haloperidol
Antipsychotic· Brands: Haldol, Serenace, DozicIMIVPO
Mechanism of action
Haloperidol is a typical antipsychotic that acts primarily by competitively blocking central dopamine D2 receptors. It has high affinity for D2 receptors and low affinity for muscarinic, alpha-adrenergic and histamine receptors. This blockade reduces dopaminergic transmission in the mesolimbic pathway, which is thought to underlie its antipsychotic effect. It also has some effect on sigma receptors and may cause inhibition of NMDA receptors, but these actions are not well defined.
Pharmacokinetics
Haloperidol is well absorbed after oral administration but undergoes extensive first-pass metabolism, resulting in an absolute bioavailability of about 60 to 70%. Peak plasma concentrations occur within 1 to 3 hours. It is extensively bound to plasma proteins and is metabolised in the liver, mainly by CYP2D6 and CYP3A4, with some activity of reduced haloperidol. The elimination half-life is approximately 24 hours but can be longer in some individuals, especially with chronic dosing. Excretion occurs in urine and faeces, with significant enterohepatic recirculation.
Indications & dosing
Schizophrenia (acute and maintenance)
Usually 2-3 times daily; titrate to response. Starting dose 0.5-2 mg twice daily.
- adult · PO: 0.5–5 mg BID · Usually 2-3 times daily; titrate to response. Starting dose 0.5-2 mg twice daily.
Acute agitation or psychotic crisis
Repeat every 4-6 hours if needed; max 20 mg/day.
- adult · IM: 5 mg PRN · Repeat every 4-6 hours if needed; max 20 mg/day.
Delirium
Use lowest effective dose; monitor QT interval in at-risk patients.
- adult · PO: 0.5–1 mg BID · Use lowest effective dose; monitor QT interval in at-risk patients.
Tourette's syndrome in children
Titrate slowly; monitor for extrapyramidal symptoms.
- pediatric · PO: 0.25–0.5 mg BID · Titrate slowly; monitor for extrapyramidal symptoms.
Contraindications & precautions
- Parkinson's disease and parkinsonian syndromes · Haloperidol can exacerbate parkinsonian symptoms.
- Dementia with Lewy bodies · Risk of severe neuroleptic reactions, including life-threatening rigidity and autonomic instability.
- Known QT prolongation or congenital long QT syndrome · Increased risk of ventricular arrhythmias and torsades de pointes.
- Comatose states or severe CNS depression · Additive depressant effects may occur.
- Monitor for extrapyramidal symptoms, especially in elderly patients and those with a history of EPS.
- Consider ECG monitoring in patients with cardiovascular disease or risk factors for QT prolongation; avoid if QT interval is prolonged.
- Use the lowest effective dose for the shortest duration to reduce the risk of tardive dyskinesia.
- Watch for signs of neuroleptic malignant syndrome (fever, muscle rigidity, altered consciousness) and discontinue immediately if suspected.
- Caution in patients with cardiovascular or cerebrovascular disease; haloperidol may increase risk of stroke in elderly patients with dementia.
Adverse effects
- Extrapyramidal symptoms (dystonia, akathisia, parkinsonism)
- Tardive dyskinesiaserious
- Neuroleptic malignant syndromeserious
- QT interval prolongation and ventricular arrhythmiasserious
- Hyperprolactinaemia
- Sedation and drowsiness
- Orthostatic hypotension
Renal & hepatic adjustment
- eGFR 0+: No dosage adjustment required. Use with caution in severe renal impairment.
- Hepatic impairment (mild): No specific dosage adjustment required. Monitor for adverse effects.
- Hepatic impairment (moderate): Consider dose reduction. Initiate at a lower dose and titrate cautiously.
- Hepatic impairment (severe): Avoid use due to increased risk of accumulation and toxicity. (avoid)
Monitoring, pregnancy & toxicity
- Blood pressure · Baseline and periodically during treatment
- Heart rate and ECG (QT interval) · Baseline and periodically, especially with risk factors or high doses
- Extrapyramidal symptoms (e.g., tremor, rigidity, akathisia) · Monitor regularly, especially during dose titration
- Serum electrolytes (e.g., potassium, magnesium) · Baseline and periodically, particularly before and during ECG monitoring
- Mental state and clinical response · Regularly to assess efficacy and adjust dose
- Pregnancy: Haloperidol may be used during pregnancy if clinically necessary, but only when the potential benefit outweighs the risk to the fetus. Use at the lowest effective dose and monitor the neonate for withdrawal or extrapyramidal symptoms if used in the third trimester.
- Toxicity: Extrapyramidal symptoms, including acute dystonia, akathisia, and parkinsonism · Administer anticholinergic agents (e.g., procyclidine) or antihistamines for dystonia. Supportive care and dose reduction.
- Toxicity: QT prolongation and ventricular arrhythmias · Continuous ECG monitoring and correction of electrolytes. Administer magnesium sulfate if torsades de pointes occurs. Avoid other QT-prolonging drugs.
- Toxicity: Severe hypotension and sedation · Supportive treatment with intravenous fluids and vasopressors if needed. Airway management and observation.
- Toxicity: Neuroleptic malignant syndrome (NMS) · Discontinue haloperidol immediately. Provide supportive care, including cooling, and use dantrolene or bromocriptine as advised by specialist.
Clinical notes
Haloperidol is used for acute and chronic psychoses, including schizophrenia and delusional disorders, and for aggressive and agitated behaviour. It may be used in mania, and as a short-term treatment in severe agitation or delirium. It is a high-potency antipsychotic with a high risk of extrapyramidal symptoms, particularly acute dystonia and akathisia, and a lower risk of sedation and anticholinergic effects. QTc interval prolongation is a concern, especially with intravenous use or in patients with cardiac disease. The National Institute for Health and Care Excellence advises caution in elderly patients with dementia, as there is an increased risk of cardiovascular events and death. Neuroleptic malignant syndrome and tardive dyskinesia are rare but serious adverse effects. Doses should be individualised, starting low and titrating to the lowest effective dose.
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BNF; local formulary