US Pharm. 2006;11:HS-3-HS-13.

Anxiety is a normal reaction that helps people cope with stress associated with daily life and difficult situations. However, when anxiety becomes irrational and excessive in day-to-day life, it becomes a disorder. Anxiety disorders are serious medical illnesses that affect approximately 40 million American adults. 1 These disorders fill people's lives with overwhelming anxiety, frustration, and fear. Unlike the relatively mild, brief anxiety caused by a stressful event, such as a business presentation, an examination, or a job interview, anxiety disorders are chronic and bothersome and can grow progressively worse.

The good news is that the majority of these disorders can be treated, and research is focusing on creating new therapies designed to help people with anxiety disorders lead productive and satisfactory lives.1 Treatments include medications, behavioral therapy, and cognitive therapy; relaxation techniques, lifestyle changes, healthy diet, aromatherapy, exercise, and herbal therapies have also been recommended for anxiety.

NIH's National Institute of Mental Health supports scientific investigation into the causes, diagnosis, treatment, and prevention of anxiety disorders and other mental illnesses. Anxiety disorders are complex and probably result from a combination of genetic, behavioral, developmental, and other factors.1,2 This article provides an overview of panic disorder, anxious depression, obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), social anxiety disorder, specific phobias, and generalized anxiety disorder (GAD). Each anxiety disorder has its own characteristics, but they are all bound together by the common theme of excessive, irrational fear and dread.

Types of Disorders
Panic Disorder
Panic disorder affects about six million adult Americans and is common in both men and women. It most often begins during late adolescence or early adulthood and typically manifests as panic attacks or sudden fear due to stressors. Although many people have one attack and never experience another, those who have panic disorders should seek treatment before the condition becomes disabling. Correct diagnosis of this disorder is imperative, as a patient may have it for years before learning that he or she has a real, but treatable, illness.1

Many people with panic disorder try to avoid the place or situation in which their first episode or panic attack occurred. This may seriously interfere with daily activities, leaving the patient homebound in severe cases. When a patient's life become so restricted, as happens in about one third of cases of panic disorder, the condition is called agoraphobia.2 As a patient with agoraphobia cannot predict when an attack will occur, he or she may develop intense anxiety between episodes, worrying when and where the next one will strike. Early treatment of panic disorder can often prevent this disabling condition.2

A panic attack may start with a pounding heart, sweats, weakness, faintness, or dizziness. Numbness of the hands, flushing, and/or chills may follow. Sometimes, people may genuinely believe they are having a heart attack, losing their mind, or on the verge of death. Panic attacks can occur at any time, even during sleep. An attack generally peaks within 10 minutes, but some symptoms may last much longer. Panic disorder is one of the most treatable of the anxiety disorders, as it responds to medications or psychotherapy in most cases.

Anxious Depression
Depression and anxiety disorders are not the same, but they seem similar at first glance. Both involve the body, mood, and thoughts. In fact, depressive disorders often accompany anxiety disorders. Depressed people are sad, hopeless, or disappointed and have difficulty concentrating. They have less energy and are overwhelmed by the day-to-day activities. In contrast, those with anxiety disorder experience fear, panic, or anxiety in situations that most people do not find threatening. Without treatment, anxiety and depression can restrict a person's ability to work, maintain relationships, or even leave the house. Because anxiety is so often associated with depressive disorders, it is essential to treat the underlying depression along with the anxiety. When the depression is resolved, anxiety symptoms often diminish.3

Obsessive-Compulsive Disorder
OCD involves persistent unwanted thoughts (obsessions) and/or repetitive behaviors (compulsions). A lot of healthy people have some OCD symptoms, such as doubting that they have locked doors or turned off the oven before leaving the house; however, in patients with OCD, these behaviors along with others (e.g., hand washing, ordering, checking, counting, and silently repeating words) take longer, cause extreme distress, and interfere with daily life.

OCD affects about 2.2 million American adults. It strikes men and women in approximately equal numbers and usually first appears in childhood, adolescence, or early adulthood. One third of adults with this disorder report having experienced their first symptoms as children. The course of the disease is variable--symptoms may come and go, ease over time, or grow progressively worse. Research evidence suggests that OCD might run in families.1

Depression or other anxiety disorders may accompany OCD, and some people may develop eating disorders that affect their general health. In addition, people with OCD may avoid situations in which they might have to confront their obsessions or use alcohol or drugs to calm themselves. If OCD becomes severe enough, it can keep a patient from holding down a job or from carrying out normal responsibilities at home. This disorder generally responds well to medication or psychotherapy.4

