Generic Name

Haloperidol

Mechanism

• Haloperidol is a typical antipsychotic that blocks dopamine D₂ receptors in the mesolimbic pathway, reducing psychotic symptoms.
• It also antagonizes 5‑HT₂, α₁‑adrenergic, and muscarinic receptors, which contributes to its side‑effect profile.

Pharmacokinetics

• Absorption: Oral bioavailability ≈ 30–40 %; IV/IM bypass first‑pass metabolism.
• Distribution: Highly lipophilic; crosses the blood‑brain barrier; ∼80–90 % protein bound.
• Metabolism: Mainly hepatic via CYP3A4 and CYP2D6 to inactive metabolites.
• Elimination: Renal excretion; oral half‑life ~4–12 h, longer IV/IM.
• Drug interactions: Levels rise with CYP3A4 inhibitors (ketoconazole, erythromycin) or P‑gp inhibitors.

Indications

• Acute agitation, delirium, or psychosis in schizophrenia, bipolar disorder, or dementia.
• Off‑label use for severe irritability in autism spectrum disorders.
• Avoid for hyperprolactinemia because D₂ antagonism elevates prolactin.

Contraindications

• Hypersensitivity to haloperidol or excipients.
• Pregnancy: Category C; use only if benefits outweigh risks.
• Severe QT prolongation or congenital long‑QT syndrome.
• Parkinsonism or other extrapyramidal disorders.
• Post‑operative period: risk of orthostatic hypotension.
• Combine with anticholinergic agents → heightened hallucination risk.

Dosing

• Adults
• IV: 0.5–5 mg, repeat every 30 min; max 15 mg/day.
• IM: 2–5 mg q4‑6 h; total ≤ 15 mg/day.
• Oral: 0.5–1 mg BID, titrate; max 10 mg/day.
• Pediatrics (6–12 yrs): 0.05–0.1 mg/kg IV/IM, titrate 0.05 mg/kg.
• Elderly: Start at ½ the adult dose; monitor sensitivity.
• Special instructions: Use a 5–10 ml syringe for IM; ensure smooth injection.

Adverse Effects

• Common:
• Extrapyramidal symptoms (EPS): dystonia, akathisia, Parkinsonism.
• Sedation, orthostatic hypotension, anticholinergic effects.
• Weight gain, metabolic disturbances.
• Serious:
• Neuroleptic malignant syndrome (NMS): fever, rigidity, autonomic instability.
• QT prolongation → torsades de pointes.
• Aggression reversal in mania.
• Severe dystonia in infants/children (rare).

Monitoring

• Baseline ECG; repeat after >3 mg IV.
• Blood pressure, pulse, orthostatic vitals.
• Routine assessment of EPS (Barnes Akathisia Scale, AIMS).
• Serum prolactin if long‑term therapy.
• Weight, fasting glucose, lipid profile every 3–6 months.

Clinical Pearls

• Ask‑Stop‑Act Protocol: For sudden IV dose increases >3 mg, monitor for NMS; keep the patient in a supportive setting.
• EEG Safety: When administering haloperidol during EEG, give 2 mg IM (not the full dose) and keep electrode sites clean to avoid irritation.
• Dystonia Management: If dystonia occurs, give 1 mg benztropine 30 min after haloperidol; avoid benztropine if Parkinson’s disease is present.
• Switching from Atypical: Cross‑taper over 5 days when moving from olanzapine or risperidone to haloperidol to mitigate rebound psychosis.
• Pregnancy Guidance: Prefer risperidone or quetiapine; if haloperidol is unavoidable, use the lowest dose for the shortest duration possible.