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Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8e

Chapter 290: Psychoses Adam Z. Tobias

INTRODUCTION & EPIDEMIOLOGY

Psychosis has been defined as a "fundamental derangement of the mind characterized by defective or lost

contact with reality."1 The Diagnostic and Statistical Manual of Mental Disorders, Fi�h Edition (DSM-V),2

defines psychotic disorders as those that include abnormalities in one or more of five domains:hallucinations, delusions, disorganized or abnormal motor behavior, disorganized thinking, and negative

symptoms. The hallmark of these psychoses, schizophrenia, has a worldwide prevalence of 0.5% to 1%3 and

a�ects approximately 2.4 million adults in the United States.4 Considered one of the leading causes of

chronic incapacity, the term schizophrenia, meaning "split mind," was coined by Eugene Bleuler in 1911.5

The economic burden of schizophrenia in the United States in 2002 was estimated at $62.7 billion6 andtypically accounts for 1.5% to 3% of the total national healthcare expenditure, with a high incidence of ED

utilization.7

The assessment of the psychotic patient presenting to the ED can be challenging, because patients may beagitated, combative, uncooperative, or unable to provide any history. The goals of evaluation are multiple.First, minimize any potential harm to the patient and ensure the safety of the ED sta� and other patients. Inthe case of an aggressive or violent patient, this may require the use of verbal de-escalation techniques orphysical or chemical restraints. Second, assess for any coexisting or confounding medical or traumaticconditions. Emergency physicians are gatekeepers to the psychiatric world, because once the patient isfunneled into the psychiatric treatment realm, organic conditions may become more di�icult to identify andtreat. Psychiatric conditions contribute to increased mortality from comorbid medical conditions as

compared to the general population.8 Finally, aim to optimize the treatment of the patient's underlyingpsychiatric illness, either by connecting him or her with the appropriate inpatient or outpatient resources, or,when possible, by contacting his or her psychiatrist.

PATHOPHYSIOLOGY

Both environmental and genetic factors contribute to the schizophrenia spectrum of disorders. The

incidence of schizophrenia is higher in those growing up in urban areas9 and in certain minority ethnic

groups,10 and the disorders have been linked to a spectrum of risk alleles. There is also overlap between the

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alleles associated with schizophrenia and those associated with other disorders such as autism and bipolar

disorder.11

Traditionally, the dopamine hypothesis, wherein excessive dopamine leads to the pathophysiology of

schizophrenia, has been the dominant theory.12 Now, it is thought that dopamine acts as the common finalpathway of a wide variety of predisposing factors, either environmental, genetic, or both, that lead to thedisease. Other neurotransmitters, such as glutamate and adenosine, may also collaborate with dopamine to

give rise to the entire picture of schizophrenia.13

CLINICAL FEATURES

HISTORY

Features of psychoses include hallucinations, delusions, disorganized thinking, and negative symptoms.

A hallucination is an "apparent, o�en strong subjective perception of an external object or event when no

such stimulus or situation is present."2 Although hallucinations may occur in any sensory modality, they aremost commonly auditory in schizophrenia and other psychotic disorders. Typically these are experienced asvoices distinct from the individual's own thoughts. Not all hallucinations are considered to be pathologic;they may be a normal part of certain religious and cultural experiences.

A delusion is "a false belief or wrong judgment, sometimes associated with hallucinations, held with

conviction despite evidence to the contrary."14 Delusions may be classified based on various themes,including grandiose (i.e., "when an individual believes that he or she has exceptional abilities, wealth, orfame"), persecutory, erotomanic (i.e., "when an individual believes falsely that another person is in love withhim or her"), and referential (i.e., "belief that certain gestures, comments, environmental cues, and so forthare directed at oneself"). Delusions are considered bizarre if they are clearly implausible. In the ED, a

nonbizarre delusion may be di�icult to distinguish from a strongly held idea.2

Typically, disorganized thinking is inferred from a patient's speech. Commonly encountered patterns mayinclude derailment or loose associations, wherein the individual switches from one topic to another;tangentiality, wherein answers to questions may be unrelated or loosely related; and word salad, wherein

the individual's speech becomes so disorganized that it becomes nearly incomprehensible.2

Negative symptoms associated with psychotic disorders include avolition (decreased motivation),diminished emotional expression, anhedonia (decreased ability to experience pleasure), asociality(decreased interest in social interaction), and alogia (decreased speech).

