What are the treatment options for anxiety?

Treatment Options for Anxiety

Start with an SSRI (escitalopram or sertraline preferred) or SNRI (venlafaxine or duloxetine) as first-line pharmacotherapy, combined with individual cognitive behavioral therapy (CBT) when available, as this combination provides superior outcomes compared to either treatment alone. 1, 2

First-Line Pharmacotherapy

Preferred SSRIs

• Escitalopram and sertraline are the top-tier first-line agents due to their established efficacy, favorable side effect profiles, and lower risk of discontinuation symptoms compared to other SSRIs 1
• Start escitalopram at 5-10 mg daily, titrating by 5-10 mg increments every 1-2 weeks to a target dose of 10-20 mg/day 1
• Start sertraline at 25-50 mg daily, titrating by 25-50 mg increments every 1-2 weeks to a target dose of 50-200 mg/day 1, 3
• Expect statistically significant improvement by week 2, clinically significant improvement by week 6, and maximal benefit by week 12 or later 1

Alternative SSRIs

• Fluoxetine (20-40 mg/day) has a longer half-life that may benefit patients who occasionally miss doses, but start at 5-10 mg daily to minimize initial anxiety or agitation 1, 4
• Paroxetine and fluvoxamine are equally effective but carry higher risks of discontinuation symptoms and should be reserved for when first-tier SSRIs fail 1

SNRIs as First-Line Alternatives

• Venlafaxine extended-release (75-225 mg/day) is effective for generalized anxiety disorder, social anxiety disorder, and panic disorder but requires blood pressure monitoring due to risk of sustained hypertension 1, 2
• Duloxetine (60-120 mg/day) has demonstrated efficacy in GAD and provides additional benefits for patients with comorbid pain conditions; start at 30 mg daily for one week to reduce nausea 1

First-Line Psychotherapy

Cognitive Behavioral Therapy

• Individual CBT is prioritized over group therapy due to superior clinical and cost-effectiveness, with large effect sizes for GAD (Hedges g = 1.01) 1, 2
• CBT should include education on anxiety, cognitive restructuring to challenge distortions, relaxation techniques, and gradual exposure when appropriate 1
• Deliver 12-20 structured CBT sessions to achieve significant symptomatic and functional improvement 1
• For social anxiety disorder specifically, use CBT protocols following the Clark and Wells model or Heimberg model through individual sessions 5

Combination Therapy Evidence

• Combination of SSRI/SNRI plus CBT provides superior outcomes compared to either treatment alone for most anxiety disorders 1, 2, 6
• In children with anxiety disorders, combination therapy achieved an 80.7% response rate versus 59.7% for CBT alone and 54.9% for sertraline alone (all superior to placebo at 23.7%) 6
• However, for social anxiety disorder in adults, there is insufficient evidence to make a strong recommendation for combined treatment due to very low certainty of evidence 7

Second-Line Options

• Pregabalin or gabapentin can be considered when first-line treatments are ineffective or not tolerated, particularly for patients with comorbid pain conditions 1
• If inadequate response after 8-12 weeks at therapeutic doses, switch to a different SSRI or SNRI rather than adding medications 1

Critical Monitoring and Side Effects

Common SSRI/SNRI Side Effects

• Nausea, sexual dysfunction, headache, insomnia, dry mouth, diarrhea, heartburn, somnolence, dizziness, and vivid dreams typically emerge within the first few weeks and often resolve with continued treatment 1

Essential Safety Monitoring

• Monitor closely for suicidal thinking and behavior, especially in the first months and following dose adjustments, with a pooled risk difference of 0.7% versus placebo (NNH = 143) 1
• Assess response using standardized anxiety rating scales (e.g., HAM-A, GAD-7) at regular intervals 1, 2
• Monitor blood pressure with venlafaxine due to risk of sustained hypertension 1

Treatment Duration and Discontinuation

• Continue medications for 6-12 months after remission to prevent relapse 8
• Discontinue gradually to avoid withdrawal symptoms, particularly with shorter half-life SSRIs; decrease by no more than 0.5 mg every 3 days or slower if needed 1, 8
• Fluoxetine's long half-life may minimize discontinuation symptoms compared to other SSRIs 4

Medications to Avoid

• Benzodiazepines (e.g., alprazolam) should be reserved for short-term use only due to risks of dependence, tolerance, and withdrawal 1, 9
• If benzodiazepines are used, alprazolam should be initiated at 0.25-0.5 mg three times daily with a maximum of 4 mg/day, and tapered by no more than 0.5 mg every 3 days when discontinuing 9
• Tricyclic antidepressants should be avoided due to unfavorable risk-benefit profile, particularly cardiac toxicity 1

Adjunctive Non-Pharmacological Interventions

• Structured physical activity and regular cardiovascular exercise provide moderate to large reduction in anxiety symptoms 1
• Breathing techniques, progressive muscle relaxation, grounding strategies, visualization, mindfulness, and sensory grounding techniques are useful adjunctive strategies 1
• Provide psychoeducation to family members about anxiety symptoms and treatment 1

Treatment Algorithm for Inadequate Response

1. Ensure adequate dose and duration (therapeutic dose for 8-12 weeks minimum) 1
2. Switch to a different SSRI or SNRI if first medication trial fails 1
3. Add or intensify CBT if not already implemented 1
4. Consider second-line options (pregabalin/gabapentin) if multiple SSRI/SNRI trials fail 1

Important Clinical Pitfalls

• Do not escalate SSRI/SNRI doses too quickly; allow 1-2 weeks between increases to assess tolerability and avoid overshooting the therapeutic window 1
• Do not abandon treatment prematurely; full response may take 12+ weeks 1
• Do not routinely combine pharmacotherapy and psychotherapy for social anxiety disorder without discussing risks, benefits, and costs with the patient, as evidence for combination therapy is very low quality 7
• Assess for comorbid conditions (depression, substance use) that may require additional intervention or modify treatment approach 5