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. Individuals 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, difficulty concentrating, trembling, twitching, irritability, agitation, sweating, restlessness, insomnia, hot flashes, and rashes and inability to fully control the anxiety (ICD-10). These symptoms must be consistent and on-going, persisting at least six months, for a formal diagnosis of GAD to be introduced. Approximately 6.8 million American adults experience GAD, and 2 percent of adult Europeans, in any given year, experience GAD.
Standardized rating scales such as GAD-7 can be used to assess severity of generalized anxiety disorder symptoms. It is the most common cause of disability in the workplace in the United States.
Prevalence
The World Health Organization’s Global Burden of Disease project did not include generalized anxiety disorders. In lieu of global statistics, here are some prevalence rates from around the world:
Australia: 3 percent of adults
Canada: Between 3 and 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)
55 to 60 percent of people diagnosed in clinical settings are women.
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
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
Long-term use of benzodiazepines can worsen underlying anxiety. with evidence that reduction of benzodiazepines can lead to a lessening of anxiety symptoms. Similarly, long-term alcohol use is associated with anxiety disorders, with evidence that prolonged abstinence can result in a disappearance of anxiety symptoms.
In one study in 1988–90, illness in approximately half of patients attending mental health services at 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, anxiety symptoms, while worsening initially during the withdrawal phase, disappeared with abstinence from benzodiazepines 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.
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 amygdala 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 generalized 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.
Diagnosis
DSM-IV-TR criteria
DSM-IV-TR diagnostic criteria for generalized anxiety disorder are as follows:
A. Excessive anxiety and worry (apprehensive expectation), occurring more-days-than-not for at least 6 months, about a number of events or activities (such as work or school performance).
B. The person finds it difficult to control the worry.
C. 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).
- restlessness or feeling keyed up or on edge
- being easily fatigued
- difficulty concentrating or mind going blank
- irritability
- muscle tension
- sleep disturbance (difficulty falling or staying asleep, or restless unsatisfying sleep)
D. The focus of the anxiety and worry is not confined to features of other Axis I disorder (such as social phobia, OCD, PTSD etc.)
E. The anxiety, worry, or physical symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
F. 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, psychotic disorder, or a pervasive developmental disorder.
ICD-10 criteria
F41.1 Generalized anxiety disorder
Note: For children different criteria may be applied (see F93.80).
A. A period of at least six months with prominent tension, worry and feelings of apprehension, about every-day events and problems.
B. At least four symptoms out of the following list of items must be present, of which at least one from items (1) to (4).
Autonomic arousal symptoms
(1) Palpitations or pounding heart, or accelerated heart rate.
(2) Sweating.
(3) Trembling or shaking.
(4) Dry mouth (not due to medication or dehydration).
Symptoms concerning chest and abdomen
(5) Difficulty breathing.
(6) Feeling of choking.
(7) Chest pain or discomfort.
(8) Nausea or abdominal distress (e.g. churning in stomach).
Symptoms concerning brain and mind
(9) Feeling dizzy, unsteady, faint or light-headed.
(10) Feelings that objects are unreal (derealization), or that one’s self is distant or “not really here” (depersonalization).
(11) Fear of losing control, going crazy, or passing out.
(12) Fear of dying.
General symptoms
(13) Hot flushes or cold chills.
(14) Numbness or tingling sensations.
Symptoms of tension
(15) Muscle tension or aches and pains.
(16) Restlessness and inability to relax.
(17) Feeling keyed up, or on edge, or of mental tension.
(18) A sensation of a lump in the throat, or difficulty with swallowing.
Other non-specific symptoms
(19) Exaggerated response to minor surprises or being startled.
(20) Difficulty in concentrating, or mind going blank, because of worrying or anxiety.
(21) Persistent irritability.
(22) Difficulty getting to sleep because of worrying.
C. The disorder does not meet the criteria for panic disorder (F41.0), phobic anxiety disorders (F40.-), obsessive-compulsive disorder (F42.-) or hypochondriacal disorder (F45.2).
D. Most commonly used exclusion criteria: not sustained by a physical disorder, such as hyperthyroidism, an organic mental disorder (F0) or psychoactive substance-related disorder (F1), such as excess consumption of amphetamine-like substances, or withdrawal from benzodiazepines.
