What are the first-line medications for anxiety?

First-Line Medications for Anxiety

Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) are the first-line pharmacological treatments for anxiety disorders due to their established efficacy and favorable safety profiles. 1, 2

First-Line Medication Options

SSRIs

• Sertraline has demonstrated efficacy in multiple anxiety disorders with a favorable side effect profile and is considered a preferred SSRI option 2, 3
• Escitalopram is recommended as a first-line treatment with potentially fewer drug interactions compared to other SSRIs 4, 1
• Paroxetine is effective for anxiety disorders but may have more discontinuation symptoms and higher risk of drug interactions 4, 5
• Fluoxetine and fluvoxamine are also effective options, with fluoxetine having a longer half-life that may be beneficial for patients who occasionally miss doses 6, 4
• Citalopram is effective but requires caution due to potential QT prolongation at doses exceeding 40 mg/day 4

SNRIs

• Venlafaxine extended-release (75-225 mg/day) is recommended as a first-line option but requires careful titration and monitoring for blood pressure increases 4, 1
• Duloxetine (60-120 mg/day) has demonstrated efficacy in anxiety disorders and provides additional benefits for patients with comorbid pain conditions 1

Medication Selection Algorithm

1. Start with an SSRI (preferably sertraline or escitalopram) 1, 2

   • Begin with lower doses and increase gradually to minimize side effects
   • Shorter half-life SSRIs (sertraline, citalopram) can be increased at 1-2 week intervals
   • Longer half-life SSRIs (fluoxetine) should be increased at 3-4 week intervals 4

2. If inadequate response or intolerable side effects:

   • Switch to a different SSRI or an SNRI (venlafaxine or duloxetine) 1, 7
   • Consider adding cognitive behavioral therapy if not already implemented 2

3. For treatment-resistant cases:

   • Consider second-line options such as pregabalin/gabapentin, particularly for patients with comorbid pain conditions 1

Efficacy and Response Timeline

• SSRIs as a class have demonstrated improvement in primary anxiety symptoms, response to treatment, and remission of disorder (moderate to high strength of evidence) 6
• The response to SSRIs typically follows a logarithmic model with:
  • Statistically significant improvement within 2 weeks
  • Clinically significant improvement by week 6
  • Maximal improvement by week 12 or later 6
• After remission, medications should be continued for 6-12 months to prevent relapse 7

Important Monitoring Considerations

• Assess response using standardized anxiety rating scales 1
• Monitor for common side effects of SSRIs/SNRIs:
  • Nausea, sexual dysfunction, headache, insomnia, dry mouth, diarrhea, heartburn, somnolence, dizziness, and vivid dreams 6, 1
• Most adverse effects emerge within the first few weeks of treatment 6
• For venlafaxine, monitor blood pressure regularly due to potential increases 1
• For duloxetine, starting at 30 mg daily for one week can reduce initial nausea 1

Clinical Pitfalls to Avoid

• Avoid benzodiazepines for routine use due to risks of dependence and withdrawal 7
• Avoid tricyclic antidepressants as first-line options due to their unfavorable risk-benefit profile, particularly cardiac toxicity 1
• Avoid concomitant administration of SSRIs with monoamine oxidase inhibitors (MAOIs) due to the risk of serotonin syndrome 4
• Be cautious with paroxetine due to potentially higher risk of suicidal thinking compared to other SSRIs 4
• Be aware of discontinuation syndrome, particularly with shorter half-life SSRIs like paroxetine, fluvoxamine, and sertraline 4

Special Considerations

• Combination therapy: Consider combining medication with cognitive behavioral therapy for optimal outcomes 4, 2
• For severe anxiety presentations, faster titration may be indicated 4
• For elderly patients or those with medical comorbidities, start with lower doses and titrate more slowly 8
• For patients with comorbid depression, an antidepressant is more likely to succeed than a benzodiazepine 8