First-generation antipsychotics. Butyrophenone derivatives
ATC code: N05AD01 (Haloperidol)
Brand names
Haldol, Haldol Decanoate, Serenace
Potent D2 receptor antagonist in mesolimbic, mesocortical, and nigrostriatal tracts. Controls positive psychosis symptoms and acute agitation. High risk of extrapyramidal side effects, neuroleptic malignant syndrome, and QT prolongation.
First line
Parenteral haloperidol (IM 2.5–10 mg) is used for acute agitation in psychotic, manic, or toxicological states. Onset 20–40 minutes. 2020 and Russian clinical guidelines support this approach. May be combined with lorazepam or midazolam for additional sedation.
Assess QT interval and potassium/magnesium levels before administration, especially before repeat dosing.
First line
Haloperidol is used in schizophrenia for acute positive symptom control and maintenance therapy. 2020 and CG178 list haloperidol as a standard first-generation antipsychotic; current guidelines favor atypical antipsychotics as first-line due to a more favorable side-effect profile, but haloperidol retains its role when parenteral administration is required and in resource-limited settings. The decanoate form provides a 4-week depot effect for patients with poor adherence.
High risk of extrapyramidal symptoms and tardive dyskinesia with long-term therapy. Not first-line in elderly patients with dementia.
Sources
Individual decision
Low-dose haloperidol (0.5–2 mg orally or IM) is used for symptomatic management of delirium with severe agitation, psychotic features, or risk of self-harm. A 2018 Cochrane systematic review showed no advantage of antipsychotics over placebo for delirium duration or mortality. Use is individual and time-limited.
Halve the dose in elderly patients. Benzodiazepines (except alcohol withdrawal delirium) worsen delirium and are not used as monotherapy.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
In elderly patients with dementia, antipsychotics are used only for severe aggression or psychotic features with risk of harm. The boxed warning (2008) and notice (2011) cite a 1.6–1.7-fold increased mortality risk with antipsychotics in elderly dementia. and Beers Criteria 2023 recommend avoiding routine use, employing minimal doses and short courses (no more than 6–12 weeks) with regular discontinuation attempts.
Use only after failure of non-pharmacological approaches and careful benefit-risk assessment. Family informed consent is mandatory.
Not recommended
In non-psychotic patients haloperidol is not used for anxiety or insomnia. International guidelines ( CG113, ) treat anxiety with SSRIs, SNRIs, CBT; benzodiazepines short-term only. Antipsychotic use for anxiety carries risks of extrapyramidal effects and QT prolongation without proven benefit.
Grapefruit juice inhibits intestinal CYP3A4, increasing haloperidol plasma concentrations. May potentiate sedation and QT prolongation. Patients are advised to avoid regular grapefruit and grapefruit juice consumption during therapy.
Source: FDA: Haldol (haloperidol) prescribing information (2024)
23 pairs found. Sorted from critical to minor.
Mechanism
Additive QT prolongation, especially with parenteral (IV) haloperidol. Torsades de pointes and fatal arrhythmias have been reported, especially in ICU patients with hypokalaemia.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Avoid the combination, especially IV haloperidol. Alternative antipsychotics with minimal QT effect: olanzapine or aripiprazole. For acute delirium in amiodarone patients: dexmedetomidine (no QT effect).
Mechanism
Additive QT prolongation and anticholinergic effect. Both drugs are sedating. In elderly patients with dementia, severe delirium and arrhythmias have been reported.
Symptoms
Drowsiness, sedation, confusion, delirium (especially in older patients). Dry mouth, constipation, urinary retention. QT prolongation on ECG with torsades de pointes risk.
Management
Avoid the combination, especially in older patients. Alternative antipsychotics with minimal QT effect: olanzapine or aripiprazole. Alternative antidepressants without QT effect: mirtazapine or agomelatine.
Mechanism
Additive QT prolongation. Azithromycin received a 2013 warning for fatal arrhythmia risk. Haloperidol (especially IV) also has a pronounced QT effect.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Avoid the combination. Alternative antibiotics: doxycycline or a cephalosporin. Alternative antipsychotics with minimal QT effect: olanzapine or aripiprazole.
Mechanism
Haloperidol is a CYP2D6 substrate; bupropion is a potent CYP2D6 inhibitor. Haloperidol plasma levels rise 2- to 3-fold. Risk of extrapyramidal symptoms and QT prolongation emerges. Both drugs also lower the seizure threshold.
Symptoms
Extrapyramidal symptoms (tremor, rigidity, akathisia), QT prolongation on ECG, seizures. Older patients: fall risk.
Management
Avoid the combination. Alternative antipsychotics without CYP2D6 dependence: olanzapine or aripiprazole. Alternative antidepressants without CYP2D6 inhibition: sertraline or escitalopram.
Mechanism
Carbamazepine induces CYP3A4 – a partial haloperidol clearance route. Haloperidol plasma levels fall by 50% and antipsychotic effect weakens.
Symptoms
Return of positive symptoms: hallucinations, delusions, agitation. In schizophrenia, risk of acute relapse.
