What is the best selective serotonin reuptake inhibitor (SSRI) for an adult patient with anxiety disorder, considering their age, medical history, and potential presence of other psychiatric conditions or chronic illnesses?

Best SSRI for Anxiety Disorders

Escitalopram and sertraline are the preferred first-line SSRIs for anxiety disorders due to their superior efficacy, favorable side effect profiles, and lower risk of discontinuation symptoms compared to other SSRIs. 1

Primary Recommendations by Anxiety Disorder Type

For Generalized Anxiety Disorder (GAD)

• Start with escitalopram (10-20 mg/day) or sertraline (50-200 mg/day) as top-tier first-line agents 1
• Begin escitalopram at 5-10 mg daily and titrate by 5-10 mg increments every 1-2 weeks 1
• Begin sertraline at 25-50 mg daily and titrate by 25-50 mg increments every 1-2 weeks as tolerated 1
• Both medications demonstrate similar efficacy with NNT = 4.70 (approximately 1 in 5 patients will respond who would not have responded to placebo) 1

For Social Anxiety Disorder

• Fluvoxamine, paroxetine, and escitalopram are first-choice medications covered by insurance in Japan, with sertraline noted as equally effective 2, 1
• All SSRIs as a class show similar efficacy for social anxiety disorder 2
• Sertraline is FDA-approved for social anxiety disorder and has demonstrated efficacy in maintaining response for up to 24 weeks 3

For Panic Disorder and PTSD

• Sertraline is particularly well-established for these conditions with FDA approval and extensive evidence 3, 4
• Sertraline maintains response in PTSD patients for up to 28 weeks following initial treatment 3

Why Escitalopram and Sertraline Are Preferred

Escitalopram advantages:

• Lower risk of discontinuation symptoms compared to paroxetine and fluvoxamine 1
• Favorable side effect profile 1
• Effective across multiple anxiety disorder subtypes 1

Sertraline advantages:

• Minimal cytochrome P450 inhibition, resulting in fewer drug-drug interactions compared to fluoxetine, fluvoxamine, and paroxetine 5
• Well-tolerated with low dropout rates (8% vs 10% for placebo in GAD trials) 6
• Proven efficacy across the full spectrum of anxiety disorders including GAD, social anxiety disorder, panic disorder, and PTSD 4, 7
• Safe in patients with medical comorbidities 4

SSRIs to Use with Caution

Paroxetine and fluvoxamine are equally effective but should be reserved for when first-tier SSRIs fail due to:

• Higher risk of discontinuation symptoms 2, 1
• Paroxetine has potentially increased suicidal thinking compared to other SSRIs 1
• More problematic side effect profiles 2

Expected Timeline and Monitoring

Response follows a logarithmic pattern:

• Statistically significant improvement may begin by week 2 1
• Clinically significant improvement expected by week 6 1
• Maximal therapeutic benefit achieved by week 12 or later 1
• Do not abandon treatment prematurely—full response may take 12+ weeks 1

Common side effects (emerge within first few weeks):

• Nausea, sexual dysfunction, headache, insomnia, dry mouth, diarrhea 1
• Most adverse effects typically resolve with continued treatment 1

Critical monitoring:

• Assess for suicidal thinking and behavior, especially in first months and after dose adjustments (pooled risk 1% vs 0.2% placebo, NNH = 143) 1
• Use standardized anxiety rating scales (e.g., HAM-A) to track response 1

If First SSRI Fails

After 8-12 weeks at therapeutic doses with inadequate response:

1. Switch to a different SSRI (e.g., sertraline to escitalopram or vice versa) 1
2. Consider adding cognitive behavioral therapy if not already implemented 1
3. Consider switching to an SNRI (venlafaxine 75-225 mg/day or duloxetine 60-120 mg/day) as second-line treatment 2, 1

Combination with Psychotherapy

Combining an SSRI 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 1
• CBT has large effect sizes for GAD (Hedges g = 1.01) 1

Critical Pitfalls to Avoid

• Do not use benzodiazepines as first-line treatment—reserve only for short-term use due to risks of dependence, tolerance, and withdrawal 1
• Do not escalate SSRI 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 contraindicated as it is activating and can exacerbate anxiety symptoms 8
• Do not use beta blockers (atenolol, propranolol) for social anxiety disorder—negative evidence supports avoiding these agents 1