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Open Access Publications from the University of California

Current Understanding of the Neurobiology of Agitation


Introduction: Managing agitation in the clinical setting is a challenge that many practitioners faceregularly. Our evolving understanding of the etiological factors involved in aggressive acts has betterinformed our interventions through pharmacologic and behavioral strategies. This paper reviews theliterature on the neurobiological underpinnings of aggressive behaviors, linking psychopathology withproposed mechanisms of action of psychiatric medications shown to be effective in mitigating agitation.

Methods: We performed a review of the extant literature using PubMed as a primary database.Investigation focused on neurobiology of agitation and its relation to the current evidence base forparticular interventions.

Results: There are well-established pathways that can lead to increased autonomic response andthe potential for violence. Psychopathology and substance-induced perceptual distortions may leadto magnification and overestimation of environmental threat, heightening the potential for aggression.Additional challenges have arisen with the advent of several novel drugs of abuse, many of whichlead to atypical clinical presentations and which can elude standard drug screens. Our interventionsstill lean on the evidence base found in Project BETA (Best Practices in Evaluation and Treatmentof Agitation). Although not a new drug and not included in the Project BETA guidelines, ketamineand its use are also discussed, given its unique pharmacology and potential benefits when otherprotocoled interventions have failed.

Conclusion: Aggression can occur due to manifold reasons in the clinical setting. Having aninformed understanding of the possible determinants of agitation can help with more tailoredresponses to individual patients, limiting the unnecessary use of medications or of interventions thatcould be deemed forceful.

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