Generalized anxiety disorder
Exam Tips
- In OSCEs, diagnose GAD by pattern: excessive uncontrollable multi-domain worry + at least 3 core symptoms + duration at least 6 months + functional impairment.
- Patients may present with physical complaints only (insomnia, headaches, GI symptoms); ask directly about pervasive worry and control of worry.
- Use and quote GAD-7 thresholds correctly: 5 mild, 10 moderate, 15 severe; use serial scores to monitor treatment response.
- Always assess suicide risk and depressive symptoms; comorbid depression materially worsens prognosis and risk.
- State key prescribing safety points: early SSRI activation, suicidality monitoring in younger adults, serotonin syndrome risk with interacting drugs, hyponatraemia/bleeding risk, and discontinuation symptoms if abruptly stopped.
- Mention contraindications/cautions: avoid abrupt benzodiazepine use long term; pregabalin requires renal dose adjustment and caution in misuse history; consider pregnancy and breastfeeding safety before starting psychotropics.
Definition
Generalized anxiety disorder (GAD) is a chronic anxiety disorder marked by persistent, excessive, and difficult-to-control worry about multiple everyday domains (for example health, family, work, or finances), rather than fear linked to one specific trigger. For diagnosis, symptoms are present on most days for at least 6 months, are accompanied by somatic and cognitive hyperarousal features, and cause clinically significant distress or functional impairment.
Pathophysiology
GAD is best understood through a biopsychosocial model. Neurobiologically, there is dysregulation of fear and salience circuits (amygdala, insula, anterior cingulate) with reduced top-down regulation from prefrontal cortex, alongside altered monoaminergic and GABAergic signalling (serotonin, noradrenaline, GABA), which contributes to hypervigilance and poor threat discrimination. HPA-axis overactivation and autonomic arousal reinforce physical symptoms (palpitations, tremor, GI upset), while cognitive mechanisms (intolerance of uncertainty, worry as negative reinforcement, attentional bias to threat) perpetuate symptoms. Genetic vulnerability interacts with childhood adversity, trauma, chronic stress, and comorbid physical disease, producing a relapsing course in many patients.
Risk Factors
- Female sex (around two-fold higher risk)
- Family history of anxiety, depression, or other psychiatric illness
- Childhood adversity (abuse, neglect, parental mental illness, family disruption, bullying)
- Past trauma (physical/sexual assault, serious accidents, sudden bereavement)
- Comorbid anxiety disorders (for example panic disorder, social anxiety)
- Chronic physical illness (for example cardiovascular disease, diabetes, respiratory disease, arthritis, cancer)
- Substance dependence/misuse (including alcohol and sedative-hypnotics)
- Socioeconomic stressors (unemployment, low socioeconomic status, low educational attainment, divorce/widowhood/separation)
Clinical Features
Symptoms
- Excessive worry across multiple life areas, present most days for at least 6 months
- Difficulty controlling worry
- Restlessness or feeling keyed up/on edge
- Easy fatigability
- Poor concentration or mind going blank
- Irritability
- Muscle tension (often neck/shoulder tension, headaches, back pain)
- Sleep disturbance (difficulty initiating/maintaining sleep, unrefreshing sleep)
- Somatic anxiety symptoms (palpitations, sweating, tremor, dry mouth, gastrointestinal discomfort)
Signs
- Often normal physical examination between episodes
- Autonomic arousal: tachycardia, sweating, fine tremor
- Observable motor tension or fidgeting/restlessness
- Muscle tenderness/tension on examination
- No focal neurological deficit (if present, consider alternative diagnosis)
Investigations
Management
Lifestyle Modifications
- Psychoeducation: explain chronic but treatable nature of GAD and the anxiety-avoidance cycle
- Low-intensity psychological interventions for milder presentations (guided self-help, psychoeducational groups, digital CBT-based resources)
- High-intensity CBT (individual) for persistent or functionally impairing GAD
- Sleep hygiene, regular physical activity, reduced caffeine/alcohol, structured daily routine
- Address social stressors and support systems; involve family/carers where appropriate and acceptable
- Regular review with symptom scales (for example repeat GAD-7) and relapse-prevention planning
Pharmacological Treatment
First-line SSRI
- Sertraline 50 mg once daily initially, increase in steps to max 200 mg once daily
Common UK first choice due to cost-effectiveness and tolerability. Discuss early transient anxiety worsening, GI upset, sexual dysfunction, sleep disturbance, and withdrawal effects if stopped abruptly.
Alternative SSRI/SNRI if ineffective or not tolerated
- Escitalopram 10 mg once daily, may increase to 20 mg once daily
- Paroxetine 20 mg once daily, may increase gradually (usual max 50 mg daily for anxiety disorders)
- Duloxetine 30 mg once daily initially, usually increase to 60 mg once daily (max 120 mg/day in divided doses)
Choose based on side-effect profile, interactions, previous response, overdose risk, and patient preference. SNRIs may raise blood pressure; monitor BP with duloxetine.
If SSRIs/SNRIs unsuitable: pregabalin
- Pregabalin 150 mg/day in 2-3 divided doses initially, titrate to 300 mg/day within 1 week; usual range 300-600 mg/day
Dose-adjust in renal impairment. Counsel on dizziness, somnolence, weight gain, dependence/misuse risk, and withdrawal symptoms on abrupt cessation.
Short-term crisis use only (generally avoid routine use)
- Diazepam 2-5 mg up to three times daily for a very short period in severe acute distress
Not for long-term GAD management due to tolerance, dependence, cognitive impairment, falls risk, and withdrawal.
Complications
- Chronic functional impairment and reduced quality of life
- Occupational and educational underperformance, sickness absence
- Comorbid major depressive disorder
- Comorbid panic disorder/social anxiety/specific phobias
- Substance misuse or dependence (alcohol, sedatives, anxiolytics)
- Increased suicidal ideation and attempts (especially with depression)
- Higher healthcare utilization and frequent reassurance-seeking consultations
- Association with chronic pain and other long-term physical health burden
Prognosis
GAD often follows a chronic fluctuating course with relatively low short- to medium-term remission rates; many patients remain symptomatic over years, and relapse after remission is common. Outcomes are worse with comorbid depression or other anxiety disorders, but meaningful improvement in symptoms and functioning is expected with evidence-based psychological therapy and/or appropriate pharmacotherapy. Continued treatment after response reduces relapse risk, and active follow-up improves long-term outcomes.