Haloperidol: Difference between revisions

| intro            = '''Haloperidol''' is a butyrophenone-class first-generation ("typical") antipsychotic. Its defining feature is high-affinity, relatively selective D₂ receptor antagonism with minimal anticholinergic activity — making it one of the more behaviorally selective typicals. Despite the broader shift toward atypicals for chronic psychiatric care, haloperidol remains widely used for acute agitation, ICU and postoperative delirium, palliative care nausea, and as a long-acting depot formulation (haloperidol decanoate) for maintenance treatment of schizophrenia.

| pharmacodynamics  = Potent D₂ antagonist with high D₂:5-HT_2A affinity ratio — the pharmacologic profile that defines a "typical" antipsychotic and underlies its extrapyramidal side effect liability. Modest α₁-adrenergic and H₁ antagonism (less than chlorpromazine). '''Minimal muscarinic activity''' — a key advantage over low-potency typicals, but also why EPS is more prominent (no built-in anticholinergic compensation). Antiemetic effect via D₂ blockade at the chemoreceptor trigger zone.

| indications      = * Schizophrenia — acute and maintenance (including decanoate for long-acting injectable maintenance)

'''Delirium, IV (off-label but common):''' 0.5–5 mg IV — '''baseline ECG required'''. Lower in elderly.

| adverse          = * '''Extrapyramidal symptoms (EPS)''' — the dominant adverse effect profile:

* '''Neuroleptic malignant syndrome''' — rare but life-threatening: hyperthermia, rigidity, autonomic instability, altered mental status, elevated CK. Stop med, supportive care, ± dantrolene/bromocriptine.

* '''QT prolongation''' — significant; baseline ECG and electrolyte monitoring especially with IV or high doses

* '''Hyperprolactinemia''' — galactorrhea, gynecomastia, sexual dysfunction, amenorrhea

* '''Sedation''' — less than chlorpromazine, more than aripiprazole

* '''Orthostatic hypotension''' — α₁ blockade; less than low-potency typicals

* '''Anticholinergic effects''' — much milder than chlorpromazine

* '''Lowered seizure threshold''' — caution in epilepsy

| interactions      = * '''QT-prolonging agents''' — azoles, fluoroquinolones, methadone, ondansetron, citalopram, certain antiarrhythmics — additive risk of torsades

* '''CYP3A4 inhibitors''' (ketoconazole, ritonavir, clarithromycin) — elevated haloperidol levels

* '''CYP2D6 inhibitors''' (fluoxetine, paroxetine, bupropion) — elevated levels

* '''CYP3A4 inducers''' (carbamazepine, rifampin, phenytoin) — reduced levels and possible loss of efficacy

* '''CNS depressants''' (benzodiazepines, opioids, alcohol) — additive sedation and respiratory depression

* '''Lithium''' — rare reports of neurotoxicity with combination

* '''Anticholinergics''' — may reduce EPS but worsen delirium/cognition

* '''Levodopa / dopamine agonists''' — mutual antagonism

| monitoring        = * '''Baseline ECG''' — and after dose changes, especially IV or high oral doses

* '''Electrolytes''' (K⁺, Mg²⁺) — for QT risk

* '''AIMS / EPS screening''' — at baseline, periodically thereafter (every 6 months for chronic use)

* '''Prolactin''' — if symptoms suggest hyperprolactinemia

* '''Glucose and lipids''' — less metabolic concern than with atypicals, but check periodically

* '''LFTs''' — at baseline and if symptoms develop

* '''Vital signs''' — orthostatic BP at initiation

* Watch for fever + rigidity + confusion — could indicate neuroleptic malignant syndrome (medical emergency).

* Don't stop abruptly — taper if discontinuing.