Eligibility for Substance Use Clinical Trials Among Emergency Psychiatry Patients: The Impact of Exclusion Criteria.

Objective: The first objective was to identify common exclusion criteria used in clinical trials. The second objective was to quantify the degree to which these criteria exclude emergency psychiatry patients. Methods: Qualitative Content Analysis was used for the first objective, identifying common exclusion criteria used in recent high-impact substance use clinical trials. A retrospective record review was used for the second objective, which examined the frequency of these exclusion criteria in a 1-month sample of adults receiving psychiatric evaluation in an emergency department. Results: Most trials had exclusions for co-occurring psychiatric problems (76.6%), medical problems (74.0%), prior or current treatment (72.7%), motivation for change (61.1%), pregnancy or lactation (57.1%), or using other specified substances of abuse (54.6%). In the clinical sample, exclusions for co-occurring psychiatric problems would make 94.7% of patients ineligible. Other exclusions had a combined effect of making 76% of patients ineligible. Conclusions: Clinical trials using typical exclusion criteria exclude nearly all emergency psychiatry patients with substance use problems.

Clinical Trials Studying Suicide Risk Reduction: Who is Excluded From Participation.

OBJECTIVE: The use of exclusion criteria in clinical trials can cause research participants to differ markedly from clinical populations, which negatively impacts generalizability of results. This study identifies and quantifies common and recurring exclusion criteria in clinical trials studying suicide risk reduction, and estimates their impact on eligibility among a clinical sample of adults in an emergency department with high suicide risk. METHOD: Recent trials were identified by searching PubMed (terms suicide, efficacy, effectiveness, limited to clinical trials in prior 5 years). Common exclusion criteria were identified using Qualitative Content Analysis. A retrospective chart review examined a one-month sample of all adults receiving psychiatric evaluation in a large urban academic emergency department. RESULTS: The search yielded 27 unique clinical trials studying suicide risk reduction as a primary or secondary outcome. After research fundamentals (e.g. informed consent, language fluency), the most common exclusion criteria involved psychosis (77.8%), cognitive problems (66.7%), and substance use (63.0%). In the clinical sample of adults with high suicide risk (N = 232), psychosis exclusions would exclude 53.0% of patients and substance use exclusions would exclude 67.2% of patients. Overall, 5.6% of emergency psychiatry patients would be eligible for clinical trials that use common exclusion criteria. CONCLUSIONS: Recent clinical trials studying suicide risk reduction have low generalizability to emergency psychiatry patients with high suicide risk. Trials enrolling persons with psychosis and substance use in particular are needed to improve generalizability to this clinical population.

Exclusion criteria limit who can enroll in trials studying suicide risk reduction.Trials most frequently exclude psychosis, cognitive problems, and substance use.Trials have poor generalizability to emergency psychiatry patients.

Ethics in placebo-controlled, acute treatment trials in schizophrenia: Two rival ethical frameworks.

Placebo-controlled, acute treatment trials in schizophrenia enroll acutely symptomatic persons, randomize them to receive placebo or antipsychotic medication for several weeks, and evaluate whether symptoms improve. These trials can have scientific benefits, especially when they test drugs with novel mechanisms of action. However, the use of placebo is ethically problematic inasmuch as standard treatment is withheld and participants are subjected to prolonged psychotic symptoms and associated risks. We propose that both deontological (duty-based) and utilitarian analyses are relevant, that it may be impossible to satisfy the ideals of both frameworks, and that researchers who conduct these trials will unavoidably encounter ethical tension and criticism even when they give careful attention to ethical aspects of study design.

Intramuscular ketamine vs. midazolam for rapid risk-reduction in suicidal, depressed emergency patients: Clinical trial design and rationale.

