What is the best medication for anxiety in an otherwise healthy adult with generalized anxiety disorder?

Best Medication for Generalized Anxiety Disorder

Escitalopram or sertraline are the best first-line medications for an otherwise healthy adult with generalized anxiety disorder, with escitalopram preferred due to its lowest potential for drug interactions and minimal discontinuation symptoms. 1

First-Line SSRI Selection

Start with escitalopram 5–10 mg daily or sertraline 25–50 mg daily, titrating by 5–10 mg (escitalopram) or 25–50 mg (sertraline) every 1–2 weeks as tolerated. 1 Target therapeutic doses are escitalopram 10–20 mg/day and sertraline 50–200 mg/day. 1, 2

• Escitalopram has the least effect on CYP450 enzymes compared to other SSRIs, resulting in the lowest risk of drug-drug interactions—a critical advantage in real-world practice where patients may require additional medications. 1
• Both agents have lower discontinuation-symptom burden than paroxetine or fluvoxamine, making them easier to adjust or stop if needed. 1
• FDA approval confirms efficacy: escitalopram demonstrated statistically significant superiority over placebo in three 8-week trials for GAD using the Hamilton Anxiety Scale. 2

Expected Timeline and Monitoring

Statistically significant improvement begins by week 2, clinically meaningful improvement by week 6, and maximal benefit by week 12 or later. 1 This logarithmic response pattern means patience is essential—do not abandon treatment prematurely. 1

• Assess response at weeks 4 and 8 using standardized scales (GAD-7 or HAM-A). 1
• Common early side effects include nausea, headache, insomnia, and sexual dysfunction; most emerge within the first few weeks and typically resolve with continued treatment. 1
• Monitor for suicidal thinking, especially in the first months and after dose changes (pooled risk 1% vs. 0.2% placebo; NNH = 143). 1

When First-Line SSRIs Fail

If inadequate response after 8–12 weeks at therapeutic doses despite good adherence, switch to a different SSRI (e.g., sertraline to escitalopram) or to an SNRI. 1

• Venlafaxine extended-release 75–225 mg/day is the evidence-based alternative when SSRIs are ineffective or not tolerated, with comparable efficacy (NNT ≈ 4.7). 1, 3
• Duloxetine 60–120 mg/day is another effective SNRI option, particularly beneficial if comorbid pain conditions exist. 1
• Venlafaxine requires blood pressure monitoring due to risk of sustained hypertension. 1

Medications to Avoid or Reserve

Paroxetine and fluvoxamine are equally effective but should be second-tier choices due to higher discontinuation symptoms and greater drug-interaction potential. 1

Benzodiazepines must be limited to short-term use only (days to a few weeks) due to risks of dependence, tolerance, cognitive impairment, and withdrawal—they are not appropriate first-line or long-term therapy. 1, 3

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

Combination with Cognitive Behavioral Therapy

Adding individual CBT (12–20 sessions) to medication provides superior outcomes compared to either treatment alone, with large effect sizes (Hedges g = 1.01). 1, 3 Individual CBT is more clinically and cost-effective than group therapy. 1

• CBT elements include psychoeducation, cognitive restructuring, relaxation techniques, and gradual exposure when appropriate. 1
• Combined treatment is particularly important for moderate-to-severe anxiety where monotherapy may be insufficient. 1

Maintenance and Discontinuation

Continue effective medication for at least 9–12 months after achieving remission to prevent relapse. 1 For recurrent episodes, longer or indefinite treatment may be necessary. 1

Taper SSRIs gradually over 10–14 days when discontinuing to avoid withdrawal symptoms (dizziness, paresthesias, anxiety, irritability). 1

Common 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 use bupropion for anxiety—it is activating and can worsen anxiety symptoms. 1
• Do not prescribe tricyclic antidepressants—they have an unfavorable risk-benefit profile, particularly cardiac toxicity. 1
• Do not overlook comorbid depression—approximately one-third of GAD patients have comorbid conditions requiring concurrent management. 1