haloperidol decanoate

General Information

Haloperidol decanoate (Haldol Decanoate) is a long-acting injectable (LAI) formulation of haloperidol used for schizophrenia maintenance.

It is a high-potency dopamine D2 antagonist. Relative to many SGAs, it tends to have low metabolic burden but a higher risk of EPS and tardive dyskinesia, with clinically relevant QTc considerations.

Depot pharmacokinetics are slow-moving: concentrations rise after injection, peak around day 6, and decline with an apparent half-life of ~3 weeks. Steady state may take 2–4 months, so dose changes may take weeks to fully translate into clinical effect.

For depot comparisons and interval planning, use the LAI Navigator and the compare tool.

Haloperidol decanoate is often selected when a high-potency first- generation antipsychotic is effective and the treatment team wants a monthly depot schedule to reduce relapse risk from missed oral doses. Practical constraints include movement-disorder monitoring, QTc risk management, and slower "steerability" versus oral dosing.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Haloperidol is a potent dopamine D2 receptor antagonist with antipsychotic effects mediated primarily through dopamine blockade.

High D2 occupancy contributes to clinical efficacy but also underlies the higher risk of EPS and prolactin elevation relative to many SGAs.

• Potent dopamine D2 receptor antagonist.
• Minimal anticholinergic receptor affinity.
• Variable activity at histamine and adrenergic receptors; orthostasis is usually modest.

Metabolism and Pharmacokinetics

• Haloperidol is metabolized by CYP3A4 and CYP2D6; interaction burden is clinically relevant when adding strong inhibitors or inducers.
• After haloperidol decanoate injection, plasma concentrations rise gradually, peak around day 6, and fall thereafter; apparent half-life is about 3 weeks per labeling.
• Steady state may take 2–4 months with monthly injections. Clinically, symptom and adverse-effect changes after dose adjustments may lag behind the clinic visit.

Dosing and Administration

• Confirm oral tolerability and response before depot conversion when feasible. Conversion is individualized; labeling commonly describes an initial monthly dose roughly 10–15× the total daily oral dose.
• The maximum first injection dose limit is clinically important; larger initial conversions may be split into two injections separated by several days (per label) to reduce early peak-related adverse effects.
• Some clinicians use a short oral overlap during conversion while depot concentrations rise. Missed-dose management is time-sensitive and should be documented at initiation.
• Dose adjustments and response assessment are slower than with oral therapy because steady state takes months; teams often reassess over multiple injection cycles before declaring non-response.

Monitoring & Labs

• Movement disorder monitoring (akathisia, parkinsonism, tardive dyskinesia) including periodic AIMS-style exams.
• ECG/QTc monitoring when clinically indicated (cardiac disease, electrolyte disturbances, QT-prolonging co-medications).
• Prolactin-related symptom review (sexual dysfunction, menstrual changes, galactorrhea).
• Injection site assessment and documentation (site rotation, local reactions).

Adverse Effects

Interactions

• Strong CYP3A4 or CYP2D6 inhibitors may increase haloperidol exposure and adverse effects; strong inducers may reduce exposure and increase relapse risk.
• Additive QTc prolongation risk occurs with other QT-prolonging agents; individualize ECG monitoring to baseline risk.
• Additive CNS depression with alcohol, benzodiazepines, opioids, and sedative hypnotics; monitor falls risk and daytime functioning.
• Combining dopamine-blocking agents increases EPS burden; consider movement-disorder monitoring when combinations are unavoidable.

Other Useful Information

• Depot effectiveness depends on workflow: reminders, reliable scheduling, and clear documentation of last injection date and site.
• Slow washout means adverse effects can persist for weeks after dose changes; prioritize early recognition and timely management.
• Use the schizophrenia hub for relapse-prevention pathways and patient-facing education links.

References

1. HALDOL Decanoate (haloperidol decanoate) injection — Prescribing Information — DailyMed (2025)
2. Haloperidol tablets prescribing information — DailyMed (2025)
3. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia — American Psychiatric Association (2020)
4. Comparative Efficacy AND Tolerability OF 15 Antipsychotic Drugs IN Schizophrenia: A Multiple Treatments Meta Analysis — The Lancet (2013)Meta-analysisschizophreniaefficacy
5. AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology — Pharmacopsychiatry (2018)