PHYSICAL EXAMINATION

Aside from grossly disorganized or abnormal motor behavior (discussed below), there are no specificphysical findings associated with the psychotic disorders. The goal of physical examination is the exclusion

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*Psychosis is more commonly seen in benzodiazepine withdrawal; can occur with ethanol intoxication or withdrawal

of coexisting medical or traumatic conditions. For agitated patients, be particularly vigilant to assess for anyself-inflicted injuries, environmental injuries such as frostbite, or injuries occurring during the restraintprocess.

Grossly disorganized or abnormal motor behavior may take on various forms, although it is likely mostfamiliar to emergency practitioners as unpredicTable agitation. Catatonia, a "marked decrease in reactivity tothe environment" is not frequently encountered in the ED. Catatonic features may range from negativism,which is a resistance to instructions, to maintenance of a rigid or inappropriate posture, to complete lack ofmotor or verbal response. Catatonic behavior may occur in association with a variety of psychiatric and

medical conditions.2

DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS

Psychotic symptoms may be caused by numerous medical conditions, including infections such as

encephalitis, meningitis, or cystitis; CNS conditions such as stroke, seizure, Parkinson's disease,15 or braintumor; and metabolic derangements such as hypoglycemia or hepatic encephalopathy. Additionally, various

medications and illicit substances may give rise to psychotic symptoms (Table 290-1).16,17,18,19

TABLE 290-1

Common Medications and Drugs of Abuse Causing Psychosis

Medications Drugs of Abuse

Corticosteroids Ethanol*

Fluoroquinolones Cocaine

Atropine and other anticholinergics Amphetamines and other stimulants (including "bath salts")

Dextromethorphan LSD and other hallucinogens

Benzodiazepines* Marijuana

Phencyclidine (PCP)

MDMA (ecstasy)

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The DSM-V, delineates specific diagnostic criteria for the schizophrenia spectrum and other psychoticdisorders (see discussion below). However, such granular distinctions are typically not necessary or relevantfor emergency assessment and treatment. Rather than making a specific psychiatric diagnosis, the EDprovider's focus should be on emergency treatment and stabilization, identification of comorbid conditions,and appropriate disposition. Assignment of a specific diagnosis should be le� to the purview of those withspecialized psychiatric training. Diagnostic testing is directed by the history and physical examination.Routine laboratory testing for otherwise sTable and cooperative psychiatric patients is of low yield and neednot be performed in most cases. Similarly, urine toxicologic screening rarely a�ects ED management and

need not be routinely obtained.20

Many psychotic patients presenting to the ED have been previously diagnosed with a psychiatric condition.In such cases, determine whether there has been an acute change from the patient's baseline and whetherthe current presentation is confounded by another condition that requires medical treatment. In cases wherethe patient is unable to aid with providing history, use other resources, including past medical records,medication lists, family members, and case workers.

For patients with new-onset psychosis, the ED is a common point of first contact with the healthcare

system.21 It is then incumbent on the provider to determine whether the patient's psychosis is the by-product of an acute medical condition, a reaction to a medication or illicit substance, or truly the new onsetof a primary psychiatric illness. Newly symptomatic patients o�en warrant a more extensive medicalevaluation than those with known underlying psychotic disorders.

DISPOSITION AND FOLLOW-UP

Psychotic patients may present anywhere along a spectrum ranging from high functioning to completelydisabled. Guide disposition decisions by considerations of patient safety and optimization of treatment.Patients thought to be violent, at risk of self-harm, or unable to care for themselves typically requireemergent psychiatric evaluation and possible inpatient psychiatric care. Patients with new-onset psychosis(not thought to be due to a medical cause) or those with worsening of underlying psychotic symptomsshould have psychiatric consultation in the ED, if available, or be transferred to a psychiatric facility. Patientswith known psychoses under apparent good control may be referred for outpatient management. Ideally,such referrals should be made in consultation with the patient's treating psychiatric provider.

Finally, patients with psychosis secondary to a medical condition or those with comorbid illness should bemanaged accordingly. Give special consideration to a patient's functional level and ability to manage themedical condition as an outpatient. For example, a schizophrenic patient with an infection that mightotherwise be treated with oral antibiotics at home might benefit from hospitalization if there is doubt aboutthe patient's ability to comply with treatment and follow-up instructions.

PHARMACOTHERAPY

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Antipsychotic (neuroleptic) medications are typically used in the treatment of schizophrenia and the otherpsychoses. The exact mechanism of action of the antipsychotics is not known. The majority of antipsychoticsblock the D2 dopamine receptors and 5-HT2A serotonin receptors in the brain to a varying degree.

