Anxiety disorder

Description

Anxiety disorders are those conditions in which the individual experiences excessive, continual or prolonged anxiety for no obvious reason or where the anxiety is significantly disproportionate to the cause. Extreme anxiety can result in intense apprehension or panic
1. Generalised Anxiety. Generalized anxiety disorder is a common chronic disorder characterized by continual or prolonged anxiety that is not focused on any one object or situation. Those suffering from generalized anxiety experience non-specific persistent fear and worry and become excessively concerned with everyday matters. Additional symptoms include the following.

• Restlessness or feeling keyed-up or on edge
• Being easily fatigued
• Difficulty concentrating or mind going blank
• Irritability
• Muscle tension
• Sleep disturbance

A diagnosis of Generalised Anxiety should be considered if the patient has the general symptoms plus at least three of the additional symptoms. Generalized anxiety disorder may have its onset in early childhood or be triggered by a significant stressful situation. It is the most common anxiety disorder to affect older adults.
2. Panic Disorder. This is characterised by the sudden onset of episodes of intense fear or apprehension. These feelings reach a maximum within ten minutes, may be brief, or may last for several hours. The attacks may be triggered by stress or surroundings; however there is often no obvious explanation. Fear itself may trigger these attacks; however the response is completely disproportionate to the cause of fear.
At least four of the following additional symptoms should be present for a diagnosis of Panic Disorder.

• Palpitations (pounding, racing or irregular heart beat)
• Sweating
• Trembling or shaking
• Dyspnoea (shortness of breath)
• Sensation of choking
• Chest pain or discomfort
• Nausea or abdominal distress
• Feeling dizzy, unsteady, lightheaded, or faint
• Derealisation or depersonalization (a feeling that you or your surroundings are unreal)
• Fear of losing control or going crazy
• Fear of dying
• Paresthesias (numbness, tingling)
• Chills or hot flashes

These two conditions may overlap with patients who have anxiety disorder being susceptible to occasional panic attacks.

Some of the parts of the brain involved in response to fear or anxiety

Anxiety or fear has a well documented physiological effect on the brain, the endocrine (hormone) system and the autonomic (involuntary) nervous system. An area of the brain known as the locus coeruleus responds to stimuli from the senses. In a relaxed state the neurons in the locus coeruleus will produce normal levels of a neurotransmitter called norepinephrine. If the senses perceive danger the neurons will produce more norepinephrine in proportion to the perceived threat. Rising levels of norepinephrine increase awareness, information processing and motivation in the prefrontal cortex and nucleus accumben by increasing the activity of neurons in these areas of the brain. They also activate the hypothalamus and, pituitary glands which stimulate the adrenal glands to produce more cortisol.
Norepinephrine also acts directly on part of the autonomic nervous system called the sympathetic system. This exerts automatic control over a variety of bodily functions including heart rate, gut motility, urine output, pupil diameter and sweating.
Significantly increased levels of hormones and neurotransmitters, particularly norepinephrine, epinephrine and cortisol can result in dramatic physiological changes, including:

• Acceleration of heart and lung action
• Paling or flushing, or alternating between both
• Inhibition of stomach and upper-intestinal action (digestion slows down or stops)
• General effect on the sphincters of the body
• Constriction of blood vessels in many parts of the body
• Liberation of nutrients (particularly fat and glucose) for muscular action
• Dilation of muscle blood vessels and muscle tension
• Inhibition of the lachrymal gland (responsible for tear production) and salivation
• Dilation of pupil (mydriasis)
• Relaxation of bladder
• Evacuation of colon
• Inhibition of erection
• Auditory exclusion (loss of hearing)
• Tunnel vision (loss of peripheral vision)
• Acceleration of instantaneous reflexes
• Shaking
• Sweating in anticipation of increased body heat due to increased muscle activity

