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In This Report

•	Highlights
•	Introduction
•	Causes
•	Risk Factors
•	Complications
•	Diagnosis
•	Treatment
•	Medications
•	Other Treatments
•	Resources
•	References

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Anxiety disorders

Highlights

Anxiety Disorders and Physical Health

• Anxiety disorders affect more than emotional health -- they are also associated with many physical illnesses, suggests important new research in the Archives of Internal Medicine. Researchers found an association between anxiety disorders and thyroid, respiratory, gastrointestinal, arthritis, migraine, and allergic conditions.
• Obesity may both contribute to and result from anxiety disorders, according to two 2006 studies. One study reported that obese people have a 25% increased risk for developing anxiety disorders. The other study indicated that anxiety and depression in childhood predict a higher body mass index in adulthood for women (but not men).

Telephone-Based Therapy

Cognitive behavioral counseling over the telephone works just as well for people with obsessive-compulsive disorder (OCD) as in-person visits, indicates a 2006 study in the British Medical Journal. A study in the Archives of General Psychiatry reports that telephone-based therapy is helpful for patients with generalized anxiety disorder and panic disorder.

Genetics and OCD

Scientists have identified a gene that may play an important role in OCD that develops in early childhood. In two separate studies in the Archives of General Psychiatry, researchers reported an association between the SL1A1 gene and early-onset OCD in males. The SL1A1 gene regulates the brain chemical messenger glutamate, a neurotransmitter involved in learning and memory.

Antidepressants and Pregnancy

In 2006, the FDA issued a public health advisory concerning the use of antidepressants during pregnancy and risks for newborn babies. The FDA noted a New England Journal of Medicine study that found that babies born to mothers who took selective serotonin reuptake inhibitor (SSRI) drugs after the 20th week of pregnancy had an increased risk for serious lung problems. In 2005, the FDA warned that use of paroxetine (Paxil) during the first trimester of pregnancy increases the risk for heart-related birth defects.

Antidepressants and Suicide Risk

The manufacturer of paroxetine has added to its prescribing label a warning on increased suicide risk for young adults. Paroxetine has also been linked to increased suicidal tendencies in children.

Introduction

Fear and stress reactions are essential for human survival. They enable people to pursue important goals and to respond appropriately to danger. In a healthy individual, the stress response (fight, fright, or flight) is provoked by a genuine threat or challenge and is used as a spur for appropriate action.

An anxiety disorder, however, involves an excessive or inappropriate state of arousal characterized by feelings of apprehension, uncertainty, or fear. The word is derived from the Latin, angere, which means to choke or strangle. The anxiety response is often not attributable to a real threat. Nevertheless it can still paralyze the individual into inaction or withdrawal. An anxiety disorder persists, while a healthy response to a threat resolves, once the threat is removed.

Anxiety disorders have been classified according to the severity and duration of their symptoms and specific behavioral characteristics. Categories include:

• Generalized anxiety disorder (GAD), which is long lasting and low-grade
• Panic disorder, which has more dramatic symptoms
• Phobias
• Obsessive-compulsive disorder (OCD)
• Post-traumatic stress disorder (PTSD)
• Separation anxiety disorder (which is almost always seen in children)

GAD and panic disorder are the most common. Anxiety disorders are usually caused by a combination of psychological, physical, and genetic factors, and treatment is, in general, very effective.

Generalized Anxiety Disorder

Generalized anxiety disorder (GAD) is the most common anxiety disorder. It affects about 5% of Americans over the course of their lifetimes. It is characterized by the following:

• A more-or-less constant state of worry and anxiety, which is out of proportion to the level of actual stress or threat in their lives.
• This state occurs on most days for more than 6 months despite the lack of an obvious or specific stressor. (It worsens with stress, however.)
• It is very difficult to control worry. For a clear diagnosis of GAD, the specific worries should be differentiated from those that would define other anxiety disorders, such as fear of panic attacks or appearing in public. Moreover, they are not obsessive like those with obsessive-compulsive disorder. (It should be noted, however, that over half of those with GAD also have another anxiety disorder or depression.)
• Patients with anxiety may experience physical symptoms (such as gastrointestinal complaints) in addition to, or even in place of, mental worries. (This latter case may be more common in people from non-Western cultures such as those with Asian backgrounds.)
• People with GAD tend to be unsure of themselves, overly perfectionist, and conforming.

Given these conditions, a diagnosis of GAD is confirmed if three or more of the following symptoms are present (only one for children) on most days for 6 months:

• Being on edge or very restless
• Feeling tired
• Having difficulty with concentration
• Being irritable
• Having muscle tension
• Experiencing disturbed sleep

Symptoms should cause significant distress and impair normal functioning and not be due to a medical condition, another mood disorder, or psychosis. It should be noted that pure GAD is uncommon. It typically occurs with other mood disorders (anxiety or depression) or substance use. In one 8-year study, nearly three-quarters of GAD patients experienced depression at some point during the course of the study. A third of GAD patients had at least two other disorders of mood, substance use, or both.

Panic Disorder

Panic disorder is characterized by periodic attacks of anxiety or terror (panic attacks). They usually last 15 - 30 minutes, although residual effects can persist much longer. The frequency and severity of acute states of anxiety determine the diagnosis. (It should be noted that panic attacks can occur in nearly every anxiety disorder, not just panic disorder. In other anxiety disorders, however, there is always a cue or specific trigger for the attack.) A diagnosis of panic disorder is made under the following conditions:

• A person experiences at least two recurrent, unexpected panic attacks.
• For at least a month following the attacks, the person fears that another will occur.

Symptoms of a Panic Attack. During a panic attack a person feels intense fear or discomfort with at least four or more of the following symptoms:

• Rapid heart beat
• Sweating
• Shakiness
• Shortness of breath
• A choking feeling or a feeling of being smothered
• Dizziness
• Nausea
• Feelings of unreality
• Numbness
• Either hot flashes or chills
• Chest pain
• A fear of dying
• A fear of going insane

Women may be more likely than men to experience shortness of breath, nausea, and feelings of being smothered. More men than women have sweating and abdominal pain. Panic attacks that include only one or two symptoms, such as dizziness and heart pounding, are known as limited-symptom attacks. These may be either residual symptoms after a major panic attack or precursors to full-blown attacks. (It should be noted that panic attacks can also accompany other anxiety disorders, such as phobias and post-traumatic stress disorder. In such cases, however, additional characteristics differentiate these disorders from panic disorder.)

Frequency of Panic Attacks. Frequency of attacks can vary widely. Some people have frequent attacks (for example, every week) that occur for months; others may have clusters of daily attacks followed by weeks or months of remission.

Triggers of Panic Attacks. Panic attacks may occur spontaneously or in response to a particular situation. Recalling or re-experiencing even harmless circumstances surrounding an original attack may trigger subsequent panic attacks.

Phobic Disorders

Phobias, manifested by overwhelming and irrational fears, are common. In most cases, people can avoid or at least endure phobic situations, but in some cases, as with agoraphobia, the anxiety associated with the feared object or situation can be incapacitating.

Agoraphobia. Agoraphobia has been somewhat misleadingly described as fear of open spaces, the term having been derived from the Greek word agora, meaning outdoor marketplace. In its severest form, agoraphobia is characterized by a paralyzing terror of being in places or situations from which the patient feels there is neither escape nor accessible help in case of an attack. (One patient described the terror of going outside as opening a door onto a landscape filled with snakes.) Consequently, people with agoraphobia confine themselves to places in which they feel safe, usually at home. The patient with agoraphobia often makes complicated plans in order to avoid confronting feared situations and places.

Social Phobia. Social phobia, also known as social anxiety disorder, is the fear of being publicly scrutinized and humiliated and is manifested by extreme shyness and discomfort in social settings. This phobia often leads people to avoid social situations and is not due to a physical or mental problem (such as stuttering, acne, or personality disorders). The incidence of social phobia is approximately 13% and has been termed "the neglected anxiety disorder" because it is often missed as a diagnosis.

