What is the first-line medication for a patient with anxiety and no significant medical history or contraindications?

First-Line Medication for Anxiety

Selective serotonin reuptake inhibitors (SSRIs), specifically escitalopram or sertraline, are the first-line pharmacological treatments for anxiety disorders in adults with no contraindications. 1

Preferred SSRI Options

Escitalopram and sertraline are the top-tier first-line agents due to their established efficacy, favorable side effect profiles, and lower risk of discontinuation symptoms compared to other SSRIs. 1 These medications demonstrate high-quality evidence for efficacy in anxiety disorders with moderate to high strength of evidence, showing improvement in primary anxiety symptoms, response rates, and remission. 1

Starting Doses and Titration

• Sertraline: Start at 25-50 mg daily, increase by 25-50 mg increments every 1-2 weeks as tolerated, targeting 50-200 mg/day 1
• Escitalopram: Start at 5-10 mg daily, increase by 5-10 mg increments every 1-2 weeks, targeting 10-20 mg/day 1

The gradual titration minimizes initial anxiety, agitation, or activation symptoms that can occur when starting SSRIs. 1

Alternative First-Line Options

SNRIs (serotonin-norepinephrine reuptake inhibitors) are equally effective first-line alternatives when SSRIs are not preferred or tolerated. 2, 1

• Venlafaxine extended-release: 75-225 mg/day, effective for generalized anxiety disorder, social anxiety disorder, and panic disorder, but requires blood pressure monitoring due to risk of sustained hypertension 1
• Duloxetine: 60-120 mg/day, particularly beneficial for patients with comorbid pain conditions 1

Expected Timeline for Response

Patients must understand that SSRI/SNRI response follows a logarithmic pattern: 1

• Week 2: Statistically significant improvement may begin
• Week 6: Clinically significant improvement expected
• Week 12 or later: Maximal therapeutic benefit achieved

Do not abandon treatment prematurely—full response may take 12+ weeks, and treatment should continue for at least 8-12 weeks at therapeutic doses before considering the trial inadequate. 1

Common Side Effects to Anticipate

Most adverse effects emerge within the first few weeks and typically resolve with continued treatment: 2, 1

• Nausea, diarrhea, dry mouth, headache
• Dizziness, somnolence or insomnia
• Sexual dysfunction
• Nervousness, tremor

Critical warning: All SSRIs carry a boxed warning for suicidal thinking and behavior (pooled absolute rates of 1% versus 0.2% for placebo). Close monitoring is essential, especially in the first months and following dose adjustments. 1

Medications to Avoid as First-Line

Benzodiazepines should NOT be used as first-line treatment due to risks of dependence, tolerance, and withdrawal. 1, 3 They should be reserved only for short-term use when rapid relief is needed while titrating SSRIs/SNRIs. 3

Tricyclic antidepressants (TCAs) should be avoided due to their unfavorable risk-benefit profile, particularly cardiac toxicity. 1

Combination with Psychotherapy

Combining medication with cognitive behavioral therapy (CBT) provides superior outcomes compared to either treatment alone, particularly for moderate to severe anxiety. 1 Individual CBT is prioritized over group therapy due to superior clinical and cost-effectiveness, with large effect sizes for generalized anxiety disorder (Hedges g = 1.01). 1

Treatment Duration

Continue effective medication for a minimum of 9-12 months after achieving remission to prevent relapse. 1 Discontinue gradually to avoid withdrawal symptoms, particularly with shorter half-life SSRIs. 1

If First SSRI Fails

After 8-12 weeks at therapeutic doses with inadequate response despite good adherence: 1

1. Switch to a different SSRI (e.g., sertraline to escitalopram or vice versa)
2. Consider switching to an SNRI (venlafaxine or duloxetine)
3. Add or intensify CBT if not already implemented

Critical Pitfalls to Avoid

• Escalating doses too quickly: Allow 1-2 weeks between increases to assess tolerability and avoid overshooting the therapeutic window 1
• Inadequate trial duration: Premature switching before 8-12 weeks at therapeutic doses 1
• Ignoring medical causes: Rule out hyperthyroidism, caffeinism, hypoglycemia, cardiac arrhythmias, and other endocrine disorders before initiating treatment 1
• Not addressing adherence barriers: Patients with anxiety commonly avoid follow-through on treatment, so proactively assess and address barriers 1