What are the treatment recommendations for Generalized Anxiety Disorder (GAD) in adults?

Treatment Recommendations for Generalized Anxiety Disorder (GAD) in Adults

First-line pharmacotherapy for GAD in adults should be selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) due to their established efficacy and favorable safety profiles.**

First-Line Pharmacological Options

SSRIs* (FDA-approved for GAD)

• Escitalopram*
• Paroxetine*
• Sertraline* (preferred in older adults)

SNRIs* (FDA-approved for GAD)

• Venlafaxine* (suggested with weak recommendation/low certainty evidence) 1
• Duloxetine*

Psychotherapy Options

• Cognitive Behavioral Therapy (CBT) - specifically developed for anxiety disorders
  • Individual therapy is preferred over group therapy for better clinical outcomes 1
  • Self-help with support based on CBT principles can be considered if patient declines face-to-face therapy 1

Treatment Algorithm

Step 1: Initial Treatment

• Begin with an SSRI* or SNRI* at a low dose and gradually titrate up
• Monitor for response over 4-8 weeks
• Common side effects to monitor: nausea, headache, insomnia, sexual dysfunction
• For SNRIs like venlafaxine*, monitor for potential increases in blood pressure 2

Step 2: Inadequate Response to First-Line Treatment

• Switch to a different SSRI* or SNRI*
• Consider augmentation with psychotherapy (CBT)

Step 3: Continued Inadequate Response

Consider one of the following:

• Pregabalin (not FDA-approved for GAD in US but has evidence for efficacy) 3
• Buspirone* (FDA-approved for GAD)
• Quetiapine (second-generation antipsychotic, off-label) 3

Step 4: Treatment-Resistant GAD

• Consider benzodiazepines* (alprazolam*, lorazepam*, clonazepam*) for short-term use only 4
  • Use with caution due to risk of dependence, tolerance, and withdrawal
  • Alprazolam* is FDA-approved for GAD with dosing typically 0.25 to 0.5 mg three times daily, maximum 4 mg/day 4

Special Considerations

Older Adults

• Prefer sertraline* or escitalopram* as first-line options 5
• Use lower starting doses and titrate more slowly
• Avoid benzodiazepines when possible due to increased risk of falls, cognitive impairment
• Consider buspirone as an alternative if sexual side effects are a concern 5

Monitoring and Follow-up

• Assess treatment response using standardized measures (e.g., GAD-7)
• Regular follow-up at 2-4 week intervals initially
• Monitor for side effects, particularly during initiation and dose changes
• For patients on benzodiazepines, reassess frequently to minimize duration of use

Important Cautions

• Benzodiazepines have higher efficacy (effect size 0.50) compared to SSRIs (0.33) and SNRIs (0.36) 6, but their use should be limited due to dependence risk
• Hyponatremia risk with SSRIs/SNRIs, especially in older adults 2
• Weight changes may occur with venlafaxine* (weight loss in 6% of patients) 2
• Discontinuation of any medication should be gradual to avoid withdrawal symptoms

Maintenance Treatment

• For patients who respond to pharmacotherapy, continue treatment for at least 6-12 months
• Consider longer-term maintenance for patients with recurrent episodes
• Periodically reassess the need for continued treatment

*FDA-approved for GAD