Drug Monograph
Haloperidol
Haldol (oral/IM lactate) · Haldol Decanoate (long-acting IM depot)
Pharmacokinetic Profile
Half-Life
14.5–36.7 h (oral); ~21 days (decanoate)
Metabolism
Hepatic via CYP3A4 (primary) and CYP2D6; glucuronidation
Protein Binding
~92% (range 89–93%)
Bioavailability
60–70% (oral)
Volume of Distribution
~7.9 L/kg
Clinical Information
Drug Class
First-generation (typical) antipsychotic
Available Doses
Tabs: 0.5, 1, 2, 5, 10, 20 mg; Solution: 2 mg/mL; IM lactate: 5 mg/mL; Decanoate: 50, 100 mg/mL
Route
Oral; IM (lactate & decanoate); IV (off-label, hospital only)
Renal Adjustment
Not specifically required; use caution
Hepatic Adjustment
Consider lower doses in hepatic impairment
Pregnancy
Risk of neonatal EPS/withdrawal with 3rd-trimester use
Lactation
Present in breast milk; monitor infant for sedation, EPS
Schedule
Not a controlled substance
Generic Available
Yes (all formulations)
Black Box Warning
Yes — Elderly dementia mortality
Indications for Haloperidol
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Schizophrenia | Adults (oral, IM lactate, decanoate); Adolescents ≥13 yr (oral) | Monotherapy | FDA Approved |
| Tourette syndrome | Children and adults (tics and vocal utterances) | Monotherapy | FDA Approved |
| Severe behavioural disorders in children | Children 3–12 years (combative, explosive hyperexcitability; after failure of non-antipsychotic therapies) | Monotherapy | FDA Approved |
| Hyperactivity in children | Children 3–12 years (impulsivity, aggression, mood lability, low frustration tolerance; after failure of psychotherapy and other medications) | Monotherapy | FDA Approved |
Haloperidol is one of the most widely used first-generation antipsychotics worldwide. Its high-potency dopamine D2 blockade provides reliable control of positive psychotic symptoms and is particularly valued in acute agitation settings where rapid onset is critical. The long-acting decanoate formulation offers monthly depot injection for schizophrenia maintenance in adults already stabilised on oral haloperidol, addressing adherence challenges common in chronic psychotic illness.
Off-Label Uses
Acute agitation / Delirium (evidence quality: high): Haloperidol is the most widely used antipsychotic for acute agitation across clinical settings and remains a mainstay for delirium management in critical care, though recent RCTs have questioned its efficacy for ICU delirium prevention.
Nausea and vomiting, including postoperative (evidence quality: moderate): Low-dose haloperidol (0.5–2 mg IV/IM) is used as an antiemetic, particularly for breakthrough nausea or in palliative care settings.
Bipolar mania — acute episode (evidence quality: moderate): Haloperidol is effective for acute manic agitation and was used in the placebo-controlled arm of several clinical trials establishing SGA efficacy.
Dosing for Haloperidol
Adult Oral Dosing
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Schizophrenia — moderate symptoms | 0.5–2 mg BID–TID | 5–20 mg/day in divided doses | 30 mg/day (usual); 100 mg/day in resistant cases | Doses >30 mg/day increase EPS risk without clear efficacy benefit for most patients Can take with or without food |
| Schizophrenia — severe symptoms or acute exacerbation | 3–5 mg BID–TID | 5–20 mg/day | 100 mg/day | Safety of prolonged use above 100 mg/day not established Chronic/resistant cases may require higher-range doses |
| Tourette syndrome — adult | 0.5–2 mg BID–TID | 2–10 mg/day | 15 mg/day | Use lowest effective dose; reassess periodically |
Paediatric Dosing (Oral)
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Tourette syndrome — children 3–12 yr (15–40 kg) | 0.05–0.075 mg/kg/day in 2–3 divided doses | Titrate by 0.5 mg increments q5–7 days | 0.075 mg/kg/day | Little evidence of benefit above 6 mg/day |
| Severe behavioural disorders — children 3–12 yr | 0.05 mg/kg/day in 2–3 divided doses | Titrate by 0.5 mg increments q5–7 days | 0.075 mg/kg/day | Reserve for failure of psychotherapy and other medications; little evidence of benefit above 6 mg/day |
Intramuscular & Depot Dosing
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Acute agitation — IM lactate | 2–5 mg IM | Repeat q4–8 h as needed (may give q1h) | 20 mg/day IM | Switch to oral as soon as practical Use total parenteral dose from preceding 24 h to estimate initial oral daily dose |
| Schizophrenia maintenance — decanoate (oral dose ≤10 mg/day) | 10–15× daily oral dose IM | 10–15× daily oral dose q4wk | 450 mg q4wk | Max first injection 100 mg; if calculated dose >100 mg, give 100 mg Day 1, remainder 3–7 days later Typical effective range: 50–200 mg q4wk |
| Schizophrenia maintenance — decanoate (oral dose >10 mg/day) | 10–20× daily oral dose IM | 10–15× daily oral dose q4wk | 450 mg q4wk | Max first injection 100 mg; increase by ≤50 mg increments q4wk until optimal response |
| Elderly (≥65 yr) or hepatic impairment — decanoate | 10–15× daily oral dose (low end of range) | Individualise; titrate cautiously | Greater susceptibility to orthostatic hypotension, EPS, and QTc prolongation | |
Clinical Pearl: IV Haloperidol and QTc Risk
IV haloperidol is widely used off-label for acute agitation and delirium, but the FDA has not approved IV administration. The 2025 Haldol Decanoate label explicitly states “Do not administer intravenously.” IV use carries a significantly higher risk of QTc prolongation and torsades de pointes compared to IM or oral routes. If IV haloperidol is used in a monitored setting, continuous ECG monitoring is recommended, and electrolytes (K+, Mg2+) should be corrected beforehand.
