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.
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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
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 score
Severity
Suggested action
0-4
Minimal
Education, reassessment
5-9
Mild
Watchful waiting, lifestyle, CBT
10-14
Moderate
CBT and/or SSRI/SNRI
15-21
Severe
CBT + 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
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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