Anxiety

Description of Medical Condition

A common acute or chronic fearful emotion with associated physical symptoms. DSM-IV-R recognizes the following sub types:

Acute situational anxiety:

Response to recent stressful event, usually transient symptoms

Adjustment disorder with anxious mood:

Persistent, maladaptive reaction following psychosocial stress and lasting up to six months

Generalized anxiety disorder:

Persistent underlying anxiety or adjustment disorder with anxious mood and significant symptoms of motor tension, autonomic hyperactivity and hypervigilance, lasting more than six months

Panic disorder:

Recurrent unexpected attacks with at least one attack (or more) associated with persistent concern about additional attacks, worries about implications of the attack (losing control, having a heart attack) or a significant change in behavior related to the attack; often leads to agoraphobia

Post-traumatic stress disorder:

Recurrent flashbacks or nightmares of catastrophic event by survivors, often associated with panic attacks and major depression

Specific phobias:

Intense recurrent fear of, and avoidance of, an object or situation

Social phobia:

Marked and persistent fear and avoidance of performance or social situations in which the person is exposed to unfamiliar people or scrutiny

Obsessive-compulsive disorder:

Persistent unwanted and disturbing thoughts and recurrent behavioral patterns (i.e., hand washing) which interfere with daily life

System(s) affected: Nervous

Genetics: Panic disorder — increased concordance in monozygotic versus dizygotic twins

Incidence/Prevalence in USA: 40 million (the most common psychiatric disorder in US)

• 12 month prevalence rate

– Panic disorder — female 3.2%, male 1.3%

– Obsessive compulsive disorder — female 2.6-3.1%, male 1.1-2.6%

– Agoraphobia — female 3.8%, male 1.7%

– Generalized anxiety disorder — female 4.3%, male 2.0%

– Social phobia — female 5.2%, male 3.8%

• Lifetime prevalence PTSD — female 10.4%, male 5.0%

Predominant age: Mainly adults, highest prevalence in 20 to 45 year age group

Predominant sex: Female > Male (social phobia female 5.27:male 3.87)

Medical Symptoms and Signs of Disease

Patterns vary with subtype of anxiety; not all present in each case

• Unrealistic or excessive anxiety or worry
• Sense of impending doom
• Nervousness
• Instability
• Tachycardia; palpitations
• Systolic click murmur
• Hyperventilation, choking sensation
• Labile hypertension
• Sighing respiration
• Nausea or abdominal distress
• Paresthesias
• Diaphoresis
• Dizziness or syncope
• Flushing
• Muscle tension
• Tremulousness
• Restlessness
• Chest tightness, pressure (pseudoangina)
• Headache, backaches, muscle spasm

What Causes Disease?

• Panic disorder, social phobia and obsessive compulsive disorder are associated with genetic factors
• Psychosocial stressors commonly trigger anxiety disorders and may provoke a genetic diathesis
• Trauma such as physical assault, rape, conflict experience provoke PTSD symptoms
• Mediated by abnormalities of neurotransmitter systems (serotonin, norepinephrine and gamma-aminobutyric acid [GABA])

Risk Factors

• Social and financial problems
• Medical illness
• Family history
• Lack of social support

Diagnosis of Disease

Differential Diagnosis

• Cardiovascular:

– Ischemic heart disease

– Valvular heart disease

– Cardiomyopathies

– Myocarditis

– Arrhythmias

– Mitral valve prolapse (most symptomatic cases are associated with panic disorder)

• Respiratory:

– Asthma

– Emphysema

– Pulmonary embolism

– Hamman-Rich syndrome

– Scleroderma

• CNS:

– Transient cerebral insufficiency

– Psychomotor epilepsy

– Essential tremor

• Metabolic and Hormonal

– Hyperthyroidism

– Pheochromocytoma

– Adrenal insufficiency

– Cushing syndrome

– Hypokalemia, hypoglycemia

– Hyperparathyroidism

– Myasthenia gravis

• Nutritional:

– Thiamine, pyridoxine, orfolate deficiency

– Iron deficiency anemia

• Intoxication:

– Caffeine

– Alcohol

– Cocaine

– Sympathomimetics

– Amphetamines

• Withdrawal

– Alcohol

– Sedative-hypnotics

• Other:

– Depression

– Panic disorder is associated with several physical disorders including:

– Mitral valve prolapse (systolic click-murmur)

– Labile hypertension

– Migraine headaches

– Irritable bowel syndrome

– Asthma (COPD)

– Interstitial cystitis

Laboratory

• Selective use of laboratory tests, (with minimal to more extensive workup depending on clinical picture). Laboratory tests often normal in anxiety disorders.
• CBC and urinalysis
• Sequential serial multiple analysis (SMA-12 panel)
• Thyroid function studies

Drugs that may alter lab results: SSRIs may raise serum levels of other medications such as warfarin (Coumadin) and tricyclic antidepressants

Disorders that may alter lab results: N/A

Pathological Findings

N/A

Special Tests

EEG, ECG, etc

Imaging

Usually none; chest x-ray possibly

Diagnostic Procedures

• Psychologic testing (e.g., Spitzer’s Patient Health Questionnaire, Hamilton’s anxiety scale)
• DSM-IV based interview

Treatment (Medical Therapy)

Appropriate Health Care

Outpatient

General Measures

• Should be based on careful workup and identification of etiology and subtype of anxiety disorders
• Adequate workup
• Identify co-existent substance abuse
• Counseling or psychotherapy along with medications
• Regular exercise program
• Biofeedback in selected cases
• Serial office visits
• Judicious reassurance after other medical disorders ruled out

Activity

Fully active

Diet

No special diet

Medications (Drugs, Medicines)

Drug(s) of Choice

• Conditions

– Acute situational anxiety:

• Short-term (up to 1 month) treatment with benzodi-azepines

– Adjustment disorder with anxiety mood:

– Benzodiazepines

– Generalized anxiety disorder:

• Azapirones-e.g., buspirone
• SSRIs

– Venlafaxine (Effexor)

– Panic disorder and social phobia:

• SSRIs

– TCAs-e.g., imipramine

– Obsessive-compulsive disorder:

– TCAs-e.g., clomipramine

– SSRIs also effective

• Drug doses

– SSRIs:

– Citalopram (Celexa) 10 mg q/day; increase by 10 mg q 7 days to maximum of 20-40 mg q/day

– Fluoxetine (Prozac) 10 mg; increase by 10 mg q 7 days to maximum daily dosage of 20-40 mg

– Paroxetine (Paxil) 10 mg; increase by 10 mg q 5 days

– Sertraline (Zoloft) 25 mg; increase by 25 mg q 5 days

– Venlafaxine (Effexor) SR 37.5 mg; increase by 37.5 mg q 5-7 days

– Benzodiazepines

– Alprazolam (Xanax) 0.25 mg bid-tid; increase by 0.25 mg if needed

– Clonazepam (Klonopin) 0.5 mg po tid, to maximum of 1.5-4.5 mg/day

– Diazepam (Valium) 2-5 mg bid; increase by 2 mg if needed

– Lorazepam (Ativan) 0.5 mg bid-tid; increase by 0.5 mg if needed (response, if any is slow, often 4-6 weeks)

– Azapirones

– Buspirone (BuSpar) 5 mg bid-tid; increase 5 mg q 2-3 days to maximum of 60 mg/day in divided doses

– Tricyclics

– Clomipramine (Anafranil) 25 mg bid; increase gradually to maximum of 250 mg/day

– Imipramine (Tofranil) 10-25 mg qhs; increase by 10-25

Contraindications:

• Benzodiazepines — 1st-trimester pregnancy, acute alcohol intoxication with depressed vital signs, acute angle-closure glaucoma, sleep apnea, history of personality disorder or substance abuse. Avoid long-term/prn use.
• Buspirone — concurrent MAO inhibitor use
• TCAs — acute myocardial infarction, bundle branch block

