AUTHORS
Sarah K. Kennedy, MD, FACEP, Assistant Professor of Clinical Emergency Medicine, Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis
Andrea Purpura, MD, Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis
Devin Doos, MD, Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis
Erin Matusz, MD, Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis
Sreeja Natesan, MD, FACEP, Assistant Program Director, Division of Emergency Medicine, Duke University Medical Center, Durham, NC
PEER REVIEWER
Steven Winograd, MD, FACEP, Attending Physician, Mt. Sinai Queens Hospital Center, Assistant Clinical Professor of Emergency Medicine, Mt. Sinai Medical School, Jamaica Queens, NY
EXECUTIVE SUMMARY
• Psychosis is a symptom of an underlying organic or psychological condition.
• Psychosis produces an alternative reality for the patient, manifested by negative symptoms (flat affect, social withdrawal, delusions) and positive symptoms (disorganized thoughts and speech, bizarre behavior, hallucinations).
• Routine laboratory testing of patients with acute psychosis and an underlying psychiatric disorder is of low yield.
• Safety for all involved is the first priority for management of the acutely agitated patient.
• When necessary, antipsychotics should be used in patients with psychosis from underlying psychiatric disorders or intoxication due to central nervous system depressants, or for pharmaceutical sedation of the acutely agitated patient with delirium.
• Benzodiazepines should be used if necessary for sedation in patients withdrawing from central nervous system depressants or intoxicated with central nervous system stimulants.
Introduction
The scope of psychosis, the medications available for de-escalation of these patients, and the necessary workup can be challenging. The safety of the patient and staff must be weighed during these high-stress situations without missing potential alternate diagnoses for psychosis.
This article will review psychosis within a myriad of differentials and discuss the potential workup and medication options for the management of these patients to help equip the emergency provider (EP) with the tools necessary to care for this unique population.
Definition and Relevancy
Primarily a clinical diagnosis, psychosis is not a disease, but rather a symptom of an underlying organic or psychological condition. Psychosis produces an alternative reality for the patient that can manifest in a multitude of ways, including negative symptoms (flat affect, social withdrawal, delusions) and positive symptoms (disorganized thought and speech, bizarre behavior, hallucinations).1-4 The umbrella term mental health disorders includes a broad range of diseases from anxiety to schizophrenia. Across the country, emergency departments (EDs) are experiencing increasing volumes of psychiatric patients presenting with psychosis. New-onset psychosis typically is manifested in teenage or early adult years.5 Further complicating the presentation of psychosis to the ED are mimics that manifest as agitation or abnormal behavior, such as psychogenic nonepileptic seizures (PNES). PNES are episodes of abnormal movements and observable behavior that often can show outward similarity to epileptic seizures but do not show the electroencephalogram (EEG) changes seen with epilepsy.6-8
Whether it is an acute exacerbation or new-onset psychosis, the emergency department is the safety net for those experiencing psychosis. Despite the growing number of Americans requiring care, the lack of resources for mental health management and treatment has created an uphill battle for the ED provider to conquer in the quest to care for this vulnerable population.9 Additionally, there is a deficiency of standardized, validated tools, particularly ED-specific ones, screening tools, and treatment to help in the care of these patients.10 The goal of this paper is to review recent literature on the care of patients with acute psychosis, new psychosis, and PNES and to help guide clinicians with the treatment of these challenging populations.
Epidemiology
The lifetime prevalence of psychotic disorders (of all types) analyzed using 28 studies from multiple countries was 7.5 per 1,000 population.11
The first episode of psychosis has been found to be age-dependent, more frequently presenting in the adolescent to young adult range (86 in 100,000 within 15-29 age group), with half as many in the middle-age range group (46 in 100,000 for the 30-59 age group).12 Additionally, the country of residence may be a contributing factor, particularly for brief psychotic disorders. A 10-fold higher incidence is found in developing countries when compared to industrialized countries, suggesting contributors related to socioeconomic status and resources.2
The prevalence of PNES is 2-33 per 100,000, with an incidence of 1.5-4 per 100,000 affected each year in the United States.6,13,14
In the United States, mental health emergencies were the 10th most common reason for ED visits in 2016, particularly for male patients 15-65 years of age and female patients 65 years of age and older.15 Recidivism rates for repeat ED visits are variable (5-56%), with schizophrenia accounting for most of the returns.16
Etiology and Risk Factors
Psychosis as a symptom has a complex etiology with many genetic or environmental risk factors that can increase susceptibility, including childhood trauma, perinatal difficulties (like hypoxia or stress), infections, exposures (such as to marijuana or tobacco smoke), and nutritional deficiencies (including vitamin D or zinc), among others.17-20 The risk of schizophrenia development has been found to be higher among those with lower incomes, immigrants, and in certain residential locations, such as more northern or southern latitudes and metropolitan areas.21,22 The diagnosis of psychosis also is not without consequence. When schizophrenia was tied to the diagnosis of primary psychosis, these patients were found to have a two- to threefold increased risk of dying when compared to the general population.22,23
For those with known psychosis, four separate factors have been shown to increase the risk for relapse: poor premorbid adjustment (the inability to achieve academically, socially, and interpersonally relevant relationships prior to the onset of psychiatric disease), drug and alcohol abuse, noncompliance of medication, and social strain from caregivers in the form of lack of support and judgment.24,25 Despite knowing some risk factors that can cause relapse, an adequate tool to predict relapse for those with known psychosis does not exist.24 About 20% of patients evaluated in the ED with acute psychosis are found to have an underlying medical cause.26 Factors associated with increased likelihood of a psychosis due to a nonpsychiatric disorder (“secondary psychosis”) include age (elderly), prior medical history, lack of prior psychiatric disease, recreational drug use (past history or current intoxication), signs of organic pathology, and lower socioeconomic status.25,27
