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Antipsychotics for initial management of the acutely agitated adult patient with psychosis

Antipsychotics for initial management of the acutely agitated adult patient with psychosis
  Formulation Route Initial dose (mg) Frequency (hours) Maximum initial dose per 24 hours (mg) Time to peak plasma concentration (hours) Notes
Second-generation agents
Olanzapine Injection (short-acting) IM, IV* 5 to 10 2 to 4Δ 30 (including oral doses) 0.25 to 0.75
  • Onset of action IM: Approximately 15 minutes; IV: 5 to 10 minutes.
  • If given IM/IV with parenteral benzodiazepine there is increased risk of excess sedation and respiratory depression; separating doses by ≥60 minutes suggested.
  • Decreased clearance in female and/or non-smoking patients; consider use of lower doses in range.
  • Moderate dose related QTc prolongation; some data suggest mild effect.
Disintegrating tablet Oral, SL 5 to 10 2 20 (including IM/IV doses) 5
Risperidone Disintegrating tablet, oral solution Oral 1 to 2 0.5 to 2 6 1.5
  • Onset of action (oral disintegrating tablet): 70 minutes on average.
  • Decreased clearance in kidney and/or hepatic impairment.
  • Moderate dose related QTc prolongation.
  • Metabolized by CYP2D6; variable efficacy due to genetic polymorphisms.
Ziprasidone Short-acting mesylate injection IM 10 to 20 2 to 4 40 0.5 to 1
  • Dose related QTc prolongation and risk of cardiac dysrhythmias; risk appears greater than other second-generation agents.
  • Onset of action IM: 15 to 20 minutes.
  • Oral preparation available.
Aripiprazole Disintegrating tablet, oral solution Oral 10 to 15 2 30 3 to 5
  • Less sedating. Minimal prolongation of QTc interval or orthostatic hypotension.
  • Metabolized by CYP2D6; variable efficacy due to genetic polymorphisms.
  • Refer to UpToDate topic on choosing treatment for severe postpartum unipolar major depression.
First-generation agents
Haloperidol Short-acting lactate injection IM, IV 2 to 10 0.5 to 2Δ 20◊ 0.5 to 1
  • Onset of action IM/IV: 30 to 60 minutes.
  • Sedation, hypotension, and prolongation of QTc interval more pronounced with injection.
  • Increased risk of acute dystonic reaction.§
  • For severe agitation, typically initial dose is 5 mg IM/IV combined with a benzodiazepine (eg, lorazepam 2 mg IM/IV).
  • Older adults should start with a lower initial dose (1 to 2 mg orally).
Oral solution Oral 2 to 10 6 30 2
Droperidol Injection (short-acting) IM, IV 2.5 to 10 2 to 4Δ 40 0.5
  • Rapid onset of 3 to 10 minutes advantageous in severely agitated violent patients.
  • Dose related QTc prolongation and risk of cardiac dysrhythmias.
  • For severe agitation, typically initial dose is 2.5 to 5 mg IM/IV combined with a benzodiazepine (eg, midazolam 2.5 to 5 mg IM/IV).
  • Increased risk of acute dystonic reaction.§
  • The approach to pharmacologic treatment of the acutely agitated patient, including specific medication choices and combinations depending upon presentation (eg, toxic ingestion, withdrawal syndrome, or known psychiatric history) is provided in the accompanying topic reviews and in an algorithm.
  • Antipsychotics should be avoided in patients with anticholinergic delirium or acute alcohol withdrawal; refer to UpToDate topic. Dose reduction by one-half is needed for older adults, debilitated patients, and if used in combination with other sedation.
  • Refer to accompanying text for discussion of electrocardiograph and other monitoring for agents known to cause prolongation of the QTc interval.
  • Antipsychotics (eg, aripiprazole, risperidone, haloperidol) are metabolized to varying degrees by CYP450 2D6, 3A4, and/or substrates of P-glycoprotein. Drug interactions and additive QTc prolongation effects can be assessed by use of the drug interactions program included within UpToDate.

IM: intramuscular; IV: intravenous; SL: sublingual.

* IV administration of olanzapine should be limited to settings where patient can be closely monitored for respiratory depression and excessive sedation.

¶ If olanzapine is administered IV, limit total dose to 10 mg per episode (ie, if initial dose was <10 mg, may repeat with additional dose after ≥10 minutes up to 10 mg total).

Δ It may be necessary to repeat initial dose or fraction thereof after 15 to 20 minutes in patients with severe agitation until desired level of sedation attained.

◊ Selected patients without schizophrenia may need a higher cumulative haloperidol dose (eg, up to 30 mg) during the first 24 hours of treatment to achieve and maintain adequate sedation.

§ Treatment of acute dystonic reactions is diphenhydramine 25 to 50 mg IM/IV or benztropine 1 to 2 mg IM/IV, which is discussed in detail separately.
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