Incidence/prevalence

  • Prevalence in community-dwelling adults is 1.5%-3% at any time and 4%-7% lifetime.
  • 15% prevalence in urban primary-care practice serving low-income population

ICD-9 codes

  • 300.02 generalized anxiety disorder (GAD)

Risk factors

  • Genetic predisposition
  • Adverse life events
  • Current or prior psychiatric disorder, e.g., major depression
  • Lack of physical activity
  • Substance abuse (cigarettes, cannabis) in adolescence and early adulthood
  • Left-handedness

History

  • Patients may state that they feel nervous, “hyper” or “wired.”
  • Functional problems, such as:
    • Insomnia
    • Inability to relax
    • Difficulty concentrating
  • Motor tension may result in:
    • Trembling, twitching, shaking, tremor
    • Muscle tension, aches, soreness
    • Restlessness
    • Fatigue
  • Autonomic hyperactivity may result in:
    • Dyspnea, smothering sensations
    • Palpitations, tachycardia
    • Sweating, cold clammy hands
    • Dry mouth
    • Dizziness, light-headedness
    • Abdominal distress, nausea, diarrhea
    • Flushes, chills
    • Frequent urination
    • Dysphagia, “lump in throat”
  • Patients may “normalize” symptoms (e.g., attribute symptoms to overexertion), and this may contribute to underdiagnosis.
  • Physical exam: Usually normal
  • Observations that may support suspicion of GAD:
    • Tremor
    • Sighing
    • Exaggerated startle response
    • Difficulty concentrating
    • Repetitive trivial motion
    • Bitten nails
    • Clammy hands
    • Irritability

Making the diagnosis

  • Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria include:
  • Excessive anxiety and worry about a number of events or activities, on more days than not, for at least six months
  • Patient finds it difficult to control worry.
  • At least three of six symptoms:
    1. Feeling restless, fidgety, jittery, keyed up, on edge, or experiencing difficulty sitting still
    2. Being easily fatigued
    3. Difficulty concentrating or “mind going blank”
    4. Irritability
    5. Muscle tension, aches, muscle soreness
    6. Trouble falling or staying asleep, or restless unsatisfying sleep
  • Focus of anxiety and worry spilling over from another disorder. (See “Rule out” section.)
  • Distress or impaired functioning

Rule out

  • Other anxiety disorder: panic disorder, social phobia (social anxiety disorder), specific phobia, agoraphobia, separation anxiety disorder, obsessive-compulsive disorder, post-traumatic stress disorder, acute stress disorder (for symptoms less than four weeks)
  • Other psychiatric disorder: depression or other mood disorder, adjustment disorder, psychotic disorder, pervasive developmental disorder
  • Any medical disorder that may cause anxiety, including:
    • Angina or MI
    • Hypoglycemia, hyperthyroidism, carcinoid syndrome, or other endocrine disease
    • Neurologic disease
    • Hypoxia due to cardiovascular disease, pulmonary insufficiency, or pulmonary embolism 
    • Febrile illnesses
    • Uremia
    • Vitamin B12 (cobalamin) deficiency
    • Vitamin B3 (niacin) deficiency (pellagra)
  • Drugs and toxins may cause or exacerbate anxiety:
    • Drug classes include amphetaminelike agents, ACE inhibitors, beta blockers, dopamine receptor agonists, statins, nonsteroidal anti-inflammatory drugs, sympathomimetic drugs, vasopressors and narcotics (opioids).
    • Other agents include acyclovir (Zovirax), baclofen (Lioresal), bupropion (Wellbutrin, Zyban), cycloserine (Seromycin), dronabinol (Marinol), efavirenz (Sustiva), levodopa (Sinemet), lidocaine (Xylocaine), mefloquine (Lariam), methylphenidate (Ritalin), metoclopramide (Reglan), theophylline, vinblastine (Velban), and
    • zaleplon (Sonata).