Regarding PNES, the etiology is thought to be multifactorial. A type of dissociative response to an upsetting event, emotion, or stimulus, PNES is categorized as a type of conversion disorder in DSM-5 that is not fictitious but does not have a neurologic basis.6-8,28 PNES is more common in females and frequently presents in adolescence or young adulthood. The risk factors associated with the diagnosis of PNES include a history of traumatic brain injury (TBI), post-traumatic stress disorder (PTSD), situational stress, intractable pain, abuse or trauma (sexual, physical, or emotional), and epilepsy or family history of epilepsy.6,13,29-33
Precipitating factors vary based on gender: Women often have a history of sexual abuse while men more commonly report job loss or forced household responsibility changes. In older patients, a frequent precipitant can be physical illness.6,30 It is not unusual to see concomitant epilepsy and PNES diagnoses in patients. It is theorized that epilepsy may be a risk factor for PNES development. This may be from biological similarities, but experiencing or witnessing seizures also can provide a framework for learned behaviors.30,32,34
Etiology and Risk Factor Considerations for Specific Populations
Specific cohorts, including children, pregnant women, and older adults, are vulnerable populations, making them difficult to study with mental health disorders partially because of the complexity of obtaining consent.
Pediatrics
Despite growing research advocating that earlier treatments result in subsequent improved outcomes for this population, there is still a marked delay in initiating treatment.12,35,36 One contributing factor for this is the inconsistency of symptoms in pediatric patients. Symptoms such as hallucinations or delusions may not be pathologic or can be present in a number of other serious conditions, such as ingestions or metabolic disorders, so children with these symptoms should be evaluated closely with a thorough workup.3,4,37
Pregnancy
Pregnancy and the postpartum period is a time of increased vulnerability for mental and behavioral health disorders. This is mainly due to an increase in hormones and physiologic changes, stress, environmental and social contributors, as well as medication changes during pregnancy.38 New-onset psychosis is rare when compared to exacerbations of chronic mental health diseases.38,39 Because of the implications for both the mother and the fetus, when psychosis is suspected, an initial thorough medical workup is warranted.39
Postpartum psychosis, occurring in one in 500 to 1,000 births, can have severe consequences for the mother and baby; it typically occurs in the setting of a prior psychiatric disorder rather than new-onset psychosis.4,39
Noncompliance is a major contributor to new mothers experiencing an acute exacerbation of their psychosis. However, mental health diseases that go untreated are associated with many complications, including short-term effects (such as impaired fetal growth, fetal distress, reduced weight at delivery, fetal malformation, or premature birth) or long-term effects (such as delay in emotional or social development).38
Unfortunately, no antipsychotics are considered completely safe during pregnancy. However, when weighing risks and benefits, the potential harm of noncompliance and subsequent decompensation typically allows for the patient to remain on stabilizing psychiatric medications. Compliance with medications has been shown to have positive outcomes for both the mother and the child, with research showing an improvement in the management of psychiatric disorder and a reduction in rates of exacerbations.38,39
Older Adults
An alteration in mental status in elderly patients is a common ED presentation. About one in four elderly patients will experience a psychotic episode in their lifetime, the majority secondary to an acute illness.40,41 Contributing risk factors and etiologies for the development of psychosis at an older age are vast and are listed in Table 1.40,41
Table 1. Etiology and Risk Factors for Elderly Patients41,42 |
|
Classification and Pathophysiology
Several important symptom definitions pertaining to psychosis are listed in Table 2. These include positive symptoms (disorganized thought and speech patterns, abnormal behavior, alternate perceptions in the form of visual or auditory hallucinations, and false beliefs in the form of delusions, paranoia) and negative symptoms (blunt affect, socially withdrawn, anhedonia, impaired attention, and apathy).3,27,43-45 Symptoms need to be characterized by length of time because that will have bearing on the disease definition, as seen in Table 3.2,45-47
Table 2. Psychosis Terminology3,43-45 |
|
|
Symptoms of Psychosis |
Definition |
|
Hallucinations |
False sensation of something that is present when it is not; can be visual, auditory, or tactile |
|
Delusions |
False belief that contradicts reality |
|
Flat affect |
Lack of emotion, blunted facies |
|
Social withdrawal |
Decreased ability to participate in social settings |
|
Bizarre, abnormal behavior |
Vast manifestation, including nakedness, responding to internal stimuli, echolalia, catatonia, waxy flexibility |
Table 3. Types of Psychosis1,46,47 |
||
|
Diagnosis |
Duration |
Definition |
|
Brief psychotic disorder |
Less than one month; completely resolves |
Sudden and temporary symptoms of hallucinations and delusional beliefs |
|
Schizophreniform |
One to six months |
Visual or auditory hallucinations and delusional beliefs |
|
Schizophrenia |
Longer than six months |
Visual or auditory hallucinations and delusional beliefs |
|
Schizoaffective disorder |
Longer than six months; has schizophrenic symptoms for at least two weeks without mood symptoms |
Diagnosed schizophrenic disorder with concurrent mood disorder (depression or mania) |
|
Schizotypal personality disorder |
Brief psychotic episodes that have decreased frequency and length than those with schizophrenia |
Strange and unusual thinking, extreme social anxiety with occasional delusions and hallucinations |
The American Psychiatric Association (APA) defines psychiatric emergencies as an acute alteration in mood, thought, or behavioral or social functioning that requires an emergent intervention.27 Within the context of the ED, which often is a resource-limited area, the initial assessment is conducted by the EP and the evaluation of the patient’s mental state should be centered around the risk of physical harm to the patient or others.38 Primary psychosis is thought to be multifactorial, although there is a genetic predisposition.