Pharmacology of Haloperidol
Mechanism of Action
Haloperidol is a potent dopamine D2 receptor antagonist of the butyrophenone class. It also binds to alpha-1 adrenergic receptors with moderate affinity but has minimal activity at muscarinic cholinergic and histamine H1 receptors. This receptor profile explains haloperidol’s clinical characteristics: strong antipsychotic efficacy against positive symptoms with relatively low sedation and weight gain compared to lower-potency FGAs or many SGAs, but with a high propensity for extrapyramidal symptoms due to potent nigrostriatal D2 blockade. Haloperidol also has significant effects on prolactin secretion through D2 blockade of the tuberoinfundibular pathway.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Oral bioavailability 60–70%; Tmax 2–6 h (oral), ~20 min (IM lactate), ~6 days (decanoate); food does not significantly affect absorption | Rapid onset with IM lactate makes it suitable for acute agitation; decanoate provides sustained release over 4 weeks |
| Distribution | Vd ~7.9 L/kg; protein binding 89–93%; highly lipophilic; brain concentrations 10–30× serum levels | Extensive tissue distribution; prolonged CNS effects even after plasma clearance; brain half-life ~6.8 days |
| Metabolism | Extensive hepatic metabolism via CYP3A4 (primary) and CYP2D6; reduced haloperidol is an active metabolite of uncertain clinical significance; glucuronidation also contributes; ~1% excreted unchanged in urine | Susceptible to CYP3A4 inducers (carbamazepine, rifampin) and CYP2D6/3A4 inhibitors (ketoconazole, fluoxetine, paroxetine); CYP2D6 poor metabolisers may have higher levels |
| Elimination | t½ 14.5–36.7 h (oral, single dose); ~18 h (IV); ~21 days (decanoate, absorption-rate limited); excreted ~40% urine, ~15% faeces as metabolites | Wide interindividual variability in elimination; decanoate requires ~3 months to reach steady state; once-daily oral dosing feasible at lower doses |
Side Effects of Haloperidol
≥10%Very Common
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Extrapyramidal symptoms (composite) | 20–40% | Includes parkinsonism, dystonia, akathisia; dose-related; highest of all commonly used antipsychotics |
| Akathisia | 15–40% | 2–7× higher than SGAs; may be misdiagnosed as psychotic agitation; propranolol or dose reduction may help |
| Hyperprolactinaemia | >50% (biochemical) | Often asymptomatic; may cause amenorrhoea, galactorrhoea, gynaecomastia, sexual dysfunction; symptomatic rate ~10–15% |
1–10%Common
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Sedation / Drowsiness | 5–15% | Less than low-potency FGAs (chlorpromazine) or many SGAs; dose-related |
| Insomnia | 5–10% | May reflect akathisia; assess for restlessness before adding sedative-hypnotic |
| Orthostatic hypotension | 5–10% | Alpha-1 blockade; risk highest with IM administration and in elderly |
| Constipation | 3–8% | Lower anticholinergic burden than chlorpromazine; still clinically relevant |
| Dry mouth | 3–5% | Relatively mild given low muscarinic affinity |
| Weight gain | 2–5% | Less than olanzapine, clozapine, or quetiapine; low metabolic risk profile |
| Blurred vision | 2–5% | Usually transient |
SeriousSerious (Regardless of Frequency)
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Tardive dyskinesia | ~5.4% per year in adults | Months to years; risk cumulative | Consider discontinuation or switch to SGA; VMAT2 inhibitors (valbenazine, deutetrabenazine) for persistent TD; risk highest in elderly women |
| QTc prolongation / Torsades de pointes | Dose-related; higher with IV use | Any time; risk increases with dose, IV route, electrolyte imbalance | Baseline and periodic ECG; correct K+, Mg2+, Ca2+; avoid co-prescription with other QT-prolonging drugs; do not use IV route without cardiac monitoring |
| Neuroleptic malignant syndrome | Rare (~0.01–0.02%) | Days to weeks after initiation or dose increase | Immediate discontinuation; ICU-level supportive care; dantrolene or bromocriptine may be considered |
| Acute dystonia | 5–10% (higher in young males) | Hours to days after first dose | IM benztropine 1–2 mg or diphenhydramine 50 mg IM; prevent with anticholinergic prophylaxis in high-risk patients |
