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.
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)
1 pair found. Sorted from critical to minor.
Mechanism
Аддитивное удлинение QT + ингибиция CYP3A4 повышает концентрацию галоперидола.
Management
ЭКГ-контроль исходно и через 48 часов. У пожилых и при сердечной патологии – избегать.
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.
haloperidol is evaluated for the following indications with varying evidence strength: Acute psychomotor agitation (evidence tier A), Schizophrenia (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.