In schizophrenia, there is evidence of a neurotransmitter dysfunction resulting in improper levels or alteration of multiple neurotransmitters, including acetylcholine, dopamine, gamma-aminobutyric acid (GABA), glutamate, and serotonin, that can result in agitation.48,49 This neurotransmitter imbalance can help explain why psychotic symptoms can be seen in conjunction with certain medications or drug ingestions, such as methamphetamines, levodopa, and cocaine, which all raise dopamine levels in the body.4
Methamphetamine, a sympathomimetic agent, is known to act on the same receptors as those that are affected in primary psychosis. Although the symptoms usually wear off once the drug is metabolized, the presentation of the patient can be quite similar to a schizophrenic exacerbation. Some people are more vulnerable to the effects of methamphetamine-induced psychosis than others, although the contributing factors are unclear and likely to be related to genetic, environmental, and social influences.50 Additionally, symptoms have the potential to be chronic if there is a history of heavy drug use or if use has been present for more than six months.51 Insomnia from stimulant use, often lasting for days at a time, also can exacerbate psychosis.50
Comorbidity
Common medical conditions that are prevalent in the schizophrenic population have been hypothesized to contribute to shorter life expectancy. Higher rates of medical disorders, such as obesity, metabolic syndrome, diabetes mellitus (DM), hypertension (HTN), hyperlipidemia (HLD), and tobacco use have been found in those with severe psychiatric disease and can contribute to cardiovascular disease.23 When compared to the average patient, people with schizophrenia have a threefold risk of sudden death due to these risk factors. 23
Also implicated in causing cardiac and metabolic diseases is obstructive sleep apnea (OSA), which is found in up to 50% of patients with schizophrenia, contributing to a reduced lifespan. OSA can resemble symptoms seen in psychosis and present as irritability, anhedonia, apathy, impulsivity, and anxiety.52
Patients with primary psychosis and substance abuse issues, particularly tobacco, cannabis, and alcohol, have been shown to have poorer outcomes. In addition to medical comorbidities that exist in psychiatric patients, psychiatric medications can predispose patients to the development of medical conditions. For example, atypical antipsychotics, such as clozapine, olanzapine, and, to a smaller degree, risperidone and quetiapine, have been found to increase the likelihood of developing DM.23
Clinical and Diagnostic Features
Psychosis is predominantly a clinical diagnosis based on symptoms listed in Table 4.2-4 When approaching a patient, cultural sensitivity should be taken into consideration, since hallucinations potentially may be an ordinary practice in some cultures. One example is cultures that communicate with the dead or a deity through hallucinations.53 Collateral information from family members or caregivers can help the EP understand any cultural context that may be important.
As discussed earlier, patients can display positive or negative symptoms. Social difficulties and increased isolation, inability to function normally, and hallucinations are the prominent signs seen in the younger population on presentation.3 Unfortunately, assessment can be difficult, especially if the patient is unable to provide coherent information.
Table 4. Symptoms and Common Behaviors of Psychosis1 |
|
|
Symptoms of Psychosis |
Behaviors of Psychosis |
|
Hallucinations |
Pacing |
|
Disorganized speech |
Loud or improper speech |
|
Flat affect |
Nakedness |
|
Social withdrawal |
Hypersexuality |
|
Delusions |
Lack of respect for personal boundaries |
Not all patients with psychotic symptoms require emergency medical or mental health assessment. However, immediate evaluation in the ED is warranted for patients with increased risk for harm to themselves or others.27
During the examination, it is important to ascertain the type of hallucination (i.e., auditory or visual) the patient is experiencing, since this can help differentiate between an organic (primary) or non-organic (secondary) psychosis. Auditory hallucinations are more common in patients with a primary psychotic disorder. In contrast, visual hallucinations are more likely to occur with secondary psychosis.4
When approaching a clinical diagnosis of psychosis, it is important to keep in mind that there are many mimics. Common diseases that have classic presentations usually result in a quick and accurate diagnosis, which includes drug-induced psychosis or exacerbation of a known primary psychosis. The more difficult cases are related to atypical presentations of common diseases, such as HIV-induced psychosis, or rare disorders that are encountered infrequently, such as Wilson’s disease.54 From an ED perspective, it is most important to recognize dangerous symptoms, ensure patient safety, and make an appropriate disposition.
PNES can present similarly to epileptic seizures, making it difficult to differentiate on initial exam. Many patients can be misdiagnosed and treated with antiepileptic medications for years (on average, seven years) before receiving a correct diagnosis.55 Several factors that seem to contribute to longer delays in diagnosis are younger age, head trauma, psychological abuse, an EEG that reveals interictal epileptiform potentials (discharges or spikes on EEG that can be seen with seizures), and treatment with anticonvulsant medications.55,56 Some common clinical characteristics of PNES are listed in Table 5.
