Introduction
Background
Find clinical information on anxiety, including anxiety symptoms, causes of anxiety, types of anxiety disorders, treatment, follow-up, and more in this article on Medscape from WebMD.
Anxiety disorders are common psychiatric disorders. Many patients with anxiety disorders experience physical symptoms related to anxiety and subsequently visit their primary care providers. Despite the high prevalence rates of these anxiety disorders, they often are underrecognized and undertreated clinical problems. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) classifies the anxiety disorders into the following categories:1
* Anxiety due to a general medical condition
* Substance-induced anxiety disorder
* Generalized anxiety
* Panic disorder
* Acute stress disorder
* Posttraumatic stress disorder (PTSD)
* Adjustment disorder with anxious features
* Social phobia
* Obsessive-compulsive disorder (OCD)
* Specific phobias
For related information, see Medscape's Anxiety Disorders Resource Center.
Case study
Ms J is a 22-year-old college student who is in her senior year in college. Over the past several months she has developed recurrent unexpected periods of chest pain accompanied by shortness of breath, trembling, numbness, tingling, and a feeling of doom. These spells began abruptly and lasted for 30-45 minutes. She began to worry more and anticipated future attacks. Her academic work began to suffer as she had increasing difficulty concentrating.
After one episode, fearing a heart attack, Ms J went to the emergency room. Her ECG and physical examination were normal and there were no laboratory abnormalities. A follow-up visit to her family physician failed to support evidence of a heart or lung disorder. Her family physician diagnosed panic disorder and suggested she consider getting some counseling. She was placed on citalopram 10 mg, increasing to 20 mg. Following several weeks on the medication, her panic spells were reduced in frequency but not completely gone. She still has recurring spells that are less severe with fewer symptoms.
Ms J went to student health where she was assigned a therapist who started cognitive behavioral therapy. This therapy focused on relaxation and changing her exaggerated thoughts about the seriousness of her symptoms. Over 6 weeks, her symptoms continued to improve and were no longer considered serious or impairing her function.
Pathophysiology
Anxiety disorders appear to be caused by an interaction of biopsychosocial factors, including genetic vulnerability, which interact with situations, stress, or trauma to produce clinically significant syndromes. In the central nervous system, the major mediators of the symptoms of anxiety disorders appear to be norepinephrine, serotonin, dopamine, and GABA. Other neurotransmitters and peptides, such as corticotropin-releasing factor, may be involved. Peripherally, the autonomic nervous system, especially the sympathetic nervous system, mediates many of the symptoms.2
The brain circuits and regions associated with anxiety disorders are beginning to be understood with the development of functional and structural imaging. The brain amygdala appears key in modulating fear and anxiety. Patients with anxiety disorders often show heightened amygdala response to anxiety cues. The amygdala and other limbic system structures are connected to prefrontal cortex regions. Prefrontal-limbic activation abnormalities have been show to reverse with clinical response to psychologic or pharmacologic interventions.
Frequency
United States
Two major studies in the United States have estimated the prevalence rates for a variety of anxiety disorders. These 2 studies are the Epidemiological Catchment Area (ECA) study and the National Comorbidity Survey (NCS) study3 . Using these and other studies, the estimated lifetime prevalence rates for individual anxiety disorders are panic disorder (2.3-2.7%), generalized anxiety disorder (4.1-6.6%), OCD (2.3-2.6%), PTSD (1-9.3%), and social phobia (2.6-13.3%).
International
The prevalence of specific anxiety disorders appears to vary between countries and cultures. A cross-national study of the prevalence of panic disorder found lifetime prevalence rates ranging from 0.4% in Taiwan to 2.9% in Italy. A cross-cultural study of the prevalence of OCD found lifetime prevalence rates ranging from 0.7% in Taiwan to 2.5% in Puerto Rico.
Mortality/Morbidity
Anxiety disorders may contribute to morbidity and mortality through neuroendocrine and neuroimmune mechanisms or by direct neural stimulation, eg, hypertension or cardiac arrhythmia.