Antipsychotics are classified as either typical or atypical.

The typical antipsychotic medications are o�en categorized as being of low, medium, or high potency. The"potency" of these drugs does not refer to their e�ectiveness, but rather to the dosing of the drug fore�ective clinical response. In general, low-potency medications tend to be more sedating and are more o�enassociated with hypotension, dizziness, and anticholinergic symptoms. High-potency medications aregenerally less sedating, but are more frequently associated with extrapyramidal e�ects such as tremors,rigidity, muscle spasms, and akathisia. Table 290-2 reviews the common typical antipsychotics.

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TABLE 290-2

Typical Antipsychotics

Generic Name Brand Name Relative Potency U.S. Food and Drug Administration Warnings

Phenothiazines      

Chlorpromazine Thorazine Low  

Mesoridazine Serentil Intermediate QTc prolongation

Thioridazine Mellaril Intermediate QTc prolongation

Perphenazine Trilafon Intermediate  

Trifluoperazine Stelazine High  

Fluphenazine Prolixin High  

Thioxanthenes      

Loxapine Loxitane Intermediate  

Thiothixene Navane High  

Dihydroindolones      

Molindone Moban Intermediate  

Butyrophenones      

Haloperidol Haldol High QTc prolongation and torsades de pointes

Droperidol Inapsine High QTc prolongation and torsades de pointes

The U.S. Food and Drug Administration (FDA) has placed black box warnings on a number of the typicalantipsychotics, due to concerns about possible cardiac dysrhythmias associated with their use. In particular,several of these medications have been associated with QTc prolongation and the FDA recommends

evaluation of the QTc interval prior their use. In clinical situations in which rapid tranquilization is necessary,

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a priori determination of the QTc interval is impractical and usually impossible. If ECG data are available from

the ED visit, these should be reviewed for evidence of QTc prolongation. Similarly, if prior ECG data are

available, incorporate them into clinical decision making. Haloperidol remains a popular and e�ective agentfor rapid tranquilization, and despite aggressive marketing claims to the contrary, its e�ectiveness is better

supported by evidence than newer agents such as aripiprazole or ziprasidone.22 Unfortunately, QTc

prolongation does not directly correlate with the clinical risk of dysrhythmias or the development of themalignant arrhythmia torsades de pointes. The black box warnings have led to apprehension in the use ofhighly e�ective medications.

The atypical antipsychotics (Table 290-3) are generally newer medications that more specifically target thedopamine receptors or inhibit the reuptake of serotonin. They also o�er increased e�icacy in the treatmentof the negative symptoms of psychosis. Based on this improved receptor specificity, adverse e�ects such assedation, extrapyramidal e�ects, QTc prolongation, and tardive dyskinesia are generally reduced but are not

completely eliminated. The incidence of hypotension does not appear to have been significantly altered. TheFDA has placed a black box warning on both typical and atypical psychotics for their o�-label use inmanaging agitation and psychosis in elderly patients with dementia. Increased rates of cerebrovascular

accidents, cardiovascular events, and mortality have been associated with chronic use.23,24

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TABLE 290-3

Atypical Antipsychotics

Drug

U.S. Food and Drug

Administration–Approved

Indications

Warnings and Common Side E�ects (BLACK BOX WARNINGS

IN CAPS)

Clozapin

(Clozaril)

Treatment-resistant

schizophrenia

Reduction in the risk of

recurrent suicidal behavior

in schizophrenic or

schizoa�ective disorders

Sedation, dizziness, hypotension, tachycardia, salivation,

weight gain, hyperthermia.

AGRANULOCYTOSIS, SEIZURES, MYOCARDITIS, OTHER

ADVERSE CARDIOVASCULAR AND RESPIRATORY EFFECTS

Olanzapine

(Zyprexa)

Schizophrenia

Bipolar disorder

Agitation associated with

schizophrenia and bipolar I

mania

CVAE, sedation, postural hypotension, hyperglycemia, weight

gain, dizziness

Quetiapine

(Seroquel)

Bipolar mania

Schizophrenia

NMS, hyperglycemia, sedation, hypotension, headache,

weight gain

CATARACT FORMATION

Risperidone

(Risperdal)

Schizophrenia

Bipolar mania

Extrapyramidal e�ects, hyperglycemia, hypotension,

hyperprolactinemia, weight gain

Ziprasidone

(Geodon)

