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
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