Alternative Approaches for Addressing Acute Agitation in Schizophrenia and Bipolar Disorder.

Importance: The prompt effective treatment of acute agitation among patients with schizophrenia or bipolar disorder can alleviate distressing symptoms for the patient and decrease the risk of escalation to aggression and the potential for serious harm to the patient, health care providers, and others.Observations: A commonly used approach for the management of acute agitation has been the intramuscular administration of antipsychotic medications and/or benzodiazepines. However, US Food and Drug Administration-approved treatments with alternative routes of delivery now include inhaled loxapine powder and, more recently, dexmedetomidine sublingual film. Two formulations of intranasal olanzapine for acute agitation are in development.Conclusions and Relevance: Intranasal formulations offer the potential for favorable pharmacokinetics and onset of action combined with ease of delivery obviating the need for injections and are thus consistent with patient-centered factors such as preference and self-administration. In this review, alternative methods of medication delivery are discussed, with an emphasis on the potential for intranasal administration to treat acute agitation in adult patients with schizophrenia or bipolar disorder.Prim Care Companion CNS Disord 2024;26(1):23nr03596. Author affiliations are listed at the end of this article.

Community-Based Crisis Services, Specialized Crisis Facilities, and Partnerships With Law Enforcement.

How a community responds to behavioral health emergencies is both a public health issue and a social justice issue. Individuals experiencing a behavioral health crisis often receive inadequate care in emergency departments, boarding for hours or days while awaiting treatment. Such crises also account for a quarter of police shootings and 2 million jail bookings per year, and racism and implicit bias magnify these problems for people of color. Fortunately, the new 988 mental health emergency number compounded with police reform movements have created momentum for building behavioral health crisis response systems that deliver comparable quality and consistency of care as we expect for medical emergencies. This paper provides an overview of the rapidly evolving landscape of crisis services. The authors discuss the role of law enforcement and various approaches to lessening the impact on individuals experiencing behavioral health emergencies, especially for historically marginalized populations. The authors provide an overview of the crisis continuum, including crisis hotlines, mobile teams, observation units, crisis residential programs, and peer wraparound services that can help ensure that linkage to aftercare is successful. The authors also highlight opportunities for psychiatric leadership, advocacy, and strategies for creating a well-coordinated crisis system that meets the needs of the community.

A Quality Measurement Framework for Emergency Department Care of Psychiatric Emergencies.

As a primary access point for crisis psychiatric care, the emergency department (ED) is uniquely positioned to improve the quality of care and outcomes for patients with psychiatric emergencies. Quality measurement is the first key step in understanding the gaps and variations in emergency psychiatric care to guide quality improvement initiatives. Our objective was to develop a quality measurement framework informed by a comprehensive review and gap analysis of quality measures for ED psychiatric care. We conducted a systematic literature review and convened an expert panel in emergency medicine, psychiatry, and quality improvement to consider if and how existing quality measures evaluate the delivery of emergency psychiatric care in the ED setting. The expert panel reviewed 48 measures, of which 5 were standardized, and 3 had active National Quality Forum endorsement. Drawing from the measure appraisal, we developed a quality measurement framework with specific structural, process, and outcome measures across the ED care continuum. This framework can help shape an emergency medicine roadmap for future clinical quality improvement initiatives, research, and advocacy work designed to improve outcomes for patients presenting with psychiatric emergencies.

The Impact of Coronavirus Disease 2019 on US Emergency Departments.

Behavioral emergencies in the United States have been increasing, with some studies reporting a doubling in the number of people experiencing symptoms related to mental health conditions, although overall visits to US emergency departments (EDs) decreased during the coronavirus disease 2019 (COVID-19) pandemic. The uncertainty surrounding the COVID-19 pandemic caused many people to avoid health care facilities, including EDs, even if they may have otherwise sought emergency care, and was associated with increases in new behavioral health diagnoses. Measures to limit the spread of COVID-19 led to people limiting their in-person contact with others, likely exacerbating preexisting mental health issues.

Effect of Sublingual Dexmedetomidine vs Placebo on Acute Agitation Associated With Bipolar Disorder: A Randomized Clinical Trial.