The associated symptoms vary in intensity, ranging from mild and tolerable anxiety to a full-blown panic attack. (Unlike a panic attack, however, social phobia is always directly related to a social situation.) Symptoms include sweating, shortness of breath, pounding heart, dry mouth, and tremor.

The disorder may be further categorized as generalized or specific social phobia:

• Generalized social phobia is the fear of being humiliated in front of other people during nearly all social situations. People with this subtype are the most socially impaired and also the most likely to seek treatment.
• Specific social phobia usually involves a phobic response to a specific event. Performance anxiety ("stage fright") is the most common specific social phobia and occurs when a person must perform in public. These patients usually feel comfortable in informal social situations.

Children with social anxiety develop symptoms in settings that include their peers, not just adults, and they may include tantrums, blushing, or not being able to speak to unfamiliar people. These children should be able to have normal social relationships with familiar people, however.

Specific Phobias. Specific phobias (formerly simple phobias) are an irrational fear of specific objects or situations. Specific phobias are among the most common medical disorders. Most cases are mild and not significant enough to require treatment.

The most common phobias are fear of animals (usually spiders, snakes, or mice), flying (pterygophobia), heights (acrophobia), water, injections, public transportation, confined spaces (claustrophobia), dentists (odontiatophobia), storms, tunnels, and bridges.

When confronting the object or situation, the phobic person experiences panicky feelings, sweating, avoidance behavior, difficulty breathing, and a rapid heartbeat. Most phobic adults are aware of the irrationality of their fear, and many endure intense anxiety rather than disclose their disorder.

Obsessive-Compulsive Disorder

Obsessive-compulsive disorder (OCD) has been described as hiccups of the mind. OCD is time-consuming, distressing, and can disrupt normal functioning. Much research suggests that a critical feature in this disorder is an overinflated sense of responsibility, in which the patient's thoughts center around possible dangers and an urgent need to do something about it.

• Obsessions are recurrent or persistent mental images, thoughts, or ideas. The obsessive thoughts or images can range from mundane worries about whether one has locked a door to bizarre and frightening fantasies of behaving violently toward a loved one.
• Compulsive behaviors are repetitive, rigid, and self-prescribed routines that are intended to prevent the manifestation of an associated obsession. Such compulsive acts might include repetitive checking for locked doors or unlit stove burners or calls to loved ones at frequent intervals to be sure they are safe. Some people are compelled to wash their hands every few minutes or to spend inordinate amounts of time cleaning their surroundings in order to subdue the fear of contagion.

Over half of OCD-sufferers have obsessive thoughts without the ritualistic compulsive behavior. Although individuals recognize that the obsessive thoughts and ritualized behavior patterns are senseless and excessive, they cannot stop them in spite of strenuous efforts to ignore or suppress the thoughts or actions. OCD often accompanies depression or other anxiety disorders. There is some evidence that the symptoms improve over time and that nearly half will eventually recover completely or have only minor symptoms.

Symptoms in children may be mistaken for behavioral problems (taking too long to do homework because of perfectionism, refusing to perform a chore because of fear of germs). Children do not usually recognize that their obsessions or compulsions are excessive.

Associated Obsessive Disorders. Certain other disorders that may be part of, or strongly associated with, the OCD spectrum include the following:

• Body dysmorphic disorder (BDD). In BDD, people are obsessed with the belief that they are ugly, or part of their body is abnormally shaped.
• Trichotillomania. People with trichotillomania continually pull their hair, leaving bald patches.
• Tourette syndrome. Symptoms of Tourette syndrome include jerky movements, tics, and uncontrollably uttering obscene words.

Obsessive-Compulsive Personality. OCD should not be confused with obsessive-compulsive personality, which defines certain character traits (e.g., being a perfectionist, excessively conscientious, morally rigid, or preoccupied with rules and order). These traits do not necessarily occur in people with obsessive-compulsive disorder.

Post-Traumatic Stress Disorder

Post-traumatic stress disorder (PTSD) is a severe, persistent emotional reaction to a traumatic event that severely impairs one’s life. It is classified as an anxiety disorder because of its symptoms. Not every traumatic event leads to PTSD, however. There are two criteria that must be present to qualify for a diagnosis of PTSD:

• The patient must have directly experienced, witnessed, or learned of a life-threatening or seriously injurious event.
• The patients' response is intense fear, helplessness, or horror. Children may behave with agitation or with disorganized behavior.

Triggering Events. PTSD is triggered by violent or traumatic events that are usually outside the normal range of human experience. There is some evidence that events most likely to trigger PTSD are those that involve deliberate and destructive behavior (e.g., murder, rape) and those that are prolonged or physically challenging. The event can also be a natural disaster. Such events include, but are not limited to, experiencing or witnessing sexual assaults, accidents, combat, natural disasters (such as earthquakes), or unexpected deaths of loved ones. PTSD may also occur in people who have serious illness and receive aggressive treatments or who have close family members or friends with such conditions.

Symptoms of PTSD. There are three basic sets of symptoms associated with PTSD. They may begin immediately after the event or can develop up to a year afterward:

• Re-experiencing. In such cases, patients persistently re-experience the trauma in at least one of the following ways: in recurrent images, thoughts, flashbacks, dreams, or feelings of distress at situations that remind them of the traumatic event. Children may engage in play, in which traumatic events are enacted repeatedly.
• Avoidance. Patients may avoid reminders of the event, such as thoughts, people, or any other factors that trigger recollection. They tend to have an emotional numbness, a sense of being in a daze or of losing contact with their own identity or even external reality. They may be unable to remember important aspects of the event.
• Increased Arousal. This includes symptoms of anxiety or heightened awareness of danger (sleeplessness, irritability, being easily startled, or becoming overly vigilant to unknown dangers).

To further qualify for a diagnosis of PTSD, patients must have at least one symptom in the re-experiencing category, three avoidance symptoms, and two arousal symptoms. Symptoms are chronic (3 months or more). Symptoms should also not be associated with alcohol, medications, or drugs and should not be intensifications of a pre-existing psychological disorder.

Acute Stress Disorder. Experts have identified a syndrome called acute stress disorder, in which symptoms of PTSD occur within 2 days to 4 weeks after the traumatic event. Acute stress disorder can accurately identify up to 94% of victims at risk for PTSD. Between 50 - 80% of these patients actually develop the more chronic and serious disorder. In other words, it is very sensitive for identification of those at highest danger for PTSD but less successful in determining specifically who will or will not recover emotionally.

Long-Term Outlook. The long-term impact of a traumatic event is uncertain. In one study of people who survived a mass killing spree in Texas, less than half of those who suffered PTSD (28% of all survivors) had recovered after a year. In another study, PTSD became chronic in 46% of the subjects. In fact, PTSD may cause physical changes in the brain, and in some cases the disorder can last a lifetime.

Separation Anxiety Disorder

Separation anxiety disorder almost always occurs in children. It is suspected in children who are excessively anxious about separation from important family members or from home. For a diagnosis of separation anxiety disorder, the child should also exhibit at least three of the following symptoms for at least 4 weeks:

• Extreme distress from either anticipating or actually being away from home or being separated from a parent or other loved one
• Extreme worry about losing or about possible harm befalling a loved one
• Intense worry about getting lost, being kidnapped, or otherwise separated from loved ones
• Frequent refusal to go to school or to sleep away from home
• Physical symptoms such as headache, stomach ache, or even vomiting, when faced with separation from loved ones

Separation anxiety often disappears as the child grows older, but if not addressed, it may lead to panic disorder, agoraphobia, or combinations of anxiety disorders.

Causes

A person's genetics, biochemistry, environment, history, and psychological profile all seem to contribute to the development of anxiety disorders. Most people with these disorders seem to have a biological vulnerability to stress, making them more susceptible to environmental stimuli than the rest of the population.

Biochemical Factors

Abnormalities in the Brain. Scientists are using imaging techniques, particularly magnetic resonance imaging (MRI), to identify different areas of the brain associated with anxiety responses.