Posttraumatic Stress Disorder
PTSD may occur in people who have experienced, witnessed, or been confronted by an event or events that involved death of others or threatened death or serious injury to themselves or others.1 In such cases, the person experiences intense fear, helplessness, or horror. In children, this may cause disorganized or agitated behavior. PTSD was first brought to public attention when it was described and diagnosed in war veterans, but it can result from any number of traumatic incidents, including violent attacks, such as rape; torture; kidnapping or being held captive; child abuse; serious car or train accidents; and natural disasters, such as floods or earthquakes. For instance, the September 11, 2001, terrorist attacks and the tsunami that hit South and Southeast Asia on December 26, 2004, triggered PTSD in many victims.

Regardless of the triggering event, PTSD can cause those affected with it to repeatedly remember the trauma in the form of nightmares, to experience problems with sleep at night and disorganization during the day, and to avoid certain places or situations that bring back those memories. In severe cases, the person may have trouble working or socializing. The disorder is often accompanied by depression, substance abuse, or one or more other anxiety disorders.5

PTSD affects about 7.7 million adult Americans, but not every traumatized person experiences full-blown disease. PTSD is diagnosed only if the symptoms last more than a month. In those who do develop PTSD, symptoms usually begin within three months of the trauma and undergo a varying course. Some people recover within six months, while others have symptoms that last much longer. In some cases, the condition may be chronic or surface years after the traumatic event. Those with PTSD can be helped by medications and careful psychotherapy.6

Social Anxiety Disorder
People with social phobia have a persistent, intense, and chronic fear of being watched and judged by others and are embarrassed or humiliated by their own actions. Their fear may be so severe that it interferes with work or school and other daily activities. Even though their actions may be excessive and unreasonable, they are unable to overcome their phobia. People with social phobia often worry for days or weeks in advance of a dreaded situation.

Social phobia can be limited to only one type of situation--such as speaking in formal or informal situations--but it may be so broad that people experience symptoms almost anytime they are around other people, possibly keeping them from going to work or school on some days. Many people with this illness have difficulty making and keeping friends. Physical symptoms often accompany the intense anxiety of social phobia and include blushing, profuse sweating, trembling, nausea, and difficulty talking.

Social phobia affects about 15 million adult Americans. Women and men are equally affected. The disorder usually begins in childhood or early adolescence, and there is some evidence that genetic factors are involved. Social phobia often occurs along with other anxiety disorders or depression. Substance abuse or dependence may develop in those who attempt to "self-medicate" their social phobia by drinking or using drugs. Social phobia can be treated successfully with psychotherapy or medications.1,7

Specific Phobias
A specific phobia is an intense, irrational fear of something that poses little or no actual danger. Some of the more common specific phobias are fear of heights (altophobia), darkness (lygophobia), fire (pyrophobia), making changes (tropophobia), water (aquaphobia), flying (aviatophobia), dogs (kynophobia), and injuries involving blood (hemaphobia). Although adults with phobias realize that their fears are irrational, they often find that facing, or even thinking about facing, the feared object or situation brings on a panic attack or severe anxiety.1,8

Specific phobias affect an estimated 19 million adult Americans and are twice as common in women as in men. The causes of specific phobias are not well understood, although there is some evidence that phobias run in families. Specific phobias usually appear during childhood or adolescence and persist into adulthood.

If the object of the phobia is easy to avoid, people with specific phobias may not feel the need to seek treatment. In some cases, phobias can be disabling and greatly interfere with daily life, causing people to make important career or personal decisions to avoid a phobic situation. Specific phobias are highly treatable with carefully targeted psychotherapy.1,9

Generalized Anxiety Disorder
GAD is associated with irregular levels of neurotransmitters in the brain. People with GAD always anticipate disaster, often worrying excessively about health, money, family, or work. Their fear is much greater than the normal levels of anxiety that people experience day to day. GAD is chronic and involves exaggerated worry and tension, even though there is little or nothing to cause it. Simply the thought of getting through the day provokes anxiety. Generalized or free-floating anxiety is distinguished from phobia because it is not triggered by a specific object or situation.

People with GAD usually realize that their anxiety is more intense than the situation warrants, but their worries are accompanied by physical symptoms, especially fatigue, headaches, muscle tension, muscle aches, difficulty swallowing, trembling, twitching, irritability, sweating, and hot flashes. They have difficulty concentrating and often have trouble falling or staying asleep.

Unlike other anxiety disorders, people with GAD do not avoid certain situations as a result of their disorder. In mild cases, people with the disorder may be able to function in social settings or on the job; however, severe GAD can be disabling, making it difficult to carry out even the most ordinary daily activities.

