When should we consider serotonin-norepinephrine reuptake inhibitors (SNRIs) for generalized anxiety disorder (GAD)?

When to Consider SNRIs for Generalized Anxiety Disorder

SNRIs should be considered as a first-line pharmacological treatment option for generalized anxiety disorder (GAD), particularly when patients have comorbid pain conditions or have not responded adequately to SSRIs. 1

First-Line Treatment Options for GAD

Psychotherapy

• Cognitive-behavioral therapy (CBT) remains the first-line non-pharmacological treatment for GAD
• Should consist of 14 sessions over approximately 4 months, with individual sessions lasting 60-90 minutes 1
• Components include psychoeducation, cognitive restructuring, gradual exposure to feared situations, and relapse prevention

Pharmacotherapy

1. SSRIs (First-line pharmacotherapy)

   • Recommended by multiple guidelines as first-line pharmacological treatment 1, 2
   • High-certainty evidence shows effectiveness in GAD with an NNTB of 7 2
   • Examples: sertraline, paroxetine, fluoxetine, escitalopram

2. SNRIs (Alternative first-line option)

   • Comparable efficacy to SSRIs in treating GAD 1, 3
   • Venlafaxine and duloxetine have the most robust evidence 4, 5
   • Duloxetine is FDA-approved for GAD in children and adolescents 7 years and older 6

Specific Indications for Choosing SNRIs Over SSRIs

SNRIs should be considered as the preferred first-line pharmacological option in the following scenarios:

1. Comorbid pain conditions

   • When GAD co-occurs with chronic pain, fibromyalgia, or neuropathic pain 1, 5
   • Duloxetine has demonstrated efficacy for both anxiety and pain conditions 5

2. Inadequate response to SSRIs

   • When patients have previously failed an adequate trial of an SSRI 7
   • The Harvard South Shore Algorithm recommends trying an SNRI after inadequate response to two different SSRIs 7

3. Need for more rapid symptom control

   • Some evidence suggests SNRIs may provide faster relief of anxiety symptoms compared to some SSRIs 5

4. Specific patient populations

   • Children and adolescents with GAD (duloxetine is FDA-approved for ages 7-17) 6
   • Japanese guidelines specifically recommend venlafaxine (SNRI) as a suggested treatment for GAD 4

Dosing and Administration of SNRIs for GAD

• Duloxetine:

  • Starting dose: 30 mg daily
  • Target dose: 60-120 mg daily
  • FDA-approved for children 7-17 years old 6
  • Monitor for side effects including nausea, dry mouth, constipation, dizziness, and fatigue 6, 5

• Venlafaxine:

  • Starting dose: 37.5-75 mg daily
  • Target dose: 75-225 mg daily
  • Extended-release formulation preferred for once-daily dosing 5

Monitoring and Follow-up

• Assess response after 4-6 weeks of starting medication 1
• Monitor for common side effects: nausea, dry mouth, headache, constipation, dizziness, and fatigue 5
• In children and adolescents, monitor weight and height regularly as decreased appetite and weight loss may occur 6
• Continue treatment for at least 6-12 months after symptom remission 1
• Gradual tapering is essential when discontinuing to avoid withdrawal symptoms 1, 5

Cautions and Considerations

• More patients discontinue SNRIs due to adverse effects compared to placebo (NNTH of 17) 2
• Discontinuation-emergent adverse events may occur in up to one-third of patients 5
• In pediatric patients, monitor for decreased appetite, weight loss, and potential impacts on growth 6
• SNRIs may increase blood pressure and heart rate in some patients 5
• Use with caution in patients with hepatic or renal impairment 1

Treatment Algorithm for GAD

1. Start with CBT as first-line treatment when available and acceptable to patient
2. For pharmacotherapy:
   • First choice: SSRI (sertraline, paroxetine, fluoxetine)
   • Alternative first choice: SNRI (duloxetine, venlafaxine) especially with comorbid pain
3. If inadequate response to first medication after 4-6 weeks:
   • Switch to a different SSRI or SNRI
4. If still inadequate response:
   • Consider augmentation strategies or alternative medication classes

Remember that treatment of GAD is generally long-term, considering the chronic nature of the condition, with the goal of not only symptom resolution but also improvement in functioning and quality of life 1.