Table 5. Common Characteristics of PNES32,57-59 |
|
Differential Diagnosis
Medical Mimics
Several medical conditions can mimic acute psychosis, especially in patients who present with acute psychosis with no prior medical or mental health disorder.26 Such patients deserve a comprehensive evaluation, usually with laboratory and imaging tests. This contrasts with those patients with known primary psychosis who are experiencing an acute exacerbation. Literature suggests avoidance of routine laboratory tests in this population because it is of low utility, although in female schizophrenic patients, it may be useful to send a urinalysis due to the higher likelihood of UTI.60
While the differential list for secondary psychosis can be vast, an important cause is drug abuse. For example, methamphetamine can produce bizarre behavior, agitation, and aggression or violence, in addition to hallucinations, delusions, and paranoia.50 Other forms of drug ingestion can cause psychosis and are discussed later. A list of differential diagnoses for acute psychosis is presented in Table 6.
Table 6. Differential Diagnosis for Acute Psychosis1,4,60-67 |
|
|
Differential Diagnosis |
|
|
Autoimmune |
|
|
Endocrine |
|
|
Infectious |
|
|
Metabolic |
|
|
Neurologic |
|
|
Nutritional |
|
|
Obstetrics |
|
|
Oncologic |
|
|
Toxicology |
|
Two other mimics for new-onset psychosis are delirium and dementia. Differentiating these conditions in patients often is difficult and can greatly affect the suggested workup. Delirium suggests an underlying medical condition that requires further evaluation, while dementia necessitates behavioral control. There are key aspects that help distinguish delirium from dementia, including onset of symptoms, an inciting medical condition, and alteration in attention, thought process, or level of consciousness.27 (See Table 7.)
Table 7. Features of Delirium vs. Dementia27 |
||
|
Features |
Delirium |
Dementia |
|
Onset |
Acute onset |
Slow/insidious onset |
|
Duration |
Days to weeks |
Months to years |
|
Course |
Intermittent/fluctuating |
Progressive worsening |
|
Reversibility |
Usually reversible after treating underlying cause |
Rarely reversible |
|
Level of consciousness |
Altered |
Normal: clear, awake, alert |
|
Memory |
Recent and immediate impaired |
Recent and remote impaired |
|
Attention |
Poor attention |
Able to pay attention and cooperate |
|
Hallucinations |
Present |
Rare; present at late/end stages |
|
Delusions |
Fleeting delusions |
None |
Drugs/Medication Mimics and Confounders
In the ED, intoxication, abuse, or dependence from alcohol or drugs is the most common cause of altered mental status.1,42,66 Paranoia can be the result of drug consumption, particularly stimulants such as cocaine, or withdrawal (such as from alcohol), which can cause hallucinations, especially visual and tactile ones.1
The growing recreational use of cannabis in the United States has been associated with increased ED visits for acute psychosis.68 Much debate regarding the development of psychosis surrounds how much this is influenced by cannabis, since other social components remain significant contributors.69 Even in healthy individuals, delta-9-THC, the psychoactive substance found in cannabis, has been shown to affect mental capacity and behavior.70,71 Unfortunately, the amount of THC found in cannabis is variable and can have different effects in different people. However, psychosis can be exacerbated with the use of increasing amounts of THC, especially in people with schizophrenia.71
Thought to be four times stronger than naturally growing cannabis, Spice is a synthetic cannabinoid. It is known by various names, including Black Mamba, Zohai, Blaze, Bliss, K2, Bombay Blue, Fake Weed, Genie, and Red X.71-73 Spice also can lead to temporary psychotic symptoms similar to those seen with THC use.
However, methamphetamine is a more common cause for drug-induced psychosis than either of these, with up to 50% of participants affected. It has been implicated in producing positive psychotic symptoms, such as hallucinations and delusions. Despite drug metabolism, for some methamphetamine users, the symptoms of psychosis can persist permanently and become indistinguishable from a primary psychotic disorder.50
Typical Workup
History of Presenting Illness
A systematic approach to patients with suspected psychosis includes a thorough history and physical exam to try to distinguish between primary and secondary psychosis. This combination can help to elicit the potential etiology or contributors of acute psychosis, with history alone having a sensitivity of 94%, while physical examination has a sensitivity of 51% for detecting a secondary cause for the presentation.42,66,74
However, patients with acute psychosis can have added barriers to obtaining a full history and exam, resulting in unreliable and incomplete information, especially for those who present with agitation, combativeness, paranoia, or altered mental status in the form of a disorganized thought process.27 Alternative history-taking strategies include speaking with emergency medical services (EMS), reading prior notes, or collecting collateral data from significant others and/or family members. Thorough documentation is important, as it allows other providers to quickly assess the patient’s baseline mental status and determine if the current presentation has changed.
