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.
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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 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 |
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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