What are alternative anxiolytics (anxiety-reducing medications) to benzodiazepines (Benzos) for treating generalized anxiety disorder?

Non-Benzodiazepine Anxiolytics for Generalized Anxiety Disorder

SSRIs and SNRIs should be considered first-line pharmacological treatments for generalized anxiety disorder due to their established efficacy, favorable safety profiles, and lower risk of dependence compared to benzodiazepines. 1

First-Line Options

SSRIs (Selective Serotonin Reuptake Inhibitors)

• Preferred options: Escitalopram (10mg daily) and sertraline - recommended for their superior safety profiles 1
• Other effective SSRIs:
  • Fluvoxamine: 50mg twice daily initially, maximum 150mg twice daily
  • Paroxetine: 10mg daily initially, maximum 40mg daily
  • Fluoxetine: Similar efficacy to other SSRIs

SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)

• Venlafaxine: 37.5mg daily initially, maximum 225mg daily 1
• Duloxetine: Particularly useful when anxiety co-occurs with chronic pain 1

Second-Line Options

Buspirone

• Indication: FDA-approved for management of anxiety disorder 2
• Dosing: Start at 5mg twice daily, can be titrated up to maximum 60mg daily 1
• Advantages:
  • Non-habit forming alternative to benzodiazepines
  • Particularly useful in patients with substance use histories
  • Effective for GAD, especially with coexisting depressive symptoms 2
• Limitations: May take 2-4 weeks for full effect

Special Populations and Considerations

Older Adults

• Start with lower doses of SSRIs (sertraline or escitalopram)
• Avoid benzodiazepines due to increased risk of falls, cognitive impairment

Patients with Comorbid Depression

• SSRIs or SNRIs are strongly preferred over benzodiazepines or buspirone 3
• Venlafaxine or duloxetine may be particularly effective for combined anxiety and depression 4

Patients with Substance Use History

• Avoid benzodiazepines
• Consider buspirone or SSRIs as safer alternatives 1

Treatment Duration and Monitoring

• Initial phase: Evaluate for side effects and treatment effectiveness every 2-4 weeks
• Maintenance: Continue treatment for at least 9-12 months after symptom remission
• Monitoring: Use standardized scales like GAD-7 to track progress
• Discontinuation: Gradual tapering to prevent discontinuation syndrome, particularly with SSRIs and SNRIs

Medications to Avoid as First-Line

Benzodiazepines

• Not recommended for routine or long-term use due to:
  • Risk of tolerance development
  • Addiction potential
  • Cognitive impairment
  • Paradoxical agitation (occurs in ~10% of patients) 1
  • Withdrawal symptoms with discontinuation

Antipsychotics

• Should be reserved for treatment-resistant cases or specific comorbidities
• Higher side effect burden compared to first-line options

Treatment Algorithm

1. Start with an SSRI or SNRI (escitalopram or sertraline preferred)
2. If ineffective after 4-6 weeks at adequate dose:
   • Switch to a different SSRI/SNRI
   • OR add buspirone
3. If still inadequate response:
   • Consider combination therapy
   • Consider referral to psychiatry for more specialized treatment options

Important Clinical Pearls

• GAD is a chronic condition requiring long-term treatment; remission is attainable but may take several months 5
• Stopping medication increases relapse risk within the first year of treatment 5
• Serotonergic antidepressants are effective long-term treatments (6-12 months minimum) even without comorbid depression 6
• The calculated Number Needed to Treat (NNT) for antidepressants in GAD is approximately 5.15 7