General anxiety disorder
Encyclopedia
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
, headache
s, 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.
'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:
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.
. Once GAD develops, it can be chronic
, but can be managed, if not all-but-alleviated, with proper treatment.
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.
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.
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).
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.
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).
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.
s and feeling
s 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.
s (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:
(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.
- Non-psychotropic drugs
and a withdrawal syndrome
. Side effects include drowsiness, reduced motor coordination
and problems with equilibrioception
. Common benzodiazepines used to treat GAD include:
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 headache
s 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.
Anxiety disorder
Anxiety disorder is a blanket term covering several different forms of abnormal and pathological fear and anxiety. Conditions now considered anxiety disorders only came under the aegis of psychiatry at the end of the 19th century. Gelder, Mayou & Geddes explains that anxiety disorders are...
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
Health
Health is the level of functional or metabolic efficiency of a living being. In humans, it is the general condition of a person's mind, body and spirit, usually meaning to be free from illness, injury or pain...
issues, money
Money
Money is any object or record that is generally accepted as payment for goods and services and repayment of debts in a given country or socio-economic context. The main functions of money are distinguished as: a medium of exchange; a unit of account; a store of value; and, occasionally in the past,...
, death
Death
Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....
, family
Family
In human context, a family is a group of people affiliated by consanguinity, affinity, or co-residence. In most societies it is the principal institution for the socialization of children...
problems, friend problems, relationship problems or work difficulties. Individuals often exhibit a variety of physical symptoms, including fatigue, fidgeting
Fidgeting
Fidgeting is the act of moving about restlessly. Fidgeting may be a result of nervousness, agitation, boredom or a combination of these. It may be a result of genes and is often an unconscious act. Fidgeting may involve playing with one's fingers, hair, or items of clothing. A common act of...
, headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
s, nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
, numbness in hands and feet, muscle tension, muscle aches
Myalgia
Myalgia means "muscle pain" and is a symptom of many diseases and disorders. The most common causes are the overuse or over-stretching of a muscle or group of muscles. Myalgia without a traumatic history is often due to viral infections...
, difficulty swallowing
Swallowing
Swallowing, known scientifically as deglutition, is the process in the human or animal body that makes something pass from the mouth, to the pharynx, and into the esophagus, while shutting the epiglottis. If this fails and the object goes through the trachea, then choking or pulmonary aspiration...
, bouts of difficulty breathing
Breathing
Breathing is the process that moves air in and out of the lungs. Aerobic organisms require oxygen to release energy via respiration, in the form of the metabolism of energy-rich molecules such as glucose. Breathing is only one process that delivers oxygen to where it is needed in the body and...
, difficulty concentrating
Attention
Attention is the cognitive process of paying attention to one aspect of the environment while ignoring others. Attention is one of the most intensely studied topics within psychology and cognitive neuroscience....
, trembling
Tremor
A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving to-and-fro movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, face, head, vocal folds, trunk, and legs. Most tremors occur in the...
, twitching
Muscle contraction
Muscle fiber generates tension through the action of actin and myosin cross-bridge cycling. While under tension, the muscle may lengthen, shorten, or remain the same...
, irritability
Irritability
Irritability is an excessive response to stimuli. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessive sensitivity to stimuli; It is usually used to refer to anger or frustration....
, agitation
Psychomotor agitation
Psychomotor agitation is a series of unintentional and purposeless motions that stem from mental tension and anxiety of an individual. This includes pacing around a room, wringing one's hands, pulling off clothing and putting it back on and other similar actions...
, sweating
Sweating
Perspiration is the production of a fluid consisting primarily of water as well as various dissolved solids , that is excreted by the sweat glands in the skin of mammals...
, restlessness
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
, insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
, 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
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
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 OrganizationWorld Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
's Global Burden of Disease
Global burden of disease
The global burden of disease is a comprehensive regional and global assessment of mortality and disability from 107 diseases and injuries and ten risk factors. The GBD is assessed using the GBD study by the World Health Organization , and is an example of an evidence-based input to public health...
