Haloperidol Half-Life
The elimination half-life of haloperidol after oral administration ranges from approximately 15-18 hours following single doses, but extends dramatically to 3-21 days (mean 3.9 days) after chronic administration, with some patients showing detectable levels for over 2 months. 1
Acute vs. Chronic Dosing
The half-life of haloperidol varies substantially based on duration of treatment:
- Single-dose administration: 14.5-36.7 hours (approximately 15-18 hours in most studies) 1, 2
- Chronic administration: Geometric mean of 3.9 days, with 42% of patients showing half-lives ≥3 days and some extending beyond 30 days 1
- Detectable plasma levels: Can persist for a mean of 13.8 days after discontinuation following chronic use 1
This dramatic prolongation after chronic dosing is clinically critical and substantially longer than what occurs after acute administration. In one study of 31 chronically treated patients, 58% had half-lives of 1.2-2.3 days while 42% had half-lives ≥3 days, demonstrating significant interpatient variability 1.
Depot Formulation Differences
Haloperidol decanoate has a markedly longer half-life of approximately 21 days, justifying monthly administration intervals 3. This extended-release formulation can result in:
- Mean half-life of 21 days for the decanoate ester 3
- Detectable levels persisting >2 months in patients who received prior decanoate formulations 1
- Conversion dosing approximately 15-20 times the oral daily dose 3
Clinical Implications for Dosing
Once-daily dosing is adequate for most chronic patients based on the 24-hour elimination half-life reported in standard dosing studies 4. A study comparing twice-daily (10 mg BID) versus once-daily (20 mg QD) schedules found mean plasma concentrations of 16.6 ng/mL and 12.7 ng/mL respectively, both within therapeutic range 4.
Factors Affecting Half-Life
After chronic administration, specific patient factors influence haloperidol elimination:
- Race: African-American patients showed significantly longer half-lives (all 4 African-American patients had half-lives ≥3 days, p=0.014) 1
- CYP2D6 metabolism: Poor metabolizers demonstrated half-lives ≥3 days 1
- Prior decanoate exposure: Patients with prior haloperidol decanoate use within one year showed substantially prolonged elimination 1
- Bioavailability: Oral bioavailability averages 0.64 (64%), comparable between schizophrenic patients and normal volunteers 2
Comparison to Other Antipsychotics
In delirium management studies, haloperidol is classified as a long half-life antipsychotic alongside risperidone and olanzapine, contrasted with quetiapine as a short half-life agent 5. This classification has implications for sustained symptom control versus flexibility in dose adjustment.
Discontinuation Considerations
The prolonged half-life after chronic use substantially reduces the risk of withdrawal or discontinuation syndromes, as washout occurs gradually over days to weeks 6. However, this same property becomes a disadvantage when rapid drug elimination is needed due to adverse effects, toxicity, or unplanned pregnancy 6.