Emergency department (ED) visits for suicidal ideation or behavior have been increasing in all age groups, particularly younger adults. A rapid-acting treatment to reduce suicidal thinking, adapted for ED use, is needed. Previous studies have shown a single dose of ketamine can improve depression and suicidal ideation within hours. However, most studies used 40 min intravenous infusions which can be impractical in a psychiatric ED. The ER-Ketamine study we describe here is a randomized midazolam-controlled clinical trial (RCT; NCT04640636) testing intramuscular (IM) ketamine's feasibility, safety, and effectiveness to rapidly reduce suicidal ideation and depression in a psychiatric ED. A pre-injection phase involves screening, informed consent, eligibility confirmation, and baseline assessment of suicidal ideation, depression, and comorbidities. The randomized double-blind IM injection is administered in the ED under research staff supervision, vital sign monitoring, pharmacokinetic blood sampling, and clinical assessments. The post-injection phase occurs on a psychiatric inpatient unit with follow-up research assessments through four weeks post-discharge. Outcome measures are feasibility, safety, and effects on suicidal ideation and depression at 24 h post-injection, and through follow-up. The target sample is N = 90 adults in a major depressive episode, assessed by ED clinicians as warranting hospitalization for suicide risk. Here we report design, rationale, and preliminary feasibility and safety for this ongoing study. Demographics of the 53 participants (ages 18 to 65 years) randomized to date suggest a diverse sample tending towards younger adults.

Eligibility of emergency psychiatry patients for clinical trials studying depression.

BACKGROUND: Differences often exist between people with depression who are eligible for clinical trials and those seen in clinical practice. The impact of exclusion criteria on eligibility has been previously reported for inpatients and outpatients, but has not been assessed for emergency psychiatry patients; a group that overlaps with inpatients and outpatients but also has important distinctives. Understanding the frequencies of commonly used exclusion criteria in this population could inform interpretation of existing data (generalizability) and highlight opportunities/needs for future trials. METHODS: We reviewed 67 clinical trials studying depression using Qualitative Content Analysis to identify common and recurring exclusion criteria. We examined the frequency of these exclusion criteria among a clinical sample of emergency psychiatry patients. RESULTS: Most clinical trials had exclusions for basic research requirements, age, symptom severity, psychosis, and substance use. Applying 9 commonly used exclusion criteria to the clinical population resulted in a 3.3 % eligibility rate (95 % CI 1.2 %-7.0 %). Exclusions for psychosis (85.1 % of trials), substance use (83.6 % of trials), and suicide risk (65.7 % of trials) would likely exclude 93 % of emergency psychiatry patients. The prevalence of psychosis, substance use, and suicide risk was much higher among emergency psychiatry patients than among previously studied populations. LIMITATIONS: Some eligibility criteria could not be measured. The Qualitative Content Analysis consolidated similar exclusion criteria, losing potentially important nuances in wordings. CONCLUSIONS: Exclusion criteria commonly used in contemporary clinical trials of depression limit generalizability to emergency psychiatry patients, due in large part to exclusions for psychosis, substance use, and suicide risk.

Physical Assault in the Psychiatry Emergency Room.

Previous studies of physical assaults in hospitals focused primarily on inpatient psychiatric units, leaving unanswered questions about the extent to which findings generalize to psychiatric emergency rooms. Assault incident reports and electronic medical records from one psychiatric emergency room and two inpatient psychiatric units were reviewed. Qualitative methods were used to identify precipitants. Quantitative methods were used to describe characteristics of each event, as well as demographic and symptom profiles associated with incidents. During the five-year study period, there were 60 incidents in the psychiatric emergency room and 124 incidents on the inpatient units. Precipitating factors, incident severity, means of assault, and interventions were similar in both settings. Among patients in the psychiatric emergency room, a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder with manic symptoms (Adjusted Odds Ratio (AOR) 27.86) and presenting with thoughts to harm others (AOR 10.94) were associated with an increased likelihood of having an assault incident report. Similarities between assaults in the psychiatric emergency room and inpatient psychiatric units suggest that the broader literature from inpatient psychiatry can be generalized to the psychiatric emergency room setting, although some differences exist. Reprinted from J Am Acad Psychiatry Law 2020; 48:484-495, with permission from The American Academy of Psychiatry and the Law. Copyright © 2020.

