Psychiatry/Behavioral · PANCE / PANRE

Generalized Anxiety Disorder (GAD)

Excessive, hard-to-control worry about multiple domains >=6 months with physical and cognitive symptoms.

Also known as: GAD, generalized anxiety, chronic anxiety

Overview

Persistent and excessive anxiety and worry about multiple events or activities, occurring more days than not for >=6 months, accompanied by physical and cognitive symptoms and causing significant distress or functional impairment.

Epidemiology

Lifetime prevalence ~5-9%; 12-month prevalence ~3%. Female-to-male ratio ~2:1. Median onset age 30, though prodromal anxiety often present from childhood. Frequently comorbid with MDD, other anxiety disorders, and substance use.

Try two board-style Generalized Anxiety Disorder questions

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Question 1PsychiatryEasy
A 35-year-old man reports 7 months of excessive, hard-to-control worry about work, health, and finances, accompanied by muscle tension, restlessness, difficulty concentrating, and poor sleep. He has no medical illness, substance use, or other psychiatric diagnosis to account for the symptoms. Which of the following is the most appropriate first-line pharmacotherapy?
  • ABuspirone
  • BClonazepam
  • CSertraline
  • DPropranolol
Reveal answer & full explanation
Correct answer: C — Sertraline
  • ABuspirone
  • BClonazepam
  • CSertraline
  • DPropranolol

Why Sertraline is correct

  • Excessive, difficult-to-control worry across multiple domains for more than 6 months with muscle tension, restlessness, concentration difficulty, and sleep disturbance meets DSM-5 criteria for generalized anxiety disorder (GAD)
  • SSRIs such as sertraline or escitalopram (or an SNRI) are first-line pharmacotherapy for GAD per current guidance, with durable benefit against the core cognitive worry
  • Combining medication with cognitive behavioral therapy (CBT) is more effective than either modality alone

Why the others are wrong

  • Buspirone — a reasonable adjunct or alternative for GAD but less effective than SSRIs and not first-line; it tempts learners who buzzword-match 'anxiolytic' to any anxiety disorder
  • Clonazepam — benzodiazepines give rapid relief but cause tolerance, dependence, and cognitive impairment and are avoided as maintenance therapy for chronic GAD (right-symptom-wrong-strategy trap)
  • Propranolol — blunts peripheral autonomic symptoms in performance or situational anxiety but does not treat the pervasive worry that defines GAD; it catches learners who confuse GAD with performance anxiety
Question 2PsychiatryMedium
A 34-year-old woman reports 8 months of excessive worry about her job, finances, and her children's health that she finds difficult to control. She also notes restlessness, poor concentration, irritability, and trouble sleeping, and recently has felt warmer than usual and lost 4 kg without dieting. On exam her heart rate is 104/min, she has a fine resting tremor, and her skin is warm and slightly moist. Her GAD-7 score is 14. Which of the following is the most appropriate next diagnostic test?
  • ASerum thyrotropin assay
  • BDexamethasone suppression
  • CFasting plasma glucose level
  • DPlasma free metanephrines
Reveal answer & full explanation
Correct answer: A — Serum thyrotropin assay
  • ASerum thyrotropin assay
  • BDexamethasone suppression
  • CFasting plasma glucose level
  • DPlasma free metanephrines

Why Serum thyrotropin assay is correct

  • Before diagnosing generalized anxiety disorder, an organic medical mimic must be excluded, and hyperthyroidism is the classic one.
  • This patient's heat intolerance, unintentional weight loss, resting tremor, tachycardia, and warm moist skin are red flags that her anxiety symptoms could be thyrotoxic in origin.
  • TSH (thyrotropin) is the most sensitive initial screen for thyroid dysfunction; a suppressed value would redirect the workup away from a primary anxiety disorder. Standard initial GAD labs are TSH, CBC, and BMP.

Why the others are wrong

  • Plasma free metanephrines — screen for pheochromocytoma, which causes paroxysmal headache, palpitations, and diaphoresis with spells of hypertension; her sustained, gradual symptoms with weight loss and heat intolerance point to thyroid disease first.
  • Fasting plasma glucose level — new-onset diabetes can produce unintentional weight loss and recurrent hypoglycemia can mimic adrenergic anxiety, but neither accounts for heat intolerance with a fine resting tremor, tachycardia, and warm moist skin, so glucose testing does not outrank thyroid screening here.
  • Dexamethasone suppression — evaluates for hypercortisolism, which typically presents with central weight gain, striae, and hypertension rather than weight loss and tremor, so it is not the appropriate first study.
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Risk factors

  • Female sex, family history of anxiety or mood disorders
  • Behavioral inhibition in childhood
  • Adverse childhood experiences
  • Chronic medical illness, chronic pain
  • Caffeine, stimulants, withdrawal states

Pathophysiology

Hyperactivity of amygdala-driven fear circuits with reduced prefrontal cortical regulation. Imbalance among GABAergic inhibition and glutamatergic, serotonergic, and noradrenergic transmission. Heritability ~30%.

