Usage
- Haloperidol is prescribed for the management of various psychotic disorders including schizophrenia, schizoaffective disorder, and other psychotic conditions. It is also used to control tics and vocalizations in Tourette’s syndrome and to manage severe behavioral problems in children when other treatments have failed. It can also be used to treat acute agitation and delirium.
- Pharmacological Classification: Haloperidol is classified as a first-generation antipsychotic (also known as a neuroleptic).
- Mechanism of Action: Haloperidol primarily acts as a dopamine D2 receptor antagonist in the mesolimbic and mesocortical pathways of the brain. This action is believed to be responsible for its antipsychotic effects.
Alternate Names
- While “haloperidol” is the generic name, it is also marketed internationally under various brand names, the most common being Haldol, Haldol Decanoate (depot injection), and Haloperidol LA. Regional variations may exist.
How It Works
- Pharmacodynamics: Haloperidol exerts its therapeutic effects primarily through dopamine D2 receptor antagonism. It also has some affinity for alpha-adrenergic, histamine H1, and serotonin 5-HT2 receptors, which contributes to some of its side effects.
- Pharmacokinetics:
- Absorption: Haloperidol is well-absorbed orally, but its bioavailability can vary. The decanoate ester has a slow release profile, allowing for monthly injections.
- Metabolism: It is extensively metabolized in the liver, primarily by CYP3A4 enzymes.
- Elimination: Haloperidol is eliminated through both renal and hepatic routes, with a half-life of approximately 24 hours (oral) and much longer for the decanoate formulation.
- Mode of Action: By blocking dopamine D2 receptors, haloperidol reduces dopaminergic neurotransmission in the brain, particularly in the mesolimbic and mesocortical pathways, believed to be involved in psychosis.
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: As a potent D2 receptor antagonist, Haloperidol also has affinities for alpha-1 adrenergic, histamine H1, and serotonin 5-HT2A receptors which can mediate some of its side effects. CYP3A4 hepatic enzyme interactions are a critical consideration when co-prescribing with Haloperidol.
- Elimination Pathways: Primarily hepatic metabolism through CYP3A4 with renal and biliary excretion of metabolites.
Dosage
Standard Dosage
Adults:
- Oral: 0.5-5 mg two to three times daily initially, adjusted as needed. The maximum daily dose is generally 100 mg, though higher doses may be used in some cases. Maintenance doses are often lower.
- IM (Haloperidol Lactate): 2-5 mg every 4-8 hours, adjusted as needed. Maximum daily dose is generally 20 mg.
- IM (Haloperidol Decanoate): 10-15 times the daily oral dose given monthly, not exceeding 100 mg initially.
Children:
- 3-12 years: 0.05-0.15 mg/kg/day orally in divided doses. Dosage should be titrated carefully based on response and tolerability.
- Below 3 years: Use with extreme caution. Safety and efficacy not fully established.
Special Cases:
- Elderly Patients: Start with half the lowest adult dose and titrate cautiously due to increased sensitivity.
- Patients with Renal Impairment: Dose adjustment may be necessary based on the degree of impairment.
- Patients with Hepatic Dysfunction: Dose reduction is generally recommended.
- Patients with Comorbid Conditions: Cardiovascular disease, seizures, and other conditions may require dose adjustments and careful monitoring.
Clinical Use Cases
- Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use: Haloperidol can be used to manage agitation and delirium in these settings, typically with IV or IM administration of haloperidol lactate. Dosing must be individualized.
- Emergency Situations: Acute agitation, psychosis, can be managed with IM haloperidol lactate.
Dosage Adjustments:
- Dosage should be adjusted based on patient response, tolerability, and renal/hepatic function.
- Drug interactions, particularly with CYP3A4 inhibitors or inducers, can necessitate dosage modifications.
