haloperidol

General Information

Haloperidol (brand Haldol) is a first-generation (typical) antipsychotic of the butyrophenone class, used for schizophrenia, acute agitation, and maintenance in patients who benefit from high-potency D2 blockade.

This profile emphasizes adult schizophrenia management, acute agitation protocols, and long-acting decanoate maintenance; pediatric and Tourette’s uses fall outside current scope.

The compare tool, evidence library, the Schizophrenia hub, and the LAI Navigator support side-by-side dosing/risk review and maintenance planning.

Favored for cost, familiarity, and depot availability, but high EPS, tardive dyskinesia, and QTc prolongation risks limit chronic use compared with SGAs.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Haloperidol is a potent antagonist of dopamine D2 receptors with limited serotonergic activity, yielding strong antipsychotic efficacy and high EPS risk.

Minimal histamine or muscarinic blockade confers lower sedation and anticholinergic burden than low-potency FGAs.

• High-affinity antagonist at dopamine D2 receptors.
• Moderate antagonist at adrenergic α1 receptors.
• Minimal serotonergic, histaminergic, or muscarinic receptor activity.

Metabolism and Pharmacokinetics

• Oral bioavailability ~60%; peak levels 2–6 hours after oral dosing; IM onset within 20 minutes.
• Approximately 92% protein bound with volume of distribution ~18 L/kg.
• Metabolized hepatically via CYP3A4 and CYP2D6 with glucuronidation to reduced haloperidol and other metabolites.
• Half-life ~18 hours (oral); decanoate apparent half-life ~21 days.
• Eliminated ~60% fecal and ~40% renal primarily as metabolites.

Dosing and Administration

• Schizophrenia (oral): initiate 1–5 mg two or three times daily; maintenance 5–20 mg/day divided; doses >30 mg/day increase EPS risk.
• Acute agitation: 2–5 mg IM/IV every 4–8 hours (max 20 mg/day IM); ECG and vital-sign monitoring are commonly used with IV administration.
• Decanoate LAI: initial total dose 10–20× total daily oral dose; max 100 mg per injection (split remainder 3–7 days later) with short oral overlap as needed; maintenance 50–200 mg IM every 4 weeks.

Monitoring & Labs

• Extrapyramidal symptoms are monitored periodically; prophylaxis is generally reserved for clear need.
• QTc: ECG monitoring is often considered when risk factors or higher doses are present.
• LAI: Haloperidol decanoate every 4 weeks—product-specific conversion guidance is typically used.
• Regular AIMS screening for tardive dyskinesia (typically every 3–6 months; every 3 months in higher-risk groups or with dose increases).
• Prolactin-related symptoms (sexual dysfunction, amenorrhea, galactorrhea) and overall quality-of-life impact—consider switching if persistent.
• Orthostatic vitals and falls risk, especially in older adults and when combined with other CNS depressants or antihypertensives.
• Metabolic monitoring (weight/BMI, glucose, lipids) periodically as part of comprehensive schizophrenia care, even though metabolic risk is lower than many SGAs.

Monitoring focuses on EPS/TD prevention and cardiac safety (QTc), with additional attention to prolactin effects and falls risk in vulnerable patients.

Adverse Effects

Interactions

• CYP3A4 or CYP2D6 inhibitors (ketoconazole, clarithromycin, fluoxetine, paroxetine, quinidine) increase levels—EPS/QTc risk can rise and dose reduction may be needed.
• CYP3A4 inducers (carbamazepine, rifampin) decrease levels—may require higher doses with careful monitoring.
• Combinations with other QTc-prolonging drugs (class IA/III antiarrhythmics, macrolides, fluoroquinolones) are generally avoided when possible.
• Additive CNS depression with alcohol, benzodiazepines, opioids.
• Antagonizes levodopa/dopamine agonists; use is generally avoided in Parkinson’s disease.

Other Useful Information

• Baseline and periodic ECG monitoring is often considered, especially with IV use or cardiac risk factors.
• Prophylactic anticholinergic therapy is sometimes used during initiation in high-risk patients for acute dystonia or Parkinsonism.
• Regular AIMS assessments help track tardive dyskinesia.
• Decanoate is administered deep IM using Z-track technique; IV administration is avoided.

References

1. HALDOL tablets prescribing information — DailyMed (2025)
2. HALDOL decanoate prescribing information — DailyMed (2025)
3. Comparative Efficacy AND Tolerability OF 15 Antipsychotic Drugs IN Schizophrenia: A Multiple Treatments Meta Analysis — The Lancet (2013)Meta-analysisschizophreniaefficacy
4. Pharmacokinetics of haloperidol: a review — Drug Metabolism Reviews (2012)
5. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia — American Psychiatric Association (2020)Guidelineschizophreniaclinical