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)
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 stressorStressor
Stressor is a chemical or biological agent, environmental condition, an external stimulus or an event that causes stress to an organism. An event that triggers the stress response may include for example:...
. Once GAD develops, it can be chronic
Chronic (medicine)
A chronic disease is a disease or other human health condition that is persistent or long-lasting in nature. The term chronic is usually applied when the course of the disease lasts for more than three months. Common chronic diseases include asthma, cancer, diabetes and HIV/AIDS.In medicine, the...
, 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 useLong-term effects of alcohol
The long term effects of alcohol range from possible health benefits for low levels of alcohol consumption to severe detrimental effects in cases of chronic alcohol abuse...
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
Panic disorder
Panic disorder is an anxiety disorder characterized by recurring severe panic attacks. It may also include significant behavioral change lasting at least a month and of ongoing worry about the implications or concern about having other attacks. The latter are called anticipatory attacks...
or social phobia
Social anxiety disorder
Social anxiety disorder , also known as social phobia, is an anxiety disorder characterized by intense fear in social situations causing considerable distress and impaired ability to function in at least some parts of daily life...
, was determined to be the result of alcohol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
or benzodiazepine dependence
Benzodiazepine dependence
Benzodiazepine dependence or benzodiazepine addiction is a condition during which a person is dependent on benzodiazepine drugs. Dependence can be either a psychological dependence, physical dependence, or a combination of the two...
. In these patients, anxiety symptoms, while worsening initially during the withdrawal phase, disappeared with abstinence from benzodiazepines or alcohol. Sometimes anxiety pre-existed alcohol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
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 amygdalaAmygdala
The ' are almond-shaped groups of nuclei located deep within the medial temporal lobes of the brain in complex vertebrates, including humans. Shown in research to perform a primary role in the processing and memory of emotional reactions, the amygdalae are considered part of the limbic system.-...
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
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
, and cerebellum
Cerebellum
The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...
areas. In those with generalized anxiety disorder these connections functionally seem to be less distinct and there is greater gray matter
Gray Matter
"Gray Matter" is a short story by Stephen King, first published in the October 1973 issue of Cavalier magazine, and later collected in King's 1978 collection Night Shift. It is set in the same area as King's novel Dreamcatcher.-Setting:...
in the central nucleus. Another difference is that the amygdala areas have decreased connectivity with the insula
Insular cortex
In each hemisphere of the mammalian brain the insular cortex is a portion of the cerebral cortex folded deep within the lateral sulcus between the temporal lobe and the frontal lobe. The cortical area overlying it towards the lateral surface of the brain is the operculum...
and cingulate areas that control general stimulus salience while having greater connectivity with the parietal cortex and prefrontal cortex
Prefrontal cortex
The prefrontal cortex is the anterior part of the frontal lobes of the brain, lying in front of the motor and premotor areas.This brain region has been implicated in planning complex cognitive behaviors, personality expression, decision making and moderating correct social behavior...
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.
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 disorderNote: 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 Palpitations or pounding heart, or accelerated heart rate. Sweating. Trembling or shaking. Dry mouth (not due to medication or dehydration).
- Symptoms concerning chest and abdomen Difficulty breathing. Feeling of choking. Chest pain or discomfort. Nausea or abdominal distress (e.g. churning in stomach).
- Symptoms concerning brain and mind Feeling dizzy, unsteady, faint or light-headed. Feelings that objects are unreal (derealization), or that one's self is distant or "not really here" (depersonalization). Fear of losing control, going crazy, or passing out. Fear of dying.
- General symptoms Hot flushes or cold chills. Numbness or tingling sensations.
- Symptoms of tension Muscle tension or aches and pains. Restlessness and inability to relax. Feeling keyed up, or on edge, or of mental tension. A sensation of a lump in the throat, or difficulty with swallowing.