Side Effects
Common Side Effects:
- Extrapyramidal symptoms (EPS): Parkinsonism, dystonia, akathisia, tardive dyskinesia
- Sedation, drowsiness
- Dry mouth, constipation, blurred vision
- Dizziness, headache
Rare but Serious Side Effects:
- Neuroleptic malignant syndrome (NMS)
- QT prolongation, torsades de pointes
- Agranulocytosis, leukopenia
Long-Term Effects:
- Tardive dyskinesia
- Metabolic syndrome
Adverse Drug Reactions (ADR):
- NMS, QT prolongation, severe dystonic reactions, agranulocytosis.
Contraindications
- Hypersensitivity to haloperidol
- Coma
- Parkinson’s disease
- Dementia with Lewy bodies
- Severe CNS depression
- Concomitant use of drugs that prolong the QT interval
Drug Interactions
- CNS depressants (alcohol, benzodiazepines, opioids)
- Antihypertensives
- QT prolonging agents (e.g. amiodarone, quinidine, certain antibiotics)
- CYP3A4 inhibitors and inducers (e.g., ketoconazole, rifampin)
- Lithium
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C. Haloperidol should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus.
- Breastfeeding: Haloperidol is excreted in breast milk. Use with caution, monitor infant for side effects.
Drug Profile Summary
- Mechanism of Action: Dopamine D2 receptor antagonist.
- Side Effects: EPS, sedation, dry mouth, constipation.
- Contraindications: Parkinson’s disease, dementia with Lewy bodies, coma, QT prolonging drugs.
- Drug Interactions: CNS depressants, QT prolonging drugs, CYP3A4 inhibitors/inducers.
- Pregnancy & Breastfeeding: Use with caution; potential fetal/neonatal risks.
- Dosage: Adult: 0.5-5 mg 2-3 times/day (oral); Child: 0.05-0.15 mg/kg/day.
- Monitoring Parameters: EPS, ECG (QT interval), mental status, complete blood count.
Popular Combinations
- Haloperidol is sometimes combined with other psychotropics, such as antidepressants or mood stabilizers, to address comorbid conditions. However, combining with other QT prolonging agents should be strictly avoided.
Precautions
- Monitor for EPS, NMS, QT prolongation, and other side effects.
- Exercise caution in elderly patients and those with renal or hepatic impairment.
- Avoid abrupt discontinuation.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Haloperidol?
A: Adults: 0.5-5 mg orally 2-3 times/day initially. Children: 0.05-0.15 mg/kg/day orally. Elderly: Initiate at half the adult dose. Adjust based on response and tolerability.
Q2: What are the common side effects of haloperidol?
A: Extrapyramidal symptoms (EPS), such as parkinsonism, dystonia, akathisia, and tardive dyskinesia are common. Sedation, dry mouth, and constipation are also frequently observed.
Q3: What are the contraindications for Haloperidol?
A: Parkinson’s disease, Dementia with Lewy bodies, coma, hypersensitivity to haloperidol, and concomitant use of drugs known to prolong the QT interval.
A: Primarily by CYP3A4 enzymes in the liver.
Q5: What are the signs and symptoms of Neuroleptic Malignant Syndrome (NMS)?
A: High fever, muscle rigidity, altered mental status, autonomic instability (e.g., tachycardia, labile blood pressure).
Q6: What is the difference between haloperidol and haloperidol decanoate?
A: Haloperidol is the immediate-release form, while haloperidol decanoate is a long-acting injectable formulation given every 4 weeks.
Q7: Can Haloperidol be used in pregnant or breastfeeding women?
A: Haloperidol should be used in pregnancy only if the benefit clearly outweighs the risk. It is excreted in breast milk, so caution is advised during breastfeeding. The infant should be monitored for potential side effects.
Q8: How should Haloperidol be discontinued?
A: Gradually taper the dose to minimize withdrawal symptoms. Abrupt cessation can exacerbate symptoms or cause rebound psychosis.
Q9: What should be monitored in patients taking haloperidol?
A: Monitor for EPS, ECG (QT interval), complete blood count, and any signs of NMS. Regular assessment of mental status and overall clinical response is also necessary.
