What medication is recommended for sedating agitated patients with no significant medical contraindications?

Medication for Sedating Agitated Patients

For undifferentiated acute agitation in patients without significant medical contraindications, benzodiazepines (lorazepam 2-4 mg IM/IV or midazolam) or antipsychotics (olanzapine 10 mg IM, droperidol 5 mg IM/IV, or haloperidol 5 mg IM) are equally effective as first-line monotherapy, with the choice depending on suspected etiology and clinical context. 1

Primary Treatment Algorithm

For Cooperative Patients (Oral Route Preferred)

• Olanzapine 10 mg orally is the preferred first-line agent for cooperative agitated patients, achieving adequate sedation in 78.9% within 20 minutes 2
• Olanzapine demonstrates superior safety with minimal QTc prolongation (2 ms) compared to haloperidol (7 ms), making it safer for patients with cardiac concerns 3
• Alternative: Combination of oral risperidone plus lorazepam 2 mg produces similar improvement to haloperidol plus lorazepam in cooperative agitated patients 3, 1

For Non-Cooperative Patients (Parenteral Route Required)

Choose based on suspected etiology:

Undifferentiated Agitation (Unknown Cause)

• Midazolam IM shows superior sedation at 15 minutes compared to other options 1
• Olanzapine 10 mg IM effectively sedates 78.9% of patients within 20 minutes, with remaining patients responding to repeat dose within 25 minutes 2
• Droperidol 5 mg IM/IV works faster than haloperidol when rapid sedation is required 1

Suspected Alcohol/Substance Withdrawal

• Lorazepam 2-4 mg IM/IV is first-line when agitation may involve alcohol withdrawal or seizures, as benzodiazepines are therapeutic (not just symptomatic) for withdrawal-related agitation 1, 4
• Haloperidol 5 mg IM shows slightly better efficacy (40% sedated within 20 minutes) compared to olanzapine (0% within 20 minutes) for alcohol intoxication, though not statistically significant 2

Psychiatric Illness (Psychosis/Mania)

• Olanzapine 10 mg IM sedates 90% of psychiatric patients within 20 minutes 2
• Haloperidol 5 mg IM plus lorazepam 2 mg sedates 94.1% within 20 minutes 2
• Combination therapy may be superior to monotherapy with higher improvement rates and lower extrapyramidal side effects 5, 6

Organic Medical Causes (Delirium, Metabolic)

• Olanzapine 10 mg IM is superior, sedating 79.1% within 20 minutes versus haloperidol's 25% 2
• Avoid benzodiazepines as first-line for postoperative or medical delirium unless specifically indicated for withdrawal, as they increase delirium duration and may cause paradoxical agitation 7

Sympathomimetic Poisoning (Cocaine, Amphetamines)

• Benzodiazepines are recommended to control psychomotor agitation, relax muscles, and treat seizures 7
• Antipsychotics can be used but may exacerbate agitation in anticholinergic or sympathomimetic toxicity 1

Combination Therapy Considerations

• Haloperidol 5 mg plus lorazepam 2 mg IM produces more rapid sedation than monotherapy in undifferentiated agitation 4, 1
• Combination treatment demonstrates higher improvement rates and lower incidence of extrapyramidal side effects compared to either agent alone 5, 6

Special Population Dosing

Elderly or Debilitated Patients

• Olanzapine 2.5-5 mg IM (reduced from standard 10 mg dose) 8
• Haloperidol 5 mg IM (reduced dose) for geriatric patients 8
• Patients over 50 years experience more profound sedation with all agents 3

Traumatic Brain Injury

• Haloperidol 5 mg IM shows slightly better efficacy (44.4% sedated within 20 minutes) compared to olanzapine (25%), though not statistically significant 2

Critical Safety Considerations

Avoid These Combinations

• Do not use benzodiazepines as first-line for postoperative delirium except when specifically indicated for withdrawal 7
• Avoid antipsychotics in anticholinergic or sympathomimetic toxicity as they may worsen agitation 1
• Avoid haloperidol in Parkinson's disease or Lewy body dementia due to severe extrapyramidal symptom risk 3

Monitoring Requirements

• Assess for orthostatic hypotension prior to subsequent doses of IM olanzapine, especially after maximal dosing (3 doses of 10 mg at 2-4 hour intervals) 8
• Monitor vital signs every 5-15 minutes during the first hour after medication administration 4
• Obtain baseline ECG if using droperidol (FDA black box warning for QT prolongation, though large series show safety in ED settings) 1

Repeat Dosing

• Olanzapine: If agitation persists, subsequent doses up to 10 mg may be given, but efficacy of repeated doses not systematically evaluated; maximum 30 mg total daily dose 8
• Do not exceed 10 mg injections more frequently than 2 hours after initial dose and 4 hours after second dose 8

Important Caveats

• Physical restraints without effective sedation are associated with death in severely agitated patients; restraints should be removed as soon as safely possible 7
• Ketamine provides rapid sedation (mean 7.2 minutes) but is associated with higher intubation rates (30.5% overall, 1.8% when used in ED) and should be reserved for refractory cases 9
• Atypical antipsychotics (risperidone, olanzapine, ziprasidone) are preferred alternatives to haloperidol when availability and cost permit, offering comparable efficacy with fewer extrapyramidal side effects 3, 5, 6