- Other non-specific symptoms Exaggerated response to minor surprises or being startled. Difficulty in concentrating, or mind going blank, because of worrying or anxiety. Persistent irritability. 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
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 thoughtThought
"Thought" generally refers to any mental or intellectual activity involving an individual's subjective consciousness. It can refer either to the act of thinking or the resulting ideas or arrangements of ideas. Similar concepts include cognition, sentience, consciousness, and imagination...
s and feeling
Feeling
Feeling is the nominalization of the verb to feel. The word was first used in the English language to describe the physical sensation of touch through either experience or perception. The word is also used to describe experiences, other than the physical sensation of touch, such as "a feeling of...
s influence behavior
Behavior
Behavior or behaviour refers to the actions and mannerisms made by organisms, systems, or artificial entities in conjunction with its environment, which includes the other systems or organisms around as well as the physical environment...
. 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
Exposure therapy
Exposure therapy is a technique in behavior therapy intended to treat anxiety disorders and involves the exposure to the feared object or context without any danger in order to overcome their anxiety. Procedurally it is similar to the fear extinction paradigm in rodent work...
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
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
.
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 inhibitorSelective serotonin reuptake inhibitor
Selective serotonin re-uptake inhibitors or serotonin-specific reuptake inhibitor are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. The efficacy of SSRIs is disputed...
s (SSRIs), which are antidepressants that influence brain chemistry to block the reabsorption of serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
in the brain
Human brain
The human brain has the same general structure as the brains of other mammals, but is over three times larger than the brain of a typical mammal with an equivalent body size. Estimates for the number of neurons in the human brain range from 80 to 120 billion...
. SSRIs are mainly indicated for clinical depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
, but are also very effective in treating anxiety disorders. Common side effects include nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
, sexual dysfunction
Sexual dysfunction
Sexual dysfunction or sexual malfunction refers to a difficulty experienced by an individual or a couple during any stage of a normal sexual activity, including desire, arousal or orgasm....
, headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
, diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, constipation
Constipation
Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...
, among others. Common SSRIs prescribed for GAD include:
- fluoxetineFluoxetineFluoxetine is an antidepressant of the selective serotonin reuptake inhibitor class. It is manufactured and marketed by Eli Lilly and Company...
(Prozac, Sarafem) - paroxetineParoxetineParoxetine is an SSRI antidepressant. Marketing of the drug began in 1992 by the pharmaceutical company SmithKline Beecham, now GlaxoSmithKline...
(Paxil, Aropax) - escitalopramEscitalopramEscitalopram is an antidepressant of the selective serotonin reuptake inhibitor class. It is approved by the U.S...
(Lexapro, Cipralex) - sertralineSertralineSertraline hydrochloride is an antidepressant of the selective serotonin reuptake inhibitor class. It was introduced to the market by Pfizer in 1991. Sertraline is primarily used to treat major depression in adult outpatients as well as obsessive–compulsive, panic, and social anxiety disorders in...
(Zoloft)
Pregabalin
PregabalinPregabalin
Pregabalin is an anticonvulsant drug used for neuropathic pain and as an adjunct therapy for partial seizures with or without secondary generalization in adults. It has also been found effective for generalized anxiety disorder and is approved for this use in the European Union. It was designed...
(Lyrica) acts on the voltage-dependent calcium channel
Voltage-dependent calcium channel
Voltage-dependent calcium channels are a group of voltage-gated ion channels found in excitable cells with a permeability to the ion Ca2+...
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
Lorazepam
Lorazepam is a high-potency short-to-intermediate-acting 3-hydroxy benzodiazepine drug that has all five intrinsic benzodiazepine effects: anxiolytic, amnesic, sedative/hypnotic, anticonvulsant, antiemetic and muscle relaxant...
, alprazolam
Alprazolam
Alprazolam is a short-acting anxiolytic of the benzodiazepine class of psychoactive drugs. Alprazolam, like other benzodiazepines, binds to specific sites on the GABAA gamma-amino-butyric acid receptor...
and venlafaxine
Venlafaxine
Venlafaxine is an antidepressant of the serotonin-norepinephrine reuptake inhibitor class. First introduced by Wyeth in 1993, now marketed by Pfizer, it is licensed for the treatment of major depressive disorder , as a treatment for generalized anxiety disorder, and comorbid indications in...
