What is the first-line treatment for anxiety?

First-Line Treatment of Anxiety

Cognitive Behavioral Therapy (CBT) is the first-line treatment for anxiety disorders, with SSRIs (escitalopram or sertraline) or SNRIs (venlafaxine or duloxetine) as the first-line pharmacological options when psychotherapy is unavailable, not preferred by the patient, or when combined treatment is needed. 1, 2, 3

Psychotherapy as Primary First-Line Treatment

Individual CBT should be offered as the initial treatment approach for most patients with anxiety disorders. 1, 3

• CBT demonstrates large effect sizes (Hedges g = 1.01 for generalized anxiety disorder) and has the highest level of evidence among psychotherapies 2, 3
• Individual CBT sessions are superior to group therapy in both clinical effectiveness and cost-effectiveness 2, 3
• A structured course of 12-20 CBT sessions is recommended to achieve significant symptomatic and functional improvement 2
• CBT includes specific components: psychoeducation about anxiety, cognitive restructuring to challenge distortions, relaxation techniques, and gradual exposure when appropriate 2
• Self-help CBT with professional support is a viable alternative if face-to-face CBT is not feasible or desired 3

First-Line Pharmacotherapy

When medication is indicated (patient preference, lack of access to CBT, or inadequate response to psychotherapy alone), start with an SSRI or SNRI: 1, 2, 3

Preferred SSRIs (Top-Tier First-Line):

• Escitalopram 10-20 mg/day: Start at 5-10 mg daily, titrate by 5-10 mg increments every 1-2 weeks 2
• Sertraline 50-200 mg/day: Start at 25-50 mg daily, titrate by 25-50 mg increments every 1-2 weeks 2
• These two agents have the most favorable side effect profiles and lowest risk of discontinuation symptoms 2, 3

Alternative SSRIs (Equally Effective but Higher Discontinuation Risk):

• Fluoxetine 20-40 mg/day: Start at 5-10 mg daily, longer half-life beneficial for patients who occasionally miss doses 2
• Fluvoxamine: Effective but carries higher risk of discontinuation symptoms; reserve for when first-tier SSRIs fail 2
• Paroxetine: Should be avoided due to highest risk of discontinuation syndrome and potentially increased suicidal thinking 2, 3

SNRIs as First-Line Alternatives:

• Venlafaxine extended-release 75-225 mg/day: Effective for generalized anxiety disorder, panic disorder, and social anxiety disorder; requires blood pressure monitoring 1, 2
• Duloxetine 60-120 mg/day: Start at 30 mg daily for one week to reduce nausea, then increase; additional benefits for comorbid pain conditions 2

Treatment Timeline and Monitoring

Response follows a logarithmic pattern with specific milestones: 2

• 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
• Do not abandon treatment prematurely—full response may take 12+ weeks 2

Monitor for common side effects: nausea, sexual dysfunction, headache, insomnia, dry mouth, diarrhea, dizziness 2

Critical monitoring: Watch for suicidal thinking and behavior, especially in the first months and following dose adjustments (pooled risk difference 0.7% vs placebo, NNH = 143) 2

Adjunctive Non-Pharmacological Interventions

Structured physical activity and exercise should be recommended as adjunctive treatment: 1

• Exercise provides moderate to large reduction in anxiety symptoms 1
• Regular cardiovascular exercise is recommended alongside primary treatment 2
• Breathing techniques, progressive muscle relaxation, grounding strategies, and mindfulness are useful adjunctive strategies 2

Treatment Algorithm for Inadequate Response

If first SSRI fails after 8-12 weeks at therapeutic doses: 2

1. Switch to a different SSRI (e.g., sertraline to escitalopram or vice versa) 2
2. Consider adding CBT if not already implemented 1, 2
3. Alternative: Switch to SNRI (venlafaxine or duloxetine) 2

Second-line pharmacological options when first-line treatments fail: 2

• Pregabalin/Gabapentin can be considered, particularly for patients with comorbid pain conditions 2

Treatment Duration

For first episode of anxiety: Continue pharmacological treatment for at least 4-12 months after symptom remission 3, 4

For recurrent anxiety: Longer-term or indefinite treatment may be beneficial 3

Discontinuation: Taper gradually to avoid withdrawal symptoms, particularly with shorter half-life SSRIs; decrease by no more than 0.5 mg every 3 days for medications like alprazolam 2, 5

Special Populations

Elderly patients: Prefer sertraline and escitalopram due to lower potential for drug interactions; avoid paroxetine and fluoxetine due to higher adverse effect rates 3

Cancer survivors with moderate anxiety: Offer CBT, behavioral activation, structured physical activity/exercise, or psychosocial interventions with empirically supported components (relaxation, problem solving) 1

Critical Pitfalls to Avoid

• Do not use benzodiazepines as first-line treatment due to dependence risk, tolerance, and lack of long-term efficacy 4, 6
• Avoid tricyclic antidepressants (TCAs) due to unfavorable risk-benefit profile, particularly cardiac toxicity 2
• Do not escalate SSRI/SNRI doses too quickly—allow 1-2 weeks between increases to assess tolerability and avoid overshooting the therapeutic window 2
• Do not use beta blockers (atenolol, propranolol) for social anxiety disorder based on negative evidence 2
• Pharmacotherapy alone is not optimal—combining medication with CBT provides superior outcomes 1, 2