Haloperidol (Haldol)

Class

First-generation (typical) antipsychotic; high-potency butyrophenone derivative

Mechanism

Potent dopamine D₂ receptor antagonist; minimal anticholinergic or antihistaminergic activity contributes to its high risk of extrapyramidal symptoms (EPS) and low sedative burden.

FDA-Approved Use

Schizophrenia, Tourette’s disorder, severe behavioral disturbances

Off-Label Use

Acute agitation, delirium, psychosis in dementia, aggression in neurodevelopmental disabilities (higher adverse risk), and chemotherapy-induced nausea and vomiting

Formulation

Oral tablets, oral solution, short-acting intramuscular (IM), intravenous (IV, off-label), and long-acting IM decanoate injection

Titration

Oral dosing often begins at 1–2 mg p.o. twice daily, titrated as needed based on clinical response and tolerability. In acute settings, IM dosing ranges from 2.5–10 mg per injection, repeated as needed. The long-acting decanoate injection is typically given every 4 weeks, with oral overlap required for the first 1–2 weeks.

Dose Range

Oral: 1–20 mg/day in divided doses; Decanoate IM: 50–200 mg every 4 weeks

Kinetics

Metabolized primarily by CYP3A4 and CYP2D6. The decanoate form has a prolonged half-life (up to 3 weeks), reaching steady state after multiple injections.

Common AEs

Extrapyramidal symptoms (including parkinsonism, dystonia, and akathisia), sedation, restlessness, and orthostatic hypotension

Serious/Rare AEs

Tardive dyskinesia, neuroleptic malignant syndrome (NMS), QTc prolongation, sudden cardiac death, and hyperprolactinemia

Monitoring

Baseline and periodic evaluation for EPS (e.g., AIMS scale every 6–12 months), ECG if cardiac risk factors or IV use, and annual metabolic screening. Consider prolactin or LFTs if symptomatic.

Black Box Warning

Increased mortality in elderly patients with dementia-related psychosis

Considerations

Haloperidol is frequently used to manage acute agitation or psychosis in dementia, intellectual disability, and traumatic brain injury (TBI), but must be used cautiously due to high EPS risk, fall risk, and its black box warning for increased mortality in elderly individuals with dementia-related psychosis. Long-acting formulations may support adherence in chronic psychotic illness but require close monitoring for motor side effects.