An important historical piece of information is whether the patient’s current mental status is different from the person’s baseline chronic psychiatric disease. In the absence of a mental status change in the setting of a known psychiatric illness, further investigation beyond the history and exam typically is not needed.26 However, if the patient is exhibiting altered mental status or is acting differently than usual, continued investigation into a medical cause must be performed.66 All patients should be asked about past or present thoughts of suicide or homicide, prior suicide attempts, and violence.49
Physical Examination
A complete physical exam (including a neurologic and mental status exam) is important in determining whether continued testing is indicated. Vital signs should be reviewed, and the patient should be fully exposed; this allows for inspection on the physical exam but also allows the EP to ensure the patient does not have any hidden weapons.49,66 Vital sign irregularities, visual hallucinations, focal neurologic abnormalities, delirium, evidence of trauma, and signs of drug intoxication or withdrawal could indicate a secondary psychosis, and a medical illness should be considered.4,42,49
Indications for Advanced Workup
Laboratory. All workups should be guided by the history, physical exam, and family history considerations. American College of Emergency Physicians (ACEP) Critical Issues in the Diagnosis and Management of the Adult Psychiatric Patient in the Emergency Department does not recommend routine laboratory testing (level C recommendation).75 Once a thorough history and physical exam have been completed in a patient with a psychiatric complaint, particularly in known psychiatric illness, and the patient has been deemed medically cleared and ready for further psychiatric evaluation, laboratory testing rarely changes management.27,76-78 However, there is agreement that premenopausal women should have a urine pregnancy test (UPT); while it is unlikely to change care in the ED, this information can be useful during inpatient treatment. If the patient is unlikely to provide a UPT, a serum test should be considered.42
When the history and physical alone do not account for the patient’s actions, if a new psychiatric illness is present, or in populations with higher disease rates (immunosuppressed, elderly), further investigation should be considered. Some populations in which a medical workup could be indicated are included in Table 8.27,78 However, there is no consensus on what defines standard of care in these patients.27,39,54,75,76
Table 8. Indications for Medical Workup for Acute Psychosis27 |
|
A rapid point-of-care (POC) glucose is the most important test on initial presentation to the ED.42 Additional laboratory and diagnostic testing are listed in Table 9.2,4,42,54,79 Tests for disorders that may not be clinically apparent should be considered in new-onset or undifferentiated psychotic patients, such as thyroid stimulating hormone, vitamin B12 levels, ceruloplasmin levels, and HIV antibodies.54
Table 9. Potential Laboratory Workup for Acute Psychosis2,4,42,54,79 |
|
|
Test |
Pearl |
|
Complete blood count (CBC) |
Assess for anemia, leukocytosis, eosinophilia |
|
Basic metabolic panel (BMP) |
Assess electrolytes, renal function |
|
Hepatic function test/liver function tests (LFT) |
Assess for liver function |
|
Urinalysis |
Assess for urinary tract infection or sexually transmitted infection |
|
Urine drug screen |
Assess for potential drug ingestion contributors for presentation |
|
Serum drug screen |
Assess for alcohol, acetaminophen, or aspirin ingestion |
|
Endocrine tests: parathyroid, thyroid function tests |
Assess contributors to presentation such as hyperparathyroidism, hyperthyroidism, or hypothyroidism |
|
Vitamin tests: B12, niacin, folate |
Assess for deficiency that may contribute to the presentation |
|
Infectious disease testing: HIV, syphilis, sexually transmitted disease (gonorrhea, chlamydia, trichomonas) |
Assess if high-risk behaviors or symptoms that correspond to development of a sexually transmitted disease |
Imaging. Advanced neuroimaging encompasses modalities such as computed tomography (CT) and magnetic resonance imaging (MRI). The history and physical exam should guide the clinician to determine if advanced imaging is necessary. Imaging has been shown to be less helpful for the initial presentation of acute psychosis because these patients usually are young and physically healthy without signs of secondary causes.2,54,79 However, elderly patients or those with significant head trauma, headaches, or neurologic abnormality may have a structural cause and would be more likely to benefit from an emergent head CT or MRI.4,27,54,80 In a small number of patients, stroke can precipitate psychosis, usually seen within six months of neurologic insult.81,82
Although these imaging studies may not provide a diagnosis, a negative scan still can be a meaningful piece of information, particularly in excluding medical disease in a first-time psychosis presentation. MRI is more sensitive in discovering abnormalities that can be associated with psychiatric disease (such as brain masses, white matter disease, or epilepsy), so it is the test of choice if one is performed.54
Psychogenic Non-Epileptiform Seizures
A number of conditions may present to the ED with seizure-like symptoms.29,83 (See Table 10 for some common causes.) Although there is a broad differential that needs to be considered initially, PNES is mistaken most often as epilepsy and is included as a diagnosis in an estimated 20-50% of patients admitted for video EEG (vEEG) evaluation.14,28,34 Additionally, it is thought that 10-30% of patients with PNES have concomitant epilepsy.32,57,84
Table 10. Differential Diagnosis for Seizure-Like Symptoms29,83 |
|
There is no clinical presentation that is pathognomonic for PNES. If attempting to distinguish between epileptic seizures and PNES in the ED, the workup and treatment should follow typical epileptic seizure evaluation and management. A history and examination (including a full neurologic assessment) should be completed. An electrocardiogram (ECG) should be obtained to evaluate for arrhythmias. Labs, including a pregnancy test, antiepileptic drug (AED) levels if pertinent, and electrolytes, can be helpful. After an epileptic seizure, lactate and creatine kinase frequently are elevated, while sodium and glucose levels typically are low. Laboratory evaluation in the workup of a patient with an established diagnosis of PNES usually is not indicated, but it can be considered if concern exists for superimposed disease. Neuroimaging, lumbar puncture, consultation, and admission also can be included when indicated.83
Workup Considerations for Specific Populations
Pediatrics
Medical workups more specific to the pediatric population can include blood work or urine tests to evaluate for substance use, genetic diseases, metabolic diseases or derangements, and vitamin levels.3 A head CT may not be useful in a young patient presenting with acute psychosis unless historical or physical exam features, such as head trauma, a history of headaches, suspicion for neurologic infections, or neurologic exam abnormality, are present during the evaluation.85 Brain MRI could be performed if the EP has a concern for rare diseases, such as epilepsy, encephalitis, or Wilson’s disease, as this would be a better diagnostic modality.