| Sudden death / Cardiac arrest | Very rare | Any time; associated with high doses and IV use | Avoid IV administration outside monitored settings; use lowest effective dose; screen cardiac risk factors |
| Seizures | Rare | Any time; lowers seizure threshold | Not recommended in patients with seizure history unless benefits clearly outweigh risks; maintain antiseizure therapy if used |
DiscontinuationDiscontinuation Considerations
Withdrawal Dyskinesia
May unmask TD
Abrupt cessation can unmask or worsen tardive dyskinesia that was being suppressed by D2 blockade; taper gradually when possible.
Psychotic Relapse
Risk increases rapidly
Cross-taper to an alternative antipsychotic; decanoate has a long washout (~3 months to clear) offering a buffer period.
Managing Extrapyramidal Symptoms
EPS are the most clinically limiting adverse effect of haloperidol. Acute dystonia requires emergent treatment with IM anticholinergics (benztropine or diphenhydramine). Parkinsonism may respond to dose reduction or addition of oral benztropine 1–2 mg BID. Akathisia is often refractory to anticholinergics; propranolol 20–80 mg/day is the preferred first-line treatment. Prophylactic anticholinergic co-prescription is commonly considered in young males receiving IM haloperidol to prevent acute dystonia. If EPS are persistent and distressing, switching to a second-generation antipsychotic should be considered.
Drug Interactions with Haloperidol
Haloperidol is metabolised primarily by CYP3A4 and CYP2D6, and is itself a CYP2D6 inhibitor. Its QTc-prolonging effect creates clinically important pharmacodynamic interactions with other QT-prolonging drugs. The combination of pharmacokinetic vulnerability and pharmacodynamic QT risk makes interaction screening essential before initiation.
MajorQTc-Prolonging Agents
MechanismAdditive QTc prolongation
EffectIncreased risk of torsades de pointes and sudden death; especially with Class IA/III antiarrhythmics, macrolides, fluoroquinolones, methadone
ManagementAvoid concomitant use when possible; if unavoidable, obtain baseline ECG, correct electrolytes, and monitor QTc
FDA PI 2025MajorCYP3A4 Inhibitors (ketoconazole, itraconazole, clarithromycin)
MechanismDecreased haloperidol metabolism; increased plasma levels
EffectElevated haloperidol exposure increases EPS and QTc risk
ManagementReduce haloperidol dose; monitor for EPS and QTc prolongation
FDA PI 2025MajorCarbamazepine / Rifampin
MechanismStrong CYP3A4 induction; rifampin produced a ~3.3-fold decrease in haloperidol levels in clinical studies
EffectSubtherapeutic haloperidol levels; loss of psychotic symptom control
ManagementMay need to increase haloperidol dose substantially; monitor clinical response closely; reduce dose when inducer is discontinued
FDA PIModerateCYP2D6 Inhibitors (fluoxetine, paroxetine, bupropion, quinidine)
MechanismInhibition of secondary metabolic pathway
EffectModerately increased haloperidol levels; more EPS risk
ManagementMonitor for adverse effects; consider dose reduction
FDA PIModerateLithium
MechanismUnknown; rare encephalopathic syndrome reported
EffectRare cases of encephalopathy, EPS, fever, confusion, elevated CPK; usually reversible on discontinuation
ManagementMonitor closely for early neurological signs; discontinue haloperidol if encephalopathic signs appear
FDA PIModerateLevodopa / Dopamine Agonists
MechanismPharmacological antagonism at D2 receptors
EffectMutual attenuation of therapeutic effects; haloperidol contraindicated in Parkinson’s disease
ManagementDo not co-administer; use quetiapine, clozapine, or pimavanserin for psychosis in PD
FDA PIModerateCNS Depressants / Opioids / Alcohol
MechanismAdditive CNS depression
EffectEnhanced sedation, respiratory depression; opioid doses may need reduction by up to 50%
ManagementUse lowest effective doses of both agents; monitor respiratory status closely
FDA PIMinorEpinephrine (as vasopressor)
MechanismHaloperidol blocks alpha-1 receptors, leaving beta-2 vasodilation unopposed
EffectParadoxical worsening of hypotension
ManagementUse norepinephrine, phenylephrine, or metaraminol instead if vasopressor required
