Choosing a Pharmacologic Agent

Approaches to agitation management have evolved from the “somewhat draconian strategy of ‘restrain and sedate,’ which was believed to represent the optimal approach.5 Today, it is “recognized that more humane, patient-centered approaches result in improved short- and long-term outcomes, including fewer injuries, better therapeutic alliance, improved throughput, and reduced resource use and costs.”5 For this reason, nonpharmacologic approaches are considered to be optimal. If pharmacologic intervention is indicated, however, the agent should preferably be non-invasive, have a rapid onset, and provide short-term control of aggressive behavior without compromising the physician-patient relationship in the long term.6

Currently, loxapine is the only formulation specifically indicated for agitation associated with bipolar disorder or schizophrenia that is administered via a non-intramuscular route.6 While non-invasive formulations do require some patient cooperation, which may not be possible in a severely agitated patient, they have the potential to improve overall patient experience, thereby facilitating future cooperation between patients and healthcare providers.6

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Dundar et al noted certain methodological limitations of their study, urging that their findings should be “interpreted with considerable caution.” Differing treatment doses employed across the trials, and different methods of treatment administration made the data synthesis difficult. Moreover, it was difficult to extract data from the trial publications regarding AEs, due to “inconsistent reporting.” For this reason, they highlighted the importance of reviewing the safety information found in the relevant summary of product characteristics that accompanies each agent. They suggested that future trials should focus on quality of life outcomes and have clear and thorough reporting of AEs.


1.      Dundar Y, Greenhalgh J, Richardson M, Dwan K. Pharmacological treatment of acute agitation associated with psychotic and bipolar disorder: a systematic review and meta-analysis. Hum Psychopharmacol. 2016 May 5. [Epub ahead of print]

2.      Schleifer JJ. Management of acute agitation in psychosis: an evidence-based approach in the USA. Advances in Psychiatric Treatment. 2011;17:91–100.

3.      Lindenmayer JP. The pathophysiology of agitation. J Clin Psychiatry. 2000;61 Suppl 14:5-10.

4.      Nordstrom K, Allen MH. Alternative delivery systems for agents to treat acute  agitation: progress to date. Drugs. 2013;73(16):1783-92.

5.    Zeller SL, Citrome L. Managing Agitation Associated with Schizophrenia and Bipolar Disorder in the Emergency Setting. West J Emerg Med. 2016;17(2):165-172.

6.      Pollack CV Jr. Inhaled loxapine for the urgent treatment of acute agitation associated with schizophrenia or bipolar disorder. Curr Med Res Opin. 2016 Jul;32(7):1253-60.