An MRI (magnetic resonance imaging) of the brain creates a detailed image of the complex structures in the brain. An MRI can give a three-dimensional depiction of the brain, making location of problems such as tumors or aneurysms more precise.

Important research in anxiety disorders is focusing on changes in the amygdala, which is sometimes referred to as the "fear center." This part of the brain regulates fear, memory, and emotion and coordinates these resources with heart rate, blood pressure, and other physical responses to stressful events. Some evidence suggests that the amygdala in people with anxiety disorders is highly sensitive to novel or unfamiliar situations and reacts with a high stress response.

Obsessive-compulsive disorder (OCD) is the anxiety disorder most strongly associated with specific brain dysfunction. For example, abnormalities in a specific pathway of nerves have been linked to OCD, attention deficit disorder, and Tourette’s syndrome. The symptoms of the three disorders are similar and they often coexist.

A number of imaging studies have reported less volume in the hippocampus in people with post-traumatic stress disorder. This important region is related to emotion and memory storage.

Neurotransmitters. Studies suggest that an imbalance of certain substances called neurotransmitters (chemical messengers in the brain) may contribute to anxiety disorders. The neurotransmitters targeted in anxiety disorders are gamma-aminobutyric acid (GABA), serotonin, dopamine, and epinephrine. Serotonin appears to be specifically important in feelings of well-being, and deficiencies are highly related to anxiety and depression.

Examples of study findings on some neurotransmitters are:

• Abnormalities in the neurotransmitters gamma-aminobutyric acid (GABA) and serotonin may have a particular role in susceptibility to generalized anxiety disorder. GABA helps prevent nerve cells from over-firing and serotonin is a brain chemical important in feelings of well-being.
• Serotonin is a major player in OCD.
• Changes in serotonin and dopamine have been observed in social phobia.
• People with post-traumatic stress disorder have abnormalities in stress hormones (cortisol) and neurotransmitters associated with stress (epinephrine and norepinephrine). Such imbalances could account for the higher anxiety levels and a tendency to startle easily after a threat in people with PTSD.

Corticotropin-releasing factor (CRF), which is believed to be a stress hormone and a neurotransmitter, is thought to be involved in depression and anxiety by causing changes in serotonin levels.

Abnormalities in Breathing Functions. Many people, including children, with anxiety disorders are very sensitive to the effects of carbon dioxide (CO2). These people generally have higher than normal levels of cortisol -- the major stress hormone. In such cases, exposure to excessive CO2 causes these individuals to hyperventilate, in which their breathing becomes rapid and their heart rate quickens. The same response also occurs during danger. Over time, then, a series of such responses creates a pattern of impaired breathing and a sense of panic that evolves into a full-fledged anxiety disorder. Since CO2 is released from the lungs when people exhale, the condition may be aggravated in crowded spaces, such as airplanes or elevators.

Genetic Factors

Up to 50% of people with panic disorder and 40% of patients with generalized anxiety (GAD) have close relatives with the disorder. (About half of GAD patients also have family members with panic disorder, and about 30% have relatives with simple phobias.) One study reported the risk for inheriting a major phobia ranges from 25 - 37%.

Obsessive-compulsive disorder (OCD) is also strongly related to a family history of the disorder. Close relatives of people with OCD are up to 9 times more likely to develop OCD themselves. Researchers are making progress in identifying specific genetic factors that might contribute to an inherited risk. Of particular interest are genes that regulate specific neurotransmitters (brain chemical messengers), including serotonin and glutamate. In 2006, several important studies in the Archives of General Psychiatry suggested that the SLC1A1 gene, which is associated with glutamate regulation, may play an important role in early-onset OCD in boys. Research is also pinpointing regions on specific chromosomes (1, 3, 7, 6, 9, 15) that may contain genes linked to OCD.

Family Dynamics

The influence of the family on anxiety is complicated by both genetic and psychological factors.

Panic Disorder and Family Influence. Certain psychodynamic theories suggest, and a few studies support the idea, that some people may develop panic disorder if they cannot resolve the early childhood conflict of dependence vs. independence. In one study, for example, young adults who had experienced childhood anxiety were more likely to live with their parents until their early to mid-twenties. Many people with panic disorder perceive their parents as being extremely controlling and overly protective while showing little actual affection.

Phobias and Family Influence. Several studies show a strong correlation between a parent's fears and those of the offspring. Although an inherited trait may be present, some researchers believe that many children can "learn" fears and phobias, just by observing a parent or loved one's phobic or fearful reaction to an event. People who have social phobias and severe agoraphobia generally report less parental affection and more strictness, overprotection, and encouragement of dependence than those without these disorders. One 2000 study found similar traits in parents of children with social phobias. Such parents were also likely to have social phobias and depression.

Obsessive-Compulsive Disorder and Family Influence. One study found that parental influence played no part in obsessive-compulsive disorder if the OCD patient was also not suffering from depression. However, depression coexists in two-thirds of OCD patients, and in the study patients who had both OCD and depression reported lower levels of parental care and overprotectiveness.

Traumatic Events

Traumatic events generally trigger anxiety disorders in individuals who are susceptible to them because of psychological, genetic, or biochemical factors. The clearest example is post-traumatic stress disorder. Specific traumatic events in childhood, particularly those that threaten family integrity, such as spousal or child abuse, can also lead to other anxiety and emotional disorders. Some individuals may even have a biological propensity for specific phobias, for instance of spiders or snakes, that have been triggered and perpetuated after a single exposure.

Medical Conditions

Although no causal relationships have been established, certain medical conditions have been associated with panic disorder. They include migraines, obstructive sleep apnea, mitral valve prolapse, irritable bowel syndrome, chronic fatigue syndrome, and premenstrual syndrome.

PANDAS

The acronym PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus) is a term for an autoimmune condition associated with group A streptococcal infection in children (the cause of "strep throat" and rheumatic fever). Children with PANDAS develop tic-related disorders, including OCD and Tourette’s syndrome. In such cases, the OCD symptoms develop abruptly soon after the infection. It is unlikely to be an important cause of OCD.

Risk Factors

As many as 25% of all American adults experience intense anxiety at sometime in their lives. The prevalence of true anxiety disorders is much lower, although they are still the most common psychiatric conditions in the United States and affect more than 20 million Americans.

Gender. With the exception of obsessive-compulsive disorder (OCD) and possibly social anxiety, women have twice the risk for most anxiety disorders as men. A number of factors may increase the reported risk in women, including hormonal factors, cultural pressures to meet everyone else's needs except their own, and fewer self-restrictions on reporting anxiety to doctors.

Age. In general, phobias, OCD and separation anxiety show up early in childhood, while social phobia and panic disorder are often diagnosed during the teen years. Studies suggest that 3 - 5% of children and adolescents have some anxiety disorder. Indeed, this may be an underestimation, particularly since symptoms in children may differ from those in adults. One study indicated that if such children could be identified as early as 2 years of age they possibly could be treated to avoid later anxiety disorders.

Personality Factors. Children's personalities may indicate higher or lower risk for future anxiety disorders. For example, research suggests that extremely shy children and those likely to be the target of bullies are at higher risk for developing anxiety disorders later in life. Children who cannot tolerate uncertainty tend to be worriers, a major predictor of generalized anxiety. In fact, such traits may be biologically based and due to a hypersensitive amygdala -- the "fear center" in the brain.

Family History and Dynamics. Anxiety disorders run in families. Genetic factors play a role in some cases, but family dynamics and psychological influences are also often at work. For example, in a 2002 study, toddlers tended to avoid rubber snakes or spiders if their mothers indicated a negative response to these objects by their facial expressions. Girls had a stronger response than did boys. Studies are reporting the anxiety in new mother can affect their infants. One study reported a higher rate of crying and an impaired ability to adapt to new situations in infants of mothers who had been stressed and anxious during pregnancy. In another, infants of mothers with panic disorder had higher levels of stress hormones and more sleep disturbances than other children.

Social and Economic Factors. Several studies reported a significant increase in anxiety levels in children and college students in the past two decades compared to children in the 1950s. In two 2000 studies, anxiety was associated with a lack of social connections and a sense of a more threatening environment.

