Improving the pharmacotherapeutic treatment of agitation associated with bipolar disorder

ABSTRACTIntroduction Agitation is commonly encountered in people with bipolar disorder, particularly when experiencing a manic episode. The number of approved pharmacological agents to manage acute episodes of agitation in this population is limited.Areas covered A search was conducted using the US National Library of Medicine PubMed.gov resource for English-language papers of clinical trials and reviews/meta-analyses, using the text words 'bipolar disorder' AND 'agitation,' as well as any papers with both two text words in the title, without any date restrictions.Expert opinion Existing pharmacologic options approved by regulatory authorities for the treatment of acute episodes of agitation associated with bipolar disorder have similar degrees of efficacy but differ in their tolerability profiles and ease of use, giving clinicians an opportunity to individualize treatment. The goal is to treat mild-moderate agitation before it evolves into severe agitation, encouraging noninvasive pharmacologic treatment options. Inhaled loxapine and sublingual dexmedetomidine are newer options with rapid onset of action and may be preferable for patients willing to cooperate with treatment.KEYWORDS: Aripiprazolebipolar disorderdexmedetomidineinhaled loxapinelorazepammaniaolanzapine Article highlights Bipolar mania is associated with elevated mood and increased activity and/or energy which can precipitate agitation and result in patient and staff injury.Episodic agitation associated with bipolar disorder necessitates prompt intervention and is needed to prevent symptom escalation.Traditional oral treatment options are non-traumatizing and easy to administer, but have a slow onset-of-action with erratic absorption through the gastrointestinal system.Parenteral treatment options have a rapid onset-of-action and do not require patient participation, but can be invasive, traumatizing, and damaging to patient rapport.Sublingual and inhaled medication formulations represent alternative treatment options that more closely resemble ideal treatment, though require patient cooperation.Adequately treating bipolar disorder will have a preventative effect on future episodes of acute agitation and treatment should be fully optimized.Declaration of interestJ. Faden has, in the past 5 years, served as a consultant to BioXcel, Noven.J. Goldberg has, in the past 5 years, Consultant: Alkermes, BioXcel, Jazz Pharmaceuticals, Neuroma, Neurelis, Otsuka, Sage Pharmaceuticals, Sunovion, Supernus, Takeda. Speakers bureau: Abbvie, Alkermes, Axsome, Intracellular Therapies, Takeda-Lundbeck. Royalties: American Psychiatric Publishing, Cambridge University Press.L. Citrome has, in the past 5 years, served as consultant to AbbVie/Allergan, Acadia, Adamas, Alkermes, Angelini, Astellas, Avanir, Axsome, BioXcel, Boehringer Ingelheim, Cadent Therapeutics, Cerevel, Clinilabs, COMPASS, Eisai, Enteris BioPharma, HLS Therapeutics, Idorsia, INmune Bio, Impel, Intra-Cellular Therapies, Janssen, Karuna, Lundbeck, Lyndra, Medavante-ProPhase, Marvin, Merck, Mitsubishi-Tanabe Pharma, Neurocrine, Neurelis, Novartis, Noven, Otsuka, Ovid, Praxis, Recordati, Relmada, Reviva, Sage, Sunovion, Supernus, Teva, University of Arizona, Vanda, and one-off ad hoc consulting for individuals/entities conducting marketing, commercial, or scientific scoping research; speaker for AbbVie/Allergan, Acadia, Alkermes, Angelini, Axsome, BioXcel, Eisai, Idorsia, Intra-Cellular Therapies, Janssen, Lundbeck, Neurocrine, Noven, Otsuka, Recordati, Sage, Sunovion, Takeda, Teva, and CME activities organized by medical education companies such as Medscape, NACCME, NEI, Vindico, and Universities and Professional Organizations/Societies; owns stock (small number of shares of common stock) in Bristol-Myers Squibb, Eli Lilly, J & J, Merck, Pfizer purchased >10 years ago, and stock options in Reviva; earns royalties/publishing income from Taylor & Francis (Editor-in-Chief, Current Medical Research & Opinion, 2022-date), Wiley (Editor-in-Chief, International Journal of Clinical Practice, through end 2019), UpToDate (reviewer), Springer Healthcare (book), Elsevier (Topic Editor, Psychiatry, Clinical Therapeutics).The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Additional informationFundingThis paper was not funded.