Haloperidol

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Typical antipsychotic, Antiemetic

Haloperidol

Haldol, Serenace, Haldol Decanoate

Haloperidol is a butyrophenone-class first-generation ("typical") antipsychotic. Its defining feature is high-affinity, relatively selective D₂ receptor antagonism with minimal anticholinergic activity — making it one of the more behaviorally selective typicals. Despite the broader shift toward atypicals for chronic psychiatric care, haloperidol remains widely used for acute agitation, ICU and postoperative delirium, palliative care nausea, and as a long-acting depot formulation (haloperidol decanoate) for maintenance treatment of schizophrenia.

Experience

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Problems

Schizophrenia — acute and maintenance (including decanoate for long-acting injectable maintenance)
Acute psychosis from any cause
Severe acute agitation, especially hyperactive delirium
ICU and postoperative delirium (per common protocols, though evidence is contested)
Tourette syndrome and severe tic disorders (FDA-approved)
Off-label: refractory nausea/vomiting (palliative care, chemotherapy-associated), hiccups, hyperemesis gravidarum

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Titration strategies

Acute psychosis, oral: 0.5–5 mg PO 2–3 times daily; titrate to 5–20 mg/day total. Max 30 mg/day in severe cases. Acute agitation, IM: 2–10 mg IM, may repeat every 30–60 min as needed. Lower in elderly (0.5–2 mg). Delirium, IV (off-label but common): 0.5–5 mg IV — baseline ECG required. Lower in elderly. Maintenance, decanoate IM: 50–300 mg every 3–4 weeks. Conversion: roughly 10–20× the daily oral dose monthly. Elderly / frail / dementia: start very low (0.25–0.5 mg) and titrate slowly; mortality risk in dementia-related psychosis (FDA black box).

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Effects

Therapeutic: reduction of positive psychotic symptoms (hallucinations, delusions, thought disorder), calming, reduced agitation, antiemesis. Common adverse: extrapyramidal symptoms (acute dystonia, akathisia, parkinsonism), mild sedation, dry mouth, mild orthostatic hypotension, hyperprolactinemia.

Extrapyramidal symptoms (EPS) — the dominant adverse effect profile:
- Acute dystonia (hours–days), especially young males; treat with IM benztropine or diphenhydramine
- Akathisia (days–weeks); reduce dose, add propranolol or benzodiazepine
- Parkinsonism (weeks); reduce dose, add anticholinergic
- Tardive dyskinesia (months–years); reduce/discontinue, switch to atypical, VMAT2 inhibitor (valbenazine, deutetrabenazine)
Neuroleptic malignant syndrome — rare but life-threatening: hyperthermia, rigidity, autonomic instability, altered mental status, elevated CK. Stop med, supportive care, ± dantrolene/bromocriptine.
QT prolongation — significant; baseline ECG and electrolyte monitoring especially with IV or high doses
Hyperprolactinemia — galactorrhea, gynecomastia, sexual dysfunction, amenorrhea
Sedation — less than chlorpromazine, more than aripiprazole
Orthostatic hypotension — α₁ blockade; less than low-potency typicals
Anticholinergic effects — much milder than chlorpromazine
Lowered seizure threshold — caution in epilepsy
Black box warning: increased mortality in elderly patients with dementia-related psychosis

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Pharmacokinetics

Oral bioavailability ~60–70% (substantial first-pass); IM and IV essentially 100%. Highly protein-bound (~92%). Metabolized hepatically by CYP3A4 and CYP2D6 to multiple metabolites, including reduced haloperidol (slightly active and back-converts to parent). Half-life 14–26 hours orally; haloperidol decanoate has a terminal half-life of ~3 weeks, allowing every-3–4-week IM dosing for maintenance.

Pharmacodynamics

Potent D₂ antagonist with high D₂:5-HT_2A affinity ratio — the pharmacologic profile that defines a "typical" antipsychotic and underlies its extrapyramidal side effect liability. Modest α₁-adrenergic and H₁ antagonism (less than chlorpromazine). Minimal muscarinic activity — a key advantage over low-potency typicals, but also why EPS is more prominent (no built-in anticholinergic compensation). Antiemetic effect via D₂ blockade at the chemoreceptor trigger zone.

Interactions

QT-prolonging agents — azoles, fluoroquinolones, methadone, ondansetron, citalopram, certain antiarrhythmics — additive risk of torsades
CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin) — elevated haloperidol levels
CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion) — elevated levels
CYP3A4 inducers (carbamazepine, rifampin, phenytoin) — reduced levels and possible loss of efficacy
CNS depressants (benzodiazepines, opioids, alcohol) — additive sedation and respiratory depression
Lithium — rare reports of neurotoxicity with combination
Anticholinergics — may reduce EPS but worsen delirium/cognition
Levodopa / dopamine agonists — mutual antagonism
Pregnancy and lactation

Category C. Has a long clinical track record in pregnancy and is generally considered one of the better-studied antipsychotics for use during pregnancy when treatment is necessary. Third-trimester exposure is associated with neonatal EPS and withdrawal symptoms. Occasionally used for severe hyperemesis gravidarum. Excreted in breast milk; breastfeeding generally permitted with caution.

Monitoring

Baseline ECG — and after dose changes, especially IV or high oral doses
Electrolytes (K⁺, Mg²⁺) — for QT risk
AIMS / EPS screening — at baseline, periodically thereafter (every 6 months for chronic use)
Prolactin — if symptoms suggest hyperprolactinemia
Glucose and lipids — less metabolic concern than with atypicals, but check periodically
LFTs — at baseline and if symptoms develop
Vital signs — orthostatic BP at initiation
Patient counseling
Take at the same time each day; capsule/tablet can be taken with or without food.
Report muscle stiffness, tremor, restlessness, or abnormal involuntary movements promptly.
Watch for fever + rigidity + confusion — could indicate neuroleptic malignant syndrome (medical emergency).
Avoid alcohol and other sedatives.
Use caution with driving until response to the medicine is known.
Hard candy or sips of water for dry mouth.
Rise slowly from sitting/lying to minimize dizziness.
Don't stop abruptly — taper if discontinuing.
Stay hydrated and avoid overheating; haloperidol impairs thermoregulation.
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Haloperidol

Experience

Problems

Titration strategies

Effects

Pharmacokinetics

Pharmacodynamics

Interactions

Pregnancy and lactation

Monitoring

Patient counseling

Relevant anecdote

Relevant Literature

See also