What is the first-line anti-anxiety medication for a typical adult patient with an anxiety disorder and without significant comorbidities or a history of substance abuse?

First-Line Anti-Anxiety Medication

Selective serotonin reuptake inhibitors (SSRIs), specifically sertraline or escitalopram, are the first-line pharmacological treatment for anxiety disorders in typical adults. 1, 2

Preferred SSRI Options

Sertraline and escitalopram 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. 2

• Sertraline is FDA-approved for panic disorder, social anxiety disorder, PTSD, and OCD, with extensive evidence supporting its use across multiple anxiety disorders. 3, 4
• Escitalopram has the least effect on CYP450 enzymes, resulting in the lowest propensity for drug interactions—a critical advantage in patients taking multiple medications. 2

Alternative First-Line Options

SNRIs (venlafaxine extended-release or duloxetine) are appropriate alternatives when SSRIs are ineffective or not tolerated. 1, 2

• Venlafaxine extended-release (75-225 mg/day) is effective for generalized anxiety disorder, panic disorder, and social anxiety disorder, but requires blood pressure monitoring due to risk of sustained hypertension. 1, 2
• Duloxetine (60-120 mg/day) has demonstrated efficacy in GAD and provides additional benefits for patients with comorbid pain conditions. 2

Dosing Strategy

Start with lower doses and titrate gradually to minimize side effects:

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

Expected Timeline for Response

Patients should understand that SSRI response follows a logarithmic pattern:

• Statistically significant improvement may begin by week 2. 1, 2
• Clinically significant improvement is expected by week 6. 1, 2
• Maximal therapeutic benefit is achieved by week 12 or later. 1, 2

Do not abandon treatment prematurely—full response may take 12+ weeks. 2

Common Side Effects to Monitor

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

• Nausea, diarrhea, dry mouth, headache, dizziness, insomnia or somnolence, sexual dysfunction, sweating, tremor, and weight gain. 1, 2
• Initial anxiety or agitation can occur with SSRIs but typically resolves within 1-2 weeks. 2

Critical warning: All SSRIs carry a boxed warning for suicidal thinking and behavior, with pooled absolute rates of 1% versus 0.2% for placebo (number needed to harm = 143). 2 Close monitoring is essential, especially in the first months and following dose adjustments. 2

Medications to Avoid

Paroxetine and fluvoxamine should be reserved for when first-tier SSRIs fail due to higher risks of discontinuation symptoms. 1, 2

Benzodiazepines should be avoided as first-line treatment due to risks of dependence, tolerance, and withdrawal, and should be reserved only for short-term use if absolutely necessary. 2

Tricyclic antidepressants (TCAs) should be avoided due to their unfavorable risk-benefit profile, particularly cardiac toxicity. 2

Treatment Adjustment Strategy

If inadequate response after 8-12 weeks at therapeutic doses:

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

Combination Treatment Consideration

Combining medication with CBT provides superior outcomes compared to either treatment alone, particularly for patients with moderate to severe anxiety. 1, 2 CBT is the psychotherapy with the highest level of evidence for anxiety disorders, with large effect sizes (Hedges g = 1.01 for GAD). 2, 5

Treatment Duration

For a first episode of anxiety, continue treatment for at least 6-12 months after symptom remission. 1 For recurrent anxiety, longer-term or indefinite treatment may be beneficial. 1 Never discontinue SSRIs abruptly—taper gradually over 10-14 days to avoid discontinuation syndrome (dizziness, paresthesias, anxiety, irritability). 2