Haldol - Drug Monograph

Introduction

Haldol (haloperidol) is a first-generation (typical) antipsychotic medication belonging to the butyrophenone class. Initially approved by the FDA in 1967, it remains a cornerstone in the treatment of various psychiatric conditions. Haldol is particularly valued for its potent dopamine receptor blockade and established efficacy in managing acute agitation and chronic psychotic disorders.

Mechanism of Action

Haloperidol exerts its therapeutic effects primarily through potent antagonism of dopamine D2 receptors in the mesolimbic pathway of the brain. This dopamine blockade reduces positive symptoms of psychosis such as hallucinations, delusions, and disorganized thinking. The drug also demonstrates affinity for alpha-1 adrenergic receptors, which contributes to some of its side effect profile. Unlike newer atypical antipsychotics, haloperidol has minimal serotonergic activity.

Indications

FDA-approved indications include:

• Treatment of schizophrenia
• Management of psychotic disorders
• Control of tics and vocal utterances in Tourette's syndrome
• Treatment of severe behavioral problems in children

Non-FDA approved uses (off-label):

• Acute agitation and aggression
• Delirium management
• Bipolar disorder maintenance therapy
• Anti-emetic therapy in palliative care

Dosage and Administration

• Initial adult dose: 0.5-5 mg 2-3 times daily
• Maintenance: 2-20 mg daily (maximum 100 mg/day)

• Initial dose: 10-15 times previous daily oral dose
• Maintenance: Every 4 weeks (range 50-200 mg)

• Geriatric: Start with 0.5-1 mg 1-2 times daily
• Hepatic impairment: Reduce dose by 30-50%
• Renal impairment: No significant adjustment needed

Pharmacokinetics

• Absorption: Well absorbed orally (60-70% bioavailability)
• Distribution: Vd: 18-30 L/kg; highly protein bound (92%)
• Metabolism: Extensive hepatic metabolism via CYP3A4 and CYP2D6
• Elimination: Half-life: 18-30 hours (oral); 3 weeks (decanoate)
• Excretion: Primarily biliary (40-60%) with renal elimination of metabolites

Contraindications

• Known hypersensitivity to haloperidol
• Severe CNS depression or comatose states
• Parkinson's disease
• Dementia with Lewy bodies
• QT prolongation or significant cardiac arrhythmias

Warnings and Precautions

• Risk of QT prolongation and torsades de pointes
• Extrapyramidal symptoms (EPS) and tardive dyskinesia
• Neuroleptic malignant syndrome (NMS)
• Cerebrovascular adverse events in elderly
• Seizure threshold lowering
• Temperature regulation dysfunction

Drug Interactions

• CYP3A4 inhibitors (ketoconazole, erythromycin): ↑ haloperidol levels
• CYP3A4 inducers (carbamazepine, rifampin): ↓ haloperidol levels
• Other QT-prolonging agents (antiarrhythmics, antidepressants)
• CNS depressants (benzodiazepines, opioids, alcohol)
• Lithium (increased neurotoxicity risk)
• Anticholinergic agents (may reduce EPS but increase anticholinergic effects)

Adverse Effects

• Extrapyramidal symptoms (dystonia, akathisia, parkinsonism)
• Sedation
• Weight gain
• Constipation
• Dry mouth

• Tardive dyskinesia
• Neuroleptic malignant syndrome
• QT prolongation
• Seizures
• Blood dyscrasias
• Hyperprolactinemia

Monitoring Parameters

• Complete metabolic panel
• ECG (QTc interval)
• Complete blood count
• Prolactin level (if indicated)
• Neurological examination

• EPS assessment (AIMS scale quarterly)
• QTc monitoring (periodically and with dose changes)
• Weight and BMI
• Mental status examination
• Signs of NMS (fever, rigidity, autonomic instability)

Patient Education

• Take medication exactly as prescribed
• Do not abruptly discontinue medication
• Avoid alcohol and other CNS depressants
• Rise slowly from sitting/lying position to prevent orthostasis
• Report any muscle stiffness, tremors, or restlessness
• Notify provider of any fever, muscle rigidity, or mental status changes
• Use sun protection due to photosensitivity risk
• Be aware of potential sedation and avoid driving if affected
• Inform all healthcare providers of Haldol use

References

1. FDA Prescribing Information: Haloperidol Tablets 2. Lehne RA. Pharmacology for Nursing Care. 10th ed. Elsevier; 2022. 3. Stahl SM. Stahl's Essential Psychopharmacology. 4th ed. Cambridge University Press; 2013. 4. Marder SR, Cannon TD. Schizophrenia. N Engl J Med. 2019;381(18):1753-1761. 5. Keepers GA, et al. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia. Am J Psychiatry. 2020;177(9):868-872. 6. Miller DD. Atypical antipsychotics: sleep, sedation, and efficacy. Prim Care Companion J Clin Psychiatry. 2004;6(Suppl 2):3-7. 7. Tisdale JE, et al. Drug-induced arrhythmias: A scientific statement from the American Heart Association. Circulation. 2020;142(15):e214-e233.