It follows then, that more socially alienated populations would have higher levels of anxiety. For example, a study of Mexican adults living in California reported that native-born Mexican Americans were three times more likely to have anxiety disorders (and even more likely to be depressed) as those who had recently immigrated to the U.S. And the longer the immigrants lived in the U.S., the greater was their risk for psychiatric problems. Traditional Mexican cultural effects and social ties, appear to protect recently arrived immigrants from mental illness, even when they are poor. Eventually, however, the consequences of Americanization may lead to depression and anxiety, probably resulting from feelings of alienation and inferiority, not only in many Mexican Americans but also in other impoverished minority groups

Risk Factors for Generalized Anxiety (GAD)

GAD affects about 5% of Americans in the course of their lives and is more common in women than in men. Some experts believe that it is underdiagnosed and more common than any other anxiety disorder. It is certainly the most common anxiety disorder among the elderly. GAD usually begins in childhood and often becomes a chronic ailment, particularly when left untreated. Depression in adolescence may be a strong predictor of GAD in adulthood. Depression commonly accompanies this anxiety disorder in any case.

Risk Factors for Panic Disorder

Age and Panic Disorder. Studies indicate that the prevalence of panic disorder among adults is between 1.6 - 2% and is much higher in adolescence, 3.5 - 9%. In one study, 18% of adult patients with panic disorder reported the onset of the disorder before 10 years of age. In general, however, panic disorder tends to begin in late adolescence and peaks at around 25 years of age.

Gender and Panic Disorder. Women have about twice the risk for panic disorder as men. Panic attacks are very common after menopause. In one study, nearly 18% of older women reported panic attacks within a 6-month period, with over half of these attacks being full-blown. They tended to be associated with stressful life events and poor health. The effects of pregnancy on panic disorder appear to be mixed. It seems to improve the condition in some women and worsen it in others.

Risk Factors for Obsessive-Compulsive Disorder (OCD)

Obsessive-compulsive disorder occurs equally in men and women, and it affects about 2 - 3% of people over a lifespan. About 80% of people who develop OCD show signs of the disorder in childhood, although the disorder usually develops fully in adulthood. The only group shown to be specifically at risk for OCD is women who have just given birth.

Risk Factors for Social Phobias

Social phobia is currently estimated to be the third most common psychiatric disorder in the U.S. Studies have reported a prevalence of 7 - 12% in Western nations.

Age and Phobias. The onset of social anxiety disorder is usually in adolescence, although most people with this disorder are not diagnosed and do not receive treatment until or unless they develop an accompanying anxiety disorder.

Gender and Phobias. Unlike their response to other emotional disorders, men are more likely than women to seek treatment for this disorder, probably because social phobias can interfere strongly with many jobs in white-collar professions. Some evidence suggests, however, that the actual rates of social phobia are higher in women.

Risk Factors for Post-Traumatic Stress Disorder

Studies estimate a lifetime risk for PTSD in the U.S. of up to 8%. People exposed to traumatic events, of course, are at highest risk, but many people can go through such events and not experience PTSD. Studies estimate that 6 - 30% or more of trauma survivors develop PTSD, with children and young people being among those at the high end of the range. Women have the twice the risk of PTSD as men.

Furthermore, PTSD can occur in people not directly involved with a traumatic event. For example, 17% of the US population outside New York City reported some symptoms of post-traumatic stress 2 months after the September 11 attack on the World Trade Towers. (In the city itself, where the attack occurred, an estimated 7.5% of New York's population reported PTSD within the month of the event, which declined to 0.6% at 6 months.)

Researchers are trying to determine factors that might increase vulnerability to catastrophic events and put people at risk for develop PTSD. Some studies report the following may be risk factors:

• Pre-existing emotional disorder. People who have a history of an emotional disorder, particularly depression, before the traumatic event are at higher risk for PTSD.
• Drug or alcohol abuse
• A family history of anxiety
• A history of abuse, particularly that which threatens family integrity, such as spousal or child abuse. Studies of individuals who had suffered physical or sexual abuse or neglect as children suggest that up to one-third develop PTSD.
• An early separation from parents
• Lack of social support and poverty
• Sleep disorders. Insomnia and excessive daytime sleepiness even within a month after a traumatic event are important predictors for the development of PTSD. One specific sleep disorder -- sleep apnea -- may even intensify symptoms of PTSD, including sleeplessness and nightmares. Sleep apnea occurs when tissues in the upper throat (or airway) collapse at intervals during sleep, thereby blocking the passage of air. In one study, 91% of crime victims with PTSD had either sleep apnea or a lesser condition that partially blocked the airways during sleep. In fact, in one study treatment of sleep apnea eased PTSD. Sleep apnea has also been associated with a risk for panic disorder. [For more information, see In-Depth Report #65: Sleep apnea.]

Complications

Studies consistently report that all types of anxiety disorders can be very debilitating and seriously affect a person’s quality of life.

Association with Depression and Bipolar Disorders

Depression. Depression and nearly every anxiety disorder often go hand in hand, in both the young and old. In fact, the lifetime risk for depression in people with anxiety disorders may be higher than 70%. Furthermore, the combination of depression and anxiety is a major risk factor for both substance abuse and suicide. The following are examples of depression in specific anxiety disorders:

• Between 50 - 65% of people with panic disorder also have major depression. Some studies have suggested that treating panic disorder early enough may help prevent major depression later on.
• More than two-thirds of OCD patients suffer from depression.
• Most patients with GAD will experience at least one episode of significant depression and many develop recurrent episodes. In patients with both disorders, GAD usually precedes the onset of depression.
• Social anxiety during adolescence or young adulthood has been associated with a higher risk for depression, and the presence of both increases the chances for severe depression.
• People with PTSD are four to seven times as likely to be depressed as are people without PTSD.

Bipolar Disorder. Symptoms of panic disorder are very common in people with bipolar disorder (manic-depression). In fact, people with bipolar have 26 times the rate of panic disorder as in the general population. Furthermore, anxiety worsens bipolar disorder. According to one 2000 study, anxiety disorders in teenagers were associated with bipolar disorder in adulthood, while manic behavior in adolescence was linked to later anxiety disorders.

Increased Risk for Suicide

Evidence now strongly supports an association between panic disorder and a risk for suicidal thoughts. Studies report that up to 18% of people with panic disorder attempt suicide and up to 38.5% regularly harbor suicidal thoughts, with the risks being higher in people with both panic disorder and depression. One study reported suicide attempts in about 12% of people with social phobias or OCD. If a person has an anxiety disorder and a mood disorders (such as depression), the risk for suicide is even higher.

Alcoholism and Other Forms of Substance Abuse

Severely depressed or anxious people are at high risk for alcoholism, smoking, and other forms of addiction. Anxiety disorders are highly prevalent among people with alcoholism. Moreover, long-term alcohol use can itself cause biologic changes that may actually produce anxiety and depression.

Risk for Substance Abuse in Specific Anxiety Disorders. The following are some observations on specific anxiety disorders and substance abuse:

• Some people with GAD and panic disorders may use alcohol or drugs to self-medicate.
• Social phobia appears to pose a particular risk for alcohol abuse. People with this disorder are likely to drink in order to boost confidence. Alcohol itself has no direct beneficial effect on anxiety, but studies suggest that the belief in its effect appears to relieve anxious feelings. (Alcohol or substance abuse is not associated with specific phobias -- such as a fear of flying or spiders.)
• Heavy smoking and substance abuse are common in people with PTSD. In adolescents, the disorder not only increases the risk for drug and alcohol use but also for eating disorders.

Effects on Work, School, and Relationships

Studies consistently report that anxiety disorders have negative effects on work and relationships. Some examples:

• In one 2001 study, more than 10% of patients with GAD missed at least 6 days of work within the previous month.
• In a survey of OCD sufferers, 40% reported that they had to stop working because of the disorder. Only 40% worked full-time, while only half were married.
• A 2006 study indicated that children with OCD are more likely to be bullied than other children.
• Studies report that people with social phobias are less likely to get married, to leave home, and to finish school than those without this disorder. Their outlook worsens if they have other emotional disorders.

