What antipsychotics are commonly used in the inpatient setting for acute psychosis, including their indications, targeted receptors, and half-lives?

Antipsychotic Reference Guide for Inpatient Acute Psychosis

First-Line Agents for Acute Agitation

For rapid control of acute psychotic agitation in the inpatient setting, use either intramuscular haloperidol 5 mg combined with lorazepam 2 mg, or intramuscular olanzapine 10 mg as monotherapy. 1, 2

Typical Antipsychotics

Haloperidol (First-Generation)

• Primary indication: Acute agitation and psychosis in undifferentiated or known psychiatric patients 1
• Receptor profile: High-potency D2 dopamine receptor antagonist 3
• Half-life: 12-38 hours
• Dosing: 5 mg IM for acute agitation; can be combined with lorazepam 2 mg IM for more rapid sedation 1, 2
• Key advantage: Established standard for rapid tranquilization with predictable efficacy 2, 4
• Caution: Higher risk of extrapyramidal side effects compared to atypicals 1

Droperidol

• Primary indication: When rapid sedation is specifically required 1
• Receptor profile: D2 antagonist with alpha-adrenergic blocking properties
• Dosing: Consider as alternative to haloperidol when faster sedation needed 1
• Caution: QT prolongation concerns, though evidence for severe cardiac events is not convincing 1

Second-Generation (Atypical) Antipsychotics

Olanzapine

• Primary indication: Acute psychosis and agitation, particularly effective in hospitalized patients 5, 4
• Receptor profile: D2, D3, D4, 5-HT2A, 5-HT2C, H1, muscarinic, alpha-1 antagonist 6
• Half-life: 21-54 hours
• Dosing:
  • IM: 10 mg for acute agitation 2, 6
  • Oral maintenance: 7.5-10 mg/day initial target dose 1, 2
  • Range: 5-20 mg/day 6
• Key advantages: Superior effectiveness in acute settings with longer time to treatment discontinuation (12% discontinuation rate vs 55% for quetiapine) 5; lower motor side effects 1
• Caution: Metabolic side effects with chronic use 3

Risperidone

• Primary indication: Acute psychosis; combination therapy with lorazepam for cooperative agitated patients 1
• Receptor profile: High D2 and 5-HT2A antagonist
• Half-life: 20-24 hours (active metabolite)
• Dosing:
  • Initial target: 2 mg/day 1, 2
  • Range: 3-12 mg/day 5
• Key advantages: Effective in acute settings (88% effectiveness rate, 25% discontinuation rate) 5, 4; can be used orally with benzodiazepines 1
• Caution: Dose-dependent extrapyramidal symptoms and hyperprolactinemia 3

Ziprasidone

• Primary indication: Acute agitation when IM formulation needed 1, 7
• Receptor profile: D2, 5-HT2A antagonist with 5-HT1A partial agonism
• Half-life: 7 hours (oral), 2-5 hours (IM)
• Dosing: Available as IM formulation for acute use 1, 7
• Key advantages: IM formulation available; favorable side-effect profile 7
• Effectiveness note: Less effective than haloperidol, olanzapine, or risperidone in acute hospitalized settings (64% effectiveness rate) 4

Quetiapine

• Primary indication: Maintenance therapy after acute stabilization
• Receptor profile: D2, 5-HT2A, H1, alpha-1 antagonist 8
• Half-life: 6 hours
• Dosing: 300-750 mg/day 5
• Effectiveness note: Inferior for acute treatment (55% discontinuation rate, 64% effectiveness rate) 5, 4
• Caution: QT prolongation risk, particularly with overdose or concomitant QT-prolonging medications 8

Aripiprazole

• Primary indication: Maintenance therapy; less suitable for acute agitation
• Receptor profile: D2 partial agonist, 5-HT1A partial agonist, 5-HT2A antagonist
• Half-life: 75 hours (including active metabolite)
• Dosing: 12-30 mg/day 5
• Effectiveness note: Less effective in acute settings (52% discontinuation rate, 64% effectiveness rate, highest p.r.n. haloperidol use at 52%) 5, 4

Treatment Algorithm

Immediate Management (First 24-48 Hours)

1. For severe agitation requiring immediate control: Haloperidol 5 mg IM + lorazepam 2 mg IM 1, 2
2. For cooperative patients accepting oral medication: Oral risperidone 2 mg + lorazepam 2 mg 1
3. Alternative monotherapy: IM olanzapine 10 mg or IM ziprasidone 2, 7

Transition Phase (Days 2-7)

Transition to oral atypical antipsychotics as preferred agents due to better tolerability and fewer extrapyramidal side effects 2:

• Olanzapine 7.5-10 mg/day 1, 2
• Risperidone 2 mg/day 1, 2

Maintenance Phase (After Stabilization)

• Continue effective atypical antipsychotic at lowest dose maintaining remission 1
• Consider switching to agents with fewer metabolic effects if long-term treatment needed (cariprazine, low-dose amisulpride, lurasidone, aripiprazole, brexpiprazole) 3

Critical Monitoring Parameters

• Extrapyramidal symptoms: Particularly with haloperidol and risperidone 1, 3
• QT interval: Especially with quetiapine, ziprasidone, and droperidol 1, 8
• Metabolic effects: Weight gain, glucose, lipids with olanzapine and other atypicals 3
• Thyroid function: TSH and free T4 with quetiapine (20% reduction in T4 levels) 8
• Complete blood count: Leukopenia/neutropenia risk with quetiapine 8
• Suicide risk and depression: Throughout acute and maintenance phases 2

Common Pitfalls

• Avoid supersaturating D2 receptor doses in acute agitation—higher doses increase adverse effects without improving efficacy 9
• Do not use aripiprazole or quetiapine as first-line for acute agitation—they have significantly higher discontinuation rates and lower effectiveness (64% vs 88-92% for olanzapine/risperidone/haloperidol) 5, 4
• Assess treatment response at 4-6 weeks before switching agents 2
• Start with lower doses in first-episode psychosis (approximately one-third reduction) and elderly patients 9
• Avoid combining quetiapine with other QT-prolonging medications (Class IA/III antiarrhythmics, other antipsychotics) 8