Severe anxiety disorders may be complicated by suicide, with or without secondary mood disorders (eg, depression). Anxiety disorders have high rates of comorbidity with major depression and alcohol and drug abuse. Some of the increased morbidity and mortality associated with anxiety disorders may be related to this high rate of comorbidity. The ECA study found that panic disorder was associated with suicide attempts (odds ratio=18 compared to populations without psychiatric disorders). How much of the association of panic disorder with suicide is mediated through the association of panic disorder with mood and substance abuse disorders is unclear. Acute stress may play a role in producing suicidal behavior. Suicide attempts can be precipitated by adverse life events such as divorce or financial disaster. The effects of acute stress in producing suicidal behavior are increased in those with underlying mood, anxiety, and substance abuse problems.
Chronic anxiety may be associated with increased risk for cardiovascular morbidity and mortality.
Race
The ECA study found no difference in rates of panic disorder among white, African American, or Hispanic populations in the United States.
Some studies have found higher rates of PTSD in minority populations. Some of this association may be due to higher rates of specific traumatic events (ie, assault) in minority populations.
Sex
The female-to-male ratio for any lifetime anxiety disorder is 3:2.
Anxiety. Chart showing the female-to-male sex rat...
Anxiety. Chart showing the female-to-male sex ratio for anxiety disorders. Adapted from Kessler et al, 1994.
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Anxiety. Chart showing the female-to-male sex rat...
Anxiety. Chart showing the female-to-male sex ratio for anxiety disorders. Adapted from Kessler et al, 1994.
Age
Most anxiety disorders begin in childhood, adolescence, and early adulthood. Separation anxiety is an anxiety disorder of childhood that often includes anxiety related to going to school. This disorder may be a precursor for adult anxiety disorders. Panic disorder demonstrates a bimodal age of onset in the NCS study in the age groups of 15-24 years and 45-54 years. The median age of onset of social phobia in the NCS study was 16 years. The age of onset for OCD appears to be in the mid 20s to early 30s.
New-onset anxiety symptoms in older adults should prompt a search for an unrecognized general medical condition, a substance abuse disorder, or major depression with secondary anxiety symptoms.
Anxiety. Age of onset for anxiety disorders based...
Anxiety. Age of onset for anxiety disorders based on specific anxiety disorder type.
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Anxiety. Age of onset for anxiety disorders based...
Anxiety. Age of onset for anxiety disorders based on specific anxiety disorder type.
Clinical
History
Symptoms vary depending on the specific anxiety disorder. To rule out anxiety disorders secondary to general medical or substance abuse conditions, a detailed history and review of symptoms is essential. Review use of caffeine-containing beverages (coffee, tea, colas, Mountain Dew), over-the-counter medications (aspirin with caffeine, sympathomimetics), herbal "medications," or street drugs. Ask the patient's sleep partner about apneic episodes or myoclonic limb jerks. Concurrent depressive symptoms are common in all of the anxiety disorders. Severe anxiety disorders may produce agitation, suicidal ideation, and increased risk of completed suicide. Always ask about suicidal ideation or suicidal intent.
* Obtain a complete Mental Status Examination for each patient with anxiety symptoms. Patients may exhibit physical signs of anxiety such as sweaty palms, restlessness, and distractibility. Patients are generally oriented times 3 and cooperative. Mood may be normal or depressed. Affect is often preserved. Psychotic symptoms are not typical of uncomplicated anxiety disorders. Suicidal ideation should be assessed by asking about passive thoughts of death, desires to be dead, thoughts of harming self, or plans or acts to harm self. Homicidal ideation is uncommon. Cognition is typically intact with no impairment in memory, language, or speech. Insight and judgment are typically intact.
* Panic disorder is characterized by recurrent panic attacks (ie, periods of intense fear of abrupt onset peaking in intensity within 10 min). Four of the following must be present for a panic attack:
o Palpitations, pounding heart, or accelerated heart rate
o Sweating
o Trembling or shaking
o Shortness of breath or dyspnea
o Sensation of choking
o Chest pain or discomfort
o Nausea or abdominal distress
o Feeling dizzy, unsteady, lightheaded, or faint
o Derealization or depersonalization
o Fear of losing control or going crazy
o Fear of dying
o Paresthesias
o Chills or hot flashes
o Although not a diagnostic feature, suicidal ideation and completed suicide have been associated with panic disorder.
* Generalized anxiety disorder is characterized by excessive anxiety and worry. Worrying is difficult to control. Anxiety and worry are associated with at least 3 of the following symptoms:
o Restlessness or feeling keyed-up or on edge
o Being easily fatigued
o Difficulty concentrating or mind going blank
o Irritability
o Muscle tension
o Sleep disturbance
o Although not a diagnostic feature, suicidal ideation and completed suicide have been associated with generalized anxiety disorder.
