Key Facts

GAD is one of the most common anxiety disorders, characterised by persistent, excessive, and difficult-to-control worry about everyday events. It causes significant psychological distress and physical symptoms.

Epidemiology

Lifetime prevalence of GAD is 5-6%; 12-month prevalence 2-3%. Women are approximately twice as commonly affected as men. GAD often has a chronic course and is the most common anxiety disorder in older adults. It is frequently comorbid with depression (60%), other anxiety disorders, and substance misuse.

Aetiology

• Genetic: Heritability ~30%; shared genetic susceptibility with depression
• Neurobiological: Amygdala hyperactivation, prefrontal cortex hypofunction, altered GABA/serotonin/noradrenaline signalling
• Psychological: Intolerance of uncertainty model (Dugas); metacognitive model (Wells) — "worry about worry"
• Environmental: Adverse childhood experiences, insecure attachment, chronic stress

Pathophysiology

• Amygdala hyperactivity: Exaggerated threat detection and fear response
• Prefrontal cortex dysfunction: Impaired top-down emotional regulation
• HPA axis: Chronic stress response with elevated cortisol
• GABA deficiency: Reduced GABAergic inhibition — target of benzodiazepines and pregabalin
• Autonomic nervous system dysregulation: Reduced heart rate variability, chronic sympathetic activation

Core Features (≥6 months)

• Excessive worry about multiple everyday events (work, health, finances, family)
• Difficulty controlling the worry
• Physical symptoms: Muscle tension, restlessness, fatigue, difficulty concentrating, irritability, sleep disturbance

Associated Features

• Autonomic hyperarousal: Palpitations, sweating, dry mouth, dizziness, GI symptoms
• Hypervigilance and exaggerated startle response
• Avoidance behaviours
• Functional impairment in work and relationships

Red Flags

• Coexisting severe depression — assess suicide risk
• Substance misuse (self-medication with alcohol/benzodiazepines)
• Panic attacks — may indicate comorbid panic disorder
• Physical symptoms mimicking medical conditions — exclude organic cause

Bedside

• GAD-7: 7-item screening questionnaire (0-4 minimal, 5-9 mild, 10-14 moderate, 15-21 severe)
• PHQ-9: Screen for comorbid depression
• Functional assessment: Impact on daily life, work, relationships

Bloods

• TFTs: Exclude hyperthyroidism
• FBC: Anaemia can cause anxiety-like symptoms
• HbA1c, fasting glucose: Hypoglycaemia can mimic anxiety
• U&Es: Baseline if starting medication

Special Tests

• ECG: If palpitations prominent — exclude arrhythmia; baseline for SSRIs (QTc)
• 24h urine catecholamines/metanephrines: If phaeochromocytoma suspected

Non-pharmacological

• Step 1: Education about GAD, active monitoring
• Step 2: Guided self-help (based on CBT principles), psychoeducation groups
• Step 3: CBT (12-15 sessions) — most effective psychological therapy for GAD; applied relaxation
• All steps: Exercise, sleep hygiene, caffeine/alcohol reduction, mindfulness

Pharmacological (NICE CG113)

• First-line: Sertraline 50mg OD (titrate to 200mg); alternatives: escitalopram 10-20mg, paroxetine 20-50mg
• SNRI: Venlafaxine 75-225mg or duloxetine 60-120mg if SSRI ineffective
• Second-line: Pregabalin 150mg daily in divided doses, titrate to max 600mg/day
• Short-term crisis: Benzodiazepines (diazepam 2-5mg TDS) for maximum 2-4 weeks
• Buspirone: 5-15mg BD — alternative if others not tolerated (slow onset, 2-4 weeks)
• Beta-blockers: Propranolol 10-40mg TDS for physical symptoms (tremor, palpitations) — does not treat psychological symptoms

Referral Criteria

• Step 3 treatment failure — specialist anxiety disorder service
• Significant comorbidity (severe depression, substance misuse, personality disorder)
• Risk of suicide or self-harm
• Complex presentation or diagnostic uncertainty

• Chronic course: GAD is often persistent; ~50% have symptoms >5 years
• Remission: ~38% remit within 2 years with treatment; higher with combined CBT + pharmacotherapy
• Comorbidity: ~60% with comorbid depression; ~50% with other anxiety disorders
• Functional impact: Significant reduction in quality of life, work productivity, and social functioning
• CBT: ~50-60% response rate; benefits maintained at follow-up
• SSRIs: ~50-60% response rate; relapse common on discontinuation (continue for ≥12 months after remission)

GAD-7 Scoring

Stepped Care Model (NICE CG113)