GAD affects about 6.8 million adult Americans and about twice as many women as men. The disorder comes on gradually and can begin at any point, although the risk is highest between childhood and middle age. It is diagnosed when a person has been worrying excessively about a number of everyday problems for at least six months. There is evidence that genetics have a modest role in GAD.

GAD is commonly treated with medications. As GAD rarely occurs alone, accompanying conditions, such as anxiety disorder, depression, or substance abuse, must be treated along with it.9

Treatment of Anxiety Disorders
Effective therapies have been developed for each specific anxiety disorder. In general, there are two types of treatment for anxiety disorders: medication and talk therapy, a specific type of psychotherapy. The decision to use one or both treatments depends on the patient, the physician, the particular anxiety disorder, and any previous treatments. For example, only psychotherapy has been found effective for specific phobias.

In each case, the treatment depends upon a number of preliminary findings. The first consideration is whether symptoms are truly due to an anxiety disorder, and if so, which one. The next consideration is whether there are any coexisting conditions. Sometimes alcoholism or another coexisting condition must be treated at the same time as or before the anxiety disorder.

It is important that the patient and the health care professionals treating him or her work as a team to find the best approach. If one treatment does not work, another existing one may work. Furthermore, new treatments are always being developed.

Medications
Medications will not cure an anxiety disorder, but they can keep the symptoms under control and enable the patient to lead a normal and satisfactory life. The major classes of medications used for various anxiety disorders are discussed below.

Tricyclic Antidepressants: These medications were originally approved for treatment of depression, but they have also been found to be effective for anxiety disorders. They are initiated at low doses and gradually increased. These drugs are the oldest in the group; many physicians and patients prefer the newer drugs, as tricyclics sometimes cause dizziness, drowsiness, dry mouth, and weight gain. When these problems persist or are bothersome, a change in dosage or a switch in medications may be needed. In addition, tricyclics take several weeks to show their effects. Health care professionals should remind patients not to get discouraged and stop taking these medications before they have had a chance to work. Tricyclics are useful in treating people with co-occurring anxiety disorders and depression. Clomipramine, the only antidepressant in its class prescribed for OCD, and imipramine, prescribed for panic disorder and GAD, are examples of tricyclics.1,10

Selective Serotonin Reuptake Inhibitors: Newer than tricyclics, selective serotonin reuptake inhibitors (SSRIs) have fewer side effects and are better tolerated. They block reuptake of serotonin and have fewer effects on histaminergic and muscarinic receptors. Their once-daily dosing (with the exception of fluvoxamine) enhances compliance even in the presence of comorbid medical illness. SSRIs have fewer drug interactions than do older antidepressants, and even the SSRI inhibition of hepatic cytochrome P-450 enzymes is rarely of clinical importance. An adjustment in dosage or a switch to another SSRI will usually resolve bothersome adverse effects.

Fluoxetine, sertraline, fluvoxamine, paroxetine, and citalopram are among the SSRIs commonly prescribed for panic disorder, OCD, PTSD, and social phobia. SSRIs are often used to treat people who have panic disorder in combination with OCD, social phobia, or depression. Venlafaxine, a drug closely related to the SSRIs, is useful for treating GAD. These medications are started at a low dose and gradually increased until they reach a therapeutic level.1,10

Monoamine Oxidase Inhibitors: Monoamine oxidase inhibitors (MAOIs) are the oldest class of antidepressants. Phenelzine is the most commonly prescribed MAOI and is used to treat panic disorder and social phobia; tranylcypromine and isoprocarboxazide are prescribed for anxiety disorders. People who take MAOIs must follow a restrictive diet, as these medications can interact with foods and beverages that contain a chemical called tyramine (e.g., cheese, red wine).1,10

Benzodiazepines: High-potency benzodiazepines relieve symptoms quickly and are associated with few side effects, although drowsiness can be a problem. People can develop a tolerance to them and have to continue increasing the dosage to get the same effect. Benzodiazepines are generally prescribed for short periods of time, although they are prescribed for six months to a year when they are used to treat panic disorder. People who have had problems with drug or alcohol abuse are not usually good candidates for these medications, because they may become dependent on them.

Some people experience withdrawal symptoms when they stop taking benzodiazepines, although reducing the dosage gradually can diminish those symptoms. In some instances, the symptoms of anxiety rebound after these medications are stopped.

Benzodiazepines include clonazepam, which is used for social phobia and GAD; alprazolam, which is prescribed for panic disorder and GAD; and lorazepam, which is also useful for panic disorder.

