Generalized Anxiety Disorder ... Anxiety, Depression, Stress

Generalized anxiety disorder (GAD) is an anxiety disorder that is characterized by excessive, uncontrollable and often irrational worry about everyday things that is disproportionate to the actual source of worry. This excessive worry often interferes with daily functioning, as individuals suffering GAD typically anticipate disaster, and are overly concerned about everyday matters such as health issues, money, death, family problems, friend problems, relationship problems or work difficulties. They often exhibit a variety of physical symptoms, including fatigue, fidgeting, headaches, nausea, numbness in hands and feet, muscle tension, muscle aches, difficulty swallowing, bouts of difficulty breathing, trembling, twitching, irritability, sweating, insomnia, hot flashes, and rashes. These symptoms must be consistent and on-going, persisting at least 6 months, for a formal diagnosis of GAD to be introduced. Approximately 6.8 million American adults experience GAD.

Diagnosis
According to the Diagnostic and Statistical Manual IV-Text Revision (DSM-IV-TR), the following criteria must be met for a person to be diagnosed with Generalized Anxiety Disorder.

Excessive anxiety and worry (apprehensive expectation), occurring more days than not for at least six months, about a number of events or activities (such as work or school performance).

The person finds it difficult to control the worry.

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 6 months):

Note: Only one item is required in children.

restlessness or feeling keyed up or on edge
being easily fatigued
irritability
muscle tension
difficulty falling or staying asleep, or restless unsatisfying sleep
difficulty concentrating or the mind going blank
Symptoms can also include nausea, vomiting, and chronic stomach aches.

The focus of the anxiety and worry is not confined to features of an Axis I disorder, e.g., the anxiety or worry is not about having a panic attack (as in panic disorder), being embarrassed in public (as in social phobia), being away from home or close relatives (as in Separation Anxiety Disorder), gaining weight (as in anorexia nervosa), having multiple physical complaints (as in somatization disorder), or having a serious illness (as in hypochondriasis), and the anxiety and worry do not occur exclusively during post-traumatic stress disorder. The anxiety, worry, or physical symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

The disturbance is not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition (e.g., hyperthyroidism) and does not occur exclusively during a Mood Disorder, a Psychotic Disorder, or a Pervasive Developmental Disorder.

Prevalence
The World Health Organization's Global Burden of Disease project did not include generalised anxiety disorders.

In lieu of global statistics, here are some prevalence rates from around the world:

Australia: 3 percent of adults
Canada: Between 3-5 percent of adults
Italy: 2.9 percent
Taiwan: 0.4 percent
United States: approx. 3.1 percent of people age 18 and over in a given year (9.5 million)

Epidemiology
The usual age of onset is variable - from childhood to late adulthood, with the median age of onset being approximately 31 (Kessler, Berguland, et al., 2005). Most studies find that GAD is associated with an earlier and more gradual onset than the other anxiety disorders.

Women are two to three times more likely to suffer from generalized anxiety disorder than men, although this finding appears to be restricted to only developed countries, the spread of GAD is somewhat equal in developing nations. . GAD is also common in the elderly population.

Potential Causes of GAD
Some research suggests that GAD may run in families, and it may also grow worse during stress. GAD usually begins at an earlier age and symptoms may manifest themselves more slowly than in most other anxiety disorders. Some people with GAD report onset in early adulthood, usually in response to a life stressor. Once GAD develops, it can be chronic, but can be managed, if not all-but-alleviated, with proper treatment.

Substance induced
In one study in 1988–1990, illness in approximately half of patients attending mental health services at one British hospital psychiatric clinic, for conditions including anxiety disorders such as panic disorder or social phobia, was determined to be the result of alcohol or benzodiazepine dependence. In these patients, cessation of their anxiety symptoms corresponded with stopping the use of the benzodiazepine or alcohol. Sometimes anxiety pre-existed alcohol or benzodiazepine dependence but the dependence was acting to keep the anxiety disorders going and often progressively making them worse. Recovery from benzodiazepines tends to take a lot longer than recovery from alcohol but people can regain their previous good health. Symptoms may temporarily worsen however, during alcohol withdrawal or benzodiazepine withdrawal.

Neurology
Generalized anxiety disorder has been linked to disrupted functional connectivity of the amygdala and its processing of fear and anxiety. Sensory information enters the amgydala through the nuclei of the basolateral complex (consisting of lateral, basal, and accessory basal nuclei). The basolateral complex processes sensory related fear memories and communicate their threat importance to memory and sensory processing elsewhere in the brain such as the medial prefrontal cortex and sensory cortices. Another area the adjacent central nucleus of the amygdala that controls species-specific fear responses its connections brainstem, hypothalamus, and cerebellum areas. In those with general anxiety disorder these connections functionally seem to be less distinct and there is greater gray matter in the central nucleus. Another difference is that the amygdala areas have decreased connectivity with the insula and cingulate areas that control general stimulus salience while having greater connectivity with the parietal cortex and prefrontal cortex circuits that underlie executive functions. The latter suggests a compensation strategy for dysfunctional amygdala processing of anxiety. This is consistent with cognitive theories that suggest the use in this disorder of attempts to reduce the involvement of emotions with compensatory cognitive strategies.