* OCD is characterized by obsessions or compulsions. Obsessions or compulsions must be recognized as unreasonable or excessive and must cause marked distress.
o Obsessions include all of the following:
+ Recurrent and persistent thoughts, impulses, or images that are intrusive and knowingly inappropriate and cause anxiety or distress
+ Obsessions are very discomforting and can include fear of losing control and harming someone close to the patient, such as his or her child.
+ Patient commonly knows he or she won't act on the obsessions, but it will still cause significant distress.
+ Obsessions may be hidden by the patient for fear of being called "crazy."
+ Thoughts, impulses, or images that are not simply excessive worries about real-life problems
+ Attempts are made to ignore or suppress thoughts.
+ Thoughts, impulses, or images are recognized as being the product of the mind and not imposed from an outside force.
o Compulsions include the following:
+ Repetitive behaviors, such as handwashing, ordering, and checking, that people feel are driven and must be carried out and occur to such an extreme that a person's ability to function is impaired.
+ Behaviors or mental acts are done to reduce distress or anxiety.
* Social phobia
o Marked and persistent fear of social or performance situations to the extent that a person's ability to function at work or in school is impaired.
o Exposure to social or performance situation always produces anxiety.
o Fear/anxiety recognized as excessive
o Social or performance situations are avoided or endured with intense anxiety.
o Avoidance behavior, anticipation, or distress in the feared social or performance setting produces significant impairment in functioning.
* PTSD is a severe trauma that is experienced that includes (1) actual or threatened death or serious injury or threat to personal integrity of self or others and (2) responses that include intense fear, helplessness, or horror. (Life-threatening experiences and the attendant loss of control are key elements.)
o Persistent reexperience of the event occurs by at least 1 of the following:
+ Recurrent and intrusive recollections
+ Recurrent distressing dreams/nightmares
+ Feelings of reliving traumatic event, ie, flashbacks
+ Intense psychologic distress with internal or external cues to the trauma
+ Physiological reactivity on exposure to trauma cues
o Persistent avoidance of stimuli of trauma and numbing/avoidance behavior demonstrated by at least 3 of the following:
+ Avoidance of thoughts or conversation related to the trauma
+ Avoidance of activities, places, or people related to the trauma
+ Amnesia for important trauma-related events
+ Decreased participation in significant activities
+ Feeling detached or estranged from others
+ Restricted affect
+ Foreshortened sense of the future
o Persistent symptoms of increased arousal demonstrated by 2 or more of the following:
+ Difficulty staying or falling asleep
+ Irritability or anger outbursts
+ Difficulty concentrating
+ Hypervigilance
+ Exaggerated startle response
o Although not a diagnostic feature, suicidal and homicidal ideation have been associated with PTSD.
Physical
* Tremor
* Tachycardia
* Tachypnea
* Sweaty palms
* Restlessness
Causes
* First, evaluate for anxiety due to a known or unrecognized medical condition.
* Most presenting anxiety disorders are functional psychiatric disorders.
* The psychodynamic theory has explained anxiety as a conflict between the id and ego. Aggressive and impulsive drives may be experienced as unacceptable resulting in repression. These repressed drives may break through repression, producing automatic anxiety.
* Cognitive theory has explained anxiety as the tendency, to overestimate the potential for danger. Patients with anxiety disorder patients tend to imagine the worst possible scenario and avoid situations they think are dangerous such as crowds, heights, or social interaction.
* Substance-induced anxiety disorder (over-the-counter medications, herbal medications, substances of abuse) is a diagnosis that often is missed.