Treatment
Psychotherapy
Psychotherapy for GAD should be oriented toward combating the individual’s low-level, ever-present anxiety. Such anxiety is often accompanied by poor planning skills, high stress levels, and difficulty in relaxing. This last point is important because it the easiest one in which the therapist can play an especially effective teaching role.
Relaxation skills can be taught either alone or with the use of biofeedback. Education about relaxation and simple relaxation exercises, such as deep breathing, are excellent places to begin therapy. While biofeedback (the ability to allow the patient to hear or see feedback of their body’s physiological state) is beneficial, it is not required for effective relaxation to be taught to most people. Progressive muscle relaxation and more general imagery techniques can be used as therapy progresses. Teaching an individual how to relax, and the ability to do it in any place or situation is vital to reducing the low-level anxiety levels. Individuals who learn these skills, which can be taught in a brief-therapy framework, go on to lead productive, generally anxiety-free lives once therapy is complete. A common reason for failure to make any gains with relaxation skills is simply because the client does not practice them outside of the therapy session. From the onset of therapy, the individual who suffers from GAD should be encouraged to set a regular schedule in which to practice relaxation skills learned in session, at least twice a day for a minimum of 20 minutes (although more often and for longer periods of time is better). Lack of treatment progress can often be traced to a failure to follow through with homework assignments of practicing relaxation.
Reducing stress and increasing overall coping skills may also be beneficial in helping the client. Many people who have GAD also lead very active (some would say, “hectic”) lives. Helping the individual find a better balance in their lives between self-enrichment, family, significant other, and work may be important. People who have GAD have lived with their anxiety for such a long time they may not recognize a life without constant worrying and activity. Helping the individual realize that life doesn’t have to boring just because one isn’t always worrying or doing things may also help.
Individual therapy is usually the recommended treatment modality. Many times people who present with GAD feel a bit awkward discussing their anxiety in front of others, especially if they are less than accepting. A clear distinction should be made at the onset of the evaluation to differentiate GAD from social phobia, however, and the appropriate diagnosis should be made. It would be unwise to recommend group therapy to someone who had social phobia or GAD early on, because of the social component to either disorder. Placing a person into a group setting without minimal interpersonal and relaxation skills being taught first in individual therapy is a recipe for disaster and early treatment termination.
Non-specific factors in therapy are important to these patients, as they will make the most beneficial gains in a supportive and accepting therapeutic environment. Simply listening to the individual and offering objective feedback about their experiences is likely helpful. Examining stressors in the client’s life and helping the individual find better ways of handling these stressors is likely to be beneficial. Modeling techniques of appropriate social behaviors within therapy session may help. Clinicians should not confuse GAD with specific phobias, which have much more acute and traumatic symptoms. In the same respect, treatments for specific phobias generally are not appropriate nor effective with GAD. Some clinicians easily confuse this important distinction.
Hypnotherapy is also an appropriate treatment modality for those individuals who are highly suggestible. Often hypnotherapy is combined with other relaxation techniques.
If an individual finds themselves hyperventilating then they are breathing in too much oxygen. One of the correct things to do is to direct them to breath into a paper bag. This does increase the percent of C02 in the inhalation, which thereby helps keep the 02/C02 balance. While this technique is valid, the better technique is to slow down respiration rate and volume with slow deep breaths (without the paper bag).
Robert Fried, Ph. D. (psychologist) has a couple books out on respiration you might want to check out. One of his books is “The Hyperventilation Syndrome,” Baltimore, Johns Hopkins Univ. Press, 1987.
Medications
Medication should be prescribed if the anxiety symptoms are serious and interfering with normal daily functioning. Psychotherapy and relaxation techniques can’t be worked on effectively if the individual is overwhelmed by anxiety or cannot concentrate.
The most commonly prescribed anti-anxiety agent for this disorder has historically been benzodiazepines, despite a dearth of clinical research that shows this particular class of drugs is any more effective than others. Diazepam (Valium) and lorazepam (Ativan) are the two most prescribed benzodiazepines. Lorazepam will produce a more lengthy sedating effect than diazepam, although it will take longer to appear. Individuals on these medications should always be advised about the medications’ side effects, especially their sedative properties and impairment on performance.
