is the Program Director of the Emergency Medicine Residency at Brandon Regional Hospital and Assistant Professor of Emergency Medicine at the University of South Florida Morsani College of Medicine in Tampa, FL. He currently practices emergency medicine and specializes in substance use disorder care in the emergency department setting in Brandon, FL.

Anthony J. Furiato, DO, FACEP

Schizophrenia affects roughly 1% of the global population and is a leading cause of suffering and disability worldwide. Despite advances in the pharmacological management of the disease, some patients with 

 remain consistently symptomatic, and others experience periodic exacerbations. Sadly, community services for those with chronic schizophrenic illness are lacking in many areas, rendering the emergency department (ED) a primary location for care of this severe mental disorder.

We wish to provide a psychologically- (and psychodynamically-) informed guide to the management of schizophrenia in the ED, incorporating relevant research in the areas of pharmacotherapy, psychology, and 

. One of us (Furiato) is an emergency medicine physician with interest in the management of acute psychiatric presentations. The other (Ruffalo) is a psychotherapist with interest in the psychotherapy of schizophrenia.

Attempts to distinguish schizophrenia from the psychotic symptoms that occur in other mental and medical disorders date at least to Kraepelin’s pioneering work in the late 1800s. Another German psychiatrist, Kurt Schneider proposed the “first-rank symptoms” of schizophrenia in 1939, and his theory held widespread popularity throughout the 20th century. A recent 

of Schneider’s first-rank symptoms (FRS) concluded that FRS correctly identifies individuals with schizophrenia 75% to 95% of the time.

Schneider’s FRS include: auditory hallucinations; thought withdrawal, insertion, or interruption; thought broadcasting; somatic hallucinations; delusional perception; and feelings or actions as made or influenced by external agents. While reliance on FRS alone may not be sufficient to diagnose schizophrenia,

 recognition of FRS can aid ED physicians and mental health workers in the triage and care of patients presenting with psychotic disturbance.

Since the course of schizophrenia is generally chronic, and because comprehensive mental health systems are sorely lacking in many geographic regions of the United States, patients with schizophrenia presenting to EDs may be well-known to hospital staff. In cases wherein the patient is a poor historian, or past records are otherwise unable to be obtained, reliance on clinical skill, such as knowledge of FRS, is necessary to ascertain the diagnosis of 

In certain instances, such as a clinical suspicion of new onset schizophrenia or abnormal neurologic exam findings, use of brain imaging in the ED may be necessary to rule out organic disease of the nervous system. While a comprehensive review of brain imaging in psychosis is outside of the scope of this paper, 

 note that neuroimaging is particularly useful in first-episode psychosis when patients are of old age, have neurological symptoms, or have an atypical clinical picture.

In the ED setting, the first and most important consideration upon presentation of the acutely agitated patient with psychosis or schizophrenia is the level of risk of harm they have on themselves and on staff.

 Depending on the answer to this question, the route and type of medication can be tailored based on the specific patient. Speed of onset can dictate which route of administration is chosen, as those who are violent will need more rapid calming. These therapies should be used with combined or directly after failed verbal de-escalation techniques.

 (BZD), which are pharmacologically active on the gamma-aminobutyric acid (GABA) receptors, act on the central nervous system and are one of the most common medications used for calming and sedation in the ED.

 The largest concentrations exist in the thalamus, cortex, and cerebellum. There are many different subclasses of GABA receptors including the main α- and β- sub-units. The biochemical neurotransmitter effects include reversable binding of the excitatory neuroreceptors and neuronal firing. The primary clinical effects are anxiolysis, sedation, and amnesia.

This group of medications is also commonly used as the first-line agent of emergency treatment of seizure-disorders and epilepsy.

 Adverse events of BZDs can result in respiratory depression, hypoxia, hypotension, and paradoxical excitation reaction in those with organic brain disease. Depending on the lipid solubility of the agent and route of metabolism with patient comorbidities, half-lives vary widely as seen in the 

Common Benzodiazepines Used in the ED (IM=intramuscular, IV=intravenous, PO=oral)

Patients who can be successfully verbally calmed and deescalated can be considered for therapy with oral management with BZDs alone or in combination with antipsychotics. For those who cannot be deescalated and pose a risk of injury to themselves and staff, these medications are commonly given intramuscularly in the ED, commonly with the help of physical restraints, and in combination with antipsychotics.

Antipsychotics can be broken down into 2 main categories in the emergency setting: first-generation (typical antipsychotics) and second-generation agents (atypical antipsychotics). The importance of the class distinction are the adverse side effects seen.

 Historically, the first-generation antipsychotics were developed for the treatment of schizophrenia. They act on the multiple dopaminergic receptor (D), anticholinergic, and histamine pathways. Each drug has its own mechanism of action and level of antagonism of those pathways. The hallmark drug of the first generation and one commonly used in the ED is haloperidol.

Haloperidol has been used to great success in treating the positive symptoms of schizophrenia. One of the main limitations, and ultimately a reason which prompted and led to the development of the second-generation drug class, was extrapyramidal symptoms such as tremor, slurred speech, akathisia, dystonia, and tardive dyskinesia. The 

further treats the negative symptoms of schizophrenia and improves upon the side effect profile of the first-generation group.

 Olanzapine and ziprasidone are commonly used in the ED from the second-generation class. Significant side effects of the second-generation drugs are sedation, hypotension, weight gain, and sexual dysfunction.