* Genetic factors significantly influence risk for many anxiety disorders. Environmental factors such as early childhood trauma can also contribute to risk for later anxiety disorders. The debate whether gene or environment are primary in anxiety disorders has evolved to a better understanding of the important role of the interaction between genes and environment.4 Some individuals appear resilient to stress while others are vulnerable to stress, which precipitates an anxiety disorder.Differential Diagnoses
Acute Respiratory Distress Syndrome
Folic Acid Deficiency
Addison Disease
Food Poisoning
Adrenal Crisis
Gastritis, Acute
Alcohol-Related Psychosis
Gastritis, Chronic
Alcoholism
Goiter
Amphetamine-Related Psychiatric Disorders
Goiter, Diffuse Toxic
Anaphylaxis
Hallucinogens
Androgen Excess
Hyperaldosteronism, Primary
Anorexia Nervosa
Hypercalcemia
Apnea, Sleep
Hyperparathyroidism
Asthma
Hyperprolactinemia
Atrial Fibrillation
Hypersensitivity Reactions, Delayed
Atrial Tachycardia
Hypersensitivity Reactions, Immediate
Body Dysmorphic Disorder
Inhalant-Related Psychiatric Disorders
Brief Psychotic Disorder
Injecting Drug Use
Bulimia
Insomnia
Caffeine-Related Psychiatric Disorders
Irritable Bowel Syndrome
Cannabis Compound Abuse
Lyme Disease
Cardiogenic Shock
Malingering
Conversion Disorders
Meningitis
Delirium
Multifocal Atrial Tachycardia
Delirium Tremens
Personality Disorders
Delusional Disorder
Phobic Disorders
Depression
Premenstrual Dysphoric Disorder
Diabetes Mellitus, Type 1
Primary Hypersomnia
Diabetic Ketoacidosis
Primary Insomnia
Digitalis Toxicity
Schizoaffective Disorder
Dissociative Disorders
Schizophrenia
Dysthymic Disorder
Shared Psychotic Disorder
Encephalopathy, Dialysis
Sleep Disorder, Geriatric
Encephalopathy, Hepatic
Sleep Disorders
Encephalopathy, Hypertensive
Somatoform Disorders
Encephalopathy, Uremic
Stimulants
Epilepsy Surgery
Syndrome of Inappropriate Secretion of Antidiuretic Hormone
Esophageal Motility Disorders
Thyroiditis, Subacute
Esophageal Spasm
Tourette Syndrome
Euthyroid Hyperthyroxinemia
Undifferentiated Connective-Tissue Disease
Factitious Disorder
Unstable Angina
Fibromyalgia
Other Problems to Be Considered
Adult respiratory distress syndrome (ARDS)
AIDS
Thyrotoxicosis
Anxiety disorders have one of the longest differential diagnosis lists of all psychiatric disorders. Anxiety is a nonspecific syndrome and can be due to a variety of medical or psychiatric syndromes. A variety of anxiety symptoms, such as panic, worry, rumination, and obsessions, can present in a variety of psychiatric illnesses including mood disorders, psychotic disorders, personality disorders, somatoform disorders, and cognitive impairment disorders (eg, delirium). Anxiety also can be observed as part of a drug withdrawal or drug intoxication effect.
Other important causes in the differential include medication-induced anxiety (ie, due to epinephrine or other sympathomimetics, theophylline or other neurostimulant bronchodilators, analgesics containing caffeine, corticosteroids, antivirals, others); migraine, seizure disorders, or other CNS-based disorders; and sleep disorders such as restless legs syndrome, sleep apnea, and periodic limb movement. Heroin abuse also should be considered in the differentials.
Workup
Laboratory Studies
* When the index of suspicion for anxiety being produced by a medical disorder is low (lack of physical findings, younger age, typical anxiety disorder presentation), initial lab studies might be limited to the following:
o CBC count
o Chemistry profile
o Thyroid function tests
o Urinalysis
o Urine drug screen
* For presentations with a higher index of suspicion for other medical causes of anxiety (ie, atypical anxiety disorder presentation, older age, specific physical examination abnormalities), more detailed evaluations may be indicated as follows:
o Rule out CNS disorder using electroencephalogram, lumbar puncture, or brain CT scan, as indicated by history and associated clinical findings.
o Rule out cardiac disorder using ECG or treadmill ECG.
o Rule out infectious causes using rapid plasma reagent test, lumbar puncture (CNS infections), or HIV testing.
Imaging Studies
* Diagnostic imaging studies are not indicated in the diagnosis of primary anxiety disorders unless specific general medical conditions need to be ruled out.
* Imaging studies may be helpful, however, to rule out anxiety due to a general medical condition, eg, cephalic CT scan or MRI to evaluate for pathological intracranial processes.
Procedures
* Psychosurgery is used in rare cases of severe treatment-refractory OCD.
