Skip to Main Content


  1. Pharmacology

    1. Haloperidol and droperidol are butyrophenone neuroleptic drugs, often referred to as "first-generation" or "typical" antipsychotics, that are useful for the management of acutely agitated psychotic patients and as antiemetics. They have strong central antidopaminergic activity and weak anticholinergic and anti-alpha-adrenergic effects.

    2. Olanzapine and ziprasidone are second-generation or "atypical" antipsychotic agents. They have weaker and more selective antidopaminergic activity and a higher ratio of serotonin-to-dopamine antagonism. This provides less risk for extrapyramidal side effects. However, olanzapine has greater anticholinergic effects, and both have greater antihistaminic and anti-alpha-adrenergic effects. Therefore, they have a greater propensity to cause sedation and orthostatic hypotension.

    3. Pharmacokinetics. Haloperidol is well absorbed from the GI tract and by the intramuscular route. Droperidol is available only for parenteral use and is also well absorbed by the intramuscular route. Droperidol has a more predictable and rapid onset of 3–10 minutes, and both have peak pharmacologic effects that occur within 30–40 minutes of an intramuscular injection. Both drugs are metabolized principally by the liver. The serum half-life for haloperidol is 12–24 hours. Olanzapine and ziprasidone are well absorbed from the GI tract and by the intramuscular route. Olanzapine IM results in rapid absorption, with peak levels occurring within 15–45 minutes, whereas ziprasidone IM has peak levels occurring at approximately 30–60 minutes. Both drugs are metabolized principally by the liver. The serum half-life for olanzapine is 20–54 hours, and for ziprasidone, it is 2–5 hours.

  2. Indications

    1. Haloperidol is used for the management of acute agitated functional psychosis or extreme agitation induced by stimulants or hallucinogenic drugs, especially when drug-induced agitation has not responded to a benzodiazepine.

    2. Droperidol has a more rapid onset and greater efficacy for agitation and is also useful for drug- or toxin-induced nausea and vomiting, but its role in routine therapy is uncertain because of reports of deaths and a "black box" warning about QT prolongation (see Item IV. D below). Therefore, other antiemetic drugs (eg, metoclopramide and ondansetron) should be considered as first-line drugs to control persistent nausea and vomiting.

    3. Olanzapine and ziprasidone by the intramuscular (IM) route are approved for the management of acute agitation associated with schizophrenia, in addition to bipolar mania for olanzapine. Both have been used for the management of acute undifferentiated agitation of either psychiatric or organic (eg, drug-induced) origin. They may have comparable efficacy to haloperidol when administered by the IM route to treat acute agitation.

    4. Note: Benzodiazepines are the usual first-line therapy for stimulant (eg, cocaine or amphetamine) intoxications and alcohol withdrawal syndromes. Combining an antipsychotic with a benzodiazepine may shorten the time to sedation for the treatment of acute agitation.

    5. Nonbenzodiazepine sedatives (either propofol or dexmedetomidine) are often the preferred agents for sedation in mechanically ventilated adult ICU patients.

  3. Contraindications

    1. Severe CNS depression in the absence of airway and ventilatory control.

    2. Severe parkinsonism.

    3. Known hypersensitivity to the individual agent. Droperidol is structurally similar to haloperidol. Olanzapine is a thienobenzodiazepine and similar to clozapine. Ziprasidone has a unique chemical ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.