Importance: Acute agitation is common in patients with bipolar disorder and requires urgent management to relieve distress and to prevent escalation to aggressive behavior. Objective: To evaluate the effect of orally absorbed, sublingual dexmedetomidine, a selective α2A-adrenergic receptor agonist on symptoms of acute agitation in patients with bipolar disorder. Design, Setting, and Participants: Phase 3, randomized, double-blind, placebo-controlled trial conducted in 15 sites in the US with enrollment between February 24, 2020, and April 27, 2020, and final follow-up on May 21, 2020. A total of 380 adults with bipolar I or II disorder were randomized and 362 completed the study. Interventions: Participants were randomized to 3 groups: sublingual dexmedetomidine 180 µg (n = 127), sublingual dexmedetomidine 120 µg (n = 127), or placebo (n = 126). Main Outcomes and Measures: The primary efficacy end point was the mean change from baseline at 2 hours for the Positive and Negative Syndrome Scale-Excited Component (PEC) total score. The range of possible total scores is 5 (absence of agitation) to 35 (extremely severe). The secondary end point was the earliest time of a statistically significant change in PEC total score from baseline for the drug vs placebo. On the primary efficacy end point, to account for multiplicity associated with comparing 2 sublingual dexmedetomidine doses with placebo, the 2-sided significance level for each dose vs placebo was set at .025. Results: Of 380 patients randomized (mean age, 45.6 years; 54.8% women; and 56.1% Black individuals), 378 (99.5%) self-administered the study medication and completed the study. Baseline agitation was mild to moderate, with an overall mean PEC total score of 18.0. Two hours after taking the medication, the mean changes from baseline in PEC total score were -10.4 for sublingual dexmedetomidine 180 µg, -9.0 for sublingual dexmedetomidine 120 µg, and -4.9 for placebo. Least-square mean differences from placebo in the sublingual dexmedetomidine groups at 2 hours were -5.4 (97.5% CI, -6.6 to -4.2) for 180 µg and -4.1 (97.5% CI, -5.3 to -2.9) for 120 µg (both doses P < .001 vs placebo). Treatment effects began 20 minutes after taking the medication among patients in the sublingual dexmedetomidine groups (least-square mean difference for 180 µg, -1.1 [97.5% CI, -2.0 to -0.2]; P = .007; for 120 µg, -1.0 [97.5% CI, -1.9 to -0.1]; P = .009). Adverse events occurred in 35.7% of patients taking 180 µg of dexmedetomidine, 34.9% taking 120 µg, and 17.5% taking placebo. The most common adverse events (≥5%) in the respective 180 µg, 120 µg, and placebo groups were somnolence (21.4% and 20.6% vs 4.8%); dry mouth (4.8% and 7.1% vs 0.8%); hypotension (6.3% and 4.8% vs 0%); and dizziness (5.6% and 5.6% vs 0.8%). Conclusions and Relevance: Among patients with mild to moderate agitation associated with bipolar disorder, treatment with a sublingual film formulation of dexmedetomidine 120 µg or 180 µg, compared with placebo, resulted in significantly greater reduction in the agitation score at 2 hours. Further research is needed to understand the spectrum of patients for whom this treatment would be effective and feasible and to better understand the clinical importance of the observed effect size. Trial Registration: ClinicalTrials.gov Identifier: NCT04276883.

The capacity of schizophrenia and bipolar disorder individuals to make autonomous decisions about pharmacological treatments for their illness in real life: A scoping review.

BACKGROUND AND AIM: Having decision making capacity is central to the exercise of autonomy in mental health care. The objective of this scoping review is to summarize the evidence on the capacity of people with schizophrenia or bipolar disorder to make decisions about their treatment in real life to support medical practice. METHODS: Systematic search of observational studies on the assessment of capacity of patients with schizophrenia, psychosis, or bipolar disorder to make healthcare and treatment-related decisions, conducted in any clinical setting published up to January 31, 2020 was performed. Free text searches and medical subject headings in English were combined in PubMed, Scopus, CINAHL, and PsycInfo. Publications were selected as per inclusion and exclusion criteria. The Newcastle-Ottawa Scale for observational studies was used to assess the quality of publications. RESULTS: Thirty publications were reviewed. According to the Newcastle-Ottawa Scale criteria, the publications reviewed were good quality. Findings showed that more than 70% of schizophrenia and schizoaffective disorder outpatients understood treatment options at the point of making decisions about their illness and healthcare. Patients treated voluntarily had considerably better scores for decisional capacity than those treated involuntarily. The burden of psychiatric symptoms could compromise decisional capacity temporarily. Decision-making capacity improved over time from admission to discharge from hospital, and with treatment among psychiatry inpatients. Schizophrenia and bipolar disorder patients could be as competent as nonpsychiatric individuals in making decisions about their treatments in everyday life. CONCLUSIONS: This scoping review provides a body of evidence for healthcare professionals in need of assessing the capacity of schizophrenia and bipolar disorder patients for autonomously decide about their treatments. Decisional capacity judgements should consider variations in capacity over time and be based on the type of decision to be made, the severity of symptoms, and the specific phase of the mental disorder.

Response to inhaled loxapine in patients with schizophrenia or bipolar I disorder: PANSS-EC responder analyses.