* Electroconvulsive therapy is not effective for anxiety disorders but may successfully treat comorbid conditions, such as severe major depression, and is especially indicated when the patient is at high risk for suicide.Treatment
Medical Care
Patients with panic disorder frequently present to the emergency department with chest pain or dyspnea, fearing that they are dying of myocardial infarction. Anxiety symptoms often accompany or can exacerbate respiratory conditions such as asthma and chronic obstructive pulmonary disease.
* If clinically indicated, obtain necessary studies to rule out myocardial infarction and pulmonary embolism (ECG, chest radiograph).
* Intravenous or oral acute sedation with benzodiazepines may be used. Untreated panic attacks can subside spontaneously within 20-30 minutes, especially with reassurance and a calming environment.
* If possible, avoid long-term benzodiazepines for chronic anxiety disorders. If this approach seems necessary, obtaining a confirming opinion from a consulting psychiatrist may be helpful.
Consultations
* Most often, psychiatrists are consulted.
* In anxiety disorders secondary to a general medical condition, specialty consultation may be indicated.
Diet
* Discontinue (or decrease to a low reasonable level) caffeine-containing products such as coffee, tea, colas, and Mountain Dew.
* Over-the-counter preparations and herbal remedies should be reviewed with special caution because ephedrine and other herbal compounds may precipitate or exacerbate anxiety symptoms.
Activity
If no medical contraindication exists, recommend at least a mild-to-moderate daily exercise program. Exercise can significantly reduce anxiety associated with chronic medical conditions.
Medication
The management of individual anxiety disorders is dependent on the specific diagnosis.
Selective serotonin reuptake inhibitors (SSRIs) are helpful in a variety of anxiety disorders, including generalized anxiety disorder, panic disorder, OCD, and social phobia.
Antidepressant agents are the drugs of choice in the treatment of anxiety disorders, particularly the newer agents that have a safer adverse effect profile and higher ease of use than the older tricyclic agents; however, benzodiazepines often are used as adjunct treatment.
Some anticonvulsant medications, such as divalproex and gabapentin, may have a role in the treatment of anxiety disorders, especially in patients with high potential for abusing benzodiazepines.
Older antidepressants, such as tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs) also are effective in the treatment of some anxiety disorders. Caution in their use is warranted due to their higher toxicity and potential lethality in overdose. Their use should be limited to cases where SSRIs are ineffective or cannot be afforded. MAOIs may be especially indicated in treatment-refractory panic disorder and social anxiety disorder. Clomipramine (Anafranil, a tricyclic agent) has a US Food and Drug Administration (FDA) indication in the treatment of OCD and is the only tricyclic agent effective in the treatment of this condition. Indeed, it can be effective in cases refractory to treatment with SSRI agents. MAOI agents also may have a role in the treatment of certain subtypes of OCD refractory to conventional treatment, such as patients with symmetry obsessions or associated panic attacks.
The FDA has granted specific indications to the following disorders and agents: generalized anxiety disorder (venlafaxine, buspirone, escitalopram, paroxetine, duloxetine), social phobia (paroxetine, sertraline, venlafaxine), OCD (fluoxetine, sertraline, paroxetine, fluvoxamine), and PTSD (sertraline, paroxetine).
All SSRIs may be equal in the treatment of anxiety disorders; however, higher doses may be necessary in the treatment of OCD. Antidepressants that are not FDA-approved for the treatment of a given anxiety disorder, such as nefazodone and mirtazapine, still may be beneficial. Patients with panic disorder may be more sensitive to treatment with antidepressants and frequently need lower initial doses and slower titration to accomplish successful therapy.
Benzodiazepines are especially useful in the management of acute situational anxiety disorder and adjustment disorder where the duration of pharmacotherapy is anticipated to be 6 weeks or less and for the rapid control of panic attacks. If long-term use of benzodiazepines seems necessary, obtaining a confirmatory opinion from a second clinician may be helpful because chronic benzodiazepine use may be associated with tolerance, withdrawal, and treatment-emergent anxiety.
The risk of addiction potential with benzodiazepines should be carefully considered before use in the anxiety disorders. Avoid use in patients with a prior history of alcohol or other drug abuse. Closely monitor for evidence of unauthorized dose escalation or obtaining benzodiazepine prescriptions from multiple sources.
Initiation of antidepressant agents are thought to cause early worsening of anxiety, agitation, and irritability, particularly when used to treat anxiety.
