What is the first-line medication for treating anxiety?

First-Line Medication for Anxiety

Start with escitalopram (10-20 mg/day) or sertraline (50-200 mg/day) as your first-line medication for anxiety disorders—these SSRIs demonstrate superior efficacy and tolerability compared to other agents. 1, 2

Preferred Initial Agents

• Escitalopram and sertraline are the top-tier first-line choices due to their established efficacy, favorable side effect profiles, and lower discontinuation rates compared to other SSRIs 1, 2
• Both medications demonstrate high treatment response rates with a number needed to treat (NNT) of approximately 4.70 for SSRIs as a class 1
• These agents have dropout rates similar to placebo, indicating excellent tolerability 1

Dosing Strategy

Escitalopram:

• Start at 5-10 mg daily 1, 2
• Titrate by 5-10 mg increments every 1-2 weeks 1
• Target therapeutic dose: 10-20 mg/day 1, 2

Sertraline:

• Start at 25-50 mg daily 1, 2, 3
• Titrate by 25-50 mg increments every 1-2 weeks as tolerated 1, 2
• Target therapeutic dose: 50-200 mg/day 1, 2, 3

Expected Timeline for Response

• Statistically significant improvement begins by week 2 4, 1, 2
• Clinically significant improvement occurs by week 6 4, 1, 2
• Maximal therapeutic benefit achieved by week 12 or later 4, 1, 2
• Do not abandon treatment prematurely—full response may require 12+ weeks 1, 2
• Allow 1-2 weeks between dose increases to assess tolerability and avoid overshooting the therapeutic window 1, 2

Alternative First-Line SSRIs

• Fluoxetine (20-40 mg/day) can be considered, particularly for patients who occasionally miss doses due to its longer half-life 1, 2
• Paroxetine and fluvoxamine are equally effective but should be reserved for when first-tier SSRIs fail due to higher risks of discontinuation symptoms 4, 1, 2

SNRIs as First-Line Alternatives

• Duloxetine (60-120 mg/day) is particularly beneficial for patients with comorbid pain conditions 1, 2
  • Start at 30 mg daily for one week to reduce nausea, then increase to 60 mg 1, 2
• Venlafaxine extended-release (75-225 mg/day) is effective across all anxiety disorders but requires blood pressure monitoring due to risk of sustained hypertension 1, 2, 5
• SNRIs demonstrate comparable efficacy to SSRIs with an NNT of 4.94 1

Critical Monitoring Requirements

• Monitor closely for suicidal thinking and behavior, especially in the first months and following dose adjustments (pooled risk difference 0.7% vs placebo, NNH = 143) 4, 1
• All SSRIs carry a boxed warning for suicidal thinking and behavior through age 24 years 4
• Assess response using standardized anxiety rating scales such as HAM-A 1, 2

Common Side Effects

• Most adverse effects emerge within the first few weeks and typically resolve with continued treatment 4, 1, 2
• Common side effects include: nausea, sexual dysfunction, headache, insomnia, dry mouth, diarrhea, somnolence, and dizziness 4, 1, 2
• Start with low doses to minimize initial anxiety/agitation that can occur with SSRIs in the first few weeks 1, 2

Algorithm for Inadequate Response

• If first SSRI fails after 8-12 weeks at therapeutic doses, switch to a different SSRI (e.g., sertraline to escitalopram or vice versa) rather than increasing to supramaximal doses 1, 2
• Consider adding cognitive behavioral therapy if not already implemented 1, 2
• Combining medication with CBT provides superior outcomes compared to either treatment alone 4, 1, 2, 5

Medications to Avoid

• Tricyclic antidepressants should be avoided due to unfavorable risk-benefit profile, particularly cardiac toxicity 1, 2
• Beta blockers (atenolol, propranolol) are deprecated based on negative evidence 1, 2

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, 2, 6

Combination with Psychotherapy

• Combining medication with cognitive behavioral therapy (CBT) provides superior outcomes compared to either treatment alone 4, 1, 2, 5
• Individual CBT is prioritized over group therapy due to superior clinical and cost-effectiveness 1, 2
• CBT demonstrates large effect sizes for generalized anxiety disorder (Hedges g = 1.01) 1, 2, 5

Critical Pitfalls to Avoid

• Do not escalate doses too quickly—gradual up-titration prevents unintentionally exceeding the optimal dose, as SSRI response follows a logarithmic model with diminishing returns at higher doses 4, 1, 2
• Do not discontinue abruptly—taper gradually to avoid withdrawal symptoms, particularly with shorter half-life SSRIs 2
• Do not abandon treatment before 12 weeks—patience is crucial as maximal benefit may not occur until week 12 or later 4, 1, 2