How should agitation be managed in an adult psychiatric inpatient, including non‑pharmacologic de‑escalation and first‑line pharmacologic agents?

Managing Agitation in Psychiatric Hospital Settings

Begin immediately with verbal de-escalation techniques while simultaneously assessing for reversible medical causes; if behavioral interventions fail and the patient poses imminent risk of harm, use haloperidol 0.5–1 mg (maximum 5 mg/day) or a combination of an antipsychotic with a benzodiazepine as first-line pharmacologic treatment.

Step 1: Immediate Safety and De-escalation (First-Line)

Verbal de-escalation must be attempted before any pharmacologic intervention unless the patient presents an immediate physical threat 1, 2. The evidence strongly supports non-coercive approaches as the initial intervention, with successful outcomes occurring far more often than previously recognized when genuine commitment is applied 1.

Core De-escalation Techniques

• Respect personal space: Maintain at least two arm-lengths distance and position yourself at a 45-degree angle rather than directly facing the patient 1
• Use calm, non-threatening body language: Keep hands visible, avoid crossed arms, remove potential weapons (stethoscopes, ties, lanyards) 3, 1
• Employ simple, clear communication: Use calm tones, simple one-step commands, and allow adequate processing time before expecting responses 3, 4
• Establish collaborative dialogue: Listen actively, acknowledge the patient's concerns, and avoid arguing or being judgmental 1, 5
• Set clear, reasonable limits: Explain consequences calmly and offer choices when possible 1, 5
• Modify the environment: Reduce sensory stimulation (dim lights, decrease noise), remove other agitated patients or argumentative visitors, ensure safety-proofed rooms 3, 2

The literature identifies seven validated domains of effective de-escalation, with one-to-one interaction being the most commonly successful technique (used in 65.5% of cases) 6, 5.

Step 2: Concurrent Medical Assessment

While de-escalation is underway, systematically investigate reversible causes that commonly precipitate agitation in psychiatric patients 7, 2:

Mandatory Screening

• Point-of-care glucose (hypoglycemia is rapidly reversible) 2
• Vital signs and oxygen saturation (hypoxia, fever suggesting infection) 7, 2
• Pain assessment (untreated pain is a major contributor to agitation) 7, 4
• Urinary retention and constipation (both significantly worsen behavioral symptoms) 7, 4
• Medication review (anticholinergics, steroids, opioid neurotoxicity, withdrawal states) 7, 2
• Infection screening (UTI, pneumonia are disproportionately common triggers) 7, 4
• Metabolic panel (electrolyte abnormalities, renal dysfunction) 7, 2
• Substance intoxication/withdrawal (alcohol, benzodiazepines, sympathomimetics) 7, 2

Step 3: Pharmacologic Intervention (When De-escalation Fails)

Medications should only be administered when verbal de-escalation has failed and the patient poses substantial risk of harm to self or others 3, 2.

First-Line Pharmacologic Options

Option A: Antipsychotic Monotherapy

Haloperidol is the most extensively studied agent with 20 double-blind trials supporting its use 3, 4:

• Dose: 0.5–1 mg orally, IM, or subcutaneously 3, 7, 4
• Repeat: Every 2–4 hours as needed 7, 4
• Maximum: 5 mg per 24 hours (higher doses provide no additional benefit and significantly increase adverse effects) 3, 7, 4
• Advantages: Lower risk of respiratory depression compared to benzodiazepines, extensive safety data 3, 4
• Monitoring: ECG for QTc prolongation, extrapyramidal symptoms (occur in ~20% of patients) 3, 7, 4

Alternative atypical antipsychotics 3, 2:

• Olanzapine: 2.5–5 mg IM (onset ~15–30 minutes) 3, 7
• Ziprasidone: 10–20 mg IM (rapid onset, minimal EPS, but avoid if QTc prolonged) 8

Option B: Combination Therapy (Antipsychotic + Benzodiazepine)

The combination of a neuroleptic and benzodiazepine is frequently recommended by experts for acute agitation 3, 7:

• Haloperidol 0.5–1 mg + Lorazepam 0.5–2 mg 3, 7
• Rationale: The presence of therapeutic neuroleptic levels prevents paradoxical excitation sometimes seen when delirious/agitated patients receive lorazepam alone 7
• Maximum lorazepam: 4 mg per 24 hours for acute agitation 7

Critical safety warning: The combination of high-dose olanzapine (>10 mg) with benzodiazepines has resulted in fatalities from respiratory depression and should be avoided 8.

