The treatment of acute agitation associated with schizophrenia or bipolar disorder: investigational drugs in early stages of their clinical development, and their clinical context and potential place in therapy

ABSTRACT

Introduction

Acute agitation in patients with schizophrenia or bipolar disorder may require pharmacologic management. Ideal medication characteristics for this indication include rapid onset, minimal side effects, and noninvasive administration techniques.

Areas Covered

This review summarizes investigational agents in early clinical development for the management of acute agitation in patients with psychosis or mania; it also assesses where these agents may fit with current therapies to provide a clinical perspective. The authors conducted a broad search of clinicaltrials.gov to identify investigational agents for agitation or aggression in patients with schizophrenia or bipolar disorder. Two medications met the search criteria: dexmedetomidine film (BXCL501) and intranasal olanzapine (INP105).

Expert Opinion

Olanzapine is a well-known molecular entity in the psychiatric armamentarium but dexmedetomidine would be a new and unfamiliar agent for mental health providers. Nonetheless, although it is too early to make definitive statements about tolerability and efficacy, their unique administration mechanisms suggest that dexmedetomidine film and intranasal olanzapine may become valuable options for the rapid management of acute agitation in patients who are willing to cooperate with medication therapy.

KEYWORDS:

• Aggression
• agitation
• antipsychotics
• dexmedetomidine
• intranasal olanzapine
• mania
• psychosis
• schizophrenia

Article Highlights

• Acute agitation associated with psychosis or mania is not uncommon in emergency department or inpatient settings, and if untreated may lead to aggression

• Medications used to treat agitation in this patient population include first- and second-generation antipsychotics, and benzodiazepines, either alone or in combination

• Recent advances in agitation management include investigational drug formulations of dexmedetomidine film (BXCL501) and intranasal olanzapine (INP105)

• Although these formulations require patient participation, they are important developments because they offer rapid, IM-like absorption rates without requiring an injection

• Pending positive study outcomes, these investigational drug products could offer unique, non-invasive, acute agitation management strategies for patients with psychosis or mania

This box summarizes the key points contained in the article.

Declaration of interest

L Citrome has been a consultant for Acadia, Alkermes, Allergan, Avanir, BioXcel, Eisai, Impel, Indivior, Intra-Cellular Therapies, Janssen, Lundbeck, Luye, Merck, Neurocrine, Noven, Osmotica, Otsuka, Pfizer, Sage, Shire, Sunovion, Takeda, Teva, Vanda; speaker for Acadia, Alkermes, Allergan, Janssen, Lundbeck, Merck, Neurocrine, Otsuka, Pfizer, Sage, Shire, Sunovion, Takeda, Teva; owned stocks (small number of shares of common stock): Bristol-Myers Squibb, Eli Lilly, J & J, Merck, Pfizer purchased more than 10 years ago. 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.