Anxiety

Table of Contents

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

Abbreviations

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

TCA = tricyclic antidepressant

SSRI = selective serotonin reuptake inhibitor