Chapter 290: Psychoses

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, Fifth 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 affects 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 and typically 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 be agitated, 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 staff and other patients. In the case of an aggressive or violent patient, this may require the use of verbal de-escalation techniques or physical or chemical restraints. Second, assess for any coexisting or confounding medical or traumatic conditions. Emergency physicians are gatekeepers to the psychiatric world, because once the patient is funneled into the psychiatric treatment realm, organic conditions may become more difficult to identify and treat. 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 underlying psychiatric illness, either by connecting him or her with the appropriate inpatient or outpatient resources, or, when possible, by contacting his or her psychiatrist.

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 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 final pathway of a wide variety of predisposing factors, either environmental, genetic, or both, that lead to the disease. Other neurotransmitters, such as glutamate and adenosine, may also collaborate with dopamine to give rise to the entire picture of schizophrenia.¹³

HISTORY

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

A hallucination is an "apparent, often 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 are most commonly auditory in schizophrenia and other psychotic disorders. Typically these are experienced as voices 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, or fame"), persecutory, erotomanic (i.e., "when an individual believes falsely that another person is in love with him or her"), and referential (i.e., "belief that certain gestures, comments, environmental cues, and so forth are directed at oneself"). Delusions are considered bizarre if they are clearly implausible. In the ED, a nonbizarre delusion may be difficult to distinguish from a strongly held idea.²

Typically, disorganized thinking is inferred from a patient's speech. Commonly encountered patterns may include 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 specific physical findings associated with the psychotic disorders. The goal of physical examination is the exclusion of coexisting medical or traumatic conditions. For agitated patients, be particularly vigilant to assess for any self-inflicted injuries, environmental injuries such as frostbite, or injuries occurring during the restraint process.

Grossly disorganized or abnormal motor behavior may take on various forms, although it is likely most familiar to emergency practitioners as unpredicTable agitation. Catatonia, a "marked decrease in reactivity to the 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 of motor or verbal response. Catatonic behavior may occur in association with a variety of psychiatric and medical conditions.²

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 brain tumor; 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

The DSM-V, delineates specific diagnostic criteria for the schizophrenia spectrum and other psychotic disorders (see discussion below). However, such granular distinctions are typically not necessary or relevant for emergency assessment and treatment. Rather than making a specific psychiatric diagnosis, the ED provider's focus should be on emergency treatment and stabilization, identification of comorbid conditions, and appropriate disposition. Assignment of a specific diagnosis should be left to the purview of those with specialized 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 need not be performed in most cases. Similarly, urine toxicologic screening rarely affects 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 whether the current presentation is confounded by another condition that requires medical treatment. In cases where the 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 onset of a primary psychiatric illness. Newly symptomatic patients often warrant a more extensive medical evaluation than those with known underlying psychotic disorders.

Psychotic patients may present anywhere along a spectrum ranging from high functioning to completely disabled. 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 require emergent 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 symptoms should have psychiatric consultation in the ED, if available, or be transferred to a psychiatric facility. Patients with 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 be managed accordingly. Give special consideration to a patient's functional level and ability to manage the medical condition as an outpatient. For example, a schizophrenic patient with an infection that might otherwise be treated with oral antibiotics at home might benefit from hospitalization if there is doubt about the patient's ability to comply with treatment and follow-up instructions.

Antipsychotic (neuroleptic) medications are typically used in the treatment of schizophrenia and the other psychoses. The exact mechanism of action of the antipsychotics is not known. The majority of antipsychotics block the D₂ dopamine receptors and 5-HT_2A serotonin receptors in the brain to a varying degree. Antipsychotics are classified as either typical or atypical.

The typical antipsychotic medications are often categorized as being of low, medium, or high potency. The "potency" of these drugs does not refer to their effectiveness, but rather to the dosing of the drug for effective clinical response. In general, low-potency medications tend to be more sedating and are more often associated with hypotension, dizziness, and anticholinergic symptoms. High-potency medications are generally less sedating, but are more frequently associated with extrapyramidal effects such as tremors, rigidity, muscle spasms, and akathisia. Table 290-2 reviews the common typical antipsychotics.

