What are safe medications for managing agitation in inpatients?

Safe Medications for Managing Agitation in Inpatients

For managing agitation in inpatients, benzodiazepines (lorazepam or midazolam) or antipsychotics (typical or atypical) are recommended as effective first-line monotherapy options, with medication selection based on the underlying cause of agitation. 1

First-Line Medication Options

For Undifferentiated Agitation

• Benzodiazepines:

  • Lorazepam 0.5-1 mg orally up to four times daily as needed (maximum 4 mg/24 hours) 2
  • Midazolam 5 mg IM (achieves more effective sedation at 15 minutes than haloperidol, ziprasidone, and possibly olanzapine) 3
  • Reduced doses (0.25-0.5 mg) for elderly or debilitated patients 2

• Antipsychotics:

  • Atypical antipsychotics:

    • Olanzapine 10 mg IM (FDA-approved for agitation in schizophrenia and bipolar disorder) 4
    • Olanzapine provides more effective sedation than haloperidol with fewer extrapyramidal side effects 5, 3

  • Typical antipsychotics:

    • Haloperidol 5-10 mg IM 1
    • Consider droperidol if rapid sedation is required 1

For Agitated Patients with Known Psychiatric Illness

• Use an antipsychotic (typical or atypical) as effective monotherapy 1
• For patients with schizophrenia or bipolar disorder, olanzapine 10 mg IM has demonstrated efficacy in reducing agitation within 2 hours 4

For Agitated but Cooperative Patients

• Combination of oral benzodiazepine (lorazepam) and oral antipsychotic (risperidone) 1

Combination Therapy

• The combination of a parenteral benzodiazepine and haloperidol may produce more rapid sedation than monotherapy in acutely agitated psychiatric patients 1
• For severe agitation requiring rapid control, consider haloperidol plus promethazine (first-tier IM option) 6

Route of Administration Considerations

• Intramuscular (IM): For patients who cannot or will not take oral medication

  • First-tier options: Haloperidol plus promethazine, olanzapine alone 6
  • Second-tier options: Haloperidol with lorazepam, lorazepam alone 6

• Oral: For cooperative patients with less severe agitation

  • First-tier options: Haloperidol with lorazepam, lorazepam alone, olanzapine 6
  • Second-tier options: Haloperidol with promethazine, loxapine inhaler, risperidone 6
  • Third-tier options: Asenapine, quetiapine 6

Special Considerations

Safety Profile

• Atypical antipsychotics have lower rates of extrapyramidal side effects compared to typical antipsychotics 1
• During oral treatment, haloperidol-treated patients report significantly more acute dystonia (4.3% vs 0%) and akathisia (5.2% vs 0%) than olanzapine-treated patients 5
• IV olanzapine was associated with increased incidence of bradycardia (11% vs 3%) and somnolence (9% vs 1%) compared to IV haloperidol 7

Transition from IM to Oral Therapy

• Both IM olanzapine 10 mg and IM haloperidol 7.5 mg effectively reduce agitation, with effects sustained when transitioning to oral therapy 5
• When transitioning from IM to oral therapy, consider olanzapine 5-20 mg/day or haloperidol 5-20 mg/day 5

Delirium Considerations

• Routine use of haloperidol, atypical antipsychotics, or statins is not recommended for treating delirium 1
• However, short-term use may be warranted for patients experiencing significant distress from hallucinations, delusions, or agitation that poses physical harm 1
• Consider dexmedetomidine for delirium in mechanically ventilated adults where agitation is precluding weaning/extubation 1

Monitoring and Adverse Effects

• Monitor for:

  • Extrapyramidal symptoms (particularly with typical antipsychotics)
  • Respiratory depression (particularly with benzodiazepines)
  • QT prolongation (with antipsychotics)
  • Hypotension
  • Excessive sedation

• Most common adverse events are rare but include:

  • Extrapyramidal side effects (0.3%)
  • Hypotension (0.5%)
  • Hypoxemia (1%)
  • Intubation (0.5%) 3

Clinical Decision Algorithm

1. Assess agitation severity and patient cooperation
2. Identify underlying cause (psychiatric, medical, substance-related)
3. Choose medication based on:
   • Patient's ability to cooperate (oral vs parenteral)
   • Underlying cause of agitation
   • Medical comorbidities
   • Previous response to medications
4. For cooperative patients: Start with oral medication
5. For uncooperative patients: Use IM medication
6. Reassess response within 15-30 minutes
7. Consider additional doses if inadequate response

Remember that all antipsychotic agents should be discontinued immediately following resolution of the patient's distressing symptoms 1.