Pregnancy
The pregnant population presenting with new-onset psychosis has a high likelihood of a medical cause that should prompt a thorough medical evaluation. There is no consensus on the standard of care for the workup, but it should include a thorough history and physical (including neurologic and mental status exams), and vital signs.39 Although aforementioned ACEP guidelines state that a routine urine drug screen (UDS) is unnecessary for most ED patients, this recommendation did not extend to pregnant patients. Detecting substance abuse early through laboratory evaluation in this population may offer an important opportunity for early counseling and intervention.39
Elderly
Many elderly patients presenting with acute psychosis in the ED have causes that can be attributed to medical or physical diseases. The EP should consider depression, neglect or abuse, delirium, dementia, substance use or withdrawal, medical disease, polypharmacy or medication side effects, and psychosis while assessing older patients with abnormal behaviors and agitation. They also should always inquire about suicidality. A medical workup should be performed to evaluate for nonpsychiatric causes of their symptoms.86,87
ED Management
The most commonly researched area of treatment in the acutely psychotic patient revolves around the acutely agitated patient, which requires immediate attention by the EP. Safety for all involved must be the first and foremost issue addressed during the initial stages of care for the acutely psychotic patient.27,88 Screening for violence through rapid risk assessment at the bedside is crucial in reducing the risk for harm in the acutely agitated patient.49 The high volume, variable acuity, and time constraints make determining the cause of acute psychosis (primary or secondary) challenging.
Early intervention by trained mental health professionals for patients presenting with primary psychosis has been shown to improve outcomes.62 An example of early intervention includes the Recovery After an Initial Schizophrenia Episode (RAISE) initiative. RAISE places first-time psychotic patients into a collaborative interprofessional team with a global approach to treatment, with improved quality of life and psychopathology demonstrated as a result.89
Stable Patient
De-escalation is the first step in the approach to the acutely agitated patient in the ED, but only if the patient is not considered an immediate threat to him- or herself or to the medical staff. Employing de-escalation techniques early may help ameliorate the need for further escalation, including the potential for physical restraints, chemical restraints, or seclusion.27,49 (See Table 11.)
Table 11. De-Escalation Techniques27,43,49 |
|
De-Escalation Techniques |
|
|
PNES Management Considerations
The diagnosis of PNES is less likely to be made in the ED because it typically requires vEEG monitoring and an evaluation by neurology and psychiatry. An important principle in the case of these patients is clear and compassionate communication; it is important that the patient does not feel attacked or judged.
Increased rates of emotional disorders and psychiatric diseases, including dissociative, anxiety, mood, somatoform, and personality disorders, are observed in patients diagnosed with PNES compared to those who are healthy or with epileptic seizures.6,8,30 It has been reported that up to 70% of patients with PNES have been or eventually are diagnosed with additional psychogenic disorders.32
Several therapies, such as behavioral, cognitive, emotion management, family, group, and psychodynamic, as well as SSRIs, have been found to have some benefit and should be considered on an individual basis. This should occur in consultation with neurology and psychiatry because a significant portion of PNES cases have an associated psychiatric disease and triggers.13,29,83,90,91
A significant portion of adult patients with PNES will continue to experience seizures despite therapy. They continue to experience psychological morbidity, emotional distress, and decreased quality of life.6,13,28,90,92-95 Despite the poor prognosis seen in adults, approximately 70% of children have been found to be seizure-free five years after diagnosis.94
Management Considerations for Specific Populations
Pediatrics
It is difficult to get a reliable psychiatric exam from children. Caregivers or parents can provide vital information regarding the presence of any medical or psychiatric diagnosis, exposure to medication (intentional or accidental), the presence of hallucinations, or any potential inciting events.42
Management of pediatric patients with acute psychosis mirrors management of adults. Prior to physical or chemical restraints, verbal de-escalation techniques should be employed, with parents and caregivers helping the child adjust to an often scary and unfamiliar environment.42 For this population, literature is lacking regarding the risks and benefits of restraints, although it may be indicated to ensure patient or staff safety if there is a failure of both verbal de-escalation and medications.
Pregnancy
In addition to life stressors, pregnancy itself can induce anxiety and fear in women and should be addressed early in the acutely psychotic patient. As with other populations, initial steps should include verbal de-escalation and redirection to avoid medications, if possible. When unavoidable, the lowest dose of medication possible should be used to avoid teratogenic effects. Seclusion and restraints must be used with caution because women in their second and third trimesters are vulnerable to vena cava syndrome.38,39
Elderly
De-escalation techniques are helpful with elderly patients, and familiar caregivers should be employed to assist during these attempts at calming the patient. Restraints should be removed at the first opportunity to prevent complications, such as increased agitation, skin breakdown, decubitus ulcer formation, and others.42
Acutely Psychotic Patient
The acutely agitated patient can be unsafe for all involved. Although verbal de-escalation techniques are ideal, they are not always successful. Because patient and staff safety is of the utmost importance, medications may be needed for chemical sedation. In a cooperative patient, oral medications are the preferred route prior to escalating to intramuscular (IM) or intravenous (IV) doses.27
For uncooperative patients or when treatment is unsuccessful, physical restraints can be used as a last resort. Proper technique should be used to maintain safety for the staff and the patient. A group of at least five people should assist with the placement of restraints, and one arm should be placed in the up position on the stretcher to reduce movement or the ability to overturn the stretcher, while the other extremities are positioned in the down position.