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
Sleep architecture
Sleep architecture describes the structure and pattern of sleep and encompasses several variables. Sleep quotas refer to the amount of time spent in REM and NREM sleep. Sleep duration is the total time spent asleep in a 24 hour period. The duration of a NREM-REM cycle is also an important aspect...
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- BuspironeBuspironeBuspirone is an anxiolytic psychoactive drug of the azapirone chemical class, and is primarily used to treat generalized anxiety disorder Bristol-Myers Squibb gained FDA approval of buspirone in 1986 for treatment of GAD...
(BuSpar) is a serotonin receptor partial agonist, belonging to the azaspirodecanedioneAzaspirodecanedioneAzapirones are a class of drugs used as anxiolytics and antipsychotics. They are commonly employed as augmentations to antidepressants like the selective serotonin reuptake inhibitors as well.- List of azapirones :...
class of compounds. - DuloxetineDuloxetineDuloxetine is a serotonin-norepinephrine reuptake inhibitor manufactured and marketed by Eli Lilly. It is effective for major depressive disorder and has been shown to be as effective as venlafaxine for generalized anxiety disorder...
(Cymbalta)- SNRISNRISNRI may refer to:* Serotonin–norepinephrine reuptake inhibitor* Strategic Naval Research Institute...
- type antidepressant - ImipramineImipramineImipramine , also known as melipramine, is an antidepressant medication, a tricyclic antidepressant of the dibenzazepine group...
(Tofranil) is a tricyclic antidepressantTricyclic antidepressantTricyclic antidepressants are heterocyclic chemical compounds used primarily as antidepressants. The TCAs were first discovered in the early 1950s and were subsequently introduced later in the decade; they are named after their chemical structure, which contains three rings of atoms...
(TCA). - Other tricyclic antidepressantTricyclic antidepressantTricyclic antidepressants are heterocyclic chemical compounds used primarily as antidepressants. The TCAs were first discovered in the early 1950s and were subsequently introduced later in the decade; they are named after their chemical structure, which contains three rings of atoms...
s - as clomipramineClomipramineClomipramine is a tricyclic antidepressant . It was developed in the 1960s by the Swiss drug manufacturer Geigy and has been in clinical use worldwide ever since.- Indications :...
,etc. TCAs are thought to act on serotonin, norepinephrine, and dopamineDopamineDopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
in the brain. - VenlafaxineVenlafaxineVenlafaxine is an antidepressant of the serotonin-norepinephrine reuptake inhibitor class. First introduced by Wyeth in 1993, now marketed by Pfizer, it is licensed for the treatment of major depressive disorder , as a treatment for generalized anxiety disorder, and comorbid indications in...
(Effexor XR) is a serotonin-norepinephrine reuptake inhibitorSerotonin-norepinephrine reuptake inhibitorSerotonin–norepinephrine reuptake inhibitors are a class of antidepressant drugs used in the treatment of major depression and other mood disorders...
(SNRI). SNRIs alter the chemistries of both norepinephrineNorepinephrineNorepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
and serotonin in the brain. - AfobazoleAfobazoleAfobazole is an anxiolytic drug launched in Russia in the early 2000s. It produces anxiolytic and neuroprotective effects without any sedative or muscle relaxant actions, making it more selective in action than many currently used drugs for this application...
- Some of MAO inhibitors - such as MoclobemideMoclobemideMoclobemide is a monoamine oxidase inhibitor drug primarily used to treat depression and social anxiety. Although clinical trials with the medicine began in 1977, it is not approved for use in the United States...
,rarely NialamideNialamideNialamide is an irreversible and non-selective monoamine oxidase inhibitor of the hydrazine chemical class used as an antidepressant and anxiolytic...