Sinclair et al use the term jitteriness/anxiety syndrome to describe these effects and completed a systematic search of articles that describe these effects. No validated rating scales for jitteriness/anxiety syndrome were identified among 107 articles included in the review. No evidence indicated a difference in incidence of jitteriness/anxiety syndrome between selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), and a higher incidence was not observed in anxiety disorders. Incidence rates of jitteriness/anxiety syndrome varied widely in the published literature (4-65%). The authors concluded that jitteriness/anxiety syndrome is poorly characterized, but perception of this syndrome influences clinician prescribing. They recommend more evaluation of side effects at early points during antidepressant trials to more comprehensively describe this syndrome.5
Benzodiazepines
Several drugs in the benzodiazepine class can be used for the short-term (≤ 6 wk) control of anxiety. Drugs in this class include lorazepam, diazepam, clonazepam, and chlordiazepoxide.
Lorazepam (Ativan)
Sedative hypnotic in the benzodiazepine class that has a short onset of effect and a relatively long half-life. By increasing action of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter in the brain, may depress all levels of the CNS, including limbic and reticular formation. Available for PO, IV, or IM use.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
0.5-6 mg PO/IV/IM in divided doses
Pediatric
0.25-2 mg PO/IV/IM in divided doses
* Dosing
* Interactions
* Contraindications
* Precautions
Toxicity of benzodiazepines in CNS increases when used concurrently with alcohol, phenothiazines, barbiturates, and MAOIs
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; preexisting CNS depression, hypotension, and narrow-angle glaucoma
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Be aware of the occasional patient (frequency depends on practice setting) with benzodiazepine drug-seeking behavior, ie, malingering
In renal or hepatic impairment, myasthenia gravis, organic brain syndrome, or Parkinson disease, use shorter-acting benzodiazepines (eg, lorazepam, oxazepam) to avoid accumulation of active metabolites and drowsiness
Serotonin and norepinephrine reuptake inhibitors
Pharmacologic agents with both reuptake inhibition of serotonin and norepinephrine may be helpful in a variety of mood and anxiety disorders.
Venlafaxine (Effexor XR)
FDA-approved for generalized anxiety disorder, panic disorder and social anxiety disorder in adults. May be helpful for other anxiety disorders.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
37.5-300 mg extended-release formulation PO qd
Pediatric
Not established
* Dosing
* Interactions
* Contraindications
* Precautions
Cimetidine, MAOIs, sertraline, fluoxetine class I-C antiarrhythmics, tricyclic antidepressants, and phenothiazine may increase effects
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; patients taking MAOIs or those who have taken them within 14 days of initiating therapy
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Patients may experience hypertension; fatal reaction may occur if taken concurrently with a MAOI; exercise caution in patients with cardiovascular disorders
Duloxetine (Cymbalta)
Potent inhibitor of neuronal serotonin and norepinephrine reuptake. Indicated for generalized anxiety disorder.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
30-60 mg PO qd
Pediatric
Not established
* Dosing
* Interactions
* Contraindications
* Precautions
Metabolized by CYP1A2 and CYP2D6; coadministration with drugs that inhibit CYP1A2 (eg, fluvoxamine, cimetidine, ciprofloxacin, enoxacin) may increase duloxetine blood levels and toxicity; coadministration with drugs that inhibit CYP2D6 (eg, paroxetine, fluoxetine, quinidine) may increase duloxetine blood levels and toxicity; duloxetine moderately inhibits CYP2D6 and may decrease elimination of CYP2D6 substrates (eg, tricyclic antidepressants, phenothiazines [eg, thioridazine], type 1C antiarrhythmics [eg, propafenone, flecainide]); coadministration with MAOIs or triptans serotonin syndrome consisting of serious, sometimes fatal reactions that include hyperthermia, rigidity, myoclonus, autonomic instability, mental status changes including extreme agitation, delirium, and coma (see contraindications)
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; uncontrolled narrow-angle glaucoma; within 14 d of stopping MAOI use (do not initiate MAOIs within 5 d of stopping duloxetine)
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Observe closely for clinical worsening and suicidality when initiating treatment or following dosage change; gradually decrease dose when discontinuing, do not abruptly discontinue; caution with hepatic impairment or end-stage renal disease; recommended not to prescribe to patients with substantial alcohol use or evidence of chronic liver disease; may cause slight blood pressure increase; may activate mania or hypomania; common adverse effects include nausea, dry mouth, constipation, decreased appetite, fatigue, somnolence and increased sweating; may cause serotonin syndrome (ie, changes in mental status [agitation, hallucinations, coma], autonomic instability [tachycardia, labile blood pressure, hyperthermia], neuromuscular abnormalities [hyperreflexia, incoordination], and/or gastrointestinal tract symptoms
Antianxiety agents
Buspirone is a novel antianxiety agent with no other members in its class.