Schizophrenia

Bipolar mania

Acute agitation in

schizophrenic patients

Sedation, rash, dizziness, hypotension, hyperglycemia,

extrapyramidal e�ects

QT PROLONGATION AND RISK OF SUDDEN DEATH

Aripiprazole

(Abilify)

Schizophrenia

Bipolar disorder

NMS, CVAE, hyperglycemia, seizure, hypotension, headache,

akathisia

Asenapine

(Saphris,

Sycrest)

Schizophrenia

Bipolar mania

Blood dyscrasias, cerebrovascular e�ects, dyslipidemia,

extrapyramidal symptoms, NMS, hyperglycemia, QTc

prolongation, orthostatic hypotension, increased mortality

with chronic use in dementia patients

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Abbreviations: CVAE = cerebrovascular adverse event; NMS = neuroleptic malignant syndrome.

Drug

U.S. Food and Drug

Administration–Approved

Indications

Warnings and Common Side E�ects (BLACK BOX WARNINGS

IN CAPS)

Iloperidone

(Fanapt)

Schizophrenia

Paliperidone

(Invega,

Sustenna)

Schizophrenia

Schizoa�ective disorder

ADVERSE EFFECTS

The following side e�ects are more commonly associated with the typical antipsychotics but may also occurwith medications in the atypical class: acute dystonia, akathisia or restlessness, parkinsonism,anticholinergic e�ects, cardiovascular e�ects, and neuroleptic malignant syndrome.

Acute Dystonia

Acute dystonias are probably the most common side e�ect of antipsychotic medications seen in the ED.Muscle spasms of the neck, face, and back are the most common dystonias, but oculogyric crisis and evenlaryngospasm may also occur. Treatment with either benztropine, 1 to 2 milligrams IV, or diphenhydramine,25 to 50 milligrams IV, rapidly corrects the dystonia. For persistent reactions, both medications may be used,and benzodiazepines may be added for treatment failures. Dystonias o�en recur despite dosage reduction ordiscontinuation of the o�ending antipsychotic.

Akathisia (Motor Restlessness)

Akathisia, a sensation of motor restlessness with a subjective desire to move, can begin several days toseveral weeks a�er initiation of antipsychotic treatment. Management can be di�icult. If possible, decreasethe dosage of the antipsychotic a�er psychiatric consultation. The best treatment is probably administrationof β-blockers such as propranolol.

Antiparkinsonian or anticholinergic drugs such as benztropine, 1 milligram PO two to four times daily, mayalso a�ord some relief. In refractory cases, the antipsychotic may need to be changed to an atypical agent.

Antipsychotic-Induced Parkinson's Syndrome

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A complete Parkinson's syndrome, including bradykinesia, resting tremor, cogwheel rigidity, shu�ling gait,masked facies, and drooling, can occur, but o�en only one or two features of the syndrome are obvious.Antipsychotic dosage reduction and/or anticholinergic medication is usually e�ective.

Anticholinergic E�ects

Anticholinergic e�ects range from mild sedation to delirium. Peripheral manifestations may include drymouth and skin, blurred vision, urinary retention, constipation, paralytic ileus, cardiac dysrhythmias, andexacerbation of angle-closure glaucoma. The central anticholinergic syndrome is characterized by dilatedpupils, dysarthria, and an agitated delirium. Treatment is discontinuation of the antipsychotic andsupportive measures.

Cardiovascular E�ects

Cardiovascular side e�ects, such as orthostatic hypotension and tachycardia, are commonly encounteredwith use of the antipsychotics. These e�ects are likely related to anticholinergic and adrenergic blockade andoccur at therapeutic dosages. Typically, hypotension can be easily managed with IV fluids. In severe cases,vasopressor support may be required. Additional e�ects caused by blockade of sodium, calcium, andpotassium channels in the central nervous and cardiac systems are less well delineated. However, e�ects onspecific potassium channels in the myocardium have been linked to the drug-induced prolongation of the

QTc interval associated with several of the antipsychotics.25,26 It is this mechanism of action by which the

antipsychotics are believed to induce torsades de pointes.

Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome is an uncommon idiosyncratic reaction to neuroleptic drugs manifested byrigidity, fever, autonomic instability (tachycardia, diaphoresis, and blood pressure abnormalities), and aconfusional state. Although high-potency antipsychotics may be more likely to cause the disorder, allantipsychotics are potential o�enders. Neuroleptic malignant syndrome is a medical emergency and has amortality rate as high as 20%. Management includes immediate discontinuation of the antipsychoticmedication, hydration, and meticulous supportive treatment in an intensive care setting. Anticholinergicmedications are not helpful and may worsen the condition by further impairing centrally mediatedtemperature regulation. Medications such as dantrolene sodium or bromocriptine are sometimes used torelieve the rigidity.