Many of the antipsychotics can be administered by mouth to those who are receptive to that method and calm enough for safety. They can also be administered by intramuscular and intravenous injection for those severely agitated.

 Careful monitoring of the patient’s respiratory status by cardiac monitoring and continuous pulse oximetry must be done after administration as side effects can also include respiratory depression and hypoxia. The regular combination of BZDs and antipsychotics can compound this risk. In addition, many of the antipsychotics can have cardiac electrophysiologic effects including prolonged QT intervals and the development of ventricular tachycardic arrythmias, necessitating EKG screening once the patient is chemically calmed.

Common combinations of BZDs and antipsychotics used in the ED include: lorazepam plus haloperidol or ziprasidone, midazolam plus haloperidol or ziprasidone. The addition of the antihistamine diphenhydramine is also sometimes added to the 2-drug cocktail discussed above for patients that are extremely violent. This practice is falling out of favor as seen in a recent retrospective cohort study.

In the prehospital and ED literature, ketamine has also been examined for the 

acute management of the violently agitated patient

 Ketamine is a dissociative agent that works at the N-methyl-D-aspartic (NMDA) receptor which is thought to play a partial role in the development in schizophrenia. Ketamine, when given intramuscularly, can produce more rapid de-escalation and sedation versus the more traditional method of BZDs plus an antipsychotic.

 The drawback to the use of ketamine is the theoretical possibility of exaggerating schizophrenic episodes due to activity on the NMDA receptors. There does not appear to be an increased need to inpatient psychiatric admission or ED psychiatric evaluation versus the traditional therapy.

 More research is needed to further assess the use of ketamine in the acute agitated schizophrenic patient.

Schizophrenia is a complex, multidimensional problem that requires appreciation of both biomedical and psychosocial aspects of disease management. This is true not only in the psychiatric treatment setting but also in the ED, since patients with schizophrenia may exhibit the most severe symptoms in the acute care setting. What follows is a brief review of some techniques for interviewing and treating the patient with 

Of perhaps greatest importance is the recognition that the patient’s heightened state of anxiety has contributed to their current psychotic disintegration.

 The patient with schizophrenia often feels alone and afraid, isolated, and without any sense of basic trust or security. The threat of interpersonal contact is too much for them to bear, so they escape even deeper into their psychotic world. Care must be taken to avoid any unnecessary situations in which the patient’s anxiety is increased, as this will only worsen the psychotic symptoms.

Any attempt to challenge or question the validity of delusional themes will result in utter failure, so the ED clinician must avoid these types of confrontations. At the same time, the clinician should not tacitly agree with the patient’s deluded ideas but instead explain empathically that there are reasons why they are experiencing things differently. Again, the clinician must do everything they can to foster an environment in which some semblance of trust can be established. For the patient who is mute or otherwise difficult to engage in an interview, speaking about neutral subjects, such as the weather or sports, may help alleviate anxiety and open the patient up to answering some basic questions.

While it is of course necessary to gather some information from the patient to establish a history and determine appropriate disposition, the patient with schizophrenia may experience too many questions as an imposition. As Arieti writes, “The request for information is often interpreted by the patient as ‘an attempt to take something from him.’”

 should be less the collection of detailed information and more of a 

 while gathering an assessment of current symptoms, an attempt to relay a sense of warmth, security, and trust which will serve as the foundation for ongoing treatment.

As noted above, the administration of psychotropic medications in the ED is sometimes necessary to stabilize an aggressive or violent patient. In these cases, the ED physician and mental health professional should maximize the patient’s sense of autonomy and self-determination, for instance, by allowing the patient to choose the route of administration. The patient likely already feels that he has been violated in some way—either due to intrusive voices, paranoia, somatic delusions, or some other terrifying symptom—so the ED clinician should attempt to avoid the use of coercion to the greatest degree possible.

Lastly, we must note that in many cases of schizophrenia, psychotic symptoms are ongoing, sometimes in spite of good pharmacological and psychotherapeutic management. The mere presence of psychotic symptoms in a patient who experiences such symptoms at baseline does not warrant inpatient psychiatric hospitalization, and it is unlikely that any such admission would do anything to improve the patient’s chronic illness.

Schizophrenia is a complex, disabling condition that presents a challenge to psychiatric and emergency medicine providers alike. Due in part to the lack of a comprehensive mental health system in the United States, patients with schizophrenia frequently present to the ED for diagnosis, treatment, and acute stabilization. Knowledge of diagnostic, pharmacological, and psychosocial elements of schizophrenia is essential for competent ED care. Of chief importance is the recognition that the patient with psychosis is in a psychologically vulnerable state, worsened by anxiety, and improved with understanding, empathy, and evidence-based symptom management.

is Instructor of Psychiatry at the University of Central Florida College of Medicine in Orlando, FL, and Adjunct Instructor of Psychiatry at Tufts University School of Medicine in Boston, MA. He is a psychoanalytic psychotherapist in private practice in Tampa, FL. Disclaimer: This research was supported (in whole or in part) by HCA Healthcare and/or an HCA affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA Healthcare or any other affiliated entities.

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Psychiatric outcomes of patients with severe agitation following administration of prehospital ketamine.

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Articles

The emergency department is a primary care location for patients with schizophrenia. Here’s how to manage schizophrenia in this particular setting in an informed and caring manner. 

Anthony J. Furiato, DO, FACEP

Articles

Psychologically-Informed Management of Schizophrenia in the Emergency Department