Buspirone (BuSpar)
FDA-approved for generalized anxiety disorder in adults. Does not appear to be helpful as primary treatment for panic disorder or OCD.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
15-60 mg PO qd/bid
Pediatric
Not established
* Dosing
* Interactions
* Contraindications
* Precautions
Toxicity increased with MAOIs, phenothiazines, and CNS depressants; increases toxicity of digoxin and haloperidol
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in hepatic or renal impairment
Tricyclic antidepressants
A complex group of drugs that have central and peripheral anticholinergic effects, as well as sedative effects.
Imipramine (Tofranil)
Tricyclic antidepressant that has norepinephrine and serotonin reuptake-inhibition properties. One of the oldest agents available for the treatment of depression and has established efficacy in the treatment of panic disorder. Elderly and adolescent patients may need lower dosing or slower titration.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
Initial: 50-75 mg PO qd titrated gradually to 150 mg qd according to tolerance
Dose range: 75-300 mg qd, administered either hs or divided doses
Pediatric
Not established
* Dosing
* Interactions
* Contraindications
* Precautions
Increases toxicity of sympathomimetic agents such as isoproterenol and epinephrine by potentiating effects and inhibiting antihypertensive effects of clonidine
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; narrow-angle glaucoma; acute recovery phase following myocardial infarction; history of bipolar disorders; patients taking MAOIs or fluoxetine or those who took them in the previous 2 wk
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May impair mental or physical abilities required for performance of potentially hazardous tasks; caution in cardiovascular disease, conduction disturbances, seizure disorders, urinary retention, hyperthyroidism, or those receiving thyroid replacement; an ECG may be warranted prior to initiation of therapy with imipramine, repeat after dose stabilized to monitor any potential widening of QRS
Antidepressant, Serotonin Reuptake Inhibitor
These agents specifically inhibit presynaptic reuptake or serotonin but not noradrenaline.
Paroxetine (Paxil)
FDA-approved for panic disorder, depression, social anxiety disorder, generalized anxiety disorder, posttraumatic stress disorder, and OCD.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
10-60 mg PO qd
Pediatric
Not established
* Dosing
* Interactions
* Contraindications
* Precautions
Phenobarbital and phenytoin decrease effects; alcohol, cimetidine, sertraline, phenothiazines, and warfarin increase toxicity
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; concurrent administration with MAOIs or administering within 14 days of discontinuing an MAOI
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in history of seizures, mania, renal disease, and cardiac disease
Escitalopram (Lexapro)
FDA approved for generalized anxiety disorder. SSRI and S-enantiomer of citalopram. Used for the treatment of depression. Mechanism of action is thought to be potentiation of serotonergic activity in central nervous system resulting from inhibition of CNS neuronal reuptake of serotonin. Onset of depression relief may be obtained after 1-2 wk, which is sooner than other antidepressants.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
10 mg PO qd initially; if needed, may increase to 20 mg/d after 1 wk
Pediatric
Not established
* Dosing
* Interactions
* Contraindications
* Precautions
Primarily metabolized by CYP450 3A4 and 2C19; coadministration with alcohol or other centrally acting drugs increases CNS depression; cimetidine increases AUC and maximum serum concentration; coadministration with sumatriptan and SSRIs has caused weakness and hyperreflexia
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; administration within 14 d of receiving MAOI
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution with history of seizures, mania, suicide; common adverse effects include insomnia, ejaculation disorder (primarily ejaculatory delay), nausea, sweating, fatigue, and somnolence
Sertraline (Zoloft)
FDA-approved for panic disorder, PTSD, social phobia, and OCD. May be helpful for other anxiety disorders.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
50-200 mg PO; initiate at 25 mg/d and increase as tolerated, not to exceed 200 mg/d
Pediatric
25-100 mg PO qd
* Dosing
* Interactions
* Contraindications
* Precautions
Increases toxicity of MAOIs, diazepam, tolbutamide, and warfarin
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; within 14 d of taking an MAOI
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in preexisting seizure disorders and those who have experienced a recent myocardial infarction, have unstable heart disease, and hepatic or renal impairment
Fluoxetine (Prozac)
FDA-approved for OCD and panic disorder. May be helpful for other anxiety disorders.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
10-60 mg PO qd
Pediatric
Not established
* Dosing
* Interactions
* Contraindications
* Precautions
Increases toxicity of diazepam and trazodone by decreasing clearance; increases toxicity of MAOIs and highly protein-bound drugs
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; concurrently taking MAOIs or took them in the last 2 wk
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hepatic impairment and history of seizures; MAOIs should be discontinued at least 14 d before initiating therapy
Fluvoxamine (Luvox)
FDA approved for OCD in children (8-17 y) and adults. May be helpful for other anxiety disorders.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
50-300 mg PO qd
Pediatric
25-200 mg PO qd.Follow-up
Further Inpatient Care
* Inpatient care rarely is needed for the management of anxiety disorders unless complicated by comorbid conditions such as affective or substance abuse disorders or general medical conditions.