BACKGROUND: Efficacy of inhaled loxapine 5 or 10 mg in treating agitation was shown using the Positive and Negative Syndrome Scale - Excited Component (PANSS-EC) in two Phase III randomised, double-blind, placebo-controlled trials in 344 agitated patients with schizophrenia and 314 patients with bipolar I disorder (Clinicaltrials.gov: NCT00628589, NCT00721955). AIMS: To examine the five individual items comprising the PANSS-EC and the percentage of patients achieving a clinical response (reduction of ≥40%) in PANSS-EC (Response-40) for these two studies. METHOD: Response-40 was examined at the primary end-point (2 h) and over time. RESULTS: Response-40 and each PANSS-EC item score were statistically significant v. placebo at 2 h and at each assessment time point for both doses. CONCLUSIONS: Inhaled loxapine produced rapid improvement in agitated patients with schizophrenia or bipolar I disorder, achieving Response-40 at the first assessment (10 min post dose). These results highlight the effectiveness of loxapine across all components of agitation as measured by the PANSS-EC. DECLARATION OF INTEREST: S.Z. is a member of the speakers bureau for Grupo Ferrer. L.Z. has been a speaker and grant recipient for Teva Pharmaceuticals. J.V.C. and D.A.S. were employees of Alexza Pharmaceuticals during execution of the studies, and are currently paid consultants for and have received stock and/or stock options from Alexza Pharmaceuticals. P.P.Y. is a full-time employee and receives stock options from Teva Pharmaceuticals. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

Managing Agitation Associated with Schizophrenia and Bipolar Disorder in the Emergency Setting.

INTRODUCTION: Patient agitation represents a significant challenge in the emergency department (ED), a setting in which medical staff are working under pressure dealing with a diverse range of medical emergencies. The potential for escalation into aggressive behavior, putting patients, staff, and others at risk, makes it imperative to address agitated behavior rapidly and efficiently. Time constraints and limited access to specialist psychiatric support have in the past led to the strategy of "restrain and sedate," which was believed to represent the optimal approach; however, it is increasingly recognized that more patient-centered approaches result in improved outcomes. The objective of this review is to raise awareness of best practices for the management of agitation in the ED and to consider the role of new pharmacologic interventions in this setting. DISCUSSION: The Best practices in Evaluation and Treatment of Agitation (BETA) guidelines address the complete management of agitation, including triage, diagnosis, interpersonal calming skills, and medicine choices. Since their publication in 2012, there have been further developments in pharmacologic approaches for dealing with agitation, including both new agents and new modes of delivery, which increase the options available for both patients and physicians. Newer modes of delivery that could be useful in rapidly managing agitation include inhaled, buccal/sublingual and intranasal formulations. To date, the only formulation administered via a non-intramuscular route with a specific indication for agitation associated with bipolar or schizophrenia is inhaled loxapine. Non-invasive formulations, although requiring cooperation from patients, have the potential to improve overall patient experience, thereby improving future cooperation between patients and healthcare providers. CONCLUSION: Management of agitation in the ED should encompass a patient-centered approach, incorporating non-pharmacologic approaches if feasible. Where pharmacologic intervention is necessary, a cooperative approach using non-invasive medications should be employed where possible.

Assessment and management of agitation in psychiatry: Expert consensus.

BACKGROUND: Psychomotor agitation is associated with different psychiatric conditions and represents an important issue in psychiatry. Current recommendations on agitation in psychiatry are not univocal. Actually, an improper assessment and management may result in unnecessary coercive or sedative treatments. A thorough and balanced review plus an expert consensus can guide assessment and treatment decisions. METHODS: An expert task force iteratively developed consensus using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new, re-worded or re-rated items. RESULTS: Out of 2175 papers assessing psychomotor agitation, 124 were included in the review. Each component was assigned a level of evidence. Integrating the evidence and the experience of the task force members, a consensus was reached on 22 statements on this topic. CONCLUSIONS: Recommendations on the assessment of agitation emphasise the importance of identifying any possible medical cause. For its management, experts agreed in considering verbal de-escalation and environmental modification techniques as first choice, considering physical restraint as a last resort strategy. Regarding pharmacological treatment, the "ideal" medication should calm without over-sedate. Generally, oral or inhaled formulations should be preferred over i.m. routes in mildly agitated patients. Intravenous treatments should be avoided.

Effects of a dedicated regional psychiatric emergency service on boarding of psychiatric patients in area emergency departments.