Although helpful in maintaining a safe environment, restraints account for a large amount of agitation-related injuries and other serious complications, such as rhabdomyolysis and strangulation.42 It is imperative to follow the ED and hospital policies when employing seclusion and physical restraints, and adhere to Joint Commission, state, and federal regulations. The government and accrediting bodies closely monitor the use of involuntary commitment, transfers to psychiatric facilities, and the use of physical restraints or isolation rooms. Facilities should provide processes, policies, and training to staff.1
Suicidal and homicidal ideations should always be assessed in psychotic patients. In schizophrenia, the greatest suicide risk is in the first five years after diagnosis.62 Laws exist so that patients can be held involuntarily for further psychiatric treatment if they are considered a danger to themselves or others.62,96 Pregnant women are included, since poor oral intake, lack of prenatal care, and medical complications of mental health diseases can result in direct harm to the fetus.38 The APA developed criteria for appropriate involuntary admission. (See Table 12.) If it is determined that a patient is suicidal or homicidal, it is within the provider’s discretion to intervene by placing the patient on an involuntary detention based on one or more of the criteria.
Table 12. Six Criteria for Involuntary Admission27 |
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Medications
Three types of medications have been studied in the treatment of the acutely agitated patient: benzodiazepines, typical or first-generation antipsychotics (FGA), and atypical or second-generation antipsychotics (SGA). Historically, the most common treatment for acute agitation has been the combination treatment of haloperidol and lorazepam.97 With the development of SGAs, more options are available. Randomized controlled trials are difficult to perform in psychiatric patients; therefore, most studies on the pharmaceutical treatment of acute psychosis are observational.98 As such, most recommendations are based on expert opinion, clinical experience, or local emergency or psychiatric department culture.88,99,100
Providing a calm and safe environment for patient evaluation should drive pharmacologic treatment choice. Ideally, agitation escalation can be avoided or quickly addressed while treating the underlying psychosis cause.99,101 For example, benzodiazepines are indicated for psychosis from alcohol withdrawal and sympathomimetic abuse, while antipsychotics are used in primary psychosis.4,50,102 Considerations for specific agents are noted in Table 13 and dosages in Tables 14 and 15 on the insert card.
Table 13. Medication Consideration for Acute Psychosis |
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Benzodiazepines
Benzodiazepines bind with the GABA-benzodiazepine receptor complex. They can be useful in the treatment of anxiety, seizures, and agitation. A well-known side effect is respiratory depression; care should be used in patients with underlying respiratory disease or when combined with other sedating medications.
Despite not having the U.S. Food and Drug Administration (FDA) approval for acute agitation, lorazepam frequently is chosen in the ED because it has a quick onset, is easy to administer, and is found in most EDs. It also has the benefit of treating some coexisting diseases that can add to agitation, such as alcohol withdrawal and anxiety.42,49
Midazolam also is a popular choice for EPs; the length of time patients are sedated is shorter, while still providing a rapid onset of action. In ED patients with agitation, IM midazolam may provide more effective sedation than three common antipsychotics: haloperidol, ziprasidone, and olanzapine.100
Typical Antipsychotics/First-Generation Antipsychotics
Droperidol and haloperidol are the most common typical antipsychotics administered by EPs. They are butyrophenones and central dopamine receptor antagonists.49,88 Because of dopamine blockade, FGAs can cause extrapyramidal side effects, such as akathisia (motor restlessness), dystonia (muscle spasm or increased tone), pseudoparkinsonism, and tardive dyskinesia (repetitive involuntary body movements such as lip smacking). These symptoms can be lessened with anticholinergic medications, such as diphenhydramine or benztropine. Other significant side effects include prolonged QT, cardiac arrhythmias, and neuroleptic malignant syndrome.88,103 Some of these side effects, particularly QT prolongation, can be lessened by not giving the medications intravenously.88
Haloperidol is given frequently in the ED, either as monotherapy or as part of a combination. The combination of lorazepam with haloperidol seems to provide better sedation than haloperidol alone.49,104
Droperidol was found to have similar sedating effects to monotherapy with haldol, midazolam, and olanzapine. A systematic review found no significant difference in arrhythmias or respiratory depression between these medications. Droperidol had few negative side effects and, compared to haloperidol, was less likely to require redosing or the addition of other medications after an hour.105 In 2001, the FDA placed a black box warning on droperidol after there was some concern for QT prolongation and torsades de pointes.105,106 Reduced availability from pharmaceutical companies combined with this warning means droperidol is not readily available in many EDs.