Tricyclic antidepressants often are an effective treatment alternative to benzodiazepines and may be a better choice over a longer treatment period.
Medication for this disorder should only be used to treat acute symptoms of anxiety. Medication should be tapered off when it is discontinued.
Phillip W. Long, M.D. also notes:
“Buspirone, a new nonbenzodiazepine antianxiety drug, is non-addictive and does not impair mechanical performance such as driving. Response to buspirone occurs approximately in two weeks, as compared to the more rapid onset associated with benzodiazepines. Schwiezer et al. (1986) studied patients who previously had taken benzodiazepines for the treatment of anxiety and who were later placed on buspirone. These patients were found to have a poor response to buspirone.”
Self-Help
Self-help methods for the treatment of this disorder are often overlooked by the medical profession because very few professionals are involved in them. Many support groups exist within communities throughout the world which are devoted to helping individuals with this disorder share their commons experiences and feelings of anxiety. Individuals should first be able to tolerate and effectively handle a social group interaction. Pushing an individual into a group setting, whether it be self-help or a regular group therapy experience, is counterproductive and may lead to a worsening of symptoms.
A meta-analysis of 35 studies shows 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 that 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, Sarafem)
- paroxetine (Paxil, Aropax)
- escitalopram (Lexapro, Cipralex)
- sertraline (Zoloft)
Pregabalin
Pregabalin (Lyrica) acts on the voltage-dependent calcium channel in order to decrease the release of neurotransmitters such as glutamate, noradrenaline and substance P. Its therapeutic effect appears after 1 week of use and is similar in effectiveness to lorazepam, alprazolam and venlafaxine but pregabalin has demonstrated superiority by producing more consistent therapeutic effects for psychic and somatic anxiety symptoms. Long-term trials have shown continued effectiveness without the development of tolerance and additionally unlike benzodiazepines it does not disrupt sleep architecture and produces less severe cognitive and psychomotor impairment; it also has a low potential for abuse and dependence and may be preferred over the benzodiazepines for these reasons.
Other drugs
– Psychotropic drugs
- Buspirone (BuSpar) is a serotonin receptor partial agonist, belonging to the azaspirodecanedione class of compounds.
- Duloxetine (Cymbalta)- SNRI – type antidepressant
- Imipramine (Tofranil) is a tricyclic antidepressant (TCA).
- Other tricyclic antidepressants – as clomipramine,etc. TCAs are thought to act on serotonin, norepinephrine, and dopamine in the brain.
- Venlafaxine (Effexor XR) is a serotonin-norepinephrine reuptake inhibitor (SNRI). SNRIs alter the chemistries of both norepinephrine and serotonin in the brain.
- Some of MAO inhibitors – such as Moclobemide,rarely Nialamide
– Non-psychotropic drugs
- Propranolol (Inderal) – Sympatholytic, beta-adrenoblocker
- Clonidine – Sympatholytic
- Guanfacine – Sympatholytic
- Prazosin – Sympatholytic, alpha-adrenoblocker
Benzodiazepines
Benzodiazepines (or “benzos”) are fast-acting hypnotic sedative depressants that are also used to treat GAD and other anxiety disorders. Benzodiazepines are prescribed for generalized anxiety disorder and show beneficial effects in the short term. However, they have long term adverse effects and for this reason the FDA has only approved them for short term usage (6–12 weeks). 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, Niravam)
- chlordiazepoxide (Librium)
- clonazepam (Klonopin)
- clorazepate (Tranxene)
- diazepam (Valium)
- lorazepam (Ativan)
GAD and comorbid depression
In the National Comorbidity Survey (2005), 58 percent 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 percent, and with panic disorder, 9.9 percent. Patients with a diagnosed anxiety disorder also had high rates of comorbid depression, including 22.4 percent of patients with social phobia, 9.4 percent with agoraphobia, and 2.3 percent 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. However, Dysthymic Disorder is the most prevalent comorbid diagnosis of GAD clients.
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.