Effects of Major Anxiety Disorders on Physical Health in Adults

Anxiety disorders are associated with many different physical illnesses. Research suggests that people who have both an anxiety disorder and a physical illness have a worse quality of life and greater risk for disability than those who have only a physical illness. According to a 2006 study in the Archives of Internal Medicine, anxiety disorders tend to occur before the development of physical disorders.

Heart Disease. Anxiety has been associated with several heart problems, although the mechanisms are unclear. Some studies have observed a tendency for unhealthy cholesterol levels in people with panic disorder. A 2001 study reported an association between thicker blood vessels in both women and men with anxiety and with hardening of the arteries in men (but not in women). Another study indicated that people who experience anxiety are more likely to develop high blood pressure than those who are not anxious. Both anxiety and depression have been associated with a poor response to treatment in heart patients, including a worse outcome after heart surgery.

Cholesterol is a soft, waxy substance that is present in all parts of the body including the nervous system, skin, muscle, liver, intestines, and heart. It is made by the body and obtained from animal products in the diet. Cholesterol is manufactured in the liver and is needed for normal body functions including the production of hormones, bile acid, and vitamin D. Excessive cholesterol in the blood contributes to atherosclerosis and subsequent heart disease. The risk of developing heart disease or atherosclerosis increases as the level of blood cholesterol increases.

Some researchers speculate that intense anxiety might trigger abnormal and dangerous heart rhythms in people with existing heart problems. In other studies, panic disorders, post-traumatic stress disorder, and phobias have been associated with a higher rate of sudden death from cardiac events, including heart attack.

Gastrointestinal Disorders. Anxiety frequently accompanies gastrointestinal conditions. Of note, half the cases of irritable bowel syndrome are associated with anxiety.

Headache. Both tension and migraine headaches are associated with anxiety disorders. One study reported that 32% of people with chronic tension headaches met criteria for anxiety. Similarly, another study reported that young girls with anxiety disorders were three times more likely to have chronic headaches than those without the disorder. (Headaches in both studies were also strongly associated with depression.)

Respiratory Problems. Studies report an association between anxiety in patients with obstructive lung conditions (asthma, emphysema, and chronic bronchitis) and more frequent relapses.

Obesity. Anxiety disorders may lead to obesity, and the reverse may also be true. A 2006 study suggested that anxiety disorders and depression in childhood may lead to higher body mass index (BMI) in adult women (but not men). Another 2006 study indicated that obesity is associated with a 25% increased risk of developing anxiety and mood disorders.

Allergic Conditions. Anxiety disorders are associated with numerous allergic conditions including hay fever, eczema, hives, food allergies, and conjunctivitis.

Other Conditions. Other physical conditions associated with anxiety disorders include thyroid problems and arthritis.

Injuries from Obsessive-Compulsive Disorder

People with obsessive-compulsive disorders can experience skin problems from excessive washing, injuries from repetitive physical acts, and hair loss from repeated hair pulling (behavior known as trichotillomania).

Biologic Effects of Post-Traumatic Stress Disorder (PTSD)

Effect of PTSD on the Brain. Studies are reporting that PTSD is associated with shrinkage in the hippocampus, the part of the brain important for memory and learning. Some animal studies indicate that such damage may result from long-term exposure to cortisol, the major stress hormone. In one study, people who had suffered severe trauma scored 40% lower in tests of verbal memory than did the general population. There was no difference in IQ or in scores of other types of memory. Some studies suggest that exposure to chronic stress, common in PTSD patients, may even compromise the function of the brain’s receptors for anti-anxiety medication. On the other hand, a small hippocampal volume may itself increase stress hormone levels, so people with genetically smaller hippocampi may be susceptible to PTSD.

Effects of PTSD on Health. Studies of military veterans who have endured major traumatic events have found a higher risk for health problems. One study of Vietnam veterans reported that PTSD was associated with greater physical limitations, poorer physical health, and a lower quality of life than was found in the general population, regardless of other accompanying emotional or medical disorders. In another study of these veterans, PTSD sufferers had twice the risk for abnormal heart rhythms and four times the risk of a heart attack compared to men without PTSD.

Physical Effects of Anxiety on Children

Evidence suggests an association between anxiety in children and recurrent stomach aches. Anxiety has been associated with a higher risk for sleep disorders in children, such as frequent nightmares, restless legs syndrome, and bruxism (grinding and gnashing of the teeth during sleep).

Diagnosis

A physical examination and medical and personal history is essential. Because anxiety accompanies so many medical conditions, some serious, it is extremely important for the doctor to uncover any medical problems or medications that might underlie or be masked by an anxiety attack.

The patient should describe any occurrence of anxiety disorders or depression in the family and mention any other contributing factors, such as excessive caffeine use, recent life changes, or stressful events.

It is very important to be honest with your doctor about all conditions, including excessive drinking, substance abuse, or other psychological or mood states that might contribute to, or result from, the anxiety disorder.

Diagnosing children with an anxiety disorder can be very difficult, since anxiety often results in disruptive behaviors that overlap with attention-deficit hyperactivity or oppositional disorder. Parents and children may report different symptoms.

Ruling Out Other Conditions

People with anxiety disorders are more likely to see a family doctor before a mental health specialist, since their symptoms are often physical. Symptoms can include muscle tension, trembling, twitching, aching, soreness, cold and clammy hands, dry mouth, sweating, nausea or diarrhea, or urinary frequency. Anxiety attacks can mimic or accompany nearly every acute disorder of the heart or lungs, including heart attacks and angina (chest pain). In fact, nearly all individuals with panic disorders are convinced that their symptoms are physical and possibly life-threatening.

Depression. Depression is very common in people with an anxiety disorder, and it is sometimes difficult to distinguish one from the other because either or both can be accompanied by anxious feelings, agitation, insomnia, and problems with concentration. In fact, because the two disorders occur together so often, the American Psychiatric Association is considering a new classification: mixed anxiety and depression.

Heart Problems. Studies suggest that up to a third of patients entering the emergency room with chest pain and who are low to moderate risk for a heart attack are actually suffering from panic attacks. It is often difficult even for specialists to distinguish between heart conditions and a panic attack:

• Women who are having an actual heart attack or acute heart problem are much more likely to be misdiagnosed as having an anxiety attack than are men with similar symptoms.
• Mitral valve prolapse, a common and usually mild heart problem, may have symptoms that are nearly identical to those of panic disorder. The two conditions, in fact, frequently occur together.

Mitral valve prolapse is a disorder in which, during the contraction phase of the heart, the mitral valve does not close properly. When the valve does not close properly it allows blood to backflow into the left atrium. Some symptoms can include palpitations, chest pain, difficulty breathing after exertion, fatigue, cough, and shortness of breath while lying down.

• Two-thirds of people with a heart-rhythm disturbance called paroxysmal supraventricular tachycardia have the same symptoms as those with panic attacks.

Asthma. Asthma attacks and panic attacks have similar symptoms and can also coexist.

Hyperthyroidism. Hyperthyroidism can cause many of the same symptoms of generalized anxiety disorder and must be ruled out.

Click the icon to see an image of hyperthyroidism.

Epilepsy. The symptoms of partial seizures and panic attacks often overlap.

Other Medical Conditions. In addition, anxiety-like symptoms are seen in many other medical problems, including hypoglycemia, recurrent pulmonary emboli, and adrenal-gland tumors. Women can also experience intense anxiety attacks with hot flashes during menopause.

Medication Side Effects. Many drugs, including some for high blood pressure, diabetes, and thyroid disorders, can produce symptoms of anxiety. Withdrawal from certain drugs, often those used to treat sleep disorders or anxiety, can also precipitate anxiety reactions.

Substance Abuse. People with anxiety disorders often drink alcohol or abuse drugs in order to conceal or ameliorate symptoms, but substance abuse and dependency can also cause anxiety. In addition, withdrawal from alcohol can produce physiologic symptoms similar to panic attacks. Clinicians often have difficulty determining whether alcoholism or anxiety is the primary disorder. Overuse of caffeine or abuse of amphetamines can cause symptoms resembling a panic attack.