    • Amphetamines, anabolic steroids, ephedra, caffeine and cannabis
    • Toxins include arsenic, benzene, carbon disulfide, mercury, organophosphates and phosphorus.
    • Withdrawal states, e.g. of alcohol, caffeine and opiates, may include anxiety.

Symptom monitoring — Hamilton Anxiety Scale

  • 14 features scored as absent (0 points) to disabling (4 points).
    • Anxious mood
    • Tension (emotional)
    • Fears
    • Insomnia
    • Intellectual impairment (difficulty concentrating, poor memory)
    • Depressed mood
    • Muscular complaints (aches, pains, bruxism)
    • Sensory complaints (tinnitus, blurred vision)
    • Cardiovascular symptoms (tachycardia, palpitations, chest pain, feeling faint)
    • Respiratory symptoms (chest pressure, choking sensation, dyspnea)
    • GI symptoms
    • Genitourinary symptoms (urinary frequency or urgency, dysmenorrhea, impotence)
    • Autonomic symptoms (dry mouth, flushing, pallor, sweating)
    • Behavior at interview (fidgeting, tremor, pacing)
  • Interpretation
    • 18 points = mild anxiety
    • 25 points = moderate anxiety
    • 30 points = severe anxiety

Prognosis

  • Difficult to treat; chronic course
  • Symptoms may increase or decrease with age.
  • Remission rate only 38% at five years in series of 167 patients with GAD
  • Risk factors reducing likelihood of remission:
    • Comorbid depression
    • Personality disorder
    • Low overall life satisfaction
    • Poor spousal or family relationships
    • Low global assessment score

Treatment

  • Exercise may be therapeutic, based on expert opinion and extrapolation from association of regular physical activity with reduced prevalence of major depression and anxiety disorders.
  • Cognitive behavioral therapy effective, based on two systematic reviews of randomized trials
  • Antidepressants:
    • Anxiety sometimes follows major depression or depression mimics anxiety, so many clinicians suggest trying antidepressants first to rule out depression before using addicting agents.
    • One patient with GAD will improve for every 5.15 patients treated with antidepressants instead of placebo.
    • Specific antidepressants have been effective in randomized trials in patients with GAD and without comorbid depression:
    • Escitalopram (Lexapro) 10 mg once daily, may be increased to 20 mg daily.
    • Imipramine (generic, Tofranil, Tofranil PM): initial dose 50-75 mg once daily; average effective dose 150 mg/day, maximum 200 mg/day
    • Paroxetine (Paxil) 20-50 mg once daily
    • Sertraline (Zoloft) 50-150 mg once daily
    • Trazodone (generic, Desyrel): initial dose 150 mg/day, average effective dose 300 mg/day, maximum 400 mg/day; give in divided doses
    • Venlafaxine extended-release (Effexor XR) 75 mg or 150 mg once daily
    • Fluvoxamine (generic) and fluoxetine (generic, Prozac) have efficacy data in children
  • All antidepressants may have an increased risk for suicide, though the overall risk is very low.
  • Benzodiazepines:
    • Effective and rapid treatment, based on two systematic reviews of randomized trials
    • Increased risk of dependence, sedation, industrial accidents, and traffic accidents
    • No good evidence that short-term benefit of benzodiazepines is sustained with long-term treatment.
  • Hydroxyzine 50 mg/day
    • Reduced anxiety in randomized placebo-controlled trials
    • 12.5 mg in morning and midday, then 25 mg in evening
  • Buspirone (generic, BuSpar) 10 mg three times daily increases physician-rated improvement, based on non-
  • systematic meta-analysis of eight randomized trials.

  • Kava effective but may be unsafe due to hepatotoxicity.

Dr. Alper is research assistant professor of family and community medicine at University of Missouri-Columbia and Dr. Raglow is clinical associate professor of family and community medicine at University of Arizona in Tucson, and the medical director of Banner Good Samaritan Family Practice Center in Phoenix.

See www.dynamicmedical.com for references.