What short‑acting benzodiazepine and PRN dose are appropriate for acute anxiety in a healthy adult, and what alternative should be used if the patient has a substance‑use history, respiratory disease, is elderly, pregnant, or has severe hepatic impairment?

PRN Benzodiazepines for Acute Anxiety in Healthy Adults

For acute anxiety in a healthy adult, lorazepam 0.5–1 mg orally PRN is the most appropriate short-acting benzodiazepine, limited to intermittent use over no more than 2–4 weeks. 1, 2

Dosing and Administration for Healthy Adults

• Lorazepam 0.5–1 mg orally PRN is the preferred agent due to its intermediate half-life (10–20 hours), lack of active metabolites, and predictable absorption 1, 2
• The FDA-approved dosing range for anxiety is 2–6 mg/day in divided doses, but PRN use should involve single doses of 0.5–1 mg taken only when acute anxiety occurs, not on a fixed schedule 1
• Maximum duration should not exceed 2–4 weeks to minimize tolerance and dependence risk 2, 3
• Patients should be instructed to take a single dose at the onset of acute anxiety symptoms, with the understanding that onset of action occurs within 30–60 minutes 4

Alternative Agents for Specific Populations

Substance Use History

• Buspirone 5 mg twice daily (maximum 20 mg three times daily) is the preferred non-controlled alternative, though it requires 2–4 weeks to become effective and is only useful for mild-to-moderate anxiety 5
• SSRIs (sertraline 25–50 mg/day or escitalopram 10 mg/day) are first-line for chronic anxiety in patients with substance use history, as benzodiazepines carry high abuse potential 6, 3
• Benzodiazepines should be completely avoided in patients with active substance use disorders due to cross-tolerance, abuse liability, and risk of dose escalation 3

Respiratory Disease

• Benzodiazepines are contraindicated in patients with significant respiratory compromise (COPD, sleep apnea, respiratory failure) due to respiratory depression risk 7
• Buspirone 5 mg twice daily is the safest alternative, as it lacks respiratory depressant effects 5
• SSRIs (sertraline or escitalopram) are appropriate for chronic anxiety management without respiratory risk 6

Elderly Patients (≥65 years)

• Lorazepam 0.25–0.5 mg orally PRN (maximum 2 mg in 24 hours) is the only acceptable benzodiazepine option if absolutely necessary for acute management 6, 1
• The American Geriatrics Society strongly recommends avoiding benzodiazepines in older adults due to increased risk of cognitive impairment, delirium, falls, fractures, and paradoxical agitation (occurs in ~10% of elderly patients) 7, 6
• Preferred alternatives include:
  • SSRIs: sertraline 25 mg/day or escitalopram 10 mg/day, starting at half the standard adult dose and titrating slowly 6
  • Buspirone 5 mg twice daily for relatively healthy elderly patients with mild-to-moderate anxiety 6, 5
• Elderly patients have reduced renal clearance and increased drug accumulation even without documented renal disease, requiring dose reduction 6

Pregnancy

• Benzodiazepines should be avoided in pregnancy, particularly in the first trimester, due to potential teratogenic effects and neonatal withdrawal syndrome 3
• Non-pharmacological interventions (cognitive behavioral therapy) are first-line for anxiety in pregnancy 6
• If pharmacotherapy is essential, SSRIs (sertraline) after the first trimester may be considered with careful risk-benefit discussion, though this is beyond the scope of acute PRN management 6

Severe Hepatic Impairment

• Lorazepam or oxazepam are the only acceptable benzodiazepines in hepatic impairment, as they undergo direct glucuronidation without hepatic oxidation 8
• Lorazepam 0.5 mg orally PRN should be used at the lowest effective dose with extended dosing intervals (every 8–12 hours maximum) 8, 1
• Avoid diazepam and chlordiazepoxide, which have long half-lives and active metabolites that accumulate dangerously in hepatic dysfunction 8
• Buspirone 5 mg twice daily is a safer non-benzodiazepine alternative that does not require dose adjustment in mild-to-moderate hepatic impairment 5

Critical Safety Warnings

• Dependence develops in 30–45% of patients on chronic benzodiazepine therapy, even at therapeutic doses 9
• Withdrawal symptoms (insomnia, anxiety, tremor, perspiration, perceptual disturbances) occur in a substantial proportion of long-term users and typically last 8–10 days 10
• Psychomotor impairment and memory disruption are common, particularly when combined with alcohol 2, 3
• Elderly patients are at markedly increased risk for oversedation, ataxia, confusion, and falls 10
• Gradual taper is mandatory when discontinuing after more than 2–4 weeks of use to prevent withdrawal reactions 1

Optimal PRN Strategy

• Patient-controlled dosing with diary tracking has been shown effective: patients record anxiety episodes, precipitating factors, medication use, and response 4
• This approach enhances patient awareness and capacity to control anxiety episodes while minimizing total benzodiazepine exposure 4
• Combine with brief psychotherapy to identify triggers and develop coping mechanisms, using the medication diary as a starting point for therapy sessions 4
• Limit prescriptions to 7–14 days of intermittent use whenever possible, with explicit instructions that this is short-term symptom control, not a long-term solution 2, 9