INTRODUCTION: Mental health patients boarding for long hours, even days, in United States emergency departments (EDs) awaiting transfer for psychiatric services has become a considerable and widespread problem. Past studies have shown average boarding times ranging from 6.8 hours to 34 hours. Most proposed solutions to this issue have focused solely on increasing available inpatient psychiatric hospital beds, rather than considering alternative emergency care designs that could provide prompt access to treatment and might reduce the need for many hospitalizations. One suggested option has been the "regional dedicated emergency psychiatric facility," which serves to evaluate and treat all mental health patients for a given area, and can accept direct transfers from other EDs. This study sought to assess the effects of a regional dedicated emergency psychiatric facility design known at the "Alameda Model" on boarding times and hospitalization rates for psychiatric patients in area EDs. METHODS: Over a 30-day period beginning in January 2013, 5 community hospitals in Alameda County, California, tracked all ED patients on involuntary mental health holds to determine boarding time, defined as the difference between when they were deemed stable for psychiatric disposition and the time they were discharged from the ED for transfer to the regional psychiatric emergency service. Patients were also followed to determine the percentage admitted to inpatient psychiatric units after evaluation and treatment in the psychiatric emergency service. RESULTS: In a total sample of 144 patients, the average boarding time was approximately 1 hour and 48 minutes. Only 24.8% were admitted for inpatient psychiatric hospitalization from the psychiatric emergency service. CONCLUSION: The results of this study indicate that the Alameda Model of transferring patients from general hospital EDs to a regional psychiatric emergency service reduced the length of boarding times for patients awaiting psychiatric care by over 80% versus comparable state ED averages. Additionally, the psychiatric emergency service can provide assessment and treatment that may stabilize over 75% of the crisis mental health population at this level of care, thus dramatically alleviating the demand for inpatient psychiatric beds. The improved, timely access to care, along with the savings from reduced boarding times and hospitalization costs, may well justify the costs of a regional psychiatric emergency service in appropriate systems.

Verbal De-escalation of the Agitated Patient: Consensus Statement of the American Association for Emergency Psychiatry Project BETA De-escalation Workgroup.

Agitation is an acute behavioral emergency requiring immediate intervention. Traditional methods of treating agitated patients, ie, routine restraints and involuntary medication, have been replaced with a much greater emphasis on a noncoercive approach. Experienced practitioners have found that if such interventions are undertaken with genuine commitment, successful outcomes can occur far more often than previously thought possible. In the new paradigm, a 3-step approach is used. First, the patient is verbally engaged; then a collaborative relationship is established; and, finally, the patient is verbally de-escalated out of the agitated state. Verbal de-escalation is usually the key to engaging the patient and helping him become an active partner in his evaluation and treatment; although, we also recognize that in some cases nonverbal approaches, such as voluntary medication and environment planning, are also important. When working with an agitated patient, there are 4 main objectives: (1) ensure the safety of the patient, staff, and others in the area; (2) help the patient manage his emotions and distress and maintain or regain control of his behavior; (3) avoid the use of restraint when at all possible; and (4) avoid coercive interventions that escalate agitation. The authors detail the proper foundations for appropriate training for de-escalation and provide intervention guidelines, using the "10 domains of de-escalation."

Systematic reviews of assessment measures and pharmacologic treatments for agitation.

BACKGROUND: Agitation is a common behavioral emergency associated with high risk of injury to patients and health care professionals. There are a wide variety of approaches to assessing the severity of agitation and the risk of violence/aggression, and many different pharmacotherapies have been used to manage this condition. OBJECTIVES: Two systematic reviews were carried out. The first focused on measures used to assess agitation and predict aggression/violence and/or the need for medication. The second focused on clinical trials of the efficacy and tolerability of pharmacotherapies for agitation. METHODS: Publications relevant to each topic were identified by searches of MEDLINE through December 24, 2009. The search concerning the assessment of agitation included the terms agitation AND assessment AND (scale OR instrument); the search for clinical trials of pharmacotherapies for agitation included the terms agitation and treatment AND (emergency OR acute). Both searches were limited to reports of studies published in English involving patients aged > or =18 years. RESULTS: The literature search identified 13 scales used to assess the severity of agitation across multiple patient populations; only 3 of these reports involved the prediction of aggression/violence in patients with agitation, and 1 involved prediction of the need for medication. Thirty-one clinical trials of pharmacotherapy for agitation were identified by the literature search. Based on their results, orally administered olanzapine, risperidone, aripiprazole, quetiapine, haloperidol, and lorazepam; intramuscularly administered olanzapine, lorazepam, ziprasidone, haloperidol, aripiprazole, midazolam, and droperidol; and intravenously administered droperidol and lorazepam were effective for the treatment of agitation. The intramuscular route of administration was associated with a more rapid onset of action compared with the oral route (eg, for olanzapine, 30 minutes vs 1 hour, respectively). CONCLUSIONS: Agitation is a common behavioral emergency that may require pharmacotherapy. The management of agitated patients may be improved through the use of easy-to-administer instruments that predict the need for medication and the availability of rapid-acting treatments that are well accepted by patients and health care professionals.