Clinical presentation

Symptoms

  • Excessive worry across multiple domains (work, finances, family, health) most days for >=6 months
  • Difficulty controlling the worry
  • >=3 of: restlessness, easy fatigability, difficulty concentrating, irritability, muscle tension, sleep disturbance (only 1 needed in children)
  • Somatic complaints: headache, GI upset, palpitations, dyspnea, dizziness

Signs / physical exam

  • Tense posture, restlessness, fidgeting
  • Mild tremor, diaphoresis, tachycardia possible
  • Normal thyroid, cardiac, and neurologic exam

Classic findings

GAD-7 >=10 supports moderate-or-greater severity; >=15 severe.

Differential diagnosis

  • Panic disorder — Discrete, abrupt panic attacks peaking within minutes; persistent worry about future attacks
  • Social anxiety disorder — Anxiety circumscribed to social/performance situations and fear of negative evaluation
  • OCD — Intrusive ego-dystonic obsessions and ritualized compulsions
  • PTSD — Trauma exposure plus intrusion, avoidance, negative cognition, hyperarousal symptoms
  • Hyperthyroidism — Tremor, tachycardia, heat intolerance, weight loss; suppressed TSH
  • Pheochromocytoma — Episodic headache, palpitations, diaphoresis with paroxysmal hypertension
  • Caffeine/stimulant use or substance withdrawal — Temporal relationship; resolves with abstinence
  • Adjustment disorder with anxiety — Identifiable stressor; subthreshold duration/severity

Diagnostic workup

Diagnostic criteria

DSM-5-TR: Excessive anxiety and worry occurring more days than not for >=6 months about multiple events/activities; difficulty controlling worry; >=3 of 6 associated symptoms (restlessness, fatigue, poor concentration, irritability, muscle tension, sleep disturbance); causes significant distress/impairment; not attributable to substance or medical condition; not better explained by another mental disorder. GAD-7 screening: 5 mild, 10 moderate, 15 severe.

Labs

  • TSH, CBC, BMP
  • Consider urine drug screen, urine metanephrines if paroxysmal symptoms

Imaging

  • Not routinely indicated

Diagnostic algorithm

GAD-7 scoreSeveritySuggested action
0-4MinimalEducation, reassessment
5-9MildWatchful waiting, lifestyle, CBT
10-14ModerateCBT and/or SSRI/SNRI
15-21SevereCBT + medication; consider specialty referral
GAD-7 severity bands and treatment intensity.

Treatment

First-line

  • Cognitive behavioral therapy (CBT) — first-line; comparable to medication and durable benefits
  • SSRI — sertraline, escitalopram, paroxetine (titrate gradually to avoid initial anxiogenic effect)
  • SNRI — venlafaxine XR, duloxetine
  • Combination of CBT + medication for moderate-to-severe symptoms
  • Sleep, exercise, caffeine reduction, mindfulness practices

Second-line / adjunct

  • Buspirone — non-sedating 5-HT1A partial agonist; takes 2-4 weeks for effect; avoid combining with MAOIs
  • Hydroxyzine — sedating antihistamine; useful PRN, no dependence
  • Pregabalin or gabapentin — particularly with comorbid pain
  • Benzodiazepines (lorazepam, clonazepam, diazepam) — short-term bridge only due to dependence, falls in elderly, and cognitive effects; avoid as monotherapy and in patients with SUD

Complications

  • Comorbid depression, panic disorder, substance use disorders
  • Functional and occupational impairment
  • Increased medical utilization and somatic preoccupation
  • Cardiovascular morbidity through chronic sympathetic activation

PANCE pearls

  • Start SSRIs at low dose (e.g., sertraline 25 mg) — anxious patients are sensitive to initial activation and may stop prematurely.
  • Benzodiazepine prescribing for chronic anxiety has fallen out of favor — use only as a short bridge while SSRI takes effect, and avoid in older adults and patients with SUD.
  • Always check TSH and consider caffeine intake before initiating chronic anxiolytics.
  • USPSTF (2023) recommends screening adults <65 for anxiety; insufficient evidence for >=65 screening.

References

  • USPSTF 2023 — Screening for Anxiety Disorders in Adults: USPSTF Recommendation Statement. JAMA 2023
  • APA / NICE — NICE Clinical Guideline 113: Generalised anxiety disorder and panic disorder in adults
  • DSM-5-TR — American Psychiatric Association. DSM-5-TR (2022)
  • GAD-7 — Spitzer RL et al. A brief measure for assessing generalized anxiety disorder. Arch Intern Med 2006

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