Screening Tests

Clinicians can use various screening tests to determine the causes, type, severity, and frequency of anxiety. Such tests include the Beck Anxiety Inventory, the Hamilton Anxiety Rating Scale, and the Anxiety Disorders Interview Schedule.

Screening tests for children include the Child Behavior Checklist, which measures a child's ability to function, the Leyton Obsessional Inventory-Child Version for OCD, and the STEPP test for post-traumatic stress.

Treatment

Anxiety disorders require treatment. Simply trying to talk oneself out of anxiety is as futile as trying to talk oneself out of a heart or stomach problem. Most anxiety disorders, especially phobias, respond well to treatment. They may, however, require long-term treatment. For instance, one study reported that two-thirds of patients with GAD who were treated for only 6 weeks had a recurrence, and half of these patients required additional medications. Nevertheless, most patients do not receive appropriate care for anxiety disorders. In one study, about two-thirds of people with GAD never received any treatment. According to a 2006 Lancet study, only 19 - 40% of patients with panic disorder receive appropriate care.

Treatment Options

The standard current approach to most anxiety disorders is a combination of cognitive-behavioral therapy (CBT) with medications, typically a selective serotonin reuptake inhibitor (SSRI) or, less commonly, a tricyclic antidepressant.

Lifestyle Measures

A healthy lifestyle that includes exercise, adequate rest, and good nutrition can help to reduce the impact of anxiety attacks. Rhythmic aerobic and yoga exercise programs lasting for more than 15 weeks have been found to help reduce anxiety. Strength, or resistance, training does not seem to help anxiety.

Medications

Until recently, the anti-anxiety drugs known as benzodiazepines were the primary medications for anxiety. Increasingly, antidepressants, particularly the selective serotonin-reuptake inhibitors (SSRIs), are being used as the initial treatment. They are proving to be effective, nonaddictive, and to have relatively minor side effects.

Many standard antidepressants take 2 - 4 weeks, and sometimes up to 12 weeks, before they are fully effective. People who take them may also experience a temporary period of increased anxiety. Consequently, about a third of patients stop taking antidepressants for anxiety disorders before completing the initial phase of therapy. A combination of a benzodiazepine and an antidepressant is sometimes used to avoid the initial anxiety symptoms and to hasten control of panic symptoms. The benzodiazepine can then be withdrawn, and the antidepressant, with its negligible chance for long-term abuse, is continued.

No one should become disheartened if one drug treatment fails. Another may prove to be very effective, even it is a drug of a similar type. Drug combinations should be tried if a single drug and cognitive-behavior therapy has failed. Because many anxiety disorders are chronic, drug therapy sometimes is needed for prolonged periods, even years.

Antidepressants

Selective Serotonin Reuptake Inhibitors (SSRIs). Selective serotonin-reuptake inhibitors (SSRIs) are the first-line treatment of major depression and proving to be helpful for many anxiety disorders. They work by increasing levels of serotonin in the brain. SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), and escitalopram (Lexapro). Escitalopram is similar to citalopram and may have fewer side effects than other SSRIs. All of these drugs are proving to be very valuable for adults and even for many children with most anxiety disorders. The following are some indications for their use in specific anxiety disorders:

• Obsessive-Compulsive Disorder. SSRIs are the first-line treatment for obsessive-compulsive disorder (OCD). They reduce symptoms by 25 - 35% in about half of all patients. (SSRIs may be less effective with tics, hoarding, and compulsive behaviors than with other OCD symptoms.)
• Panic disorder. SSRIs may also be very useful in treating patients with panic disorder. Some -- but not all -- studies suggest that higher doses than those used for depression may be required in order to achieve benefits. More research is needed on the optimal dosages.
• Phobias. SSRIs may also help people with phobias, including agoraphobia and social phobias. Relapse is common in social phobia patients, and treatment for longer than a year may be needed in some patients. Combining medications with cognitive-behavioral therapy can help prevent relapse.
• Post-Traumatic Stress Disorder. SSRIs may help some people with post-traumatic stress disorder (PTSD). Their benefits may be limited. Victims of child abuse, for example, tend to respond poorly to SSRIs. A study on sertraline suggested that although it was particularly effective in women it may not offer many benefits for combat veterans. At this time sertraline (Zoloft) and paroxetine (Paxil) are specifically FDA-approved for PTSD, although studies suggest that other SSRIs may be helpful.
• Generalized Anxiety Disorder. SSRIs have been less studied for generalized anxiety, but studies on paroxetine (Paxil), sertraline (Zoloft), and escitalopram (Lexapro) suggest that SSRIs may be very effective for many people with GAD.
• Anxiety Disorders in Children. SSRIs may be effective for children who have both OCD and major depression. Fluoxetine (Prozac) is the only SSRI approved for use in children. In addition to depression, it is approved for treating children with OCD. The FDA has strongly advised against prescribing certain SSRIs, such as paroxetine, to children and young adults due to increased risk for suicidal behavior.

SSRIs can cause agitation, nausea, and low sex drive. Over time, many SSRI-treated patients gain weight, although the degree of weight gain varies depending on the drug. (For example, paroxetine poses a greater risk for weight gain than citalopram.) Elderly people taking these drugs should take the lowest effective dose possible, and those with heart problems should be monitored closely.

There have been many concerns about SSRIs and increased risk for suicidal behavior. Both adults and children who are treated with SSRIs should be carefully monitored for any worsening of depressive symptoms or changes in behavior. This is especially important during the first few months of antidepressant treatment.

Paroxetine has been linked to heart-related birth defects when women took this drug during the first trimester of pregnancy. Experts are also advising caution in prescribing other types of SSRIs to pregnant women. A 2006 study in the New England Journal of Medicine indicated that babies born to women who take SSRIs during the second half of pregnancy have an increased risk for persistent pulmonary hypertension, a serious lung condition. Other studies suggest that babies born to women who take SSRIs late in pregnancy may have more problems with irritability and difficulty feeding. Women who are pregnant or who are considering becoming pregnant should discuss the potential risks of these drugs with their doctors.

Designer Antidepressants. A number of newer antidepressants that target other neurotransmitters alone or in addition to serotonin are proving to be very promising for anxiety, including generalized anxiety disorder. They include nefazodone (Serzone), venlafaxine (Effexor), and mirtazapine (Remeron).

• Venlafaxine (Effexor) works well for both short- and long-term treatment of generalized anxiety disorder. It may have some benefits for social anxiety. In 2005, it was approved for treatment of panic disorder in adults. As with the SSRIs, and unlike other newer antidepressants, venlafaxine impairs sexual function. Of concern are reports of changes in blood pressure and heart conduction abnormalities, which may cause serious problems in elderly patients. Some patients report severe withdrawal symptoms, including dizziness and nausea. Venlafaxine can cause fatal overdose, especially if taken in combination with alcohol or other drugs. Venlafaxine should not be taken during the last trimester of pregnancy because the drug can cause complications in newborn infants.
• Nefazodone (Serzone) has shown some benefit in patients with GAD, social phobias, and panic disorder. The drug is more rapidly effective and has fewer distressing side effects, including sexual dysfunction, than SSRIs. Nefazodone is one of the only antidepressants that has a positive effect on sleep efficiency, which may particularly benefit patients with insomnia. The drug may cause an abrupt drop in blood pressure after standing up suddenly. Nefazodone has been linked with increased risk for liver failure.
• Mirtazapine (Remeron) may be an effective treatment for panic disorder, generalized anxiety disorder, obsessive-compulsive disorder, and posttraumatic stress disorder. It may work faster than other SSRIs and have stronger early actions against anxiety in patients who also suffer depression. It may cause less sexual dysfunction than some other antidepressants. It interacts with histamine, a chemical involved in allergic responses. These actions can cause drowsiness, which may make it a useful drug for patients who suffer from insomnia. The drug also causes blurred vision. The drug has been associated with weight gain, although in one study it was not significant. It does not appear to have the adverse acute effects on the heart that other newer antidepressants have, although it may slightly raise cholesterol and triglyceride levels.