* Inpatient care should be considered if suicide is a risk or detoxification is needed for comorbid substance dependence.
Further Outpatient Care
* Anxiety disorders often are chronic and require ongoing medical/psychiatric care, including psychosocial therapies and medication (pharmacotherapy).
* Psychosocial interventions in anxiety disorder
o Cognitive-behavioral therapy often is efficacious and is the treatment of choice for specific phobias. It often is used alone or in combination with pharmacotherapy in the treatment of OCD and panic disorder.
o Other psychotherapeutic approaches, such as interpersonal therapy or psychodynamic therapy, also may be helpful in the treatment of anxiety disorders.
o Marital therapy, family therapy, or group therapy may be helpful adjunct therapies in the long-term management of severe anxiety disorders. Educating families and friends enables them to cope with their loved one's disease.
o Leichsenring et al found that short-term psychodynamic psychotherapy is beneficial for patients with generalized anxiety disorder. In a randomized controlled trial of 57 patients who received either psychodynamic psychotherapy or cognitive-behavioral therapy for up to 30 weekly sessions, both treatment methods yielded comparable improvement in Hamilton Anxiety Rating Scale scores. However, in measures of trait anxiety, worry, and depression, cognitive-behavioral therapy was found to be superior.6
Inpatient & Outpatient Medications
See Medication for recommendations for specific anxiety disorders.
* Generalized anxiety disorder
* Panic disorder
* OCD
* Simple phobia
* Social phobia
* PTSD
* Adjustment disorder with anxious mood
Complications
* Agoraphobia
* Major depression
* Suicide
* Homicide (especially in patients with PTSD)
* Alcohol abuse and dependence
* Sedative abuse and dependence
* Social dysfunction and withdrawal
* Occupational impairment
* Marital and familiar dysfunction, divorce
Prognosis
* Anxiety disorders can range from mild and transient to severe and chronic.
* Early treatment improves prognosis and limits social and occupational impairment.
Patient Education
* Education can be obtained through books, newsletters, support groups, and the Internet. Some useful Web sites are as follows:
o National Institute of Mental Health, Anxiety Disorders
o SAMHSA's National Mental Health Information Center, Anxiety Disorders
o MentalHelp.net
o eMedicineHealth, Mental Health and Behavior Center and Anxiety Center
o eMedicineHealth, Stress, Anxiety, Panic Attacks, and Hyperventilation
* Family members should receive information about the effect of anxiety disorders on mood, behavior, and relationships. Family members can assist in care by reinforcing the need for medical treatment and supervision. Family members may also assist by providing a collaborative resource for monitoring the severity of the patient's anxiety symptoms and response to treatment interventions.
Miscellaneous
Medicolegal Pitfalls
* Failure to identify a medical or psychiatric cause for anxiety
* Unnecessary and invasive diagnostic testing for physical symptoms caused by anxiety
* Benzodiazepine prescription use in those with comorbid alcohol or drug dependence
* Failure to recognize cognitive and motor impairment related to chronic high-dose benzodiazepine use
* Failure to recognize factitious disorder with psychological symptoms or malingering to obtain benzodiazepine prescription
