What are the intramuscular (IM) medication options for acute psychosis?

Intramuscular Medication Options for Acute Psychosis

Primary Recommendation

For acute psychotic agitation, use intramuscular olanzapine 10 mg as first-line therapy, or alternatively haloperidol 5 mg IM combined with lorazepam 2 mg IM, with olanzapine preferred due to superior tolerability and equivalent efficacy. 1, 2

First-Line IM Options

Olanzapine 10 mg IM

• Olanzapine 10 mg IM is statistically superior to placebo and equivalent to haloperidol 7.5 mg IM for reducing agitation at 2 hours post-injection in patients with schizophrenia and bipolar mania. 2
• Does not prolong QT interval, making it safer in patients without cardiac screening. 3
• Produces significantly fewer extrapyramidal symptoms compared to typical antipsychotics. 4
• Patients may receive up to 3 injections in 24 hours, with subsequent doses given at least 2 hours apart (maximum 30 mg/day). 2

Haloperidol 5 mg IM (with or without lorazepam)

• Initial dose of 2.5-10 mg IM, with subsequent doses every 4-6 hours as needed for prompt control of acute agitation. 5, 6
• Combination of haloperidol 5 mg plus lorazepam 2-4 mg IM produces significantly greater reduction in agitation compared to either agent alone at 1 hour. 1
• Haloperidol monotherapy carries 20% risk of extrapyramidal side effects, which can be mitigated by combination with benzodiazepines. 1

Second-Line IM Options

Ziprasidone 10-20 mg IM

• More effective than haloperidol IM in reducing BPRS total scores and agitation items with lower incidence of movement disorders. 7
• AVOID in patients without cardiac history due to QT prolongation risk. 3
• Initial dose 10 mg, with subsequent doses of 5-20 mg every 4-6 hours (maximum 80 mg/day). 7

Combination Therapy: Haloperidol + Promethazine

• Haloperidol 10 mg plus promethazine 25-50 mg achieved equal tranquilization rates (96%) compared to lorazepam 4 mg at 4 hours. 1

Oral Alternative for Cooperative Patients

Risperidone 2 mg + Lorazepam 2 mg PO

• Single oral dose of risperidone 2 mg plus lorazepam 2 mg is as effective as haloperidol 5 mg IM plus lorazepam 2 mg IM for rapid control of agitation, with significant improvements at 30,60, and 120 minutes. 8
• This oral regimen is an acceptable alternative when patients are cooperative and can take oral medication. 4, 8

Critical Dosing Principles

Avoid Excessive Dosing

• Maximum recommended dose for haloperidol in first-episode psychosis is 4-6 mg/day; higher doses increase extrapyramidal symptoms without improving efficacy. 5
• Doses above 4-6 mg/day of typical antipsychotics do not demonstrate greater efficacy. 4

Transition to Oral Therapy

• Switch to oral formulation within 12-24 hours following last parenteral dose once acute agitation is controlled. 6
• Use the parenteral dose administered in preceding 24 hours as initial approximation for total daily oral dose. 6

Agents to AVOID

• Droperidol: Associated with QT prolongation; avoid without cardiac screening. 3
• Ziprasidone: QT prolongation risk limits use in emergency settings without ECG. 3
• Typical antipsychotics as monotherapy in first-episode psychosis due to 50% risk of irreversible tardive dyskinesia in elderly after 2 years of continuous use. 4

Common Pitfalls

• Changing medications before 4-6 weeks of adequate trial prevents proper efficacy assessment. 3
• Failing to monitor for extrapyramidal side effects, which compromise future medication adherence. 5, 4
• Using haloperidol monotherapy without benzodiazepine co-administration increases risk of acute dystonia and akathisia. 1
• Administering repeat doses before allowing adequate time for initial dose to reach peak effect (minimum 2 hours for olanzapine IM). 2

Special Considerations

• In elderly or debilitated patients, start with lower haloperidol doses (0.5-2.5 mg IM) and titrate more gradually. 5, 6
• Rule out organic causes of psychosis (delirium, substance intoxication, anticholinergic toxicity) before administering antipsychotics, as these conditions may worsen with dopamine blockade. 4
• Lorazepam 2 mg produces more rapid decrease in agitation scores at 1-3 hours compared to haloperidol 5 mg, but combination therapy is superior to either alone. 1