What non‑benzodiazepine pharmacologic options are appropriate for an adult with an acute anxiety episode who has no contraindications such as severe respiratory depression, uncontrolled glaucoma, or benzodiazepine dependence?

Non-Benzodiazepine Pharmacologic Options for Acute Anxiety

For an adult with an acute anxiety episode, SSRIs (escitalopram or sertraline) are the preferred first-line pharmacologic treatment, with SNRIs (venlafaxine or duloxetine) as effective alternatives when SSRIs are not tolerated or preferred. 1

First-Line SSRI Options

Escitalopram and sertraline are the top-tier first-line agents because they demonstrate the lowest potential for drug-drug interactions and the smallest discontinuation-symptom burden compared with other SSRIs. 1

Escitalopram Dosing

• Start at 5-10 mg daily and increase by 5-10 mg increments every 1-2 weeks 1
• Target therapeutic dose: 10-20 mg daily by weeks 4-6 1, 2
• FDA-approved for generalized anxiety disorder in adults 2
• Expect statistically significant improvement by week 2, clinically meaningful improvement by week 6, and maximal benefit by week 12 or later 1

Sertraline Dosing

• Start at 25-50 mg daily to minimize initial anxiety/agitation 1
• Titrate by 25-50 mg increments every 1-2 weeks as tolerated 1
• Target dose: 50-200 mg/day 1

Common SSRI Side Effects

Monitor for nausea, sexual dysfunction, headache, insomnia, dry mouth, diarrhea, heartburn, somnolence, dizziness, and vivid dreams—most emerge within the first few weeks and typically resolve with continued treatment. 1

Critical warning: All SSRIs carry a boxed warning for suicidal thinking and behavior (pooled absolute rates 1% vs 0.2% for placebo), requiring close monitoring especially in the first months and following dose adjustments. 1

First-Line SNRI Alternatives

Venlafaxine extended-release (75-225 mg/day) and duloxetine (60-120 mg/day) are effective alternatives when SSRIs fail or are not tolerated after an adequate 8-12 week trial. 1, 3

Venlafaxine XR

• Start at 75 mg daily, titrate to 75-225 mg/day 1
• Number needed to treat (NNT) = 4.94, comparable to SSRIs 1
• Requires blood pressure monitoring due to risk of sustained hypertension 1
• Higher risk of discontinuation symptoms—taper gradually over 10-14 days when stopping 1

Duloxetine

• Dose range: 60-120 mg/day 1
• Additional benefits for patients with comorbid pain conditions 1
• Start at 30 mg daily for one week to reduce nausea 1

Second-Line SSRI Options

Paroxetine and fluvoxamine are equally effective but recommended as second-tier agents due to higher rates of discontinuation symptoms and greater potential for drug-drug interactions. 1

Pregabalin as an Alternative

Pregabalin (450-600 mg/day) represents an evidence-based alternative for patients who have failed SSRIs, with faster onset of anxiolytic effects (within one week) compared to SSRIs/SNRIs and less cognitive impairment than benzodiazepines. 4, 5

• Listed as first-line option by Canadian guidelines 4
• Demonstrates similar rapid onset to benzodiazepines but without the same dependence liability 4

Medications to Avoid

Beta-blockers (atenolol, propranolol) are deprecated by Canadian guidelines for generalized and social anxiety disorder based on negative evidence. 6, 1

Benzodiazepines should be limited to short-term (days to a few weeks) adjunctive use only due to high risk of dependence, tolerance, cognitive impairment, and withdrawal syndromes—they must not be used as first-line or long-term therapy. 1, 7, 8

Essential Treatment Algorithm

1. Initiate SSRI (escitalopram 10 mg or sertraline 50 mg daily) with gradual titration 1
2. Assess response at 4 weeks—early response is the strongest predictor of 12-week outcome 1
3. If inadequate response at 8-12 weeks at therapeutic doses, switch to a different SSRI or SNRI 1
4. Consider adding individual CBT (12-20 sessions)—combined treatment yields superior outcomes compared to medication alone 1
5. Continue effective medication for 9-12 months after achieving remission to prevent relapse 1

Critical Pitfalls to Avoid

• Do not abandon treatment prematurely—full response may take 12+ weeks 1
• Do not escalate doses too quickly—allow 1-2 weeks between increases to assess tolerability 1
• Do not use benzodiazepines as first-line therapy except for severe acute symptomatic distress requiring rapid sedation (days to weeks maximum) 1, 7
• Do not prescribe beta-blockers for generalized or social anxiety disorder 6, 1
• Do not rely on medication alone—combining with CBT provides superior outcomes for moderate to severe anxiety 1