Precautions:

• Benzodiazepines — advanced age, renal insufficiency, suicidal tendency, open-angle glaucoma. Sudden discontinuation increases risk of seizures, especially with alprazolam
• Benzodiazepines with short half-lives (e.g., alprazolam) increase potential for dependency and protracted withdrawal symptoms; extreme caution with severe panic disorder who are taking other CNS sedatives or who have a history of substance abuse/dependence
• Buspirone — hepatic and/or renal dysfunction. Buspirone will not protect against benzodiazepine withdrawal seizures; taper benzodiazepines.
• TCAs — advanced age, glaucoma, benign prostate hypertrophy, hyperthyroidism, cardiovascular disease, liver disease, urinary retention, MAO inhibitor treatment

Significant possible interactions:

• Benzodiazepines — dmetidine, ethanol, oral contraceptives, disulfiram, levodopa, rifampin
• Buspirone — MAO inhibitors
• TCAs — amphetamines, barbiturates, guanethidine, clonidine, epinephrine, ethanol, norepinephrine, MAO inhibitors, propoxyphene
• SSRIs — MAO inhibitors (may cause fatal serotonin syndrome [confusion, hyperthermia, etc.]), may raise serum levels of other medications

Alternative Drugs

• Generalized anxiety disorder: Short-term use of benzodiazepine or TCAs
• Panic disorder: Although TCAs or SSRIs are the drugs of choice for panic disorder, they are slow in onset of action (2-3 weeks). Benzodiazepines may be helpful for initial control of symptoms until the SSRIs or TCAs are effective. Also, 10-20% of patients with panic do not tolerate side effects of SSRIs or TCAs. High potency benzodiazepines (alprazolam, clonazepam, lorazepam) or MAO inhibitors are effective alternatives.
• Social phobia: phenelzine — initial dose 15 mg bid. increase by 15 mg every week to a total dose of 45-90 mg. Need to be on MAOI diet and avoid stimulant medications (pseudoephedrine, SSRIs). Benzodiazepines: clonazepam.

Patient Monitoring

• Follow-up by regular office visits
• Watch for and treat associated depression
• Monitor mental status on benzodiazepines and avoid drug dependence
• Monitor blood pressure, heart rate, anticholinergic side effects on TCAs
• Periodic serum levels, if indicated, for TCAs

Prevention / Avoidance

Management of stress, to extent possible, relaxation techniques, meditation

Possible Complications

• Impaired social/occupational functioning
• Drug dependence (benzodiazepines)
• Cardiac arrhythmias (TCAs)
• Alcohol dependence

Expected Course / Prognosis

With active treatment, excellent results can often be obtained, especially with short-term anxiety disorders, including panic disorder

Obsessive-compulsive disorder, and post-traumatic stress disorder are more difficult to treat, often requiring long-term psychotherapy and medication (combination treatment)

Miscellaneous

Associated Conditions

• Depression (commonly)
• Agoraphobia
• Alcohol or substance abuse
• Somatoform disorders

Age-Related Factors

Pediatric:

Reduced dosage of medications in adolescent

Geriatric:

Reduced dosage of medications

Pregnancy

Benzodiazepines — contraindicated in first-trimester of pregnancy, and with caution later in pregnancy and during lactation. May cause lethargy and weight loss in nursing infants; avoid breastfeeding if mother taking benzodiazepines chronically or in high doses.

TCAs — some evidence of fetal risk, especially in first trimester

SSRIs — taper and discontinue, if possible, in first trimester; may be used later in pregnancy

Synonyms

Hyperventilation syndrome

Panic disorder

International Classification of Diseases

300.00 Anxiety state, unspecified

See Also

Abbreviations

DSM-IV-R = Diagnostic and Statistical Manual of Mental Disorders, 4th edition

TCA = tricyclic antidepressant

SSRI = selective serotonin reuptake inhibitor