Onset of Action for IM Zyprexa (Olanzapine)
IM olanzapine begins reducing agitation within 15-30 minutes, with peak effect at 2 hours post-injection. 1, 2, 3
Rapid Onset Timeline
Initial clinical response begins at 15 minutes: In a large prospective study of 737 agitated ED patients, olanzapine 10 mg IM showed measurable sedation at 15 minutes, though not yet at peak effect 1
50% of severely agitated patients achieve categorical response by 30 minutes: In an observational study of 74 severely agitated inpatients with bipolar mania or schizophrenia, half of patients met response criteria (PANSS-EC item scores ≤3) within 30 minutes of a single injection 2
Statistically significant reduction in agitation occurs at 30 minutes: Multiple placebo-controlled trials demonstrated that olanzapine 5-10 mg IM produced superior reduction in agitation compared to placebo starting at 30 minutes post-injection 3
Peak effect occurs at 2 hours: The FDA label and all pivotal trials used 2-hour post-injection as the primary efficacy endpoint, when maximal reduction in PANSS Excited Component scores was observed 4, 3, 5
Practical Dosing Considerations
Standard dose is 10 mg IM: This dose demonstrated the most robust and consistent effect across multiple trials, with mean PANSS-EC reductions of 9.4 points at 2 hours 3
Lower doses (5-7.5 mg) are also effective: These doses showed statistically significant superiority over placebo starting at 30 minutes, though the effect size was slightly smaller than 10 mg 3
Most patients require only one injection: Over 90% of severely agitated patients needed only a single IM injection in the first 24 hours, with sustained effect throughout the observation period 2
Second injection cannot be given until after 2 hours: Per FDA labeling and trial protocols, if additional dosing is needed, it must wait until after the 2-hour primary assessment period 4
Comparative Effectiveness
Olanzapine is slower than midazolam but faster than haloperidol: In the largest head-to-head ED study, midazolam 5 mg IM achieved more effective sedation at 15 minutes than olanzapine 10 mg IM (difference 9%, 95% CI -1% to 20%), but olanzapine was significantly more effective than both haloperidol 5 mg (difference 20%) and haloperidol 10 mg (difference 18%) at 15 minutes 1
Safety Profile During Onset Period
Minimal extrapyramidal symptoms: Unlike haloperidol, olanzapine showed 0% incidence of treatment-emergent parkinsonism in the first 24 hours, compared to 16.7% with haloperidol 7.5 mg IM 3
Hypotension is the most common adverse event: However, rates were similar across all treatment groups including placebo, and clinically significant hypotension occurred in only 0.5% of patients 1, 3
Respiratory depression and intubation are rare: In the large ED study, hypoxemia occurred in 1% and intubation in 0.5% of olanzapine-treated patients, with no difference from other agents 1
Mild sedation without excessive somnolence: Two hours post-injection, patients exhibited "mild calmness" with mean baseline agitation scores of 29.0 reduced by 19.2 points, indicating effective control without over-sedation 2
Critical Clinical Pitfall
Do not combine IM olanzapine with benzodiazepines: The combination significantly increases risk of oversedation and respiratory depression, as noted in safety guidelines 6. If a patient has recently received a benzodiazepine, consider delaying olanzapine administration or using an alternative agent.