Fear is an automatic neurophysiological state of alarm characterized by a fight or flight response to a cognitive appraisal of present or imminent danger (real or perceived). Anxiety is linked to fear and manifests as a future-oriented mood state that consists of a complex cognitive, affective, physiological, and behavioral response system associated with preparation for the anticipated events or circumstances perceived as threatening. Pathological anxiety is triggered when there is an overestimation of perceived threat or an erroneous danger appraisal of a situation which leads to excessive and inappropriate responses.
Anxiety is one of the most common psychiatric disorders but the true prevalence is not known as many people do not seek help or clinicians fail to make the diagnosis.
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Anxiety disorders appear to be caused by an interaction of biopsychosocial factors. Genetic vulnerability interacts with situations that are stressful or traumatic to produce clinically significant syndromes.
Anxiety can be caused by the following conditions:
- Herbal medications
- Substance abuse
- Childhood experiences
- Panic disorders
Anxiety is one of the most common psychiatric disorders in the general population. Specific phobia is the most common with a 12-month prevalence rate of 12.1%. Social anxiety disorder is the next most common, with a 12-month prevalence rate of 7.4%. The least common anxiety disorder is agoraphobia with a 12-month prevalence rate of 2.5%. Anxiety disorders occur more frequently in females than in males with an approximate 2:1 ratio.
The significant mediators of anxiety in the central nervous system are thought to be norepinephrine, serotonin, dopamine, and gamma-aminobutyric acid (GABA). The autonomic nervous system, especially the sympathetic nervous system, mediates most of the symptoms.
The amygdala plays an important role in tempering fear and anxiety. Patients with anxiety disorders have been found to show heightened amygdala response to anxiety cues. The amygdala and limbic system structures are connected to prefrontal cortex regions, and prefrontal-limbic activation abnormalities may be reversed with psychological or pharmacologic interventions.
History and Physical
Characteristic Symptoms Pathological Anxiety
Cognitive symptoms: fear of losing control; fear of physical injury or death; fear of "going crazy"; fear of negative evaluation by others; frightening thoughts, mental images, or memories; perception of unreality or detachment; poor concentration, confusion, distractible; narrowing of attention, hypervigilance for threat; poor memory; and difficulty speaking.
Physiological symptoms: increased heart rate, palpitations; shortness of breath, rapid breathing; chest pain or pressure; choking sensation; dizzy, light-headed; sweaty, hot flashes, chills; nausea, upset stomach, diarrhea; trembling, shaking; tingling or numbness in arms and legs; weakness, unsteadiness, faintness; tense muscles, rigidity; and dry mouth.
Behavioral symptoms: avoidance of threat cues or situations; escape, flight; pursuit of safety, reassurance; restlessness, agitation, pacing; hyperventilation; freezing, motionless; and difficulty speaking.
Affective symptoms: nervous, tense, wound up; frightened, fearful, terrified; edgy, jumpy, jittery; and impatient, frustrated.
Anxiety Disorders as defined in the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM–5; American Psychiatric Association, 2013):
- Separation Anxiety Disorder: An individual with separation anxiety disorder displays anxiety and fear atypical for his/her age and development level of separation from attachment figures. There is persistent and excessive fear or anxiety about harm to, loss of, or separation from attachment figures. The symptoms include nightmares and physical symptoms. Although the symptoms develop in childhood, they can be expressed throughout adulthood as well.
- Selective Mutism: This disorder is characterized by a consistent failure to speak in social situations where there is an expectation to speak even though the individual speaks in other circumstances, can speak, and comprehends the spoken language. The disorder is more likely to be seen in young children than in adolescents and adults.
- Specific Phobia: Individuals with specific phobias are fearful or anxious about specific objects or situations which they avoid or endure with intense fear or anxiety. The fear, anxiety, and avoidance are almost always immediate and tend to be persistently out of proportion to the actual danger posed by the specific object or situation. There are different types of phobias: animal, blood-injection-injury, and situational.
- Social Anxiety Disorder: This disorder is characterized by marked or intense fear or anxiety of social situations in which one could be the subject of scrutiny. The individual fears that he/she will be negatively evaluated in such circumstances. He/she also fears being embarrassed, rejected, humiliated or offending others. These situations always provoke fear or anxiety and are avoided or endured with intense fear and anxiety.
- Panic Disorder: Individuals with this disorder experience recurrent, unexpected panic attacks and experience persistent concern and worry about having another panic attack. They also have changes in their behavior linked to panic attacks which are maladaptive, such as avoidance of activities and situations to prevent the occurrence of panic attacks. Panic attacks are abrupt surges of intense fear or extreme discomfort that reach a peak within minutes, accompanied by physical and cognitive symptoms such as palpitations, sweating, shortness of breath, fear of going crazy, or fear of dying. Panic attacks can occur unexpectedly with no obvious trigger, or they may be expected, such as in response to a feared object or situation.
- Agoraphobia: Individuals with this disorder are fearful and anxious in two or more of the following circumstances: using public transportation, being in open spaces, being in enclosed spaces like shops and theaters, standing in line or being in a crowd, or being outside of the home alone. The individual fears and avoids these situations because he/she is concerned that escape may be difficult or help may not be available in the event of panic-like symptoms, or other incapacitating or embarrassing symptoms (e.g., falling or incontinence).
- Generalized Anxiety Disorder: The key feature of this disorder is persistent and excessive worry about various domains, including work and school performance, that the individual finds hard to control. The person also may experience feeling restless, keyed up, or on edge; being easily fatigued; difficulty concentrating or mind going blank; irritability, muscle tension, and sleep disturbance.