Tricyclic Antidepressants. The antidepressant drugs known as tricyclic antidepressants (TCAs) have also been effective in treating panic and obsessive-compulsive disorders. Studies on specific TCAs have suggested the following benefits:

• Imipramine (Tofranil, Janimine) is the most commonly used TCA for panic disorder. It is also effective in treating agoraphobia and GAD. In one study it was helpful in reducing side effects during withdrawal from benzodiazepines, the standard anti-anxiety drugs.
• Doxepin (Adapin, Sinequan) has been beneficial for people with a mix of generalized anxiety disorder and depression.
• Clomipramine (Anafranil) is also effective for panic disorders and has been approved for OCD. The drug causes significant reduction in OCD symptoms for patients, including some children, who can tolerate it. (The other tricyclics do not appear to benefit OCD patients.) Many patients stop using Anafranil, however, because of side effects.

Side effects of TCAs include sleep disturbance, abrupt reduction in blood pressure upon standing, weight gain, sexual dysfunction, and mental disturbance. Elderly patients and those with a history of seizures, cardiac problems, closed-angle glaucoma, and urinary retention or obstruction should be closely supervised when taking tricyclics.

Monoamine Oxidase Inhibitors. Monoamine oxidase inhibitors (MAOIs), typically phenelzine (Nardil) or tranylcypromine (Parnate), are antidepressants used for panic disorder or OCD that does not respond to other treatments. Moclobemide (Manerix, Aurorix) is a newer MAOI available in Canada and Europe that showed some benefits for social phobias in some, but not all studies.

MAOIs commonly cause weight gain, drowsiness, dizziness, sexual dysfunction, and insomnia. The main problem with most of these drugs is the need for dietary restrictions. Severe high blood pressure (hypertension) can be brought on by eating certain foods that have a high tyramine content including cheese, red wine, vermouth, dried meats and fish, canned figs, and fava beans. MAOIs can also lead to serious hypertensive interactions with certain drugs, including some common over-the-counter cough medications and decongestants. They can also cause birth defects and should not be taken by pregnant women.

Benzodiazepines

Benzodiazepines are effective medications for most anxiety disorders and have been the standard of treatment for years. However, their use has been associated with a high risk for dependency and abuse. (Some reports suggest they are harder to withdraw from than heroin.) Therefore, they have been supplanted in most cases by SSRIs and by newer antidepressants. Benzodiazepines include:

• Alprazolam (Xanax) and clonazepam (Klonopin) are effective for panic disorder, some phobias, and generalized anxiety disorder. Benzodiazepines in combination with selective serotonin reuptake inhibitors may be particularly helpful in the treatment of panic attacks, although there is no standard as yet for the safest and most effective method for administering this combination.
• Other benzodiazepines, including diazepam (Valium), lorazepam (Ativan), and chlordiazepoxide (Librium), are used mainly for generalized anxiety.

Side Effects. Benzodiazepines have many side effects. The most common are daytime drowsiness and a hung-over feeling. In rare cases, they can cause agitation. The may worsen respiratory problems. The drugs stimulate eating and can cause weight gain. In one 2002 study, 33% of patients experienced incontinence at least twice a week. Highest risk was in long-acting drugs, such as chlordiazepoxide. Benzodiazepines can interact with certain drugs, including cimetidine (Tagamet), antihistamines, and oral contraceptives. Benzodiazepines are potentially dangerous when used in combination with alcohol. Overdoses can be serious, although they are very rarely fatal.

The elderly are more susceptible to side effects and should usually start at half the dose prescribed for younger people. These drugs increase the risk of falling, which can increase the risk for hip fracture in older people. Also of concern are studies showing a high risk of automobile accidents in people who take benzodiazepines. Benzodiazepines taken during pregnancy are associated with birth defects, and they should not be used by pregnant women or by nursing mothers.

Loss of Effectiveness and Dependence. Eventually these drugs can lose their effectiveness with continued use at the same dosage. As a result, patients may want to increase their dosage to prevent anxiety. This causes dependency, which can occur after as short a time as several weeks of taking these drugs. Some evidence suggests that the risk for abuse exists only in people who are already susceptible to substance abuse.

Withdrawal and its Treatments. Withdrawal symptoms can be very severe, even in people who rapidly discontinue benzodiazepines after taking them for only 4 weeks. Some experts believe that benzodiazepines are harder to withdraw from than heroin. Symptoms include sleep disturbance and anxiety, which can develop within hours or days after stopping the medication. Some patients experience stomach distress, sweating, and insomnia, which can last from 1 - 3 weeks. The longer the drugs are taken and the higher their dose, the more severe these symptoms can become. Simply tapering off gradually helps about 60% of people to withdraw. Certain medications (anti-seizure drugs, antidepressants, buspirone) may also be helpful in assisting with withdrawal.

Azapirones

Azapirones, such as buspirone (BuSpar) and gepirone (Ariza, Variza), act on serotonin receptors called 5-HT(1A). Buspirone has been the most intensively studied. It appears to work as well as a benzodiazepine for treating generalized anxiety disorder. It usually takes several days to weeks for the drug to be fully effective. It is not useful against panic attacks.

Buspirone does not produce any immediate euphoria or change in sensation, so some people believe, erroneously, that the drug doesn't work. Such qualities result in a very low potential for abuse. In fact, unlike the benzodiazepines, buspirone is not addictive, even with long-term use, so it may be particularly useful for the patient whose anxiety disorder coexists with alcoholism or drug abuse.

Buspirone also seems to have less pronounced side effects than benzodiazepines and no withdrawal effects, even when the drug is discontinued quickly. Common side effects include dizziness, drowsiness, and nausea. Buspirone should not be used with monoamine oxidase inhibitors (MAOIs).

Beta-Blockers

Beta-blockers, including propranolol (Inderal) and atenolol (Tenormin), block the nerves that stimulate the heart to beat faster. They affect only the physiologic symptoms of anxiety and are most helpful for phobias, particularly performance anxiety. Beta-blockers are less effective for other forms of anxiety.

Clonidine

Clonidine, a drug that relaxes blood vessels, has been used to treat children with post-traumatic stress disorder. Some experts believe it should be tried for anxiety disorders if other therapies fail. The drug can have severe side effects.

Atypical Antipsychotics

In certain severe cases, drugs called atypical antipsychotics may be useful. They include risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), ziprasidone (Geodon), and others. In one study, risperidone was useful in combination with an SSRI for OCD patients who did not respond to an SSRI alone. They are also possibly useful for severe GAD. Common side effects include sleepiness and dizziness. Most cause weight gain. In high doses they may cause extrapyramidal symptoms, which involve the nerves and muscles controlling movement and coordination. The risk for these side effects, however, are far less than with older antipsychotic drugs. Still, there are many risks associated with all antipsychotic drugs. [For more information on antipsychotics, see In-Depth Report #47: Schizophrenia.]

Anticonvulsants

Pregabalin (Lyrica) and gabapentin (Neurontin) are drugs used to treat seizures and other conditions. Small studies suggest that these drugs may be useful for certain anxiety disorders, such as social phobia, general anxiety disorder, and post-traumatic stress disorder. A 2005 study suggested that pregabalin worked as well as the benzodiazepine alprazolam (Xanax) for treatment of generalized anxiety disorder.

Investigational Drugs

Glucocorticoids. Scientists are investigating whether the stress hormone cortisol can help reduce fear in people with phobias. In a preliminary research study, a cortisone drug helped reduce fear and anxiety in patients with social and spider phobias.

Other Treatments

Cognitive-Behavioral Therapy

The goal of cognitive-behavioral therapy (CBT) is to regain control of reactions to stress and stimuli, thus reducing the feeling of helplessness that often accompanies anxiety disorders. CBT works on the principle that the thoughts that produce and maintain anxiety can be recognized and altered using various techniques that change behavioral responses and eliminate the anxiety reaction. Many studies have shown that a combination of CBT and medication works best for treating anxiety disorders.