Management
During carbamazepine therapy, increase haloperidol 1.5- to 2-fold under clinical monitoring. Alternative anticonvulsants without induction: sodium valproate, levetiracetam, lamotrigine (no CYP3A4 induction).
Mechanism
Dual mechanism: both prolong QT (additively), and ciprofloxacin blocks CYP1A2 – a partial haloperidol clearance route. Haloperidol levels rise.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Avoid the combination. Alternative antibiotics: a cephalosporin or nitrofurantoin. Alternative antipsychotics with minimal QT effect: olanzapine or aripiprazole.
Mechanism
Additive QT prolongation. Haloperidol is one of the strongest QT prolongers among typical antipsychotics, especially parenterally. Citalopram does so dose-dependently.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Avoid the combination, especially IV haloperidol. Alternative antipsychotics with minimal QT effect: olanzapine or aripiprazole. Alternative antidepressants: mirtazapine or agomelatine.
Mechanism
Additive QT prolongation. Clarithromycin also blocks CYP3A4 – the main haloperidol clearance route – and haloperidol levels rise.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Avoid the combination. Alternative antibiotics: azithromycin or doxycycline. Alternative antipsychotics with minimal QT effect: olanzapine or aripiprazole.
Mechanism
Additive QT prolongation. Torsades de pointes has been reported with dronedarone plus other QT-prolonging drugs. Haloperidol is particularly dangerous parenterally (IV).
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.
Management
Avoid the combination, especially IV haloperidol. Alternative antipsychotics with minimal QT effect: olanzapine or aripiprazole. For acute delirium: dexmedetomidine.
Mechanism
Additive QT prolongation. Escitalopram prolongs QT dose-dependently ( Lexapro caps at 20 mg/day) and haloperidol prolongs QT too. In patients with hypokalaemia, hypomagnesaemia, ischaemic heart disease, or bradycardia, torsades de pointes risk is especially high.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Avoid the combination. Alternative antipsychotics with minimal QT effect: olanzapine or aripiprazole. Alternative antidepressants: mirtazapine or agomelatine.
Mechanism
Dual mechanism. Fluconazole prolongs QT and blocks CYP3A4 and CYP2D6 – haloperidol metabolic routes. Haloperidol plasma levels rise; QT effects add up.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.
Management
Avoid the combination. Alternative antifungals: terbinafine or echinocandins. Alternative antipsychotics with minimal QT effect: olanzapine or aripiprazole.
Mechanism
Ketoconazole is a potent CYP3A4 inhibitor – the main haloperidol metabolic route. Haloperidol plasma levels rise 2- to 3-fold. Ketoconazole itself prolongs QT; effects add up.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.
Management
Avoid the combination. Alternative antifungals: terbinafine or echinocandins. Alternative antipsychotics: olanzapine or aripiprazole.
Mechanism
Mirtazapine prolongs QT dose-dependently, additively with haloperidol (especially parenteral). Plus combined sedation.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.
Management
Avoid the combination with mirtazapine above 30 mg and parenteral haloperidol. At low doses and normal potassium, the combination is acceptable with ECG monitoring at 2 weeks. Alternative antipsychotics with minimal QT effect: olanzapine or aripiprazole.
Mechanism
Additive CNS depression and sedation. Severe hypotension and respiratory depression have been reported, especially in older patients.
Symptoms
Drowsiness, slowed breathing (rate below 12/min), cyanosis of lips. Severe cases include respiratory arrest. Older patients: fall risk.
Management
Avoid the combination in older patients. For opioid-induced nausea, use ondansetron (no QT issue in short courses in older patients) or metoclopramide. For acute delirium, dexmedetomidine (no respiratory depression).
Mechanism
Dual antipsychotic therapy – additive risk of extrapyramidal symptoms, sedation, QT prolongation, and metabolic side effects. Polypharmacy without therapeutic rationale in most cases.
Symptoms
Sedation, extrapyramidal symptoms (tremor, rigidity, akathisia), QT prolongation on ECG. Metabolic effects: weight gain, dyslipidaemia (from quetiapine).
Management
Avoid the combination. Choose one antipsychotic: quetiapine for schizophrenia with anxious-depressive component or bipolar disorder; haloperidol for acute psychotic agitation. If dual therapy is needed, restrict to short-term use during acute psychotic episodes.
Mechanism
Rifampicin strongly induces CYP3A4 – the main haloperidol metabolic route. Haloperidol plasma levels fall by 70%; antipsychotic effect weakens.
Symptoms
Return of positive symptoms: hallucinations, delusions, agitation. In schizophrenia: risk of acute relapse.
Management
During anti-TB therapy, increase haloperidol 2- to 3-fold with clinical monitoring. Alternative antipsychotics without CYP3A4 dependence: olanzapine or aripiprazole.
Mechanism
Sertraline at high doses prolongs QT, additively with haloperidol. Sertraline also weakly blocks CYP2D6, so haloperidol levels may rise.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.
Management
Avoid the combination with sertraline above 100 mg and parenteral haloperidol. Alternative antipsychotics with minimal QT effect: olanzapine or aripiprazole. Alternative antidepressants: mirtazapine or agomelatine.
