Stage 4: Antipsychotics I — First-Generation
Concept 2 of 8
R4.2

Haloperidol

High-potency FGA workhorse — rapid agitation control, IM/IV available, prominent EPS.

Haloperidol IM for acute agitation: rapid onset (~30 min), well-studied, available everywhere. The default high-potency option in ED and acute inpatient settings.

Haloperidol — Haldol — is the high-potency FGA workhorse. It is the most studied, most familiar, and most accessible antipsychotic in emergency settings. In every emergency department in the world that handles psychiatric agitation, haloperidol is part of the toolkit. Its pharmacology is essentially pure D2 antagonism with minimal off-target effects.

Drug card
Class
High-potency first-generation antipsychotic
Mechanism
Potent D2 antagonist; minimal H1, M1, or alpha-1 effects
Typical dose
PO 0.5-20 mg/day; IM 2-10 mg per dose for acute agitation; decanoate 50-200 mg IM monthly
Half-life
~24 hours (PO, range ~15-37h); IM ~21 hours; decanoate ~3 weeks
FDA indications
Schizophrenia, acute psychosis, severe agitation, Tourette syndrome, delirium agitation (off-label)
Key adverse effects
Acute dystonia (high incidence), akathisia, parkinsonism, tardive dyskinesia, NMS, QTc prolongation (particularly with IV)

Black box: Increased mortality in elderly patients with dementia-related psychosis

Rapid IM agitation control: workhorse for ED and inpatient acute psychiatric agitation. IV haloperidol associated with QTc prolongation and torsades — use cautiously, ECG monitoring. Often combined with lorazepam ("B-52": haldol 5 + benadryl 50 + ativan 2 — historical regimen).

For acute agitation, intramuscular haloperidol 2-10 milligrams produces antipsychotic effect within about thirty minutes. It is often combined with intramuscular lorazepam for synergistic effect and with benztropine prophylactically to prevent acute dystonia. The classic combination — sometimes called "B-52" historically — was haloperidol 5 mg plus diphenhydramine 50 mg plus lorazepam 2 mg. Modern regimens vary but the principle persists: D2 blockade for the psychosis, GABA enhancement for the calming, anticholinergic for the EPS prevention.

Mechanism in practice

Haloperidol is the prototype high-potency FGA — tight, selective D2 blockade that delivers strong antipsychotic effect and strong EPS in the same stroke.

Mechanism
Potent, selective D2 receptor blockade
Effect
Strong antipsychotic effect; reliable control of agitation and positive symptoms
Clinical applications
Workhorse for acute agitation and psychosis; available IM and as long-acting decanoate for adherence-limited patients.
Mechanism
High-potency D2 blockade in the nigrostriatal pathway
Effect
Prominent extrapyramidal symptoms — acute dystonia, parkinsonism, akathisia
Clinical applications
Anticholinergic co-treatment (e.g., benztropine) often given prophylactically with IM haloperidol; monitor for akathisia.
Mechanism
Minimal histaminergic, cholinergic, and adrenergic activity
Effect
Little sedation, weight gain, or orthostasis
Clinical applications
Hemodynamically 'clean' — useful in the medically fragile or delirious patient where sedation and hypotension are unwanted.
Mechanism
QTc prolongation, especially IV
Effect
Risk of torsades de pointes
Clinical applications
ECG and electrolyte awareness, particularly with IV use or in patients with cardiac risk factors.

Mechanism note: Haloperidol's value is potent, hemodynamically clean antipsychotic effect; its cost is high EPS burden. The decanoate form solves adherence in chronic psychosis.

The EPS profile is haloperidol's defining clinical concern. Acute dystonia is especially common in young men in the first hours to days. Akathisia is frequently underrecognized and undertreated. Parkinsonism develops over days to weeks. Tardive dyskinesia is the long-term risk that accumulates over months and years. Prophylactic anticholinergic — benztropine 1-2 mg — is often added with each haloperidol dose for patients at high risk, particularly young men receiving IM doses.

EPS profile: high incidence of acute dystonia particularly in young men. Co-administration of anticholinergic (benztropine) often prophylactic. Akathisia frequently underrecognized.

IV haloperidol can prolong QTc and has been associated with torsades. ECG monitoring is appropriate when IV use is prolonged or combined with other QTc-prolonging agents.

Haloperidol decanoate is the long-acting injectable form, dosed monthly in oily depot. It was foundational for adherence-limited schizophrenia, predating modern SGA LAIs. It is largely supplanted by paliperidone palmitate, aripiprazole maintena, and other SGA LAIs where available — those have better tolerability profiles. Haloperidol decanoate remains in use in cost-constrained settings and for patients with established response.

Haloperidol decanoate: long-acting IM monthly. Useful for adherence-limited schizophrenia. Loading and transition strategies critical — long half-life means slow steady state.

For rapid agitation control, haloperidol remains a first-line tool. For long-term schizophrenia maintenance, SGA LAIs have largely taken over. The choice today reflects the setting and the patient's specific situation.

Prescribing reality
Cost
Generic: ~$10-30/month oral. Decanoate (LAI) ~$30-80/dose.
Generic status
Generic for decades.
Formulary typical
Tier 1 generic. No PA.
Access friction
Pharmacies universally stock oral. Decanoate sometimes requires advance order. IM in ED is universally available.

Prescriber tip: For rapid agitation, IM haloperidol + IM lorazepam + IM benztropine is the standard combination — cheap, reliable, every ED has it. Reserve for acute use; chronic use rare today.

The anchor

Haloperidol is the high-potency FGA workhorse for acute agitation and schizophrenia — rapid action, multiple formulations including decanoate, but significant EPS burden requires anticipation and management.

Prove it

A young man with acute psychosis receives IM haloperidol 5 mg. Two hours later he develops painful neck twisting and tongue protrusion. What is happening and how is it managed?

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