What are alternative PRN (pro re nata) medications for severe anxiety if alprazolam (Xanax) is not preferred?

Alternative PRN Medications for Severe Anxiety

For patients requiring PRN medication for severe anxiety who prefer not to use alprazolam, lorazepam (1 mg) or midazolam (2.5 mg) are recommended first-line alternatives, with quetiapine (25 mg) as an effective non-benzodiazepine option. 1, 2

Benzodiazepine Alternatives

First-line Benzodiazepine Options

• Lorazepam

  • Dosing: 1 mg subcutaneous or intravenous (up to 2 mg maximum)
  • Can also be given orally or sublingually
  • Advantages: Intermediate duration of action reduces risk of interdose anxiety
  • Cautions: Use lower doses (0.25-0.5 mg) in older/frail patients or those with COPD
  • Side effects: May cause drowsiness, paradoxical agitation 1

• Midazolam

  • Dosing: 2.5 mg subcutaneous or intravenous every hour PRN (up to 5 mg maximum)
  • Advantages: Rapid onset of action for acute anxiety
  • Cautions: Use lower doses (0.5-1 mg) in older/frail patients or those with COPD
  • Side effects: May cause drowsiness, dizziness, paradoxical agitation 1

Second-line Benzodiazepine Option

• Diazepam
  • Dosing: 5-10 mg orally PRN
  • Advantages: Demonstrated equal efficacy to alprazolam in panic disorder
  • Disadvantages: Longer half-life may lead to accumulation with repeated dosing 3

Non-Benzodiazepine Alternatives

Atypical Antipsychotics

• Quetiapine (First-line non-benzodiazepine)

  • Dosing: 25 mg (immediate release) orally PRN
  • Advantages: Less risk of dependence than benzodiazepines, recommended by American College of Critical Care Medicine for anxiety with delirium
  • Side effects: Sedation, orthostatic hypotension
  • Cautions: Lower starting dose (12.5 mg) for elderly or frail patients 1, 2

• Olanzapine

  • Dosing: 2.5-5 mg orally or subcutaneous PRN
  • Available as orally disintegrating tablet for rapid absorption
  • Side effects: Drowsiness, orthostatic hypotension
  • Caution: Do not combine with benzodiazepines due to risk of oversedation and respiratory depression 1

• Risperidone

  • Dosing: 0.5 mg orally PRN
  • Available as orally disintegrating tablet
  • Side effects: Increased risk of extrapyramidal symptoms if dose exceeds 6 mg/24h 1

• Aripiprazole

  • Dosing: 5 mg orally or intramuscular PRN
  • Advantages: Less likely to cause extrapyramidal side effects
  • Side effects: May cause headache, agitation, anxiety, insomnia 1

Clinical Decision Algorithm

1. Assess for contraindications to benzodiazepines:

   • History of substance abuse
   • Severe pulmonary insufficiency
   • Severe liver disease
   • Myasthenia gravis
   • Elderly patients at high risk for falls

2. If benzodiazepines are appropriate:

   • Choose lorazepam for patients who need oral/sublingual options
   • Choose midazolam for patients needing rapid onset of action
   • Adjust dose based on age, frailty, and comorbidities

3. If benzodiazepines are contraindicated or not preferred:

   • Choose quetiapine as first-line non-benzodiazepine option
   • Consider olanzapine for patients who need rapid absorption (using ODT)
   • Consider aripiprazole for patients at risk for extrapyramidal symptoms

Important Precautions

• Monitor for orthostatic hypotension with any antipsychotic medication
• Avoid all antipsychotics in patients at risk for torsades de pointes (baseline QT prolongation)
• Do not use haloperidol in patients with Parkinson's disease or Lewy body dementia 2
• Start with lower doses in elderly patients and titrate slowly
• Avoid combining benzodiazepines with olanzapine due to risk of oversedation and respiratory depression 1
• Consider clonazepam for patients who experience interdose anxiety with shorter-acting benzodiazepines 4

Dosing Pearls

• For benzodiazepine-naïve patients experiencing severe anxiety, start with lower doses
• If a patient receives two bolus doses in an hour, consider doubling the infusion rate if using continuous administration 1
• Titrate to effect while monitoring for adverse effects, particularly sedation and orthostatic hypotension