- Non-psychotropic drugs
- Propranolol (Inderal) - Sympatholytic, beta-adrenoblocker
- ClonidineClonidineClonidine is a sympatholytic medication used to treat medical conditions, such as high blood pressure, some pain conditions, ADHD and anxiety/panic disorder...
- Sympatholytic - GuanfacineGuanfacineGuanfacine is a sympatholytic. It is an agonist of the α2A subtype of norepinephrine receptors. These receptors are concentrated heavily in the prefrontal cortex and the locus coeruleus, with the potential to improve attention abilities via modulating post-synaptic α2A receptors in the prefrontal...
- Sympatholytic - PrazosinPrazosinPrazosin, trade names Minipress, Vasoflex, Pressin and Hypovase, is a sympatholytic drug used to treat high blood pressure and Anxiety, PTSD and Panic Disorder. It belongs to the class of alpha-adrenergic blockers. Specifically, prazosin is selective for the alpha-1 receptors on vascular smooth...
- Sympatholytic, alpha-adrenoblocker
Benzodiazepines
Benzodiazepines (or "benzos") are fast-acting hypnotic sedatives 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. 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 dependencePhysical dependence
Physical dependence refers to a state resulting from chronic use of a drug that has produced tolerance and where negative physical symptoms of withdrawal result from abrupt discontinuation or dosage reduction...
and a withdrawal syndrome
Benzodiazepine withdrawal syndrome
Benzodiazepine withdrawal syndrome—often abbreviated to benzo withdrawal—is the cluster of symptoms which appear when a person who has taken benzodiazepines long term and has developed benzodiazepine dependence stops taking benzodiazepine drug or during dosage reductions...
. Side effects include drowsiness, reduced motor coordination
Motor coordination
thumb|right|Motor coordination is shown in this animated sequence by [[Eadweard Muybridge]] of himself throwing a diskMotor coordination is the combination of body movements created with the kinematic and kinetic parameters that result in intended actions. Such movements usually smoothly and...
and problems with equilibrioception
Equilibrioception
Equilibrioception or sense of balance is one of the physiological senses. It helps prevent humans and animals from falling over when walking or standing still. Balance is the result of a number of body systems working together: the eyes , ears and the body's sense of where it is in space ideally...
. Common benzodiazepines used to treat GAD include:
- alprazolamAlprazolamAlprazolam is a short-acting anxiolytic of the benzodiazepine class of psychoactive drugs. Alprazolam, like other benzodiazepines, binds to specific sites on the GABAA gamma-amino-butyric acid receptor...
(Xanax, Xanax XR, Niravam) - chlordiazepoxideChlordiazepoxideChlordiazepoxide, is a sedative/hypnotic drug and benzodiazepine. It is marketed under the trade names Angirex, Klopoxid, Librax , Libritabs, Librium, Mesural, Multum, Novapam, Risolid, Silibrin, Sonimen and Tropium.Chlordiazepoxide was the first benzodiazepine to be synthesised and...
(Librium) - clonazepamClonazepamClonazepamis a benzodiazepine drug having anxiolytic, anticonvulsant, muscle relaxant, and hypnotic properties. It is marketed by Roche under the trade name Klonopin in the United States and Rivotril in Australia, Brazil, Canada and Europe...
(Klonopin) - clorazepateClorazepateClorazepate , also known as clorazepate dipotassium, is a drug that is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, sedative, hypnotic and skeletal muscle relaxant properties. Clorazepate is a prodrug for desmethyldiazepam, which is rapidly produced as an active metabolite...
(Tranxene) - diazepamDiazepamDiazepam , first marketed as Valium by Hoffmann-La Roche is a benzodiazepine drug. Diazepam is also marketed in Australia as Antenex. It is commonly used for treating anxiety, insomnia, seizures including status epilepticus, muscle spasms , restless legs syndrome, alcohol withdrawal,...