This is known as the “fight or flight” or stress response and prepares the body for a rapid and effective response to perceived threats. Most of the physiological changes are designed to shut down any unnecessary activities increase blood flow and energy supply to muscles, and maximise alertness and visual focus. The physiological response may be mild or dramatic depending on the degree of perceived threat. The levels of the various neurotransmitters and hormones that trigger this response are normally controlled by a feedback mechanism that switches off the response at certain levels or when the threat has been removed, neutralised or reassessed. One of the main control mechanisms in this feedback process is thought to be binding of gamma-aminobutyric acid (GABA) to receptors on neurons in the brain, which stops the neuron firing.  Failure of this mechanism can result in excessive or prolonged firing of neurons and an uncontrolled physiological response.
Low or moderate levels of anxiety or fear may trigger some of the above physiological changes at low or moderate levels. High levels of anxiety or fear may trigger most of these physiological changes at dramatic levels.
Generalised anxiety disorder is thought to be due to repeated triggering of the stress response, and/or a failure to switch off the response at an appropriate level.  This may be due to continual exposure to situations which generate fear or stress or exposure to relatively normal situations which the patient has learned to fear. . In some cases the trigger may be difficult to identify.
 Alternatively, it may be due to exposure to normal levels of fear or stress in an individual with a defective feedback control mechanism.
The stress response may become a panic attack if the stress response is excessive or if the feedback control mechanism fails to function at the appropriate level.
Repeated or constant triggering of the stress response can result in excessive fatigue, high blood pressure, digestive disorders, anorexia, repeated infections and erectile dysfunction. These disorders may further increase anxiety generating a vicious circle of deteriorating physical and mental health.
In many cases, anxiety is associated with depression. This may be the body's attempt to limit damage from over activation of the stress response by shutting down all unnecessary activity.
Anxiety disorders can be triggered by substance abuse, medications, herbal remedies and other toxic substances. These types of anxiety disorders are often misdiagnosed or under-diagnosed.
A substance-induced anxiety disorder may be caused by alcohol, amphetamines (and related substances), caffeine, cannabis (marijuana), cocaine, hallucinogens, inhalants and phencyclidine (PCP) or related substances.
Anxiety symptoms can also result from withdrawal from alcohol, sedatives, hypnotics, and anxiolytics or cocaine.
Some of the medications which may induce anxiety symptoms include anaesthetics and analgesics, sympathomimetics (epinephrine or norepinephrine, for example) or other bronchodilators, anticholinergic agents, anticonvulsants, antihistamines, insulin, thyroid preparations, oral contraceptives, antihypertensive and cardiovascular medications, antiparkinsonian medications, corticosteroids, antidepressant medications, lithium carbonate, and antipsychotic medications.
Heavy metals and toxins, such as volatile substances like fuel and paint, organophosphate insecticides, nerve gases, carbon monoxide, and carbon dioxide may also induce anxiety.

Signs & Symptoms

Patients with generalised anxiety disorder may present with a variety of symptoms including  rapid heartbeat, shortness of breath, increased sweating, stomach cramping, a feeling of a lump in the throat or inability to swallow, frequent need to urinate, dry mouth, nausea, diarrhoea, clammy hands, head, neck or backaches or non-specific body aches. Patients may also complain of uncontrolled shaking or trembling or twitching, usually precipitated by anxiety inducing situations. 

Treatment

Patients with panic disorder frequently present with chest pain or dyspnoea (shortness of breath), fearing that they are dying of myocardial infarction. Anxiety symptoms often accompany or can exacerbate respiratory conditions such as asthma and chronic obstructive pulmonary disease.
Intravenous or oral acute sedation with benzodiazepines may be used if indicated.
Untreated panic attacks can subside spontaneously within 20-30 minutes, especially with reassurance and a calming environment.
Discontinue or replace any suspect medication if possible,
Discontinue or reduce caffeine and alcohol intake
Treatment options available include lifestyle changes; psychotherapy, especially cognitive behavioral therapy; and pharmaceutical therapy. Education, reassurance and some form of cognitive-behavioral therapy should be used, either alone, or in combination with medication.