Persons Who Engage in Self-Harm While in the Emergency Department: A Case-Control Analysis.

ABSTRACT: Some patients engage in self-harm behaviors while in the emergency department. Risk factors for self-harm have been described for inpatient and outpatient/community settings, but not among emergency department patients. Authors conducted case-control, retrospective reviews of medical records and incident reports for emergency department patients in two academic medical centers. Variables were analyzed using conditional logistic regression. There were 113 individuals who engaged in self-harm while in the emergency department and 226 individuals who did not. Four variables were significant in the final model: a history of nonsuicidal self-harm (odds ratio [OR], 4.28; 95% confidence interval [CI], 1.95-9.41), opioid use in the prior 2 weeks (OR, 2.89; CI, 1.19-7.02), current manic episode (OR, 3.59; CI, 1.33-9.70), and a history of seizures (OR, 4.19; CI, 1.16-15.14). Risk of self-harm while in the emergency department may be mitigated with interventions that support adaptive coping skills, promptly address pain and withdrawal symptoms, and treat mania.

Self-harm During Visits to the Emergency Department: A Qualitative Content Analysis.

BACKGROUND: Some patients engage in self-harm behaviors while in the emergency department, both suicidal and nonsuicidal self-harm. Little is known about what motivates these behaviors. This gap in the empirical literature limits efforts to develop early identification and risk mitigation strategies. OBJECTIVE: To describe methods and motivations when patients self-harm in the emergency department. METHOD: Authors reviewed self-harm incident reports and medical records from two urban academic emergency departments. Event timing and self-harm methods were extracted. Authors performed a qualitative content analysis of self-harm narratives to examine the question, "Which factors motivate patients to engage in deliberate (nonaccidental) self-harm in the emergency department?" RESULTS: The sample included 184 self-harm incidents involving 118 unique patients. A wide variety of self-harm methods were present in the data. Suicidal intent was present in a minority of incidents. Other motives included psychosis, intoxication, aggression, managing distress, communication, and manipulation. CONCLUSIONS: Self-harm behaviors in the emergency department encompassed a variety of methods and motivations. These findings suggest risk mitigation strategies that emphasize suicide screening, reducing environmental hazards, and increasing observation are unlikely to achieve the goal of zero harm. Strategies focusing on engagement may create more fruitful opportunities to improve patient safety.

Antipsychotic Maintenance Treatment for Patients With Schizophrenia: The Need for Placebo-Controlled Trials and The Risk of Paradigm Shifts.

Background and Hypothesis: There is limited evidence guiding clinicians and patients on how long to continue antipsychotic medication beyond the first 1-2 years of treatment. Data from long-term (beyond 2 years) placebo-controlled trials would be informative but would be resource-intensive and technically difficult to obtain. Philosophy and history offer perspective on whether schizophrenia researchers should invest in such trials. Study Design: Essay. Results: In Descartes' model of science, knowledge grows by accumulation and evolves from simpler toward more complex areas. From this perspective, the most important questions are when and how to build this evidence base. In Kuhn's model of science, paradigm shifts can occur that reframe which questions and answers are meaningful. From this perspective, the question of whether to invest in long-term placebo-controlled trials is especially important. An historical review of schizophrenia over the past century indicates that major paradigm shifts have occurred regarding schizophrenia treatments, what counts as evidence, and the definition of schizophrenia. Conclusions: While long-term placebo-controlled trials would add value within the current paradigm, if a paradigm shift occurs there is a risk that this value would not be maintained in the new paradigm.

Medication Use and Physical Assaults in the Psychiatric Emergency Department.

