What are the recommended medications for Generalized Anxiety Disorder (GAD)?

Recommended Medications for Generalized Anxiety Disorder (GAD)

For patients with Generalized Anxiety Disorder (GAD), selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are the first-line pharmacological treatments due to their established efficacy and favorable safety profiles. 1, 2, 3

First-Line Medications

• SSRIs are recommended as initial pharmacotherapy for GAD due to their efficacy, tolerability, and safety profile 1, 2, 3

  • Escitalopram (10-20 mg/day) has demonstrated effectiveness in both short and long-term treatment of GAD with advantages over benzodiazepines and some other SSRIs 4, 5
  • Sertraline is another preferred SSRI option, particularly in older adults 2
  • Paroxetine and fluvoxamine are effective but may have more discontinuation symptoms 1

• SNRIs are also considered first-line options with strong evidence for GAD treatment 1, 3

  • Duloxetine (60-120 mg/day) has demonstrated efficacy in GAD and has additional benefits for patients with comorbid pain conditions 1
  • Venlafaxine (75-225 mg/day) is effective for GAD but requires careful titration and monitoring for blood pressure increases 1

Second-Line Medications

• Buspirone (15-60 mg/day) is an azapirone that may be considered when:

  • Sexual side effects from SSRIs/SNRIs are problematic
  • A non-sedating, non-addictive alternative is needed
  • It's particularly suitable for relatively healthy older adults 6, 2, 7

• Pregabalin/Gabapentin (calcium channel α2δ ligands) can be considered when first-line treatments are ineffective or not tolerated 1, 2

  • These medications have shown efficacy in GAD and may be particularly helpful for patients with comorbid pain conditions 1

Treatment Algorithm

1. Initial treatment: Start with an SSRI (preferably escitalopram or sertraline) or SNRI (duloxetine or venlafaxine) 1, 4, 2

   • Begin with lower doses and titrate gradually to minimize side effects
   • Escitalopram starting dose: 10 mg once daily, may increase to 20 mg after at least one week if needed 4

2. Inadequate response: If the first medication trial is unsuccessful after 4-8 weeks at an adequate dose:

   • Switch to a different SSRI or SNRI 2, 3
   • Consider adding cognitive behavioral therapy (CBT) if not already implemented 1, 8

3. Third-line options: If two trials of SSRIs/SNRIs are unsuccessful:

   • Consider pregabalin/gabapentin 2
   • Consider buspirone, particularly if sexual side effects are problematic 2, 7

4. Treatment-resistant cases: For patients who fail multiple medication trials:

   • Low-dose quetiapine may be considered, though with caution due to metabolic side effects 2
   • Consider referral to a psychiatrist for specialized care 1

Important Monitoring Considerations

• Assess response using standardized anxiety rating scales (e.g., HAM-A) 1, 9

• Monitor for common side effects:

  • SSRIs/SNRIs: nausea, sexual dysfunction, headache, insomnia 1, 4
  • Duloxetine: nausea (can be reduced by starting at 30 mg daily for one week) 1
  • Venlafaxine: blood pressure increases, discontinuation symptoms 1

• For escitalopram, if discontinuation is needed, taper gradually to minimize withdrawal symptoms 4

Clinical Pitfalls to Avoid

• Benzodiazepines should be avoided as primary long-term treatment due to risks of dependence, cognitive impairment, and falls (especially in older adults) 2, 7

  • May be appropriate for short-term use during initiation of SSRIs/SNRIs while awaiting their full effect

• Tricyclic antidepressants (TCAs) should be avoided due to their unfavorable risk-benefit profile, particularly cardiac toxicity 1, 8

• Inadequate treatment duration: GAD is often chronic and requires long-term treatment (typically at least 12 months after achieving response) 3

• Abrupt discontinuation: Always taper medications gradually, particularly SNRIs and paroxetine, to minimize discontinuation symptoms 4