What is the first-line treatment for anxiety disorders?

First-Line Treatment for Anxiety Disorders

Selective serotonin reuptake inhibitors (SSRIs)—specifically sertraline or escitalopram—are the recommended first-line pharmacological treatment for anxiety disorders, with cognitive behavioral therapy (CBT) as the preferred psychotherapy or as combination treatment. 1, 2

Pharmacotherapy Approach

Preferred First-Line Agents

Start with either sertraline or escitalopram as these SSRIs have the most favorable evidence profiles for effectiveness, tolerability, and safety across anxiety disorder subtypes 1, 2:

• Sertraline: Begin at 25-50 mg daily, titrate by 25-50 mg increments every 1-2 weeks as tolerated, target dose 50-200 mg/day 2, 3
• Escitalopram: Begin at 5-10 mg daily, titrate by 5-10 mg increments every 1-2 weeks, target dose 10-20 mg/day 2

These agents are prioritized because they have lower potential for drug interactions and more favorable discontinuation profiles compared to other SSRIs 1, 4.

Alternative First-Line Options

If SSRIs are ineffective or not tolerated, switch to an SNRI 1, 2:

• Venlafaxine extended-release: 75-225 mg/day, effective across generalized anxiety disorder, panic disorder, and social anxiety disorder 5, 1, 2
  • Critical monitoring requirement: Check blood pressure regularly due to risk of sustained hypertension 2
• Duloxetine: 60-120 mg/day, particularly beneficial if comorbid pain conditions exist 2

Agents to Avoid or Use with Caution

• Paroxetine and fluoxetine should generally be avoided due to higher rates of adverse effects, more severe discontinuation symptoms, and greater drug interaction potential 1, 2, 4
• Benzodiazepines are not recommended for routine use despite their efficacy, given dependency risks and should be reserved for short-term crisis management only 6, 7

Psychotherapy Approach

Cognitive behavioral therapy (CBT) is the psychotherapy with the highest level of evidence for anxiety disorders, demonstrating large effect sizes (Hedges g = 1.01 for generalized anxiety disorder) 1, 2, 8:

• Individual CBT sessions are superior to group therapy for both clinical effectiveness and cost-effectiveness 1, 2
• Structured protocol of 12-20 sessions is recommended for optimal outcomes 2
• Self-help CBT with professional support is a viable alternative when face-to-face therapy is not feasible 1

Treatment Timeline and Monitoring

Expected Response Pattern

• Statistically significant improvement may begin by week 2 2
• Clinically significant improvement expected by week 6 2
• Maximal therapeutic benefit achieved by week 12 or later 2

Common pitfall: Abandoning treatment prematurely before 12 weeks or escalating doses too quickly before allowing adequate time to assess response at each dose level 2.

Treatment Duration

• First episode: Continue pharmacotherapy for at least 4-12 months after symptom remission 1, 6
• Recurrent anxiety: Consider longer-term or indefinite treatment 1, 4
• Regular monitoring using validated scales (e.g., GAM-A, GAD-7) is essential 2

Combination Therapy Considerations

While evidence for superiority of combined pharmacotherapy plus CBT over either alone is insufficient to make a definitive recommendation, combining both modalities is reasonable in clinical practice, particularly for patients with severe symptoms or inadequate response to monotherapy 5, 1, 8.

Special Population: Elderly Patients

For patients over 60 years old, sertraline and escitalopram remain preferred due to lower drug interaction potential 1, 4:

• Start at half the standard adult dose (sertraline 25 mg, escitalopram 5 mg) 4
• Titrate more gradually at 1-2 week intervals for shorter half-life agents, 3-4 weeks for longer half-life agents 4
• Avoid paroxetine and fluoxetine entirely in elderly patients 1, 4

Common Adverse Effects and Management

Most SSRI/SNRI adverse effects emerge within the first few weeks and typically resolve with continued treatment 2:

• Nausea, headache, insomnia, sexual dysfunction, dizziness 2
• Initial anxiety or agitation can occur—this is why starting at lower doses is critical 2
• Never discontinue abruptly—taper gradually to avoid discontinuation syndrome (dizziness, paresthesias, anxiety, irritability) 4, 9

Treatment Algorithm for Inadequate Response

If symptoms are stable or worsening after 8 weeks at therapeutic doses with good adherence 4:

1. Switch to a different SSRI (e.g., sertraline to escitalopram or vice versa) 2, 4
2. Switch to an SNRI (venlafaxine or duloxetine) 2
3. Add CBT if not already implemented 2
4. Consider pregabalin as second-line option 2, 7