A number of CBT approaches work well for treating many types of anxiety disorders. Studies suggest that CBT is also helpful for patients who have additional conditions, such as depression, a second anxiety disorder, or alcohol dependency. (It may take longer to achieve a successful outcome in such cases, however.) CBT is often given along with drug treatment. A study in the Journal of the American Medical Association found that children and adolescents with OCD responded better to CBT alone than the antidepressant setraline (Zoloft) alone, but most patients did best when they were treated with a combination of CBT and sertraline.

Both individual and group treatments work well. (However, people with social phobia may do better in individual sessions.) Several recent studies also indicate that telephone-based behavioral therapy works well for people with OCD, generalized anxiety disorder, and panic disorders.

Anxiety disorders are chronic, however, and recurrence is common. Some studies indicate that between 30 - 82% of people with panic disorder and phobias have a recurrence of attacks at an average of 9 months, even after successful short-term therapy. Medications, then, are also generally recommended for most patients.

Basic Cognitive Therapy Techniques. Treatment usually takes about 12 - 20 weeks. The essential goal of cognitive therapy is to understand the realities of an anxiety-provoking situation and to respond to reality with new actions based on reasonable expectations.

• First, the patient must learn how to recognize anxious reactions and thoughts as they occur. One way of accomplishing this is by keeping a daily diary that reports the occurrences of anxiety attacks and any thoughts and events associated with them. A patient with OCD, for instance, may record repetitive thoughts.
• These entrenched and automatic reactions and thoughts must be challenged and understood. Again, using the OCD example, one approach is to record and play back the words of the repetitive thoughts, over exposing the patient to the thoughts and reducing their effect. One effective approach for patients with generalized anxiety disorder targets their intolerance of uncertainty and helps them develop methods to cope with it.
• Patients are usually given behavioral homework assignments to help them change their behavior. For example, a person with generalized social phobia may be asked to buy an item and then return it the next day. As the patient performs this action, he or she observes any unrealistic fears and thoughts triggered by such an event.
• As the patient continues with self-observation, they begin to perceive the false assumptions that underlie the anxiety. For example, OCD patients may learn to recognize that their heightened sense of responsibility for preventing harm in non-threatening situations is not necessary or even useful.
• At that point, the patient can begin substituting new ways of coping with the feared objects and situations.

Systematic Desensitization. Systematic desensitization is a specific technique that breaks the link between the anxiety-provoking stimulus and the anxiety response. This treatment requires the patient to gradually confront the object of fear. There are three main elements to the process:

• Relaxation training
• A list composed by the patient that prioritizes anxiety-inducing situations by degree of fear
• The desensitization procedure itself, confronting each item on the list, starting with the least stressful

This treatment is especially effective for simple phobias, social phobias, agoraphobia, and post-traumatic stress syndrome.

Exposure and Response Treatment. Exposure treatment purposefully generates anxiety by exposing the patient repeatedly to the feared object or situation, either literally or using imagination and visualization. It uses the most fearful stimulus first. (This differs from the desensitization process because it does not involve relaxation or a gradual approach to the source of anxiety.)

Exposure treatments are usually either known as flooding or graduated exposure:

• Flooding exposes the person to the anxiety-producing stimulus for as long as 1 - 2 hours.
• Graduated exposure gives the patient a greater degree of control over the length and frequency of exposures.

In both cases, the patient experiences the anxiety over and over until the stimulating event eventually loses its effect. Combining exposure with standard cognitive therapy may be particularly beneficial. This approach has helped certain patients in most anxiety disorder categories, including post-traumatic stress disorder.

Modeling Treatment. Phobias can often be treated successfully with modeling treatment:

• The therapy typically uses an actor who approaches an anxiety-producing object or engages in a fear-provoking activity that is similar to the patient's specific problem. Either a live or videotaped situation may be used, although the live model is considered to be more effective.
• The patient observes this event and tries to learn how to behave in a comparable manner.

Other Forms of Psychotherapy

Other forms of psychotherapy, commonly called emotion-based psychotherapy (EBT) or "talk" therapy, deal more with childhood roots of anxiety and usually, although not always, require longer treatments. They include interpersonal therapy, supportive psychotherapy, attention intervention, and psychoanalysis. All work is done during the sessions. Some experts believe that such therapies might be more useful for generalized anxiety, which may require more sustained work to process and recover from early traumas and fears. Studies suggest that although emotion-based psychotherapies are not as effective as cognitive-behavioral therapy (CBT) in treating panic disorders, patients tend to stay in longer in EBT than in CBT. Some experts suggest adding elements of EBT to the usual CBT and medication treatments.

Alternative Procedures

Biofeedback. Biofeedback uses special sensors that allow patients to recognize anxiety states by changes in specific physical functions, such as changes in pulse rate, skin temperatures, and muscle tone. Eventually they learn to modify these changes, which in turn helps relieve anxiety.

Breathing Retraining. Breathing retraining techniques may help reduce the physical effects of anxiety. For example, hyperventilation is one of the primary physical manifestations of panic disorders. This involves rapid, tense breathing, resulting in chest pain, dizziness, tingling of the mouth and fingers, muscle cramps, and even fainting. By practicing measured, controlled breathing at the onset of a panic attack, patients may be able to prevent full attacks.

Meditation. A major analysis reported that meditative techniques, especially transcendental meditation (TM), were associated with reduced anxiety. TM uses a mantra (a word that has a specific chanting sound but no meaning). The meditator repeats the word silently, letting thoughts come and go. (Note: Most research on TM has been conducted by the founding organization. A number of other meditative techniques are available that may be equally beneficial.) The only potential risks from meditating are in people with psychosis in whom meditating may trigger a psychotic event.

Relaxation Techniques. Relaxation methods, such as learning how to gradually relax one's muscles, may also be helpful. In one study, relaxation was as helpful for patients with GAD as cognitive therapy.

Acupuncture. One small study reported that acupuncture relieved anxiety before surgery. Whether this study has any relevance to anxiety disorders is unknown.

Transcranial Magnetic Stimulation and Other Neurostimulation

Transcranial magnetic stimulation (TMS) uses high frequency magnetic pulses to target and stimulate specific areas of the brain. Research has particularly focused on possible benefits for obsessive-compulsive behavior. Some studies have found some improvement in mood, but more research is needed to determine its value for reducing anxiety and obsessions.

In 2006, the U.S. National Institutes of Health funded a large study to examine whether deep brain stimulation (DBS) can help patients with OCD. DBS involves implanting tiny stimulators into the brain to block abnormal nerve signals that cause obsessive symptoms. These “brain pacemakers” are approved to treat epilepsy and Parkinson’s disease. Researchers hope that DBS may eventually provide a new treatment option for patients with severe OCD.

Surgery

A surgical technique called cingulotomy involves interrupting the cingulate gyrus, a bundle of nerve fibers in the front of the brain. It is sometimes used as a last resort for patients with severe OCD. A variation of this procedure using magnetic resonance imaging (MRI) to guide the surgeon has resulted in long-term improvement in about 25 - 33% of OCD patients in whom it is performed. The procedure is generally safe with few serious complications and does not affect intellect or memory.

Resources

• www.nimh.nih.gov -- National Institute of Mental Health
• www.adaa.org -- Anxiety Disorders Association of America
• www.nami.org -- National Alliance on Mental Illness
• www.psych.org -- The American Psychiatric Association
• www.apa.org -- The American Psychological Association
• www.istss.org -- International Society for Traumatic Stress Studies
• www.ncvc.org -- National Center for Victims of Crime
• www.ncptsd.va.gov -- National Center for Post-Traumatic Stress Disorders
• www.rainn.org -- Rape, Abuse, and Incest National Network
• www.aacap.org -- American Academy of Child and Adolescent Psychiatry
• www.aabt.org -- Association for Behavioral and Cognitive Therapies
• www.ocfoundation.org -- Obsessive Compulsive Foundation

References

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