What are the medications for long-term management of anxiety?

Long-Term Anxiety Medications

Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) are the first-line medications for long-term management of anxiety disorders due to their proven efficacy and favorable safety profiles. 1, 2

First-Line Medications

SSRIs

SSRIs have the strongest evidence for long-term anxiety management:

• Sertraline: 50-200mg daily

  • FDA-approved for social anxiety disorder, panic disorder, PTSD 3
  • Effective for reducing panic attacks and providing protection from relapse for up to 36 weeks 4
  • Lower potential for drug interactions compared to other SSRIs 5

• Escitalopram: 10-20mg daily

  • Effective for generalized anxiety disorder (GAD) with continued efficacy in 24-week extension studies 6
  • Demonstrated long-term efficacy in relapse prevention studies 7
  • May have the least effect on CYP450 isoenzymes, resulting in fewer drug interactions 5

• Paroxetine: 10-40mg daily

  • Effective for anxiety disorders but has higher risk of discontinuation syndrome 5
  • Associated with increased risk of suicidal thinking compared to other SSRIs 5

• Fluoxetine: Longer half-life allows for once-weekly dosing in maintenance phase 8

• Fluvoxamine: 50-150mg twice daily

  • Greater potential for drug-drug interactions 5

SNRIs

SNRIs are also effective first-line options:

• Venlafaxine: 37.5-225mg daily

  • Effective for social anxiety disorder 5
  • Similar efficacy to SSRIs with NNT = 4.94 5

• Duloxetine: 30-60mg daily

  • FDA-indicated for GAD in children and adolescents 7+ years old 5
  • Particularly beneficial if pain symptoms are present 1

Second-Line Medications

• Buspirone: 5-20mg three times daily

  • Useful for patients with substance use history 1

• Mirtazapine: Faster onset of action compared to other antidepressants

  • Particularly useful for patients with insomnia 1

• Bupropion: 100mg daily to 100mg three times daily

  • Useful for patients who experienced sexual side effects with SSRIs/SNRIs 1

Special Considerations

Dosing and Administration

• Start with lower doses and titrate slowly, especially in elderly patients 5, 1
• For mild to moderate anxiety, increase doses at 1-2 week intervals for shorter half-life SSRIs (sertraline, citalopram) 5
• For longer half-life SSRIs (fluoxetine), increase at 3-4 week intervals 5
• After remission, medications should be continued for 6-12 months to prevent relapse 2

Adverse Effects

Common side effects of SSRIs and SNRIs include:

• Gastrointestinal: Nausea, vomiting, diarrhea
• Neurological: Headache, dizziness, insomnia/somnolence
• Others: Sexual dysfunction, increased sweating

Serious but rare adverse effects:

• Serotonin syndrome (especially when combined with MAOIs)
• Increased suicidal thinking (particularly in young adults)
• QT prolongation (particularly with citalopram at doses >40mg/day) 5

Discontinuation

• Discontinuation syndrome is more common with shorter-acting SSRIs (paroxetine, fluvoxamine, sertraline) 5
• Symptoms include dizziness, fatigue, sensory disturbances, anxiety, irritability
• Taper medications slowly over 10-14 days to minimize withdrawal symptoms 1

Medication Selection Algorithm

1. First attempt: SSRI (sertraline or escitalopram)

   • Lower risk of drug interactions
   • Well-established efficacy in multiple anxiety disorders
   • Good long-term safety profile

2. If inadequate response or intolerance to first SSRI:

   • Try a different SSRI or switch to an SNRI

3. If inadequate response to multiple SSRIs/SNRIs:

   • Consider augmentation with bupropion or mirtazapine
   • Consider buspirone as an alternative

4. For treatment-resistant cases:

   • Combination therapy (medication plus CBT) shows superior outcomes 5

Monitoring

• Reassess symptoms every 2-4 weeks during medication changes 1
• Monitor for side effects, particularly during initiation and dose changes
• Evaluate for suicidal ideation, especially in young adults
• Reassess need for medication after 9 months of treatment 1

Cautions

• Benzodiazepines are not recommended for routine long-term use due to risk of dependence, though they may have higher tolerability than other classes 9
• Avoid MAOIs with SSRIs/SNRIs due to risk of serotonin syndrome 5
• Use caution when prescribing SSRIs/SNRIs with other serotonergic medications 5