What are the recommended first‑line pharmacologic treatments and dosing for an adult with generalized anxiety disorder?

First-Line Pharmacologic Treatment for Generalized Anxiety Disorder

Start with escitalopram 10 mg once daily or sertraline 25–50 mg once daily as your first-line pharmacologic treatment for an adult with generalized anxiety disorder, titrating upward over 4–6 weeks to target doses of escitalopram 10–20 mg/day or sertraline 50–200 mg/day. 1, 2

Preferred First-Line Agents

• Escitalopram and sertraline are the top-tier SSRIs because they have the lowest risk of discontinuation symptoms, fewest drug-drug interactions, and most favorable tolerability profiles compared to other SSRIs like paroxetine or fluvoxamine. 1

• Start escitalopram at 10 mg once daily (morning or evening, with or without food), and if needed, increase to 20 mg after a minimum of one week. 2

• Start sertraline at 25–50 mg daily to minimize initial anxiety or agitation, then titrate by 25–50 mg increments every 1–2 weeks as tolerated, targeting 50–200 mg/day. 1

Alternative First-Line: SNRIs

• Venlafaxine extended-release (75–225 mg/day) or duloxetine (60–120 mg/day) are effective alternatives when SSRIs are ineffective, not tolerated, or when the patient has comorbid chronic pain. 1, 3

• Venlafaxine requires blood pressure monitoring due to risk of sustained hypertension, particularly at doses above 150 mg/day. 1

• Duloxetine-related nausea can be reduced by starting at 30 mg daily for one week before advancing to the target dose of 60–120 mg/day. 1

Expected Timeline and Monitoring

• Statistically significant improvement begins by week 2, clinically meaningful improvement appears by week 6, and maximal therapeutic benefit is reached by week 12 or later—do not abandon treatment prematurely. 1

• Assess response using standardized scales (GAD-7 or HAM-A) at baseline, weeks 2,4,6, and 12 to objectively track symptom reduction. 1

• Common side effects—nausea, sexual dysfunction, headache, insomnia, dry mouth, diarrhea—emerge within the first few weeks and typically resolve with continued treatment. 1

• Monitor for suicidal thinking and behavior, especially in patients under age 25 during the first months and after dose adjustments (pooled risk 1% vs. 0.2% placebo, NNH = 143). 1

Dosing Adjustments for Special Populations

• Elderly patients and those with hepatic impairment should receive 10 mg/day of escitalopram as the maximum recommended dose. 2

• No dosage adjustment is necessary for mild or moderate renal impairment, but use escitalopram with caution in severe renal impairment. 2

What to Avoid

• Do not use tricyclic antidepressants (TCAs) due to unfavorable risk-benefit profile, particularly cardiac toxicity. 1

• Reserve benzodiazepines for short-term use only (days to a few weeks) due to high risk of dependence, tolerance, cognitive impairment, and withdrawal syndromes—they are not appropriate first-line or long-term therapy. 1

• Beta-blockers (atenolol, propranolol) are deprecated for GAD based on negative evidence and should not be prescribed. 1

• Paroxetine and fluvoxamine are equally effective but carry higher risks of discontinuation symptoms and drug interactions, so reserve them for when first-tier SSRIs fail. 1

If First SSRI Fails After 8–12 Weeks

• Switch to a different SSRI (e.g., sertraline to escitalopram or vice versa) or to an SNRI (venlafaxine XR or duloxetine) after confirming an adequate trial at therapeutic doses with good adherence. 1

• Add individual cognitive-behavioral therapy (CBT) if not already implemented—combining medication with CBT provides superior outcomes compared to either treatment alone. 1, 4

Maintenance and Discontinuation

• Continue effective medication for a minimum of 9–12 months after achieving remission to prevent relapse, then reassess periodically. 1

• Taper gradually over at least 10–14 days when discontinuing to avoid withdrawal symptoms (dizziness, paresthesias, anxiety, irritability), particularly with shorter half-life SSRIs. 1, 2

Critical Pitfalls to Avoid

• Do not escalate doses too quickly—allow 1–2 weeks between increases to assess tolerability and avoid overshooting the therapeutic window. 1

• Do not stop treatment before 12 weeks unless intolerable side effects occur, because full response may take 12+ weeks and early discontinuation increases relapse risk. 1, 5

• Do not ignore comorbid conditions—approximately one-third of GAD patients have comorbid depression, substance use, or other psychiatric disorders that require concurrent management. 1