FDA PIMonitoring for Haloperidol
- ECG (QTc)Baseline; during treatment as clinically indicated
RoutineEssential at baseline, especially if risk factors present (cardiac disease, electrolyte abnormalities, concomitant QT-prolonging drugs). Continuous monitoring recommended with IV administration. - Serum ElectrolytesBaseline; as clinically indicated
RoutineK+, Mg2+, Ca2+, phosphorus. Correct hypokalaemia and hypomagnesaemia before initiation. Monitor during diuretic co-prescription or conditions causing electrolyte loss. - EPS Assessment (AIMS, SAS, BARS)Each visit; AIMS at least q6 months
RoutineScreen for akathisia, parkinsonism, and tardive dyskinesia at every visit. Use AIMS at least every 6 months in adults, every 3 months in elderly. Annual TD risk ~5.4% with haloperidol. - Metabolic PanelBaseline, 12 wk, then annually
RoutineFasting glucose, HbA1c, lipids. Haloperidol has lower metabolic risk than SGAs but monitoring remains standard for all antipsychotics per APA/ADA guidelines. - Body WeightBaseline, monthly × 3, then quarterly
RoutineLower weight gain risk than SGAs, but still warrants tracking. - Prolactin LevelIf symptoms arise
Trigger-basedHaloperidol consistently elevates prolactin. Check if amenorrhoea, galactorrhoea, sexual dysfunction, or gynaecomastia develop. Consider switching to a prolactin-sparing agent. - CBCBaseline; if pre-existing low WBC or symptoms of infection
Trigger-basedLeukopenia, neutropenia, and agranulocytosis have been reported (rare). Discontinue if ANC <1000/mm3. - Blood PressureEach visit; orthostatic during initiation
RoutineMonitor orthostatic vitals during dose titration and in elderly patients.
Contraindications & Cautions for Haloperidol
Absolute Contraindications
- Severe toxic CNS depression or comatose states from any cause.
- Known hypersensitivity to haloperidol or any excipient (anaphylaxis and angioedema reported).
- Parkinson’s disease — severe EPS exacerbation, confusion, falls, and impaired antiparkinson drug effects.
- Dementia with Lewy bodies — extreme sensitivity to antipsychotics with severe neurological reactions.
Relative Contraindications (Specialist Input Recommended)
- Significant QTc prolongation or risk factors (congenital long QT, recent MI, decompensated heart failure, uncorrected electrolyte imbalance).
- Thyrotoxicosis — risk of severe neurotoxicity with haloperidol.
- History of seizures or EEG abnormalities — haloperidol lowers seizure threshold.
Use with Caution
- Elderly patients (increased sensitivity to orthostatic hypotension, EPS, TD, and anticholinergic effects)
- Cardiovascular or cerebrovascular disease
- Hepatic impairment (reduced metabolism; consider lower doses)
- Patients on concomitant CYP3A4/2D6 inhibitors or QT-prolonging drugs
FDA Boxed Warning
Increased Mortality in Elderly Patients with Dementia-Related Psychosis
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death (1.6–1.7× versus placebo). Deaths were primarily cardiovascular or infectious in nature. Haloperidol is not approved for use in patients with dementia-related psychosis.
Patient Counselling for Haloperidol
Purpose of Therapy
Haloperidol helps control symptoms of schizophrenia, tics, or severe behavioural disturbances by restoring the balance of dopamine, a natural chemical in the brain. It does not cure the underlying condition but can significantly reduce hallucinations, delusions, tics, and agitation when taken consistently.
How to Take
Haloperidol tablets or liquid can be taken with or without food. Take the medication at the same time each day. Do not stop taking haloperidol suddenly without your prescriber’s guidance, as symptoms may return and movement side effects may worsen. If you are receiving the long-acting injection (decanoate), you will visit your clinic every four weeks for your injection.
Movement Problems (EPS)
Tell patientYou may notice muscle stiffness, tremor, restlessness, or unusual movements. These are among the most common side effects and can often be managed by dose adjustment or additional medication. Tell your prescriber about any new movement symptoms immediately.
