What non‑benzodiazepine first‑line medication can be used for an adult with an acute anxiety episode who has no contraindications such as severe respiratory depression, uncontrolled glaucoma, or benzodiazepine dependence?

Non-Benzodiazepine First-Line Medication for Acute Anxiety

For an adult with an acute anxiety episode, selective serotonin reuptake inhibitors (SSRIs)—specifically escitalopram or sertraline—are the recommended first-line pharmacological treatment, not benzodiazepines. 1

Why SSRIs Are Preferred Over Benzodiazepines

• SSRIs demonstrate high-quality evidence for efficacy in anxiety disorders with moderate to high strength of evidence, showing improvement in primary anxiety symptoms, response to treatment, and remission rates. 1
• Benzodiazepines should be limited to short-term use only (days to a few weeks) due to high risk of dependence, tolerance, cognitive impairment, and withdrawal syndromes. 1
• Benzodiazepines are not recommended for initial treatment of anxiety disorders except in specific circumstances such as alcohol or benzodiazepine withdrawal. 2
• Long-term benzodiazepine use carries risks of cognitive disorders, dependence, and withdrawal syndromes that outweigh benefits in most anxiety presentations. 3

Specific SSRI Recommendations

First-Tier Options

• 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 and increase by 5-10 mg increments every 1-2 weeks, targeting 10-20 mg/day. 1
• Start sertraline at 25-50 mg daily and titrate by 25-50 mg increments every 1-2 weeks as tolerated, targeting 50-200 mg/day. 1

Expected Timeline

• Statistically significant improvement may begin by week 2, with clinically meaningful improvement expected by week 6, and maximal therapeutic benefit achieved by week 12 or later. 1
• Do not abandon treatment prematurely—full response may take 12+ weeks, and patience in dose escalation is crucial for optimal outcomes. 1

Alternative First-Line Options

SNRIs as Equally Valid First-Line

• Venlafaxine extended-release (75-225 mg/day) or duloxetine (60-120 mg/day) are effective alternatives when SSRIs are not preferred or tolerated. 1
• Venlafaxine requires blood pressure monitoring due to risk of sustained hypertension. 1
• Duloxetine has additional benefits for patients with comorbid pain conditions. 1

Buspirone for Specific Populations

• Buspirone is an option for relatively healthy older adults when avoiding sexual side effects is a priority, though it is generally less effective than SSRIs. 4

Critical Warnings and Monitoring

Common Side Effects

• Most adverse effects emerge within the first few weeks and typically resolve with continued treatment, including nausea, sexual dysfunction, headache, insomnia, dry mouth, diarrhea, and dizziness. 1
• Starting with lower doses and titrating gradually minimizes initial anxiety/agitation that can occur with SSRIs. 1

Suicide Risk

• All SSRIs carry a boxed warning for suicidal thinking and behavior, with pooled absolute rates of 1% versus 0.2% for placebo (NNH = 143). 1
• Close monitoring is essential, especially in the first months and following dose adjustments. 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. 1
• Individual CBT (12-20 sessions) is more clinically effective and cost-effective than group therapy for adult anxiety disorders. 1

When Benzodiazepines May Be Considered

• Benzodiazepines are effective at providing sedation and potentially anxiolysis in the acute management of severe symptomatic distress associated with delirium or extreme agitation. 2
• Short-term use is justified only in patients with severe symptomatic distress and/or impairment of ability to cope, and only for days to weeks. 5
• The clinical decision to use benzodiazepines must involve assessment of the level of patient distress, safety risks, and patient mobility. 2

Common Pitfalls to Avoid

• Do not use benzodiazepines as first-line or long-term therapy for anxiety disorders—they are deliriogenic and associated with falls in those with functional mobility. 2
• Do not escalate SSRI doses too quickly—allow 1-2 weeks between increases to assess tolerability and avoid overshooting the therapeutic window. 1
• Do not stop treatment before 9-12 months after recovery to prevent relapse. 2
• Taper SSRIs gradually when discontinuing to avoid withdrawal symptoms, particularly with shorter half-life agents like sertraline and paroxetine. 1