(Valium) - lorazepamLorazepamLorazepam is a high-potency short-to-intermediate-acting 3-hydroxy benzodiazepine drug that has all five intrinsic benzodiazepine effects: anxiolytic, amnesic, sedative/hypnotic, anticonvulsant, antiemetic and muscle relaxant...
(Ativan)
GAD and comorbid depression
In the National Comorbidity Survey (2005), 58 percent of patients diagnosed with major depressionClinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
were found to have an anxiety disorder; among these patients, the rate of comorbidity with GAD was 17.2 percent, and with panic disorder
Panic disorder
Panic disorder is an anxiety disorder characterized by recurring severe panic attacks. It may also include significant behavioral change lasting at least a month and of ongoing worry about the implications or concern about having other attacks. The latter are called anticipatory attacks...
, 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
Social phobia
Social phobia may refer to any of the following conditions:* Social anxiety disorder – a diagnosis referring to clinically excessive social anxiety...
, 9.4 percent with agoraphobia
Agoraphobia
Agoraphobia is an anxiety disorder defined as a morbid fear of having a panic attack or panic-like symptoms in a situation from which it is perceived to be difficult to escape. These situations can include, but are not limited to, wide-open spaces, crowds, or uncontrolled social conditions...
, 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
Mixed anxiety-depressive disorder
Mixed anxiety-depressive disorder is a diagnostic category defining patients who suffer from both anxiety and depressive symptoms of limited and equal intensity accompanied by at least some autonomic features...
, 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
Substance abuse
A substance-related disorder is an umbrella term used to describe several different conditions associated with several different substances .A substance related disorder is a condition in which an individual uses or abuses a...
or other conditions associated with stress
Stress (medicine)
Stress is a term in psychology and biology, borrowed from physics and engineering and first used in the biological context in the 1930s, which has in more recent decades become commonly used in popular parlance...
, such as irritable bowel syndrome
Irritable bowel syndrome
Irritable bowel syndrome is a diagnosis of exclusion. It is a functional bowel disorder characterized by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits in the absence of any detectable organic cause. In some cases, the symptoms are relieved by bowel movements...
. Patients with physical symptoms such as insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
or headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
s 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.
See also
- Anxiety disorderAnxiety disorderAnxiety disorder is a blanket term covering several different forms of abnormal and pathological fear and anxiety. Conditions now considered anxiety disorders only came under the aegis of psychiatry at the end of the 19th century. Gelder, Mayou & Geddes explains that anxiety disorders are...
- Anxiety Disorders Association of AmericaAnxiety Disorders Association of AmericaThe Anxiety Disorders Association of America is the only U.S. nonprofit organization solely dedicated to increasing awareness and improving the diagnosis, treatment, and cure of anxiety disorders in children and adults. The Anxiety Disorders Association of America is the leader in education,...
- Clinical depressionClinical depressionMajor depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
- Cognitive behavioral therapy
- Social anxiety disorderSocial anxiety disorderSocial anxiety disorder , also known as social phobia, is an anxiety disorder characterized by intense fear in social situations causing considerable distress and impaired ability to function in at least some parts of daily life...
Further reading
- Kessler RC, Chiu WT, Demler O, Walters EE. Prevalence, severity, and comorbidity of twelve-month DSM-IV disorders in the National Comorbidity Survey Replication (NCS-R). Archives of General Psychiatry, 2005 Jun;62(6):617-27.
- Brown, T.A., O'Leary, T.A., & Barlow, D.H. (2001). Generalised anxiety disorder. In D.H. Barlow (Ed.), Clinical handbook of psychological disorders: A step-by-step treatment manual (3rd ed.). New York: Guilford Press.
- Barlow, D. H., & Durand, V. M. (2005). Abnormal psychology: An integrative approach. Australia; Belmont, CA: Wadsworth.
External links
- Sharp Seniors – Information on generalised anxiety disorder
- Mayo Clinic – Information on diagnosis and treatment for GAD
- WebMD – Information on symptoms and causes of GAD
- Anxiety Disorders Association of America – Information for families, clinicians and researchers