Mechanism
Additive QT prolongation. Haloperidol strongly prolongs QT, especially parenterally (IV). Tacrolimus prolongs QT with hypomagnesaemia. Combined action raises torsades de pointes risk.
Symptoms
QT prolongation on ECG, dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.
Management
Avoid the combination, especially IV haloperidol. Alternative antipsychotics with minimal QT effect post-transplant: olanzapine or aripiprazole. For acute delirium: dexmedetomidine (no QT effect).
Mechanism
Tramadol lowers seizure threshold and prolongs QT. Haloperidol is a strong QT prolonger, especially parenterally. Additive seizure and torsades de pointes risk.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.
Management
Avoid the combination. For analgesia on haloperidol, use paracetamol, an NSAID, or morphine/oxycodone. Alternative antipsychotics: olanzapine or aripiprazole.
Mechanism
Additive QT prolongation. Venlafaxine at high doses (above 150 mg/day) prolongs QT; haloperidol does so on its own (especially parenterally).
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.
Management
Avoid the combination with high venlafaxine doses and parenteral haloperidol. At low venlafaxine doses (75 mg) and oral haloperidol, the combination is acceptable with ECG monitoring at 2 weeks. Alternative antipsychotics with minimal QT effect: olanzapine or aripiprazole.
Mechanism
Additive CNS depression and sedation. In older patients: high delirium and fall risk.
Symptoms
Deep sedation, drowsiness, ataxia, confusion (especially in older patients). Orthostatic hypotension possible (haloperidol blocks α1-adrenoceptors).
Management
The combination is used briefly in acute agitation or psychotic episodes. In older patients: lorazepam at minimum dose with olanzapine or aripiprazole (less α1-blockade than haloperidol) is preferable.
Mechanism
Additive hypotension (haloperidol blocks α1-adrenoceptors) and sedation. Haloperidol prolongs QT; amlodipine does not contribute to QT.
Symptoms
Lower blood pressure, postural dizziness, fatigue. Older patients: fall risk.
Management
Avoid the combination, especially with parenteral haloperidol. Alternative antipsychotics with minimal α1-blockade: olanzapine or aripiprazole.
Mechanism
Additive hypotension (haloperidol blocks α1-adrenoceptors) and QT prolongation risk (haloperidol is a known QT prolonger).
Symptoms
Lower blood pressure, postural dizziness, syncope. ECG: QT prolongation. Older patients: fall risk.
Management
Avoid the combination, especially parenteral haloperidol. Alternative antipsychotics with minimal α1 and QT effect: olanzapine or aripiprazole. For acute delirium: dexmedetomidine.
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Boxed warning
FDA boxed warning: increased mortality in elderly patients with dementia-related psychosis treated with antipsychotics. Haloperidol is not FDA-approved for dementia-related psychosis. An additional warning concerns sudden death, QT prolongation, and torsades de pointes with intravenous use and high doses.
FDA category C. Third-trimester use is associated with extrapyramidal and withdrawal symptoms in the newborn. Used only when safer alternatives are unavailable and benefit outweighs risk. Decision made jointly with psychiatrist and obstetrician.
Passes into breast milk in small amounts. LactMed classifies as having limited data; if used during lactation, monitor the infant for sedation and extrapyramidal symptoms.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Haloperidol is evaluated for the following indications with varying evidence strength: Schizophrenia (evidence tier A), Acute psychomotor agitation (evidence tier A), Delirium (evidence tier B). See the full indication matrix with dosing and citations above on this page.
Common side effects of Haloperidol (≥ 1 in 100): Extrapyramidal symptoms: akathisia, parkinsonism, acute dystonia, Sedation, somnolence, Dry mouth, constipation, Orthostatic hypotension, Hyperprolactinemia with galactorrhea and menstrual disturbances. See the Safety section for uncommon and serious reactions.
FDA category C. FDA category C. Third-trimester use is associated with extrapyramidal and withdrawal symptoms in the newborn. Used only when safer alternatives are unavailable and benefit outweighs risk. Decision made jointly with psychiatrist and obstetrician.
Passes into breast milk in small amounts. LactMed classifies as having limited data; if used during lactation, monitor the infant for sedation and extrapyramidal symptoms.
Haloperidol is contraindicated in: Hypersensitivity to haloperidol; Coma of any cause; CNS depression (alcohol, opioids, barbiturates); Parkinson disease and parkinsonism; Dementia with Lewy bodies. Full list in the Safety section.
FDA boxed warning: increased mortality in elderly patients with dementia-related psychosis treated with antipsychotics. Haloperidol is not FDA-approved for dementia-related psychosis. An additional warning concerns sudden death, QT prolongation, and torsades de pointes with intravenous use and high doses.
with appropriate dosing and side-effect monitoring, the drug remains a useful psychiatric tool. Modern algorithms prefer atypicals, but haloperidol holds a niche in resource-limited settings and as IM for agitation.
risk exists, but with routine AIMS monitoring and timely dose reduction or switch to atypicals, manifestations are often reversible or minimal.
FDA boxed warning cites increased mortality; use is limited to severe cases and short courses.