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Acute Agitation Requiring IM Antipsychotics David N. Osser, MD, Associate Professor of Psychiatry Harvard Medical School Brockton Division of the VA Boston Healthcare System General Editor - Psychopharmacology Algorithm Project Harvard South Shore Residency Training Program

Acute agitation Common behavioral emergency High risk of violence and aggression

Evidence of efficacy

31 trials Systematic review SGAs Haloperidol Midazolam Lorazepam Effective (compared with placebo) IM route more rapid onset than the oral route Midazolam Lorazepam Zeller, S. L., et al(2010). Systematic reviews of assessment measures and pharmacologic treatments for agitation. Clinical therapeutics, 32(3), 403-425.

Combination: haloperidol + lorazepam Combination: more effective than either treatment alone (Garza-Trevino 1989, Battaglia 1997, Breier 2002).

Combination: haloperidol + lorazepam Low EPS risk Anticholinergic use: appears unnecessary Combination: more effective than either treatment alone (Garza-Trevino 1989, Battaglia 1997, Breier 2002).

Industry-sponsored trials Haloperidol New IM SGAs: superior to haloperidol alone IM SGAs Ziprasidone Olanzapine Aripiprazole

Industry-sponsored trials Haloperidol New IM SGAs: superior to haloperidol alone High rate of EPS IM SGAs Haloperidol Lorazepam Not studied Ziprasidone Olanzapine Aripiprazole

RCT: IM treatments 100 agitated pts in an ER Most of them had schizophrenia Mantovani, C.,et a;. (2013). Are low doses of antipsychotics effective in the management of psychomotor agitation? A randomized, rated-blind trial of 4 intramuscular interventions. Journal of clinical psychopharmacology, 33(3), 306-312.

RCT: IM treatments 100 agitated pts in an ER Haloperidol Benzodiazepine RCT: IM treatments Haloperidol Antiparkinson Olanzapine 100 agitated pts in an ER Most of them had schizophrenia Ziprasidone Mantovani, C.,et a;. (2013). Are low doses of antipsychotics effective in the management of psychomotor agitation? A randomized, rated-blind trial of 4 intramuscular interventions. Journal of clinical psychopharmacology, 33(3), 306-312.

RCT: IM treatments 100 agitated pts in an ER Similar efficacy Haloperidol Benzodiazepine RCT: IM treatments Haloperidol Antiparkinson Similar efficacy Olanzapine 100 agitated pts in an ER Most of them had schizophrenia Ziprasidone Mantovani, C.,et a;. (2013). Are low doses of antipsychotics effective in the management of psychomotor agitation? A randomized, rated-blind trial of 4 intramuscular interventions. Journal of clinical psychopharmacology, 33(3), 306-312.

Side effects: 60% greater Haloperidol Benzodiazepine RCT: IM treatments Haloperidol Antiparkinson Similar efficacy Olanzapine Side effects: 60% greater 100 agitated pts in an ER Most of them had schizophrenia Ziprasidone Mantovani, C.,et a;. (2013). Are low doses of antipsychotics effective in the management of psychomotor agitation? A randomized, rated-blind trial of 4 intramuscular interventions. Journal of clinical psychopharmacology, 33(3), 306-312.

Recommendations

Recommendations Haloperidol 5 mg + Lorazepam 2 mg Can be repeated once or twice every 30 to 60 minutes Rapid, safe and cost-effective treatment

Chlorpromazine Ahmed, U., Jones, H., & Adams, C. E. (2010). Chlorpromazine for psychosis induced aggression or agitation. The Cochrane Library.

Avoid IM chlorpromazine High risk of sudden, serious hypotension Ahmed, U., Jones, H., & Adams, C. E. (2010). Chlorpromazine for psychosis induced aggression or agitation. The Cochrane Library.

Avoid IM chlorpromazine High risk of sudden, serious hypotension Same effectiveness as haloperidol Ahmed, U., Jones, H., & Adams, C. E. (2010). Chlorpromazine for psychosis induced aggression or agitation. The Cochrane Library.

Oral PRN antipsychotics: Often used Usually not necessary for less severe agitation A benzodiazepine is just as effective

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