- Substance/Medication-Induced Anxiety Disorder: This disorder involves anxiety symptoms due to substance intoxication or withdrawal or to medical treatment.
- Anxiety Disorder Due to Other Medical Conditions: Anxiety symptoms are the physiological consequence of another medical condition. Examples include endocrine disease: hypothyroidism, hypoglycemia, and hypercortisolism; cardiovascular disorders: congestive heart failure, arrhythmia, and pulmonary embolism; respiratory illness: asthma and pneumonia; metabolic disturbances: B12 or porphyria; neurological illnesses: neoplasms, encephalitis, and seizure disorder.
When the history and examination do not suggest the symptoms as arising from any other medical disorder, the initial laboratory studies may be limited to the following: complete blood cell count (CBC) chemistry profile, thyroid function tests, urinalysis, and urine drug screen.
If the anxiety symptoms are atypical or there are some abnormalities noted in the physical examination more detailed evaluations may be indicated to identify or exclude underlying medical conditions. This would include the following: electroencephalography, brain computed tomography (CT) scan, electrocardiography, tests for infection, arterial blood gas analysis, chest radiography, and thyroid function tests.
Treatment / Management
Acute anxiety may require treatment with a benzodiazepine. Chronic anxiety treatment consists of psychotherapy, pharmacotherapy, or a combination of both.
Pharmacotherapy: selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), benzodiazepines, tricyclic antidepressants, mild tranquilizers, and beta-blockers treat anxiety disorders. 
- SSRIs (fluoxetine, sertraline, paroxetine, escitalopram, and citalopram) are an effective treatment for all anxiety disorders and considered first-line treatment.
- SNRIs (venlafaxine and duloxetine) are considered as effective as SSRIs and also are considered first-line treatment, particularly for generalized anxiety disorder (GAD).
- Tricyclic antidepressants (amitriptyline, imipramine, and nortriptyline) are useful in the treatment of anxiety disorders but cause significant adverse effects.
- Benzodiazepines (alprazolam, clonazepam, diazepam, and lorazepam) are used for short-term management of anxiety. They are fast-acting and bring relief within 30 minutes to an hour. They are effective in promoting relaxation and reducing muscular tension and other symptoms of anxiety. Because they work quickly, they are effective when taken for panic attacks or overwhelming episodes. Long-term use may require increased doses to achieve the same effect, which may result in problems related to tolerance and dependence.
- Buspirone is a mild tranquilizer that is slow acting as compared to benzodiazepines and takes about 2 weeks to start working. It has the advantage of being less sedating and also not being addicting with minimal withdrawal effects. It works for GAD.
- Beta-blockers (propranolol and atenolol) control the physical symptoms of anxiety such as rapid heart rate, a trembling voice, sweating, dizziness, and shaky hands. They are most helpful for phobias, particularly social phobia.
Psychotherapy: One of the most effective forms of psychotherapy is cognitive-behavioral therapy. It is a structured, goal-oriented, and didactic form of therapy that focuses on helping individuals identify and modify characteristic maladaptive thinking patterns and beliefs that trigger and maintain symptoms. This form of therapy focuses on building behavioral skills so that patients can behave and react more adaptively to anxiety-producing situations. Exposure therapy is utilized to move individuals towards facing the anxiety-provoking situations and stimuli which they typically avoid. This exposure results in a reduction in anxiety symptoms as they learn that their anxiety is causing them to experience false alarms and they do not need to fear the situation or stimuli and can cope effectively with such a situation.
- Atrial fibrillation
- Diabetic ketoacidosis
- Substance abuse
Anxiety disorders have very high morbidity including substance abuse, alcoholism, and major depression. In addition, constant anxiety also increases the risk of adverse cardiac events. In others, anxiety impairs the ability to develop social relationships and worsens the quality of life. Severe anxiety has also been linked to high rates of suicide.
Pearls and Other Issues
Characteristic Features Noted in Individuals with Clinical Anxiety
- False alarms: The presence of intense fear in the absence of threat cues or very minimal threat provocation.
- Persistence: There is a future-oriented perspective that involves the anticipation of threat or danger which causes the patient to experience a heightened level of apprehension and thoughts about impending potential threat, regardless of whether it materializes.
- Impaired Functioning: Anxiety interferes with effective and adaptive coping in the face of a perceived threat and the person’s daily social or occupational life.
- Stimulus hypersensitivity: In clinical states, fear is elicited by a wider range of stimuli or situations of relatively mild intensity that would be innocuous to a person who does not have clinical anxiety.
- Dysfunctional cognition and cognitive symptoms: Thinking characterized by overestimation of threat or danger appraisal of a situation that is not confirmed in any way.
Enhancing Healthcare Team Outcomes
Anxiety disorders are very common and can present in diverse ways. Because the condition is underdiagnosed and associated with high morbidity, it is best managed by an interprofessional team consisting of a mental health nurse, psychiatrist, psychotherapist, social worker, and a primary care provider. Family members need to be educated about the disorder and help monitor the symptoms and provide support. A mental health nurse should closely follow these patients as suicidal ideations are not rare. The pharmacist should educate the patient on different medications, their benefits, and potential adverse effects. Collaboration between the team members is vital to ensure that no patient is neglected and that all patients are receiving an acceptable standard of care.
The outlook for patients with anxiety is guarded. Data indicate that the high rates of mortality are associated with adverse cardiac events. In those with social phobia, the condition leads to significant functional impairment and a very poor quality of life. The risk of suicides is also high in this population. Patients with anxiety need lifelong follow-up because, despite drug therapy, relapse rates are high. (Level V)
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