Atypical Antipsychotics/Second-Generation Antipsychotics
Atypical antipsychotics are dopamine antagonists as well, but this newer class also blocks serotonin and has effects on histamine, norepinephrine, and alpha-2 receptors.42 Since the dopamine receptors are not blocked as strongly as by the typical antipsychotic class, SGAs usually have a more desirable side effect profile, including fewer extrapyramidal symptoms and less QT prolongation.42,49
Commonly used medications from this class include olanzapine, risperidone, ziprasidone, quetiapine, and aripiprazole.42,88 Risperidone and quetiapine are given orally, while olanzapine, ziprasidone, and aripiprazole are available as oral or IM doses. Oral dosing of olanzapine and risperidone have been found to be equally effective in treating acute agitation. Oral risperidone works equally as well as IM haloperidol. Additionally, when compared to the typical IM haloperidol and lorazepam, oral lorazepam and risperidone worked just as well.88 Olanzapine has been shown to have greater sedation compared to haloperidol.100
Medication Considerations for Specific Populations
Pediatrics
Typical and atypical antipsychotics are considered acceptable treatments for pediatric schizophrenia, but SGAs are chosen more frequently based on a reduced chance of neurologic side effects and provider comfort with the medication. Both are effective treatments, but cause extrapyramidal side effects.3,42 Of the antipsychotics, one medication that has a safe profile in pediatrics while producing minimal side effects is olanzapine.42 Diphenhydramine also is considered a safe medication alternative in children.42
Pregnancy
Benzodiazepines are thought to be detrimental to fetal development, but the effects of short-term or one-time treatment in the ED are largely unknown. There may be a slightly increased risk of oral cleft malformations, but the studies are not robust.39 Even with these findings, a single dose of benzodiazepines is considered relatively safe in the setting of acute agitation.38,42
New-onset psychosis during gestation is rare, and this presentation should prompt a medical evaluation. More commonly, an exacerbation of a prior mental health disease will be encountered. Untreated severe psychosis is more harmful to the pregnant patient and fetus than treatment with antipsychotics, but this decision should be made in conjunction with psychiatry and the patient because there could be possible fetal harm.39 The lowest dose possible should be used, and medications should be reviewed for teratogenic effects.
Diphenhydramine is considered safe in pregnancy and may be all that is needed for mild cases.38 Extended use of haloperidol has been linked to a slight risk of limb defects, but it can be used as an alternative for severe or refractory cases.38,42 No teratogenic effects are known to be related to risperidone.42
Elderly
Elderly patients respond differently to medications than their younger counterparts do. Lower dosages of medications should be considered, and titration should be slower because pharmacologic breakdown and excretion can be reduced and polypharmacy can occur in the setting of renal or hepatic dysfunction. This can help with side effects, such as oversedation.42,111 In general, benzodiazepines should not be used, since significant effects (such as delirium, reduced respiratory drive, and falls) can be seen after even one dosing.27,42 FGAs and SGAs are acceptable choices, but they can prolong the QTc interval, so cardiac monitoring should take place while in the ED.42
Disposition and Prognosis
Admission typically is recommended for patients with acute psychosis to allow evaluation of medical causes for secondary psychosis or early treatment of undiagnosed primary psychosis. Early recognition and treatment of mental health disease results in improved outcomes and decreased frequency of relapses, both functional and clinical.24,44,54,89
A first episode of psychosis can be triggered by many factors, but drug abuse is a common cause. If patients can remain free of substances for at least 18 months, they have a better chance at remission and their outcomes actually are improved compared to patients who never abused illicit substances.62 Psychosocial treatment should be used initially for patients using methamphetamines; this can improve the chances of sustained improvement.50
Prior to any discharge, it is imperative to adequately assess suicidal and homicidal risk. Prior attempts of self-harm, current suicide plan, or presentation with psychosis all are important risk factors to consider and, when present, frequently result in admission.112
Unfortunately, most EDs do not have the capacity to comprehensively care for patients with primary acute psychosis. Barriers include limited space, overcrowding, and provider knowledge or time needed to care for psychiatric illnesses thoroughly.113 These barriers are most pronounced outside of typical work hours and holidays since staff and resources are more limited. This leads to overcrowding and longer length of stay in the ED, which has been linked with higher mortality and worse outcomes in those who have mental health disorders.113 Prompt recognition and transport to appropriate psychiatric emergency service hospitals is in the patient’s best interest.
Summary
The emergency provider is responsible for deciding if a patient is a danger to themselves or those around them. Most of the time, this is easy to do, but if a patient is experiencing psychosis and is uncooperative or agitated, additional help may be needed.
De-escalation techniques always should be used first; this allows patients to maintain autonomy and play an active role in their own care. If de-escalation is unsuccessful, chemical or physical restraints may be necessary to keep the patient and treatment team calm and safe, and to allow an evaluation. Benzodiazepines, FGAs, and SGAs are used most frequently.
While in new-onset psychosis, labs and imaging frequently are in the workup, in acute exacerbations further testing typically is not indicated unless an underlying medical cause is suspected. Special populations in the ED include pediatric, pregnant, and elderly patients, who may require additional or altered workups, evaluations, and treatments.
PNES is a frequent presentation seen in the ED and often can resemble epileptic seizures. During an initial evaluation, workups can include laboratory testing and imaging. Neurology and psychiatry should be involved with the patient’s care. This allows for an empathetic in-depth discussion about the disease and specialized evaluation and treatments.
REFERENCES
A complete list of references is available online: http://bit.ly/2pueSxk.
This article will review psychosis within myriad differentials and discuss the potential workup and medication options for the management of these patients to help equip the emergency provider with the tools necessary to care for this unique population.
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