regarding the use of benzodiazepines for panic disorder is the potential for dependence, cognitive impairment, and abuse, especially after long-term use.

• Patients should be instructed not to drive, abstain from alcohol or other CNS depressant medications or operate dangerous equipment while taking benzodiazepines.

• Benzodiazepines elicit a sense of well-being, whereas discontinuation of benzodiazepines produces a well-documented and unpleasant withdrawal syndrome

BenzodiazepinesMaintenance (mg) Starting (mg)

0.5-2 tid 0.25-0.5 tid  Alprazolam

0.5-2 bid 0.25-0.5 bid Clonazepam

5-30 bid 2-5 bid Diazepam

0.5-2 bid 0.25-0.5 bid Lorazepam

Agoraphobia

• Fear of being in places or situations from which escape might be difficult, embarrassing, or in which help may be unavailable in the event of having a panic attack Often results in avoidance of the feared places or situations, for example: Crowds Stores Bridges Tunnels Traveling on a bus, train, or airplane Theaters Standing in a line Small enclosed rooms

Social phobia

• [ Marked and persistent fear of one or more social or performance situations in which the person is concerned about negative evaluation or scrutiny by others, for example: Public speaking Writing, eating, or drinking in public Initiating or maintaining conversations Fears humiliation or embarrassment, perhaps by manifesting anxiety symptoms (e.g., blushing or sweating) Feared social or performance situations are avoided or endured with intense anxiety or distress

Treatment• Drugs for the treatment of social phobia include (1) selective serotonin reuptake inhibitors

(SSRIs), (2) the benzodiazepines, (3) venlafaxine , and (4) buspirone .

• Most clinicians consider SSRIs the first-line treatment choice for patients with generalized social phobia. The benzodiazepines alprazolam and clonazepam are also efficacious in both generalized and specific social phobia. Buspirone has shown additive effects when used to augment treatment with SSRIs.

• In severe cases, successful treatment of social phobia with both irreversible MAOIs such as phenelzine and reversible inhibitors of monoamine oxidase such as moclobemide Therapeutic dosages of phenelzine range from 45 to 90 mg a day, with response rates ranging from 50 to 70 percent, and approximately 5 to 6 weeks are needed to assess the efficacy.

• The treatment of social phobia associated with performance situations frequently involves the use of adrenergic receptor antagonists shortly before exposure to a phobic stimulus. – The two compounds most widely used are atenolol (Tenormin), 50 to 100 mg every morning or 1

hour before the performance, and propranolol (20 to 40 mg).

Specific phobia• Marked and persistent fear that is excessive, unreasonable, cued by

the presence or anticipation of a specific object or situation, for example: Flying Enclosed spaces Heights Storms Animals (e.g., snakes or spiders) Receiving an injection Blood Provokes an immediate anxiety response Recognition that the fear is excessive or unreasonable Avoidance, anticipatory anxiety, or distress is significantly impairing

Phopia • Acrophobia fear of heights • Agoraphobia fear of open places • Ailurophobia fear of cats • Hydrophobia fear of water • Claustrophobia fear of closed spaces• Cynophobia fear of dogs • Mysophobia fear of dirt and germs • Pyrophobia fear of fire• Xenophobia fear of strangers • Zoophobia fear of animals

Treatment

• A common treatment for specific phobia is exposure therapy. • In this method, therapists desensitize patients by using a series of

gradual, self-paced exposures to the phobic stimuli, and they teach patients various techniques to deal with anxiety, including relaxation, breathing control, and cognitive approaches.

• The cognitive-behavioral approaches include reinforcing the realization that the phobic situation is, in fact, safe.

• receptor antagonists may be useful in the treatment of specific

phobia, especially when the phobia is associated with panic attacks. Pharmacotherapy (e.g., benzodiazepines), psychotherapy, or combined therapy directed to the attacks may also be of benefit.

Diagnostic Criteria for OCD • Obsessions

1. Repetitive thoughts (e.g., feeling contaminated after touching an object)

2. Repetitive images (e.g., recurrent sexually explicit pictures)

3. Repetitive impulses (e.g., need for symmetry or putting things in specific order)

• Compulsions

1. Repetitive activities (e.g., hand washing, checking, ordering, need to ask)

2. Repetitive mental acts (e.g., counting, repeating words silently, praying)

• Reduction in the frequency of obsessive thoughts and in the time spent performing compulsive acts

• Reduction in the degree of anxiety.

• Treatment for OCD may not completely eliminate obsessions or compulsions, but patients may feel remarkably improved with partial resolution of their symptoms

TREATMENT:Goals of therapy

• Cognitive behavior therapy CBT is the treatment of choice for mild OCD

• Exposure involves having the patient perform actions that were formerly avoided. For instance, if a patient avoided touching the flush handle on a bathroomtoilet, exposure would involve holding onto the handle.

TREATMENT:Nonpharmacologic

• The Food and Drug Administration (FDA) has approved five antidepressants for the management of OCD:

1. Clomipramine (60-70% Response)2. Fluoxetine3. Fluvoxamine4. Paroxetine5. Sertraline.

TREATMENT:PHARMACOLOGIC TREATMENTS

TREATMENT:PHARMACOLOGIC TREATMENTS