What is the recommended first‑line treatment for an adult with generalized anxiety disorder?

First-Line Treatment for Generalized Anxiety Disorder in Adults

Escitalopram or sertraline are the recommended first-line medications for adults with generalized anxiety disorder, combined with individual cognitive-behavioral therapy when feasible. 1, 2

Preferred Pharmacologic Options

First-Tier SSRIs

• Escitalopram is the top-tier choice due to its favorable side-effect profile, minimal drug-interaction potential, and lowest discontinuation-symptom burden among all SSRIs. 1, 2

  • Start at 5–10 mg once daily and increase by 5–10 mg every 1–2 weeks to a target of 10–20 mg/day. 1, 3
  • The FDA label specifies that 10 mg/day is effective, with increases to 20 mg after a minimum of one week if needed. 3

• Sertraline is equally preferred as a first-line agent with comparable efficacy and tolerability to escitalopram. 1, 2

  • Start at 25–50 mg once daily and increase by 25–50 mg every 1–2 weeks to a target of 50–200 mg/day. 1, 2

• Gradual titration is essential to minimize early-treatment anxiety, agitation, or activation symptoms that can occur when initiating SSRIs. 1, 2

Expected Response Timeline

• Statistically significant improvement may be observed as early as week 2 of SSRI therapy. 1, 2
• Clinically meaningful improvement typically becomes evident by week 6. 1, 2
• Maximal therapeutic benefit is generally reached by week 12 or later—do not discontinue prematurely, as full response often requires 12 weeks or longer. 1, 2

Alternative First-Line Pharmacologic Options

SNRIs as Effective Alternatives

• Duloxetine (60–120 mg/day) is an effective alternative SNRI for GAD, with additional benefits for patients who have comorbid pain conditions. 1, 4

  • The FDA label recommends starting at 30 mg once daily for 1 week to allow adjustment, then increasing to 60 mg once daily. 4
  • There is no evidence that doses greater than 60 mg/day confer additional benefit, though 120 mg/day has been studied. 4

• Venlafaxine extended-release (75–225 mg/day) is another effective SNRI option when SSRIs are ineffective or not tolerated after an adequate 8–12 week trial. 1, 2, 5

  • Blood-pressure monitoring is required because venlafaxine can cause sustained hypertension. 1, 2

Second-Tier SSRIs (Reserved for Later Use)

• Paroxetine and fluvoxamine have comparable efficacy to escitalopram and sertraline but are reserved as second-tier agents due to higher rates of discontinuation symptoms and greater potential for drug-drug interactions. 1, 2, 5

First-Line Psychotherapy

Individual Cognitive-Behavioral Therapy

• Individual CBT (12–20 sessions) has the highest level of evidence for GAD, with a large effect size (Hedges g ≈ 1.0). 1, 2
• Individual CBT is preferred over group CBT because it yields superior clinical outcomes and is more cost-effective. 1, 2
• Core CBT components include psychoeducation about anxiety, cognitive restructuring of distorted thoughts, relaxation techniques, and graded exposure when appropriate. 1, 2
• If face-to-face CBT is unavailable or declined, a self-help CBT program with professional support is an acceptable alternative. 1, 2

Combined Treatment Approach

• For moderate-to-severe GAD, combining an SSRI with individual CBT yields greater symptom reduction and functional improvement than either modality alone, 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. 1, 2

Common Adverse Effects and Monitoring

• Typical SSRI/SNRI side effects include nausea, sexual dysfunction, headache, insomnia, dry mouth, diarrhea, heartburn, sedation, dizziness, and vivid dreams. 1, 2
• Most adverse effects appear early (within the first few weeks) and usually resolve with continued therapy. 1, 2
• All SSRIs carry a boxed warning for suicidal ideation/behavior; close monitoring is essential during the first months and after dose adjustments, with pooled absolute rates of 1% versus 0.2% for placebo. 1, 2

Strategy for Inadequate Response

If there is no adequate response after 8–12 weeks at therapeutic doses with good adherence: 1, 2

1. Switch to a different SSRI (e.g., from sertraline to escitalopram or vice versa). 1, 2
2. Add individual CBT if it has not yet been implemented. 1, 2
3. Consider an SNRI (venlafaxine or duloxetine) as a second-line pharmacologic option. 1, 2, 5

Medications to Avoid

• Benzodiazepines should be limited to short-term adjunctive use (days to a few weeks) because of high risks of dependence, tolerance, cognitive impairment, and withdrawal syndromes—they are not first-line or long-term treatments for GAD. 1, 2, 6
• Beta-blockers (atenolol, propranolol) are not recommended for GAD according to Canadian guidelines due to negative evidence. 1, 2

Duration of Treatment

• Continue effective medication for at least 9–12 months after remission to reduce relapse risk. 1, 2
• Monitor symptoms monthly until stability is achieved, then every 3 months thereafter. 1, 2
• Taper the medication gradually over 10–14 days (or longer) when discontinuing to avoid withdrawal symptoms, 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

Critical 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 stay within the therapeutic window. 1, 2
• Do not interpret lack of early improvement as treatment failure; a full response often requires ≥12 weeks of continuous therapy. 1, 2