Which is faster or stronger for sedation, Haldol (haloperidol) vs Zyprexa (olanzapine) vs Geodon (ziprasidone) injection?

Rapid Sedation for Acute Agitation: Comparative Efficacy

Intramuscular midazolam achieves the fastest sedation (median 8.5 minutes), followed by olanzapine (median 11.5 minutes), with haloperidol being significantly slower (median 23 minutes), making midazolam the strongest and fastest option for putting patients to sleep. 1, 2

Speed of Onset Rankings

Midazolam is definitively fastest:

• Achieves adequate sedation in a median of 8.5 minutes 2
• At 15 minutes post-injection, midazolam sedated 18% more patients than ziprasidone (Geodon), 30% more than haloperidol 5mg, and 28% more than haloperidol 10mg 1
• Produces significantly faster sedation compared to olanzapine (p=0.03) and haloperidol (p=0.002) 2

Olanzapine (Zyprexa) ranks second:

• Median time to sedation of 11.5 minutes 2
• At 15 minutes, olanzapine sedated 20% more patients than haloperidol 5mg and 18% more than haloperidol 10mg 1
• In acute undifferentiated agitation, IM olanzapine 10mg effectively sedated 78.9% of patients within 20 minutes 3
• Shows faster onset of action than lorazepam, though both are equivalent by 24 hours 4

Haloperidol (Haldol) is slowest:

• Median time to sedation of 23 minutes, nearly triple that of midazolam 2
• Consistently underperforms compared to both midazolam and olanzapine across multiple studies 1, 2

Ziprasidone (Geodon) shows intermediate speed:

• Significant calming effects emerge at 30 minutes post-administration 5
• At 15 minutes, ziprasidone performed 8% worse than olanzapine 1
• Rapid reduction in agitation scores (BARS) at 15 minutes after initial 10mg dose 4

Sedation Strength and Efficacy

By 60 minutes, all agents achieve similar sedation rates:

• Midazolam: 98% adequately sedated 2
• Haloperidol: 97% adequately sedated 2
• Olanzapine: 87% adequately sedated 2

Olanzapine demonstrates superior efficacy in specific populations:

• In psychiatric agitation, olanzapine sedated 90% of patients within 20 minutes 3
• In agitation from organic medical conditions, olanzapine rapidly sedated 79.1% versus haloperidol's 25% 3
• Shows distinct calming versus nonspecific sedative effects 5

Safety Considerations

Cardiac safety profile varies significantly:

• Olanzapine has minimal QTc prolongation (only 2ms mean increase), making it the safest cardiac option 6
• Haloperidol causes 7ms QTc prolongation 6
• Ziprasidone shows variable QTc prolongation (5-22ms) and should be avoided in patients with cardiac risk factors 6, 7

Extrapyramidal symptoms differ markedly:

• Olanzapine and ziprasidone have notably absent movement disorders and extrapyramidal symptoms 6, 5
• Haloperidol carries higher risk of extrapyramidal symptoms even at low doses 6
• In the comparative study, only 2 patients (0.3%) across all groups experienced extrapyramidal effects 1

Serious adverse events are rare but important:

• One cardiac arrest occurred in the haloperidol group 2
• Hypotension occurred in 0.5% of patients 1
• Eight fatalities have been reported with IM olanzapine when combined with other CNS depressants, necessitating strict avoidance of simultaneous benzodiazepine use 5, 8

Clinical Decision Algorithm

For fastest sedation (emergency situations):

• Use midazolam 5mg IM as first-line 1, 2
• Expect sedation within 8-10 minutes 2

For psychiatric agitation with cardiac concerns:

• Use olanzapine 10mg IM as first-line 6, 3
• Provides excellent efficacy (90% sedation at 20 minutes) with minimal cardiac effects 3

For agitation with unknown etiology:

• Olanzapine 10mg IM is effective in 78.9% within 20 minutes 3
• Avoid combining with benzodiazepines due to fatality risk 5

Avoid haloperidol when:

• Rapid sedation is critical (it takes 2-3 times longer) 2
• Patient has cardiac disease or risk factors 6
• Patient has Parkinson's disease or dementia with Lewy bodies 6

Important Caveats

Ziprasidone requires specific precautions:

• Obtain baseline ECG if cardiac risk factors present 6
• Avoid in patients with known QTc prolongation, recent MI, or cardiac arrhythmia 7
• Should not be used in patients with QTc >500ms 7

Olanzapine has a critical drug interaction:

• Never combine IM olanzapine with benzodiazepines or other CNS depressants due to reported fatalities 5, 8
• Monitor blood pressure and heart rate, as transient reductions may occur 8