Objective: To evaluate the relationship between medications used to treat acute agitation (antipsychotics, mood stabilizers, and benzodiazepines) and subsequent assault incidence in the psychiatric emergency department.Methods: Medication orders and assault incident reports were obtained from electronic health records for 17,056 visits to an urban psychiatric emergency department from 2014 to 2019. Assault risk was modeled longitudinally using Poisson mixed-effects regression.Results: Assaults were reported during 0.5% of visits. Intramuscular (IM) medications were ordered in 23.3% of visits overall and predominantly were ordered within the first 4 hours of a visit. IM medication orders were correlated with assault (incident rate ratio [IRR] = 24.2; 95% CI, 5.33-110.0), often because IM medications were ordered immediately subsequent to reported assaults. Interacted with time, IM medications were not significantly associated with reduction in subsequent assaults (IRR = 0.700; 95% CI, 0.467-1.04). Neither benzodiazepines nor mood stabilizers were associated with subsequent changes to the risk of reported assault. By contrast, antipsychotic medications were associated with decreased assault risk across time (IRR = 0.583; 95% CI, 0.360-0.942).Conclusions: Although assault prevention is not the sole reason for ordering IM medications, IM medication order rates are high relative to overall assault incident risk. Of the 3 major categories of medications ordered commonly in the psychiatric emergency setting, only antipsychotic medications were associated with measurable decreases in subsequent assault risk. As antipsychotic medication can have a significant side effect burden, careful weighing of the risks and benefits of medications is encouraged.

The Impact of the COVID-19 Pandemic on Psychiatric Emergency Service Volume and Hospital Admissions.

BACKGROUND: During the COVID-19 pandemic, there have been an increasing number of emergency department visits for behavioral health reasons, even as overall emergency department volumes have decreased. The impact of the pandemic and related public health interventions on specialized psychiatric emergency services has not been described. These services provide high-intensity care for severely ill patients who are likely to be homeless and underserved. OBJECTIVE: We describe the change in total volume and psychiatric hospitalization rates among three psychiatric emergency services across the United States. METHODS: Changes in volumes and hospitalization were assessed for statistical significance using a seasonal autoregressive integrated moving average with exogenous factors model from January 2018 to December 2020. RESULTS: The pandemic's impact on volumes and hospitalization varied by site. In Denver (CO), there was a statistically significant 9% decrease in overall volumes, although an 18% increase in hospitalizations was not significant. In New York City (NY), there was a significant 7% decrease in volumes as well as a significant 6% decrease in hospitalizations. In Portland (OR), volumes decreased by 4% and hospitalizations increased by 6% although differences did not reach statistical significance. CONCLUSIONS: There has been a decrease in volume at these services after the pandemic, but there are substantial variations in the magnitude of change and demand for hospitalization by region. These findings suggest a need to understand where patients in crisis are seeking care and how systems of care must adapt to changing utilization in the pandemic era.

Violence in Psychiatric Settings: Demographic and Clinical Characteristics of Patients Who Were Targets of Aggression.

ABSTRACT: Violence is a serious concern in the psychiatric inpatient and emergency setting. Much of the research on victims of inpatient violence has focused on identifying and supporting staff who are at risk of being victimized when working in psychiatric settings. This article presents an analysis of 72 patients who were targeted during incidents of patient-on-patient physical aggression in hospital-based psychiatric settings (both inpatient and emergency) from 2014 to 2018. Results suggest that patients who are at risk of being targeted by another patient while in the hospital tend to be younger, are more likely to be male, and present with manic symptoms and recent cannabis use. These variables have all been identified as risk factors for perpetration of violence by patients with mental illness. This study adds to a literature demonstrating a consistent overlap between individuals with mental illness who are victimized and those who initiate violence.

A historical review of placebo-controlled, relapse prevention trials in schizophrenia: The loss of clinical equipoise.

Recent ethical critiques have proposed that placebo-controlled, relapse prevention trials in schizophrenia are no longer justifiable and are therefore unethical. This review provides an historical perspective on the justifications for these trials and how arguments evolved over several decades. We identified 87 placebo-controlled, relapse prevention trials published over the last seventy years and examined the purpose for each trial. We found that first-generation trials had compelling justifications, yet these arguments changed considerably over time. Second-generation trials offered comparatively weaker-and sometimes no-justifications for their conduct. Without clear and compelling justifications for a given trial, it is not ethical to continue using this study design.

