What medications are used to treat anxiety?

Medications for Anxiety

SSRIs (selective serotonin reuptake inhibitors) and SNRIs (serotonin-norepinephrine reuptake inhibitors) are the first-line pharmacological treatments for anxiety disorders, with escitalopram and sertraline being the preferred initial choices due to their superior efficacy, favorable side effect profiles, and lower risk of discontinuation symptoms. 1

First-Line Medication Options

Preferred SSRIs

• Escitalopram (10-20 mg/day) and sertraline (50-200 mg/day) are top-tier first-line agents with the best evidence for efficacy and tolerability 1, 2
• Start escitalopram at 5-10 mg daily and titrate by 5-10 mg increments every 1-2 weeks as tolerated 1
• Start sertraline at 25-50 mg daily and titrate by 25-50 mg increments every 1-2 weeks as tolerated 1
• These agents have fewer drug-drug interactions compared to other SSRIs 2

Alternative SSRIs

• Fluoxetine has a longer half-life that may benefit patients who occasionally miss doses 1
• Paroxetine is effective but carries higher risk of discontinuation syndrome and potentially increased suicidal thinking compared to other SSRIs—reserve for when first-tier SSRIs fail 1, 2
• Fluvoxamine is effective but has greater potential for drug-drug interactions through multiple CYP450 pathways (CYP1A2, CYP2C19, CYP2C9, CYP3A4, CYP2D6) 3, 2
• Citalopram is effective but avoid doses exceeding 40 mg/day due to QT prolongation risk and potential for Torsade de Pointes 3, 2

SNRIs

• Venlafaxine extended-release (75-225 mg/day) is effective for generalized anxiety disorder, social anxiety disorder, and panic disorder 1, 2
• Requires blood pressure monitoring due to risk of sustained hypertension 1
• Has higher risk of discontinuation symptoms—taper gradually when stopping 3
• Duloxetine (60-120 mg/day) is effective for GAD with additional benefits for comorbid pain conditions 1
• Start duloxetine at 30 mg daily for one week to reduce nausea, then increase to 60 mg 1

Second-Line Options

• Pregabalin/Gabapentin can be considered when first-line treatments fail or are not tolerated, particularly for patients with comorbid pain 1
• Benzodiazepines (e.g., alprazolam) are FDA-approved for anxiety disorders and panic disorder but are NOT recommended for routine use due to dependence risk 4, 5
• Other classes (antipsychotics, beta blockers, MAOIs, tricyclic antidepressants) have inadequate evidence or unfavorable risk-benefit profiles 3, 1

Treatment Algorithm

Initial Treatment

1. Start with escitalopram or sertraline at low doses 1
2. Titrate gradually every 1-2 weeks to minimize side effects 1, 2
3. Combine with cognitive behavioral therapy (CBT) for optimal outcomes—CBT alone has large effect sizes (Hedges g = 1.01 for GAD) 1

If First SSRI Fails After 8-12 Weeks

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

Expected Timeline

• Statistically significant improvement occurs within 2 weeks 1
• Clinically significant improvement by week 6 1
• Maximal improvement by week 12 or later 1

Critical Safety Considerations

Common Side Effects

• Nausea, sexual dysfunction, headache, insomnia, dry mouth, diarrhea, somnolence, dizziness, vivid dreams 1
• Most adverse effects emerge within the first few weeks of treatment 1
• Behavioral activation/agitation can occur early in treatment—start low and titrate slowly 3

Serious Adverse Reactions

• Serotonin syndrome: Can occur when combining serotonergic medications (SSRIs, SNRIs, MAOIs, tramadol, dextromethorphan, St. John's wort) 3
• Symptoms include mental status changes, neuromuscular hyperactivity (tremors, clonus), autonomic hyperactivity (hypertension, tachycardia, diaphoresis) 3
• Contraindication: Never combine SSRIs with MAOIs due to serotonin syndrome risk 3, 2
• Abnormal bleeding risk, especially with concurrent NSAIDs or aspirin 3
• Use caution in patients with seizure disorders 3

Discontinuation Syndrome

• Paroxetine, fluvoxamine, and sertraline have highest risk of discontinuation symptoms 3, 2
• Symptoms include dizziness, fatigue, headaches, nausea, insomnia, anxiety 2
• Always taper gradually when stopping, particularly with shorter half-life SSRIs 1

Treatment Duration and Monitoring

• Continue medications for 6-12 months after remission 5
• Monitor response using standardized scales (e.g., Hamilton Anxiety Rating Scale) 1
• Reassess medication need periodically—systematic studies support 4 months for anxiety disorder and 4-10 weeks for panic disorder, though longer treatment is common 4
• For panic disorder, patients have been treated up to 8 months without loss of benefit 4

Important Clinical Pitfalls

• Avoid tricyclic antidepressants due to unfavorable risk-benefit profile, particularly cardiac toxicity 1
• Avoid beta blockers (atenolol, propranolol) for social anxiety disorder based on negative evidence 1
• Do not use benzodiazepines as routine first-line treatment despite FDA approval 5
• Start with lower doses in younger children and monitor closely for behavioral activation 3
• Educate patients in advance about potential side effects, particularly early activation/agitation 3