What can be given as needed (PRN) for agitation and psychosis?

PRN Medications for Agitation and Psychosis

For acute agitation and psychosis, use either a benzodiazepine (lorazepam 1-2 mg) or an antipsychotic (haloperidol 0.5-5 mg IM, or olanzapine 2.5-10 mg) as monotherapy, with lorazepam being the preferred first-line agent for undifferentiated agitation due to its rapid onset and favorable safety profile. 1, 2

First-Line Options

Benzodiazepines (Preferred for Undifferentiated Agitation)

Lorazepam is the most appropriate PRN medication for acute agitation in patients with bipolar disorder and schizophrenia, demonstrating efficacy in reducing agitation scores at 30,60, and 120 minutes after administration. 2

• Dosing: Start with 1 mg PO/IM/IV/SC PRN, can repeat every 1 hour if needed (though 4-8 hour intervals are often sufficient) 1, 2
• Maximum dose: Up to 2 mg per dose 1
• Dose reduction: Use 0.25-0.5 mg in elderly, frail patients, or those with COPD, especially if co-administered with antipsychotics 1, 2
• Routes available: PO, sublingual, IM, IV, or SC 1

Midazolam is an alternative benzodiazepine option:

• Dosing: 2.5 mg SC/IV every 1 hour PRN (up to 5 mg maximum) 1
• Dose reduction: 0.5-1 mg in elderly/frail patients or when combined with antipsychotics 1
• May have a role as crisis medication for severe agitation and distress 1

Antipsychotics (Preferred for Known Psychotic Illness)

For patients with known psychiatric illness requiring antipsychotics, use an antipsychotic as effective monotherapy for both agitation management and initial drug therapy. 1

Typical Antipsychotics

Haloperidol:

• Dosing: 0.5-1 mg PO/SC/IM PRN every 1 hour as needed (can give every 8-12 hours if scheduled dosing required) 1
• For prompt control: 2-5 mg IM for acutely agitated patients with moderately severe to very severe symptoms 3
• Dose reduction: Use 0.25-0.5 mg in elderly or frail patients and titrate gradually 1
• Cautions: May cause extrapyramidal symptoms (EPS), prolongs QTc interval; do not use in Parkinson's disease or Lewy body dementia 1
• Can also be given IV with ECG monitoring 1

Droperidol (if available and not contraindicated):

• Consider for rapid sedation: More effective than haloperidol when rapid sedation is required 1
• Produces lower sedation scores, requires fewer repeat doses, and results in shorter ED lengths of stay compared to lorazepam 1
• FDA black box warning: Potential for dysrhythmias, though large patient series suggest safety when used appropriately 1

Atypical Antipsychotics

Olanzapine:

• Dosing: 2.5-5 mg PO/SC/IM PRN 1
• Scheduled dosing: Start with 2.5-5 mg daily (usually at bedtime) if needed 1
• Dose reduction: Lower doses in elderly patients and those with hepatic impairment 1
• Cautions: May cause drowsiness, orthostatic hypotension; CRITICAL WARNING - fatalities reported with concurrent benzodiazepine use, especially high-dose olanzapine 1
• Available as oral disintegrating tablet (ODT) 1

Risperidone:

• Dosing: 0.5 mg PO PRN (can give up to every 12 hours if scheduled dosing required) 1
• Dose reduction: Lower doses in elderly and those with severe renal or hepatic impairment 1
• Cautions: Increased risk of EPS if dose exceeds 6 mg/24 hours; may cause insomnia, agitation, anxiety, drowsiness, orthostatic hypotension 1
• Available as ODT 1

Quetiapine:

• Dosing: 25 mg PO PRN (immediate release), can give every 12 hours if scheduled 1
• Dose reduction: Lower doses in elderly and those with hepatic impairment 1
• Advantages: Sedating, less likely to cause EPS than other atypical antipsychotics 1
• Cautions: May cause orthostatic hypotension, dizziness 1
• Oral route only 1

Aripiprazole:

• Dosing: 5 mg PO or IM PRN (give every 24 hours if scheduled dosing required) 1
• Dose reduction: Lower doses in elderly and poor CYP2D6 metabolizers 1
• Advantages: Less likely to cause EPS 1
• Cautions: May cause headache, agitation, anxiety, insomnia, dizziness, drowsiness; CYP2D6 and 3A4 drug interactions 1

Combination Therapy

For cooperative patients: Oral lorazepam (2 mg) combined with oral risperidone (2 mg) is effective for agitated patients who can take oral medications 1, 4

For severe agitation: The combination of parenteral benzodiazepine and haloperidol may produce more rapid sedation than monotherapy 1

Clinical Decision Algorithm

1. Assess patient cooperation and severity:

   • Cooperative patient with mild-moderate agitation → Oral lorazepam 1 mg or oral antipsychotic 1, 2
   • Uncooperative or severe agitation → IM/IV lorazepam 1-2 mg or IM haloperidol 2-5 mg 1, 3

2. Consider underlying diagnosis:

   • Known psychotic illness (schizophrenia, bipolar with psychosis) → Antipsychotic preferred 1
   • Undifferentiated agitation → Benzodiazepine preferred 1, 2
   • Alcohol/benzodiazepine withdrawal → Benzodiazepine monotherapy (treatment of choice) 1

3. Evaluate for contraindications:

   • Parkinson's disease or Lewy body dementia → Avoid typical antipsychotics and risperidone; consider quetiapine 1
   • QTc prolongation → Avoid haloperidol, droperidol, chlorpromazine 1
   • Severe pulmonary insufficiency, liver disease, myasthenia gravis → Use benzodiazepines with extreme caution 1
   • COPD or respiratory compromise → Reduce benzodiazepine doses significantly 1

Critical Safety Warnings

Avoid combining high-dose olanzapine with benzodiazepines - fatalities have been reported with this combination due to risk of oversedation and respiratory depression. 1

Monitor for paradoxical agitation with benzodiazepines, which occurs in approximately 10% of patients. 2

Increased fall risk with both benzodiazepines and antipsychotics, especially in elderly or frail patients - use lowest effective doses. 1, 2

Both antipsychotics and benzodiazepines can themselves cause or worsen delirium and agitation - use lowest effective dose for shortest time possible. 1

Atypical antipsychotics increase risk of death in elderly patients with dementia (RR 1.36), though this risk must be balanced against severe agitation. 5

Practical Considerations

Start medications on PRN basis initially - regular scheduled dosing should only be implemented if persistent distressing symptoms require it, and for the shortest period possible. 1

For patients already on standing antipsychotics (like your patient on risperidone 0.5 mg): Adding lorazepam PRN is preferable to acutely increasing antipsychotic doses, as it addresses immediate agitation while allowing time to optimize the standing regimen and reduces risk of excessive sedation. 2

Reassess frequently - if repeated doses are needed within 4-8 hours, consider whether scheduled dosing or adjustment of standing medications is warranted. 3