Call prescriberUrgently if you develop a stiff neck, difficulty swallowing, eyes rolling upward (dystonia), or high fever with severe muscle rigidity (possible NMS).
Heart Rhythm
Tell patientHaloperidol can affect your heart rhythm. Your doctor may order heart tracings (ECG) to monitor this, especially if you take other medications that can also affect heart rhythm.
Call prescriberIf you experience palpitations, fainting, dizziness, or chest pain.
Dizziness & Low Blood Pressure
Tell patientYou may feel dizzy when standing up quickly, especially in the first few days. Rise slowly from sitting or lying down. Stay well hydrated.
Call prescriberIf you faint or fall.
Drowsiness
Tell patientHaloperidol may cause drowsiness, especially early in treatment. Avoid driving or operating machinery until you know how it affects you. Avoid alcohol.
Call prescriberIf sedation is excessive and does not improve after the first week.
Hormonal Effects
Tell patientHaloperidol raises a hormone called prolactin, which can cause missed periods, breast discharge, or sexual difficulties. These effects are reversible and treatable.
Call prescriberIf you develop persistent menstrual changes, breast discharge, or troubling sexual side effects.
Sources
Regulatory (PI / SmPC)
- HALDOL DECANOATE (haloperidol decanoate injection). Full Prescribing Information. Janssen Pharmaceuticals, Inc. Revised 10/2025. FDA LabelPrimary source for decanoate dosing, contraindications (including PD and DLB), QTc warnings, and adverse reactions from clinical trials.
- HALDOL (haloperidol) Injection. Full Prescribing Information. Janssen Pharmaceuticals, Inc. Drugs.com PISource for IM lactate dosing, oral dosing, paediatric indications, and Tourette syndrome dosing.
- HALDOL (haloperidol) Tablets. Full Prescribing Information. FDA Label (2008)Comprehensive older label with detailed pharmacokinetic data and dosing in special populations.
Key Clinical Trials
- Leucht S, Cipriani A, Spineli L, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. 2013;382(9896):951-962. DOILandmark network meta-analysis comparing efficacy and tolerability of antipsychotics; haloperidol used as comparator in many included trials.
- Girard TD, Exline MC, Carson SS, et al. Haloperidol and ziprasidone for treatment of delirium in critical illness. N Engl J Med. 2018;379(26):2506-2516. DOIMIND-USA trial showing haloperidol did not shorten delirium duration in ICU patients versus placebo.
- Meltzer HY, Alphs L, Green AI, et al. Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT). Arch Gen Psychiatry. 2003;60(1):82-91. DOIInterSePT trial used haloperidol decanoate as a background comparator; relevant for understanding haloperidol’s long-term safety profile.
Guidelines
- Keepers GA, Fochtmann LJ, Anzia JM, et al. The American Psychiatric Association Practice Guideline for the Treatment of Patients with Schizophrenia. Am J Psychiatry. 2020;177(9):868-872. DOIAPA guideline recommending antipsychotic selection based on individual patient risk-benefit including EPS profile.
- Correll CU, Rubio JM, Kane JM. What is the risk-benefit ratio of long-term antipsychotic treatment in people with schizophrenia? World Psychiatry. 2018;17(2):149-160. DOIComprehensive risk-benefit analysis of chronic antipsychotic use including tardive dyskinesia risk with FGAs.
Mechanistic / Basic Science
- Kapur S, Zipursky R, Jones C, et al. Relationship between dopamine D2 occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia. Am J Psychiatry. 2000;157(4):514-520. DOIPET study demonstrating the D2 occupancy threshold for antipsychotic response (65%) and EPS (>80%) relevant to haloperidol dosing.
Pharmacokinetics / Special Populations
- Kudo S, Ishizaki T. Pharmacokinetics of haloperidol: an update. Clin Pharmacokinet. 1999;37(6):435-456. DOIComprehensive PK review covering bioavailability, protein binding, CYP metabolism, and reduced haloperidol.
- Correll CU, Leucht S, Kane JM. Lower risk for tardive dyskinesia associated with second-generation antipsychotics: a systematic review of 1-year studies. Am J Psychiatry. 2004;161(3):414-425. DOISystematic review quantifying the annual TD incidence with haloperidol (~5.4%) versus SGAs (~0.8%).
- Franssen EJ, Ter Kuile MM, et al. Population pharmacokinetics of haloperidol in terminally ill adult patients. Eur J Clin Pharmacol. 2017;73(10):1271-1277. DOIPopPK model in terminally ill patients; oral bioavailability 86%, terminal half-life ~30 h.