Medication
Treatment depends on the type of disorder and severity of symptoms
Antidepressant agents are the drugs of choice in the treatment of anxiety disorders, particularly the newer agents that have fewer side effects and greater ease of use than the older tricyclic antidepressants; however, benzodiazepines are often used as adjunct treatment.

Benzodiazepines
Several drugs in the benzodiazepine class can be used for the short-term ( 6 wk) control of anxiety. Drugs in this class include lorazepam, diazepam, clonazepam, and chlordiazepoxide.

Lorazepam (Ativan)
Sedative hypnotic in the benzodiazepine class that has a short onset of effect and a relatively long half-life. By increasing action of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter in the brain, may depress all levels of the CNS, including limbic and reticular formation. Available for PO, IV, or IM use.
Adult
0.5-6 mg PO/IV/IM in divided doses
Pediatric
0.25-2 mg PO/IV/IM in divided doses

Serotonin and norepinephrine reuptake inhibitors
Pharmacologic agents with both reuptake inhibition of serotonin and norepinephrine may be helpful in a variety of mood and anxiety disorders.

Venlafaxine (Effexor XR)
FDA-approved for generalized anxiety disorder, panic disorder and social anxiety disorder in adults. May be helpful for other anxiety disorders.
Adult
37.5-300 mg extended-release formulation PO qd
Pediatric
Not established

Duloxetine (Cymbalta)
Potent inhibitor of neuronal serotonin and norepinephrine reuptake. Indicated for generalized anxiety disorder
Adult
30-60 mg PO qd
Pediatric
Not established

Antianxiety agents
Buspirone is a novel antianxiety agent with no other members in its class.

Buspirone (BuSpar)
FDA-approved for generalized anxiety disorder in adults. Does not appear to be helpful as primary treatment for panic disorder or OCD.
Adult
15-60 mg PO qd/bid
Pediatric
Not established

Tricyclic antidepressants
A complex group of drugs that have central and peripheral anticholinergic effects, as well as sedative effects.

Imipramine (Tofranil)
Tricyclic antidepressant that has norepinephrine and serotonin reuptake-inhibition properties. One of the oldest agents available for the treatment of depression and has established efficacy in the treatment of panic disorder. Elderly and adolescent patients may need lower dosing or slower titration.
Adult
Initial: 50-75 mg PO qd titrated gradually to 150 mg qd according to tolerance
Dose range: 75-300 mg qd, administered either hs or divided doses
Pediatric
Not established

Serotonin Reuptake Inhibitors
These agents specifically inhibit presynaptic reuptake of serotonin but not noradrenaline.

Paroxetine (Paxil)
FDA-approved for panic disorder, depression, social anxiety disorder, generalized anxiety disorder, posttraumatic stress disorder, and OCD.
Adult
10-60 mg PO qd
Pediatric
Not established

Escitalopram (Lexapro)
Mechanism of action is thought to be potentiation of serotonergic activity in central nervous system resulting from inhibition of CNS neuronal reuptake of serotonin. Onset of depression relief may be obtained after 1-2 wk, which is sooner than other antidepressants.
Adult
10 mg PO qd initially; if needed, may increase to 20 mg/d after 1 wk
Pediatric
Not established

Sertraline (Zoloft)
FDA-approved for panic disorder, PTSD, social phobia, and OCD. May be helpful for other anxiety disorders.
Adult
50-200 mg PO; initiate at 25 mg/d and increase as tolerated, not to exceed 200 mg/d
Pediatric
25-100 mg PO qd

Fluoxetine (Prozac)
FDA-approved for OCD and panic disorder. May be helpful for other anxiety disorders.
Adult
10-60 mg PO qd
Pediatric
Not established

Patient Management

Regular exercise, improving sleep patterns and  reducing caffeine and alcohol intake can help to reduce anxiety symptoms.