Buspirone: Buspirone, a member of a class of drugs called azipirones, has been used to treat GAD since 1986. It is not known how buspirone works in the body to reduce symptoms of anxiety. Possible side effects include dizziness, headaches, and nausea. Unlike the benzodiazepines, buspirone must be taken consistently for at least two weeks to achieve an anti-anxiety effect.1,10

Psychotherapy
Psychotherapy involves talking with a trained mental health professional, such as a psychiatrist, psychologist, social worker, or counselor, to learn how to deal with problems such as anxiety disorders.

Cognitive Behavioral Therapy: Effective for several anxiety disorders, cognitive behavioral therapy (CBT) is particularly helpful in treating panic disorder and social phobia. The cognitivecomponent helps people change thinking patterns that keep them from overcoming their fears. The behavioral component seeks to change people's reactions to anxiety-provoking situations. A key element of this component is exposure, or having people confront the things they fear. For instance, exposure and response prevention is used to treat people with OCD. If the person has a fear of dirt and germs, the therapist may encourage allowing the person's hands to remain dirty without washing for a certain period. The therapist helps the patient cope with the resultant anxiety. After the exercise has been repeated a number of times, the anxiety diminishes. Another behavioral technique is to teach the patient deep breathing as an aid to relaxation and anxiety management.1

Behavioral therapy must be directed at the person's specific anxieties. These therapies have no adverse side effects other than the temporary discomfort of increased anxiety, and they require that the therapist be well trained in the techniques in order to produce results.

CBT or behavioral therapy generally lasts about 12 weeks. Group therapy is particularly effective for people with social phobia. There is some evidence that the beneficial effects of CBT last longer than those of medications for people with panic disorder, OCD, PTSD, and social phobia.1,3

Medication may be combined with psychotherapy, and for many people, this is the best approach to treatment. Recurrences of anxiety can also be treated effectively and are managed in the same way as initial episodes. The skills learned in dealing with the initial episode can be helpful in coping with future anxiety.

Stress Reduction Techniques
Mind/body breathing exercises, physical exercise, yoga, tai chi, self-hypnosis, massage, and meditation are just some of the stress reduction techniques used for anxiety disorders. People should try these different techniques and determine which routine they can stick with even when their schedule becomes more hectic.

Conclusion
Many people with anxiety disorders benefit from joining a self-help group and sharing their problems and achievements with others. The family is of great importance in the recovery of a person with an anxiety disorder. If the family tends to trivialize the disorder or demand improvement without treatment, the affected person will suffer.

In addition to medication therapy, stress management techniques, meditation, and psychotherapy are the cornerstones of therapy in certain anxiety disorders. There is preliminary evidence that aerobic exercise may be of value, and it is known that caffeine, refined sugar, illicit drugs, and even some OTC cold medications can aggravate the symptoms of an anxiety disorder. Pharmacists have a crucial role and an exceptional opportunity in evaluating their patients' anxiety disorders and providing counseling to patients taking anxiety medications.

REFERENCES
1. National Institute of Mental Health (www.nimh.nih.gov).
2. Hyman SE, Rudorfer MV. Anxiety disorders. In: Dale DC, Federman DD, eds. Scientific American Medicine. Vol. 3. New York: Healtheon/WebMD Corp.; 2000; Sect. 13, Subsect. VIII.
3. Regier DA, Rae DS, Narrow WE, et al. Prevalence of anxiety disorders and their comorbidity with mood and addictive disorders. Br J Psychiatry Suppl. 1998;(34):24-28.
4. Simpson HB, Huppert JD, Petkova E, et al. Response versus remission in obsessive-compulsive disorder. J Clin Psychiatry. 2006;67:269-276.
5. Davidson JR. Trauma: the impact of post-traumatic stress disorder. J Psychopharmacol. 2000;14(2 Suppl 1):S5-S12.
6. Foa EB. Psychosocial therapy for posttraumatic stress disorder. J Clin Psychiatry. 2006;67(Suppl 2):40-45.
7. Grant BF, Hasin DS, Blanco C, et al. The epidemiology of social anxiety disorder in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry. 2005;66:1351-1361.
8. Bourdon KH, Boyd JH, Rae DS, et al. Gender differences in phobias: results of the ECA community survey. J Anxiety Disord. 1988;2:227-241.
9. Wilson JK, Rapee RM. Self-concept certainty in social phobia. Behav Res Ther. 2006;44:113-136.
10. Micromedex Health Series, Vol. 128, 2005.

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