Option C: Benzodiazepine Monotherapy (Limited Indications)

Benzodiazepines should NOT be first-line for agitated delirium or psychosis except in specific circumstances 3, 4:

• Alcohol or benzodiazepine withdrawal (only clear indication for monotherapy) 3, 4
• Catatonia (lorazepam challenge test) 2

Why benzodiazepines are problematic 3, 4:

• Increase delirium incidence and duration 3, 4
• Cause paradoxical agitation in ~10% of patients 3, 4
• Risk of respiratory depression, especially when combined with antipsychotics 7, 8
• Tolerance and dependence with repeated use 4

Refractory Agitation Protocol

If initial pharmacotherapy fails 7:

1. Continue haloperidol 0.5–2 mg every 1 hour until agitation is controlled (maximum 5 mg/24h) 7
2. Add lorazepam 0.5–2 mg every 4–6 hours if agitation remains refractory to high-dose neuroleptics 7
3. Consider IM administration if oral route is ineffective (IM haloperidol or IM olanzapine provide more rapid and reliable absorption) 7
4. Alternative for refractory cases: Chlorpromazine ± lorazepam (use only IV in bed-bound patients due to hypotensive effects) 7

Before escalating medications, reassess for missed reversible causes: hypoxia, metabolic derangements, infection, CNS events, urinary retention, bowel obstruction 7.

Step 4: Physical Restraints (Last Resort Only)

Physical restraints should be minimized whenever possible and used only when 4, 2:

• Imminent risk of serious harm to self or others
• Pharmacologic and verbal interventions have failed
• Patient requires protection during medical evaluation or treatment

When restraints are necessary 2:

• Use the least restrictive method possible
• Ensure continuous monitoring (face-to-face physician examination required)
• Reassess need frequently (every 15–30 minutes)
• Document clearly the indication, alternatives attempted, and ongoing monitoring

Special Populations

Elderly Patients

• Start with lower doses: Haloperidol 0.5 mg, lorazepam 0.25–0.5 mg 3, 4
• Maximum haloperidol: 5 mg/24h (same as adults, but reach this maximum more cautiously) 3, 4
• Higher risk: Paradoxical agitation, falls, delirium, respiratory depression 3, 4

Pregnant Patients

• Avoid benzodiazepines in first trimester (risk of cleft palate) 2
• Haloperidol is relatively safe in pregnancy when necessary 2
• Consult obstetrics for any pharmacologic intervention 2

Pediatric Patients

• Behavioral interventions are even more critical (child life specialists can be invaluable) 3
• Medication dosing: No controlled trials exist; extrapolate from adult data with caution 3
• Combination therapy: Benzodiazepine + antipsychotic is suggested by experts for severe agitation 3

Common Pitfalls to Avoid

1. Do not skip de-escalation attempts unless immediate physical threat exists 1, 2
2. Do not use benzodiazepines as first-line for psychotic or delirious agitation 3, 4
3. Do not exceed haloperidol 5 mg/24h in routine practice (no added benefit, increased harm) 3, 7, 4
4. Do not combine high-dose olanzapine (>10 mg) with benzodiazepines (fatal respiratory depression risk) 8
5. Do not forget to obtain or review baseline ECG when using haloperidol or olanzapine (both prolong QT interval) 7
6. Do not continue medications indefinitely without reassessing need and attempting taper 4
7. Do not add multiple agents simultaneously without first optimizing the current regimen 8

Monitoring Requirements

For all patients receiving pharmacologic treatment 7, 4:

• Vital signs: Blood pressure, heart rate, respiratory rate, oxygen saturation (every 15–30 minutes initially)
• Mental status: Level of sedation, orientation, response to stimuli
• Extrapyramidal symptoms: Tremor, rigidity, akathisia, dystonia (20% incidence with haloperidol) 3, 7
• ECG monitoring: QTc interval if using haloperidol or olanzapine 7
• Respiratory status: Especially critical if benzodiazepines are used 7, 8