Haloperidol

Haloperidol is a high-potency butyrophenone antipsychotic used for schizophrenia, acute agitation, mania, delirium and Tourette syndrome. It is cheap and available in oral, short-acting injection and long-acting decanoate forms. It causes frequent extrapyramidal effects and dose-related QT prolongation, and intravenous use is unlicensed.

Classification. First-generation (typical) antipsychotic, butyrophenone.

Mechanism. Potent dopamine D2 receptor antagonist, with little antimuscarinic, antihistamine or alpha-1 blockade, which explains low sedation and hypotension but high extrapyramidal risk.

Pharmacokinetics. Oral bioavailability about 60%; peak in 2 to 6 hours orally and 20 minutes intramuscularly. Metabolised by CYP3A4, CYP2D6 and glucuronidation. Half-life 14 to 37 hours orally; decanoate about 3 weeks.

Schizophrenia, adults (oral).

• Start 1 to 2 mg once or twice daily (0.5 to 1 mg in older adults).
• Titration: increase by 1 to 2 mg every few days based on response and extrapyramidal effects.
• Usual 3 to 10 mg daily. Maximum 20 mg daily; doses over 10 mg rarely add benefit.
• Duration: at least 12 months after a first episode, longer after relapse.

Acute agitation or psychosis (intramuscular). 2 to 5 mg, repeated after 4 to 8 hours as needed; maximum 18 mg intramuscular in 24 hours. Reduce to 0.5 to 2 mg in older adults.

Delirium causing distress or danger (off-label). 0.5 to 1 mg orally or intramuscularly, repeated after 1 to 2 hours if needed; usual maximum 5 mg in 24 hours.

Tourette syndrome (specialist use). Start 0.5 mg daily and increase every 5 to 7 days based on response; most patients need 1 to 5 mg daily.

Maintenance depot (decanoate, intramuscular).

• Convert from oral: 10 to 15 times the daily oral dose, given every 4 weeks. First dose not over 100 mg; give the remainder 3 to 7 days later.
• Maintenance usually 50 to 200 mg every 4 weeks. Maximum 300 mg every 4 weeks.
• Continue oral cover for the first few weeks.

Intravenous use. Unlicensed and associated with torsades de pointes; used only in monitored settings with a baseline QTc under 450 ms and electrolytes corrected.

Contraindications. Coma or severe CNS depression, Parkinson disease, Lewy body dementia, known QT prolongation or torsades, uncorrected hypokalaemia, recent myocardial infarction or decompensated heart failure, hypersensitivity. Boxed-warning-level increase in mortality in older adults with dementia-related psychosis.

Serious adverse effects. Neuroleptic malignant syndrome, torsades de pointes, acute dystonia, parkinsonism, akathisia, tardive dyskinesia, seizures, hyperprolactinaemia, agranulocytosis (rare), cholestatic jaundice (rare).

Common adverse effects. Extrapyramidal symptoms, restlessness, sedation, dry mouth, constipation, sexual dysfunction, galactorrhoea and amenorrhoea, mild weight gain.

Interactions. Fluoxetine, paroxetine and quinidine raise levels; carbamazepine, phenytoin and rifampicin lower them. QT-prolonging drugs (macrolides, quinolones, ondansetron, quinine, artemether-lumefantrine, chloroquine, methadone, citalopram) add to risk. Lithium combined with high haloperidol doses can cause neurotoxicity. Levodopa is antagonised.

Common prescribing errors. Giving intravenous haloperidol without an ECG; escalating the dose over 10 mg daily without benefit; missing hypokalaemia; no anticholinergic available for acute dystonia.

Special groups.

• Pregnancy: use only if benefit outweighs risk; third-trimester exposure can cause neonatal extrapyramidal symptoms and withdrawal.
• Breastfeeding: excreted in milk; monitor the infant for sedation and extrapyramidal symptoms; low-dose use is acceptable if needed.
• Children: specialist use only; aged 3 to 12 years (15 to 40 kg) start 0.5 mg daily and increase by 0.5 mg every 5 to 7 days to 0.05 to 0.15 mg/kg daily.
• Older adults: start 0.5 mg; high risk of parkinsonism, falls and mortality in dementia.
• Kidney impairment: no adjustment.
• Liver impairment: reduce the dose.
• Regional: khat can precipitate or worsen psychosis; ask about use, and prefer the lowest effective dose, short courses and early review.

Formulations. Tablets 0.5 mg, 1.5 mg, 5 mg and 10 mg; oral liquid 2 mg/mL; injection 5 mg/mL; decanoate 50 mg/mL and 100 mg/mL. Deep intramuscular injection; decanoate volume under 3 mL at each site.

Baseline. ECG, potassium and magnesium, weight, blood pressure, fasting glucose or HbA1c, lipids, prolactin if symptomatic, and a baseline rating of extrapyramidal symptoms.

Monitoring. Weight and waist at baseline, 4, 8 and 12 weeks, then annually; fasting glucose or HbA1c and lipids at baseline, 12 weeks, then annually. Check extrapyramidal symptoms at each review and rate abnormal movements every 6 to 12 months. Repeat the ECG after dose increases or when a QT-prolonging drug is added; stop or reduce if QTc is over 500 ms. For acute dystonia give procyclidine 5 to 10 mg by intramuscular or slow intravenous injection.

Stopping. Reduce gradually over several weeks to limit relapse and withdrawal dyskinesia.

Referral and escalation. Refer to psychiatry for first-episode psychosis, treatment resistance after two adequate antipsychotic courses (consider clozapine) or persistent extrapyramidal symptoms. Fever with rigidity and altered consciousness (neuroleptic malignant syndrome), syncope or QTc over 500 ms needs emergency care.