SCHIZOPHRENIA SPECTRUM OF DISORDERS

The schizophrenia spectrum of disorders is listed in Table 290-4. Some of the more commonly encounteredconditions are discussed in detail below.

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TABLE 290-4

The Schizophrenia Spectrum of Disorders

Schizophrenia

Brief psychotic disorder

Substance/medication-induced psychotic disorder

Schizotypal personality disorder

Unspecified catatonia

Unspecified schizophrenia spectrum and other psychotic disorder

Catatonia associated with another mental disorder

Delusional disorder

Schizoa�ective disorder

Schizophreniform disorder

Psychotic disorder due to another medical condition

Catatonic disorder due to another medical condition

Other specified schizophrenia spectrum and other psychotic disorder

Schizophrenia is the most common form of psychosis. It typically involves a wide range of impairments infunctioning and may a�ect all areas of a patient's life, including occupational and social aspects. It usuallybegins to manifest between the late teens and the mid-30s and is o�en preceded by a prodromal phase. Itscourse is characterized by acute episodes and periods of partial or full remission. There is a male-to-femalerate ratio of 1.4, and the incidence varies significantly based on socioeconomic, racial, and geographic

factors, with a higher incidence among migrants, urban populations, and ethnic minorities.27,28,29 Patients

with schizophrenia have high rates of medical comorbidity and concomitant substance abuse.30,31

Signs of the disturbance must be present for at least 6 months for a formal diagnosis, and symptoms cannotbe attribuTable to another medical condition or the e�ects of a substance. Diagnostic criteria are listed inTable 290-5.

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*Must have two or more criteria and at least one must be delusions or disorganized speech.

TABLE 290-5

Diagnostic Criteria for Schizophrenia2

Criterion A* Other Selected Criteria

Hallucinations Disturbance present for at least 6 months

Disorganized speech Significant deficiencies in major areas of function (work, self-care,

interpersonal relations)

Delusions Depression, bipolar disorder, schizoa�ective disorder ruled out

Negative symptoms Not attributable to another medical condition or substance

Grossly disorganized or catatonic

behavior

 

Schizophreniform disorder di�ers from schizophrenia only in its duration of symptoms (1 to 6 months) and inthe absence of impaired social and occupational functioning as a diagnostic criterion. In contrast, briefpsychotic disorder lasts between 1 day and 1 month and involves the sudden onset of at least one of the

following: delusions, hallucinations, disorganized speech, or grossly disorganized or catatonic behavior.2

Schizotypal (personality) disorder is considered part of the schizophrenia spectrum but is classified as apersonality disorder, and its treatment is generally more similar to that of other personality disorders than tothat of the other psychoses. The disorder is characterized by eccentricities of behavior, a reduced capacity forclose relationships, and a pattern of social and interpersonal deficits.

Delusional disorder is diagnosed in the absence of schizophrenia and involves the presence of one or moredelusions for at least 1 month. Risk factors include low socioeconomic status, family history of psychiatricdisorders, older age, immigration, and exposure to stressful events, with persecutory delusions being the

most common.32 The central theme of the somatic type, and a potential trigger for an ED visit, is apreoccupation with health and organ function. For example, individuals may be convinced that they have an

infestation of insects on their skin or that a part of their body is not functioning.2

Schizoa�ective disorder is about one-third as prevalent as schizophrenia.33 It is characterized by Criterion Aof schizophrenia (see Table 290-5) occurring concurrently with a major mood episode (major depressive ormanic). Furthermore, delusions or hallucinations must be present for at least 2 weeks in the absence of the

mood symptoms. Patients may have problems with self-care, restricted social contact, and poor insight.34,35

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1. 

2. 

3. 

4. 

5. 

6. 

7. 

8. 

Patients with schizophrenia and schizoa�ective disorder have a 5% lifetime risk of suicide, with higher risk in

patients with depressive symptoms.36

Catatonia may occur in the context of various conditions and is categorized as either catatonia associatedwith another mental disorder, catatonic disorder due to another medical condition, or unspecified catatonia.Medical conditions associated with catatonia include encephalitis, head trauma, hepatic encephalopathy,and neoplasms. The acute presentation of catatonia o�en includes stupor, and therefore patients o�en havetheir first clinical contact in the ED. It is therefore important to recognize that catatonia is frequently

associated with an organic cause.37

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