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Anxiety (Generalized Anxiety Disorder)

Basics

  • Persistent, excessive, difficult-to-control worry.
  • Associated symptoms: motor tension, autonomic hyperactivity, sleep/concentration disturbances.
  • Systems affected: nervous (sympathetic overactivity), cardiac (tachycardia), pulmonary (dyspnea), GI (nausea, irregular bowels).

Epidemiology

  • Lifetime prevalence in US: 5.1–11.9%.
  • Onset typically in adulthood; median age 31 years.
  • Female:male ratio 2:1.

Etiology & Pathophysiology

  • Neurotransmitter abnormalities: serotonin, norepinephrine, GABA.
  • Altered brain function: increased amygdala and prefrontal cortex activity.
  • Genetics: serotonin transporter gene (5HT1A) involvement.

Risk Factors

  • Adverse life events (illness, poverty).
  • Family history.
  • Comorbid psychiatric disorders.

General Prevention

  • Physical activity and cardiorespiratory fitness reduce risk.
  • CBT and parental interventions in childhood may prevent onset.

Commonly Associated Conditions

  • Major depressive disorder (>60%)
  • Bipolar disorder, schizophrenia
  • Substance abuse, smoking
  • Panic disorder, agoraphobia, phobia, social anxiety, PTSD, ADHD
  • Somatoform and pain disorders

Diagnosis

History

  • DSM-5 criteria: excessive anxiety and worry >6 months, difficult to control.
  • At least 3 additional symptoms in adults (1 in children):
  • Restlessness or feeling keyed up
  • Fatigue
  • Difficulty concentrating/mind going blank
  • Irritability
  • Muscle tension
  • Sleep disturbance
  • Causes significant distress or functional impairment.
  • Not explained by other psychiatric disorders, substances, or medical conditions.

Physical Exam

  • Usually no specific findings.
  • Possible irritability, nail biting, tremor, clammy hands.

Differential Diagnosis

  • Cardiovascular: ischemic heart disease, mitral valve prolapse, arrhythmias.
  • Respiratory: asthma, COPD, pulmonary embolism.
  • CNS: stroke, seizures, dementia, migraine.
  • Metabolic/hormonal: thyroid disorders, pheochromocytoma, adrenal insufficiency, Cushing’s.
  • Drug-induced and withdrawal states.
  • Other psychiatric disorders: panic disorder, OCD, PTSD, somatization.

Diagnostic Tests & Interpretation

  • Labs generally normal.
  • Consider TSH, CBC, BMP, urine drug screen, ECG.
  • Screening tools:
  • GAD-2 (brief)
  • PHQ-4 (anxiety and depression)
  • GAD-7 (detailed assessment)
  • HAM-A, ADIS-IV, MASC, SCARED (especially in children)

Treatment

General Measures

  • Assess suicidality and comorbid substance abuse.
  • Early treatment leads to better outcomes.
  • Treatment duration ≥12 months; remission may take 4–6 months.
  • Psychological treatments effective; CBT is treatment of choice.

Medications

First Line

  • SSRIs and SNRIs: start low dose, titrate every 2–4 weeks, continue for 4–6 weeks before assessing efficacy.
  • Common SSRIs: escitalopram (start 10 mg, max 20 mg).
  • Common SNRIs: duloxetine (start 30 mg, max 120 mg), venlafaxine XR.
  • Pregabalin (off-label): 75–300 mg BID, less sexual dysfunction.

Second Line

  • Sertraline, buspirone, fluoxetine, mirtazapine, paroxetine, quetiapine.
  • Benzodiazepines: short-term use only due to dependence risk.
  • Hydroxyzine: less dependence risk; caution in elderly.

Special Populations

  • Geriatrics: avoid TCAs, long-acting benzos.
  • Pediatrics: CBT first-line; SSRI if severe.
  • Pregnancy: avoid benzodiazepines; SSRIs with caution (paroxetine category D).

Alerts

  • Benzodiazepines: caution in elderly, respiratory disease; withdrawal risk of seizures.
  • SSRIs: monitor bipolar disorder and serotonin syndrome risk.

Complementary & Alternative Medicine

  • Physical activity (strong evidence).
  • Mindfulness-based stress reduction.
  • Some evidence for acupuncture, yoga, massage, tai chi, aromatherapy.
  • Kava: potential benefit but hepatotoxicity risk.
  • Emerging: transcranial magnetic stimulation, cannabidiol, psilocybin with behavioral therapy.

Ongoing Care & Follow-Up

  • Follow-up 2–4 weeks after starting medication.
  • Continue treatment for at least 12 months.
  • Monitor mental status, suicidality, and benzodiazepine use.
  • Clinical follow-up every 6 months recommended.

Diet & Lifestyle

  • Limit caffeine, avoid alcohol and nicotine.
  • Psychoeducation on anxiety physiology helpful.
  • Encourage regular exercise.

Prognosis

  • Recovery probability 40–60%.
  • Comorbid psychiatric disorders and poor social support increase relapse risk.

Clinical Pearls

  • High comorbidity with depression; increased suicidality risk.
  • CBT and SSRIs/SNRIs are first-line therapies.
  • Start medication at low doses with gradual titration.
  • Benzodiazepines useful short term; taper and discontinue when possible.