Self-help
Common-sense action may be taken to reduce the general level of anxiety. The actions may be appropriate to a specific type of stress. For example, if there are frequent worries about financial difficulties, then financial planning may help. Other actions may improve general mental resilience. For example, exercise may help in releasing tension and, by improving fitness, enable the individual to manage tasks more easily and feel better about himself or herself.

Treatment
A meta-analysis of 35 studies shows the psychological method of cognitive behavioral therapy to be more effective in the long term than pharmacologic treatment (drugs such as SSRIs), and while both treatments reduce anxiety, CBT is more effective in reducing depression.

Cognitive behavioral therapy
Cognitive behavioral therapy (CBT) is a psychological method of treatment for GAD, which involves a therapist working with the patient to understand how thoughts and feelings influence behavior. The goal of the therapy is to change negative thought patterns that lead to the patient's anxiety, replacing them with positive, more realistic ones. Elements of the therapy include exposure strategies to allow the patient to gradually confront their anxieties and feel more comfortable in anxiety-provoking situations, as well as to practice the skills they have learned. CBT can be used alone or in conjunction with medication.

CBT usually helps one third of the patients substantially, whilst another third does not respond at all to treatment.

SSRIs
Pharmaceutical treatments for GAD include selective serotonin reuptake inhibitors (SSRIs), which are antidepressants that influence brain chemistry to block the reabsorption of serotonin in the brain. SSRIs are mainly indicated for clinical depression, but are also very effective in treating anxiety disorders. Common side effects include nausea, sexual dysfunction, headache, diarrhea, constipation, among others.

Common SSRIs prescribed for GAD include:

fluoxetine (Prozac)
paroxetine (Paxil)
escitalopram (Lexapro)
sertraline (Zoloft)

Other Drugs
Buspirone (BuSpar). Buspirone (BuSpar) is a serotonin receptor agonist belonging to the azaspirodecanedione class of compounds.
Duloxetine (Cymbalta)
Imipramine (Tofranil). Imipramine (Tofranil) is a tricyclic antidepressant (TCA). TCAs are thought to act on serotonin, norepinephrine, and dopamine in the brain.
Pregabalin (Lyrica). Pregabalin (Lyrica) acts on the voltage-dependent calcium channel in order to decrease the release of neurotransmitters such as glutamate, noradrenaline and substance P.
Venlafaxine (Effexor, Effexor XR). Venlafaxine (Effexor) is a serotonin-norepinephrine reuptake inhibitor (SNRI). SNRIs, a class of drugs related to the SSRIs, alter the chemistries of both norepinephrine and serotonin in the brain.
Propranolol (Inderal)

Benzodiazepines
Main article: Benzodiazepine
Benzodiazepines (or "benzos") are fast-acting sedatives that are also used to treat GAD and other anxiety disorders. Benzodiazepines are often prescribed for generalised anxiety disorder and show beneficial effects in the short-term. The World Council of Anxiety does not recommend the long-term use of benzodiazepines because they are associated with the development of tolerance, psychomotor impairment, cognitive and memory impairments, physical dependence and a withdrawal syndrome. Side effects include drowsiness, reduced motor coordination and problems with equilibrioception.

Common benzodiazepines used to treat GAD include:

alprazolam (Xanax, Xanax XR)
clonazepam (Klonopin)
diazepam (Valium)
lorazepam (Ativan)

GAD and Comorbid Depression
In the National Comorbidity Survey (2005), 58% of patients diagnosed with major depression were found to have an anxiety disorder; among these patients, the rate of comorbidity with GAD was 17.2%, and with panic disorder, 9.9%. Patients with a diagnosed anxiety disorder also had high rates of comorbid depression, including 22.4% of patients with social phobia, 9.4% with agoraphobia, and 2.3% with panic disorder. For many, the symptoms of both depression and anxiety are not severe enough (i.e. are subsyndromal) to justify a primary diagnosis of either major depressive disorder (MDD) or an anxiety disorder.

Patients can also be categorized as having mixed anxiety-depressive disorder, and they are at significantly increased risk of developing full-blown depression or anxiety.

Accumulating evidence indicates that patients with comorbid depression and anxiety tend to have greater illness severity and a lower treatment response than those with either disorder alone. In addition, social function and quality of life are more greatly impaired.

In addition to coexisting with depression, research shows that GAD often coexists with substance abuse or other conditions associated with stress, such as irritable bowel syndrome. Patients with physical symptoms such as insomnia or headaches should also tell their doctors about their feelings of worry and tension. This will help the patient's health care provider to recognize whether the person is suffering from GAD.

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