What is the recommended management for an adult with generalized anxiety disorder?

Management of Generalized Anxiety Disorder

First-Line Pharmacotherapy

Escitalopram or sertraline are the preferred first-line medications for generalized anxiety disorder because they have the strongest evidence for efficacy, the most favorable side-effect profiles, and the lowest risk of discontinuation symptoms compared with other SSRIs. 1, 2

Escitalopram Dosing

• Start at 5–10 mg once daily (morning or evening, with or without food) 3
• Increase by 5–10 mg increments every 1–2 weeks as tolerated 1, 2
• Target therapeutic dose: 10–20 mg/day by weeks 4–6 1, 3
• For elderly patients or those with hepatic impairment, 10 mg/day is the maximum recommended dose 3

Sertraline Dosing

• Start at 25–50 mg once daily 1, 2
• Increase by 25–50 mg increments every 1–2 weeks as tolerated 1, 2
• Target therapeutic dose: 50–200 mg/day 1, 2

Expected Response Timeline

• Statistically significant improvement may begin by week 2 1, 2
• Clinically meaningful improvement expected by week 6 1, 2
• Maximal therapeutic benefit achieved by week 12 or later 1, 2
• Do not abandon treatment prematurely; full response often requires ≥12 weeks of continuous therapy 1, 2

Second-Line Pharmacotherapy

If inadequate response after 8–12 weeks at therapeutic doses with good adherence, consider these alternatives: 1, 2

Switch to Another SSRI

• Paroxetine (10 mg daily, titrate to 20–60 mg/day) or fluvoxamine (50 mg twice daily, titrate to 150 mg twice daily) are equally effective but reserved as second-tier options due to higher discontinuation symptoms and drug-interaction potential 1, 2

Switch to an SNRI

• Venlafaxine extended-release: Start 75 mg daily, titrate to 75–225 mg/day over 4–6 weeks 1, 2
  • Requires blood pressure monitoring due to risk of sustained hypertension 1, 2
  • Number needed to treat (NNT) = 4.94, comparable to SSRIs 1
• Duloxetine: Start 30 mg daily for one week, then increase to 60–120 mg/day 1
  • Provides additional benefit for patients with comorbid pain conditions 1

First-Line Psychotherapy

Individual cognitive-behavioral therapy (CBT) is equally effective as first-line treatment and should be offered based on patient preference and availability. 1, 2

CBT Structure and Components

• 12–20 sessions over 3–4 months are recommended for significant symptomatic and functional improvement 1, 2
• Individual CBT is preferred over group therapy due to superior clinical effectiveness and cost-effectiveness 1, 2
• Core components include: psychoeducation about anxiety, cognitive restructuring to challenge distorted thoughts, relaxation techniques (breathing exercises, progressive muscle relaxation), and graded exposure when appropriate 1, 2
• If face-to-face CBT is unavailable or declined, self-help CBT with professional support is a viable alternative 1, 2

Combined Treatment Approach

For moderate-to-severe generalized anxiety disorder, combining an SSRI with individual CBT yields superior symptom reduction and functional improvement compared with either modality alone. 1, 2

• This recommendation is supported by moderate-to-high strength evidence 1, 2
• Approximately 50% of patients do not achieve complete remission with first-line pharmacotherapy alone, underscoring the need for adjunctive CBT 2

Common SSRI/SNRI Adverse Effects

Monitor for these side effects, which typically emerge within the first few weeks and usually resolve with continued treatment: 1, 2

• Nausea, sexual dysfunction, headache, insomnia, dry mouth, diarrhea, heartburn, sedation, dizziness, vivid dreams 1, 2
• All SSRIs carry a boxed warning for suicidal ideation/behavior; close monitoring is essential during the first months and after dose adjustments (pooled absolute risk: 1% vs. 0.2% for placebo) 1, 2

Medications to Avoid

Benzodiazepines

Benzodiazepines should be limited to short-term adjunctive use (days to a few weeks) only due to high risks of dependence, tolerance, cognitive impairment, and withdrawal syndromes; they are not recommended as first-line or long-term treatments for GAD. 1, 2, 4

Beta-Blockers

Beta-blockers (atenolol, propranolol) are not recommended for generalized anxiety disorder according to Canadian guidelines due to negative evidence demonstrating lack of therapeutic benefit. 1, 2

Tricyclic Antidepressants

Avoid TCAs due to unfavorable risk-benefit profile, particularly cardiac toxicity. 1

Maintenance Treatment and Relapse Prevention

• Continue effective medication for at least 9–12 months after achieving remission to prevent relapse 1, 2
• Monitor symptoms monthly until stability is achieved, then every 3 months thereafter using standardized scales (GAD-7 or HAM-A) 1, 2
• When discontinuing, taper gradually over 10–14 days (or longer) to avoid withdrawal symptoms (dizziness, paresthesias, anxiety, irritability), especially with short-half-life SSRIs 1, 2, 3

Adjunctive Non-Pharmacologic Interventions

• Structured physical activity/exercise produces moderate to large reductions in anxiety symptoms 1, 2
• Breathing exercises, progressive muscle relaxation, grounding techniques, and mindfulness are useful adjuncts to primary treatment 1, 2
• Avoid excessive caffeine and alcohol, as both can exacerbate anxiety symptoms 1, 2
• Sleep hygiene education can address insomnia, which commonly co-occurs with anxiety 1

Clinical Pitfalls to Avoid

• Do not initiate pharmacotherapy for mild anxiety (GAD-7 score 5–9) before trying evidence-based non-pharmacologic options such as CBT, which provide more durable benefits 1, 2
• Avoid rapid dose escalation; allow 1–2 weeks between titration steps to assess tolerability and prevent overshooting the therapeutic window 1, 2
• Do not interpret lack of early improvement as treatment failure; SSRI response follows a logarithmic pattern with maximal benefit often requiring ≥12 weeks 1, 2
• Do not overlook comorbid conditions: approximately one-third of patients with GAD have comorbid depression, substance use, or other psychiatric disorders that require concurrent management 1
• Patients with anxiety pathology commonly avoid follow-through on referrals; proactively assess and address barriers to treatment adherence 1