What are the recommended antidepressants, specifically Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs), for individuals with predominant anxiety?

Recommended Antidepressants for Predominant Anxiety

Escitalopram and sertraline are the preferred first-line SSRIs for individuals with predominant anxiety, with escitalopram offering superior efficacy (NNT 4.70) and fewer drug interactions, while sertraline provides a favorable alternative with robust evidence across multiple anxiety disorder subtypes. 1

First-Line SSRI Selection

Primary Recommendations

• Start with escitalopram or sertraline as initial pharmacotherapy based on their superior efficacy and tolerability profiles compared to other SSRIs 1
• Escitalopram demonstrates the strongest efficacy data with minimal CYP450 interactions, reducing risk of drug-drug interactions 1
• Sertraline shows proven effectiveness across panic disorder, PTSD, social anxiety disorder, and generalized anxiety disorder with FDA approval for these indications 2

Dosing Strategy

• Initiate at low doses with slow titration to minimize behavioral activation and agitation, particularly important in anxiety presentations 1
• For sertraline: typical dosing ranges 50-200 mg/day across anxiety disorders 2
• Allow 6-12 weeks for full therapeutic effect before concluding treatment failure—premature discontinuation is a common clinical pitfall 1

Critical Safety Considerations

• Avoid citalopram doses >40 mg/day due to QT prolongation risk and potential for Torsade de Pointes 1
• Use paroxetine cautiously as it carries higher suicidal ideation risk compared to other SSRIs and significant discontinuation syndrome 1
• Reserve fluvoxamine for cases without polypharmacy given extensive CYP450 interactions (1A2, 2C19, 2C9, 3A4, 2D6) 1

Second-Line SNRI Options

When to Consider SNRIs

• SNRIs demonstrate comparable efficacy to SSRIs (NNT 4.94) and should be considered when SSRIs fail or are not tolerated 1
• Venlafaxine has the most robust evidence among SNRIs for anxiety disorders 1
• Duloxetine is FDA-approved for GAD in children ≥7 years, making it reasonable for adult anxiety despite off-label use in other anxiety subtypes 1

SNRI-Specific Warnings

• Monitor blood pressure and pulse regularly as SNRIs cause sustained hypertension in some patients 1
• Venlafaxine carries higher suicide risk than other SNRIs and has caused overdose fatalities 1
• Duloxetine requires immediate discontinuation if jaundice, hepatomegaly, elevated transaminases, or severe skin reactions develop 1
• Venlafaxine has significant discontinuation syndrome—taper slowly when stopping 1

Critical Safety Monitoring Across All Agents

Serotonin Syndrome Prevention

• Never combine SSRIs/SNRIs with MAOIs (including linezolid, intravenous methylene blue) due to fatal serotonin syndrome risk 1
• Wait appropriate washout periods: 2 weeks for most SSRIs/SNRIs, 5 weeks for fluoxetine before starting MAOIs 1
• Exercise extreme caution when combining serotonergic agents including tramadol, meperidine, methadone, fentanyl, dextromethorphan, triptans, TCAs, amphetamines, St. John's wort, and L-tryptophan 1

Recognizing Serotonin Syndrome

• Symptoms appear within 24-48 hours of combining medications: confusion, agitation, tremors, clonus, hyperreflexia, muscle rigidity, hypertension, tachycardia, diaphoresis, fever, seizures 1

Early Treatment Monitoring

First Month Vigilance

• Monitor closely for behavioral activation in the first month, which typically resolves with dose reduction 1
• Distinguish behavioral activation (dose-related, resolves with reduction) from true mania (requires active intervention and possible discontinuation) 1
• Common early adverse effects with sertraline include nausea (25% vs 11% placebo), diarrhea (20% vs 10% placebo), and insomnia (21% vs 11% placebo) 2

Discontinuation Strategy

• Taper gradually when discontinuing, particularly with paroxetine, fluvoxamine, sertraline, and venlafaxine to avoid discontinuation syndrome 1
• Discontinuation syndrome manifests as dizziness, nausea, headache, irritability, and insomnia 1

Common Pitfalls to Avoid

• Premature discontinuation before 6-12 weeks prevents adequate assessment of therapeutic response 1
• Starting at full doses rather than low-dose initiation increases risk of early behavioral activation and treatment dropout 1
• Failing to check drug interactions, particularly with fluvoxamine's extensive CYP450 effects 1
• Inadequate monitoring for blood pressure changes with SNRIs 1