Physical Assault in the Psychiatry Emergency Room.

Previous studies of physical assaults in hospitals focused primarily on inpatient psychiatric units, leaving unanswered questions about the extent to which findings generalize to psychiatric emergency rooms. Assault incident reports and electronic medical records from one psychiatric emergency room and two inpatient psychiatric units were reviewed. Qualitative methods were used to identify precipitants. Quantitative methods were used to describe characteristics of each event, as well as demographic and symptom profiles associated with incidents. During the five-year study period, there were 60 incidents in the psychiatric emergency room and 124 incidents on the inpatient units. Precipitating factors, incident severity, means of assault, and interventions were similar in both settings. Among patients in the psychiatric emergency room, a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder with manic symptoms (Adjusted Odds Ratio (AOR) 27.86) and presenting with thoughts to harm others (AOR 10.94) were associated with an increased likelihood of having an assault incident report. Similarities between assaults in the psychiatric emergency room and inpatient psychiatric units suggest that the broader literature from inpatient psychiatry can be generalized to the psychiatric emergency room setting, although some differences exist.

Coercion and the Inpatient Treatment Alliance.

OBJECTIVE: The importance of building a strong treatment alliance is widely accepted and uncontroversial. Quantitative research suggests that coercive experiences during psychiatric treatment negatively affect the treatment alliance, but reveals little about how this happens or how patients navigate treatment relationships while experiencing coercion during psychiatric treatment. METHODS: Fifty psychiatric inpatients were interviewed at two hospitals. Patients were asked open-ended questions about the relationship between the treatment alliance and a set of coercive treatment experiences (court-mandated treatment, involuntary hospitalization, locked facilities) and whether such hospital experiences affected the patients' plans for future adherence. Interviews were audio-recorded, transcribed, and qualitatively analyzed. RESULTS: Many participants reported events where coercion made it difficult to form a treatment alliance. An imbalance of power, lack of control, and insufficient participation in treatment planning were described as experiences that interfered with the treatment alliance. Other participants felt the treatment alliance was maintained despite coercive experiences and spoke of good communication with the psychiatrist, understanding the rationale behind interventions, and feeling the psychiatrist was trying to keep the patient's best interests in mind. CONCLUSIONS: Coercive experiences remain undesirable and are frequently detrimental to the treatment alliance. Nevertheless, patients and clinicians should continue to seek a strong treatment alliance even when treatment plans include coercive elements. Efforts to improve communication, to explain the rationale for treatment plans, and to show that clinicians are trying to act in the patient's best interests may help to preserve a therapeutic alliance.

Use of Security Officers on Inpatient Psychiatry Units.

OBJECTIVE: Violent and aggressive behaviors are common among psychiatric inpatients. Hospital security officers are sometimes used to address such behaviors. Research on the role of security in inpatient units is scant. This study examined when security is utilized and what happens when officers arrive. METHODS: The authors reviewed the security logbook and the medical records for all patients discharged from an inpatient psychiatry unit over a six-month period. Authors recorded when security calls happened, what behaviors triggered security calls, what outcomes occurred, and whether any patient characteristics were associated with security calls. RESULTS: A total of 272 unique patients were included. A total of 49 patients (18%) generated security calls (N=157 calls). Security calls were most common in the first week of hospitalization (N=45 calls), and roughly half of the patients (N=25 patients) had only one call. The most common inciting behavior was "threats to persons" (N=34 calls), and the most common intervention was intramuscular antipsychotic injection (N=49 calls). The patient variables associated with security calls were having more than one prior hospitalization (odds ratio [OR]=4.56, p=.001, 95% confidence interval [CI]=1.80-11.57), involuntary hospitalization (OR=5.09, p<.001, CI=2.28-11.33), and going to court for any reason (OR=5.80, p=.004, CI=1.75-19.15). CONCLUSIONS: Security officers were often called for threats of violence and occasionally called for actual violence. Patient variables associated with security calls are common among inpatients, and thus clinicians should stay attuned to patients' moment-to-moment care needs.