IM aripiprazole for acute agitation

Prevalence of EPS was 1.7% with IM aripiprazole, 2.3% with placebo, and 12.6% with IM haloperidol. Prevalence of EPS-related adverse events was 0% with IM aripiprazole, 1.6% with placebo, and 16.5% with IM haloperidol.

Zimbroff et al³ gave IM aripiprazole, 9.75 or 15 mg; IM lorazepam, 2 mg; or placebo to 301 patients with type I bipolar disorder with manic or mixed episodes.

Two hours later, all 3 treatment groups showed significantly greater agitation improvement as shown by PANSS-EC scores, compared with placebo (Table 3).

Across 2 hours, oversedation—defined as an Agitation-Calmness Evaluation Scale score of 8 or 9—was less prevalent among patients receiving IM aripiprazole, 9.75 mg (6.7%), compared with IM aripiprazole, 15 mg (17.3%), or IM lorazepam (19.1%).

Table 2

Agitation, symptom improvement 2 hours after aripiprazole or haloperidol injection

Table 3

Agitation improvement 2 hours after aripiprazole or lorazepam injection

Safety and tolerability

IM aripiprazole was well tolerated in clinical trials and did not cause excessive sedation¹⁰ or injection-site pain.^1-3

Most frequently reported adverse events were headache (12% with IM aripiprazole vs 7% with placebo), nausea (9% vs 3%), dizziness (8% vs 5%), and somnolence (7% vs 4%).

Prevalence of akathisia or dystonia among all IM aripiprazole groups in the 3 trials was 2% and

No clinically significant ECG abnormalities were reported among the aripiprazole groups.^1-3,11

Dosing

Start at 9.75 mg every 2 hours as needed, but do not exceed 30 mg/d across 24 hours. Controlled studies have not evaluated efficacy or safety of more-frequent injections or safety of total daily doses >30 mg.

Try a lower dose (5.25 mg) for patients who are elderly or small in body size or have reacted adversely to other antipsychotics. If necessary, give another 5.25 mg in 2 hours. If the patient is still agitated 2 hours after the second dose, consider a third dose at 9.75 mg. Again, do not exceed 30 mg over 24 hours. Obtain lower doses by administering a portion of the vial.

Transitioning to oral Tx

If IM aripiprazole reduces psychotic symptoms as well as acute behaviors, switch the patient to oral aripiprazole once the risk of violence has diminished.¹² If psychosis does not improve with IM aripiprazole, weigh clinical factors before choosing an oral antipsychotic.

Only one controlled trial¹² has examined transitioning from IM aripiprazole to an oral antipsychotic. In the randomized study, 448 patients receiving IM aripiprazole, 9.75 mg; IM haloperidol, 6.5 mg; or placebo for agitation secondary to schizophrenia or schizoaffective disorder were transitioned to the oral preparation of the drug they were receiving: aripiprazole, 10 to 15 mg/d, or haloperidol, 7.5 to 10 mg/d. Placebo-group patients transitioned to oral aripiprazole.

Over 4 days, both oral treatments provided continued efficacy, suggesting that:

• patients receiving IM aripiprazole can be conveniently switched to the oral preparation
• IM and oral aripiprazole are equally safe.

Oral and IM aripiprazole doses are equivalent and the pharmacokinetics are comparable. For example, a patient receiving 20 mg/d of IM aripiprazole can take 20 mg of oral aripiprazole within 24 hours of the last injection.

Related resources

• Allen MH, Currier GW, Carpenter D, et al. Expert consensus guidelines: treatment of behavioral emergencies. J Psychiatr Pract 2005;11(suppl 1):5-108.
• Currier GW, Citrome LL, Zimbroff DL, et al. Intramuscular aripiprazole in the control of agitation. J Psychiatr Pract 2007;13:159-69.

Drug brand names

• Aripiprazole IM • Abilify
• Carbamazepine • Tegretol, others
• Fluoxetine • Prozac
• Haloperidol • Haldol
• Ketoconazole • Nizoral
• Lorazepam • Ativan
• Paroxetine • Paxil
• Quinidine • Quinaglute

Disclosure

Dr. Josiassen was principal investigator and Dr. Shaughnessy a co-investigator on a pre-approval clinical trial of IM aripiprazole. Both have conducted sponsor- and investigator-initiated studies for AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, Janssen, Novartis Pharmaceuticals Corp., Organon, Otsuka America Pharmaceuticals, Otsuka Maryland Research Institute, Pfizer, and Yamanuchi.

Acknowledgments

This article was supported in part by the Arthur P. Noyes Research Foundation.

The authors thank Margit Kacso, Cara Bendler, Dawn Filmyer, and Jon Weinstein for their technical and editorial assistance in preparing this article.