What is the first-line pharmacologic treatment for mild anxiety?

First-Line Pharmacologic Treatment for Mild Anxiety

Selective serotonin reuptake inhibitors (SSRIs)—specifically escitalopram or sertraline—are the first-line medications for mild anxiety disorders due to their established efficacy, favorable safety profile, and lack of dependence risk. 1, 2

Preferred SSRI Options

• Escitalopram and sertraline are recommended as top-tier first-line agents because they have the lowest potential for drug-drug interactions and the smallest discontinuation-symptom burden compared with other SSRIs 1, 3
• Start escitalopram at 5-10 mg daily and titrate to a target dose of 10-20 mg daily over 4-6 weeks 1
• Start sertraline at 25-50 mg daily for the first week to minimize initial anxiety or agitation, then increase to 50-200 mg daily based on response 1, 4

Alternative First-Line Options

• Venlafaxine extended-release (an SNRI) at 75-225 mg daily is an effective alternative when SSRIs are not tolerated or preferred, though it requires blood pressure monitoring due to risk of sustained hypertension 1, 2
• Duloxetine (another SNRI) at 60-120 mg daily has demonstrated efficacy in generalized anxiety disorder and offers additional benefits for patients with comorbid pain conditions 1

Expected Timeline and Response

• Statistically significant improvement may begin by week 2, with clinically significant improvement expected by week 6, and maximal therapeutic benefit achieved by week 12 or later 1
• Allow a full 8-12 weeks at therapeutic doses before declaring treatment failure, as SSRI response follows a logarithmic model with diminishing returns at higher doses 1
• Continue effective medication for a minimum of 9-12 months after achieving remission to prevent relapse 1

Critical Monitoring Requirements

• Assess for suicidal thinking and behavior at every visit, especially during the first 1-2 months and following dose adjustments, as SSRIs carry a pooled risk of 1% versus 0.2% for placebo (number needed to harm = 143) 1, 4
• Monitor for common early side effects including nausea, headache, insomnia, sexual dysfunction, and initial anxiety/agitation—most resolve within the first few weeks of continued treatment 1
• Use standardized anxiety rating scales (e.g., GAD-7, HAM-A) to objectively track symptom response 1

Combination with Psychotherapy

• Combining an SSRI with individual cognitive behavioral therapy (CBT) provides superior outcomes compared to either treatment alone for moderate to severe anxiety, with CBT demonstrating large effect sizes (Hedges g = 1.01 for generalized anxiety disorder) 1, 2
• A structured course of 12-20 CBT sessions targeting anxiety-specific cognitive distortions and gradual exposure techniques is recommended 1
• Individual CBT is prioritized over group therapy due to superior clinical and cost-effectiveness 1

Medications to Avoid

• Benzodiazepines should be reserved for short-term use only (days to a few weeks) due to high risks of dependence, tolerance, cognitive impairment, and withdrawal syndromes—they must not be used as first-line or long-term therapy 1, 2
• Tricyclic antidepressants (TCAs) should be avoided due to their unfavorable risk-benefit profile, particularly cardiac toxicity 1
• Paroxetine and fluvoxamine are equally effective but carry higher risks of discontinuation symptoms and should be reserved for when first-tier SSRIs fail 1

Common Pitfalls to Avoid

• Do not escalate doses too quickly—allow 1-2 weeks between increases to assess tolerability and avoid overshooting the therapeutic window 1
• Do not switch medications before allowing adequate trial duration (6-8 weeks at therapeutic dose), as premature switching leads to missed opportunities for response 1
• Do not discontinue SSRIs abruptly—taper gradually to avoid withdrawal symptoms, particularly with shorter half-life agents like sertraline and paroxetine 1
• Do not commence pharmacotherapy for mild anxiety before trialing evidence-based non-pharmacologic interventions such as CBT, which provide more durable benefits 1