What are the recommended medications for treating agitation?

Medications for Agitation

For acute agitation, first-line pharmacologic treatment should be intramuscular (IM) atypical antipsychotics (ziprasidone 10-20 mg or olanzapine 10 mg) or benzodiazepines (lorazepam 2 mg), with combination therapy of haloperidol 5 mg plus lorazepam 2 mg reserved for severe cases requiring rapid control.

First-Line Monotherapy Options

Atypical Antipsychotics (Preferred)

IM ziprasidone and IM olanzapine represent the preferred initial approach for acute agitation in psychiatric settings due to superior tolerability and lower risk of extrapyramidal symptoms compared to typical antipsychotics. 1, 2

• Ziprasidone IM: 10-20 mg IM, with the 20 mg dose showing statistically significant reduction in agitation at 30 minutes post-dose; can be repeated every 2 hours as needed 1

  • Onset of action: 15-30 minutes; peak effect: 60 minutes; duration: 2-4 hours 1
  • Well-tolerated with minimal extrapyramidal symptoms, dystonia, or excessive sedation 1
  • Caution: Avoid in patients with QTc prolongation or known cardiac conditions 2

• Olanzapine IM: 10 mg IM for adults; 2.5-10 mg for elderly or medically compromised patients 1, 3

  • Onset: 15-45 minutes; peak: 15-45 minutes; duration: up to 24 hours 1
  • Shows faster onset and greater efficacy than haloperidol or lorazepam with fewer adverse effects 2
  • Critical warning: Do not combine with benzodiazepines or other CNS depressants due to risk of severe adverse events including fatalities 2

Benzodiazepines (Alternative First-Line)

Lorazepam IM 2-4 mg is equally effective as typical antipsychotics for acute agitation and carries lower risk of extrapyramidal symptoms. 1

• Onset: 15 minutes IM; peak: 60 minutes; duration: 6-8 hours 1
• Can be repeated every 30-60 minutes as needed 1
• Particularly useful when substance-induced agitation or medical causes are suspected 1
• Caution: Risk of respiratory depression, paradoxical disinhibition (especially in children and developmentally disabled), and additive CNS depression with other sedatives 1, 4

Combination Therapy for Severe Agitation

When monotherapy is insufficient, the combination of haloperidol 5 mg IM plus lorazepam 2 mg IM provides superior agitation control compared to either agent alone. 1

• This combination can be administered in the same syringe 1
• Shows significantly greater decrease in agitation scores at 1 hour compared to monotherapy 1
• Requires fewer repeat doses than single agents 1

Typical Antipsychotics (Second-Line)

Haloperidol should be reserved as second-line therapy due to significant risk of extrapyramidal symptoms and, rarely, cardiac arrhythmias. 1

• Adult dose: 5-10 mg IM; can repeat every 30-60 minutes 1
• Pediatric dose: 0.5-2 mg for children; 5-10 mg for adolescents 1
• Onset: 20-30 minutes IM; peak: 30-60 minutes; duration: 4-8 hours 1
• Associated with extrapyramidal symptoms in approximately 20% of patients 1

Population-Specific Considerations

Elderly Patients with Dementia

In elderly patients with agitation, atypical antipsychotics should be used at lower doses with extreme caution due to increased mortality risk. 1, 3

• Risperidone: Start 0.25 mg daily at bedtime; maximum 2-3 mg/day divided 1
• Olanzapine: Start 2.5 mg daily at bedtime; maximum 10 mg/day divided 1
• Quetiapine: Start 12.5 mg twice daily; maximum 200 mg twice daily (more sedating) 1
• Typical antipsychotics carry 50% risk of tardive dyskinesia after 2 years of continuous use in elderly patients 1

Pediatric Patients

For agitated children and adolescents, combination therapy with an antipsychotic plus antihistamine (diphenhydramine) is preferred over benzodiazepines due to lower risk of paradoxical disinhibition. 1

• Risperidone + diphenhydramine or Haloperidol + diphenhydramine are recommended combinations 1
• Benzodiazepines cause paradoxical behavioral disinhibition more frequently in younger children 1

Palliative Care/Delirium

For severe delirium with agitation, haloperidol 0.5-2 mg every 1 hour PRN until controlled, with lorazepam 0.5-2 mg every 4-6 hours added only if refractory to high-dose neuroleptics. 1

• Alternative agents: risperidone 0.5-1 mg BID, olanzapine 2.5-15 mg daily, or quetiapine 50-100 mg BID 1

Critical Safety Considerations

Avoid Anticholinergic Agents in Specific Contexts

Do not use antipsychotics in patients with anticholinergic toxicity or delirium, as their anticholinergic properties will worsen the condition. 1

• This includes intoxication from hallucinogens or other anticholinergic drugs 1

Monitoring Requirements

All patients receiving chemical restraint require close monitoring for: 1

• Respiratory depression
• Hypotension and orthostatic changes
• Cardiac dysrhythmias (especially with haloperidol and ziprasidone)
• Extrapyramidal symptoms and dystonic reactions

Drug-Specific Contraindications

• Ziprasidone: Contraindicated in QTc prolongation 2
• Olanzapine IM: Never combine with benzodiazepines or CNS depressants 2
• Benzodiazepines: Use cautiously in respiratory compromise or concurrent CNS depressants 4

Algorithm for Medication Selection

1. Assess for reversible medical causes (hypoxia, metabolic derangements, substance intoxication/withdrawal) 1

2. For psychiatric agitation without medical comorbidity:

   • Start with ziprasidone 20 mg IM or olanzapine 10 mg IM 1, 2
   • Alternative: lorazepam 2 mg IM 1, 4

3. For severe agitation requiring rapid control:

   • Use haloperidol 5 mg + lorazepam 2 mg IM combination 1

4. For substance-induced or medically complex agitation:

   • Prefer lorazepam 2-4 mg IM alone 1
   • Avoid antipsychotics if anticholinergic toxicity suspected 1

5. For elderly/dementia patients:

   • Use lowest effective doses of atypical antipsychotics 1
   • Avoid typical antipsychotics due to tardive dyskinesia risk 1

6. For pediatric patients:

   • Combine antipsychotic with antihistamine rather than benzodiazepine 1