The U.S. Food and Drug Administration (FDA) has placed black box warnings on a number of the typical antipsychotics, due to concerns about possible cardiac dysrhythmias associated with their use. In particular, several of these medications have been associated with QT_c prolongation and the FDA recommends evaluation of the QT_c interval prior their use. In clinical situations in which rapid tranquilization is necessary, a priori determination of the QT_c interval is impractical and usually impossible. If ECG data are available from the ED visit, these should be reviewed for evidence of QT_c prolongation. Similarly, if prior ECG data are available, incorporate them into clinical decision making. Haloperidol remains a popular and effective agent for rapid tranquilization, and despite aggressive marketing claims to the contrary, its effectiveness is better supported by evidence than newer agents such as aripiprazole or ziprasidone.²² Unfortunately, QT_c prolongation does not directly correlate with the clinical risk of dysrhythmias or the development of the malignant arrhythmia torsades de pointes. The black box warnings have led to apprehension in the use of highly effective medications.

The atypical antipsychotics (Table 290-3) are generally newer medications that more specifically target the dopamine receptors or inhibit the reuptake of serotonin. They also offer increased efficacy in the treatment of the negative symptoms of psychosis. Based on this improved receptor specificity, adverse effects such as sedation, extrapyramidal effects, QT_c prolongation, and tardive dyskinesia are generally reduced but are not completely eliminated. The incidence of hypotension does not appear to have been significantly altered. The FDA has placed a black box warning on both typical and atypical psychotics for their off-label use in managing 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

ADVERSE EFFECTS

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

Acute Dystonia

Acute dystonias are probably the most common side effect of antipsychotic medications seen in the ED. Muscle spasms of the neck, face, and back are the most common dystonias, but oculogyric crisis and even laryngospasm 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 often recur despite dosage reduction or discontinuation of the offending antipsychotic.

Akathisia (Motor Restlessness)

Akathisia, a sensation of motor restlessness with a subjective desire to move, can begin several days to several weeks after initiation of antipsychotic treatment. Management can be difficult. If possible, decrease the dosage of the antipsychotic after psychiatric consultation. The best treatment is probably administration of β-blockers such as propranolol.

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

Antipsychotic-Induced Parkinson's Syndrome

A complete Parkinson's syndrome, including bradykinesia, resting tremor, cogwheel rigidity, shuffling gait, masked facies, and drooling, can occur, but often only one or two features of the syndrome are obvious. Antipsychotic dosage reduction and/or anticholinergic medication is usually effective.

Anticholinergic Effects

Anticholinergic effects range from mild sedation to delirium. Peripheral manifestations may include dry mouth and skin, blurred vision, urinary retention, constipation, paralytic ileus, cardiac dysrhythmias, and exacerbation of angle-closure glaucoma. The central anticholinergic syndrome is characterized by dilated pupils, dysarthria, and an agitated delirium. Treatment is discontinuation of the antipsychotic and supportive measures.

Cardiovascular Effects

Cardiovascular side effects, such as orthostatic hypotension and tachycardia, are commonly encountered with use of the antipsychotics. These effects are likely related to anticholinergic and adrenergic blockade and occur at therapeutic dosages. Typically, hypotension can be easily managed with IV fluids. In severe cases, vasopressor support may be required. Additional effects caused by blockade of sodium, calcium, and potassium channels in the central nervous and cardiac systems are less well delineated. However, effects on specific potassium channels in the myocardium have been linked to the drug-induced prolongation of the QT_c 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 by rigidity, fever, autonomic instability (tachycardia, diaphoresis, and blood pressure abnormalities), and a confusional state. Although high-potency antipsychotics may be more likely to cause the disorder, all antipsychotics are potential offenders. Neuroleptic malignant syndrome is a medical emergency and has a mortality rate as high as 20%. Management includes immediate discontinuation of the antipsychotic medication, hydration, and meticulous supportive treatment in an intensive care setting. Anticholinergic medications are not helpful and may worsen the condition by further impairing centrally mediated temperature regulation. Medications such as dantrolene sodium or bromocriptine are sometimes used to relieve the rigidity.

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

Schizophrenia is the most common form of psychosis. It typically involves a wide range of impairments in functioning and may affect all areas of a patient's life, including occupational and social aspects. It usually begins to manifest between the late teens and the mid-30s and is often preceded by a prodromal phase. Its course is characterized by acute episodes and periods of partial or full remission. There is a male-to-female rate 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 cannot be attribuTable to another medical condition or the effects of a substance. Diagnostic criteria are listed in Table 290-5.

Schizophreniform disorder differs from schizophrenia only in its duration of symptoms (1 to 6 months) and in the absence of impaired social and occupational functioning as a diagnostic criterion. In contrast, brief psychotic 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 a personality disorder, and its treatment is generally more similar to that of other personality disorders than to that of the other psychoses. The disorder is characterized by eccentricities of behavior, a reduced capacity for close 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 more delusions for at least 1 month. Risk factors include low socioeconomic status, family history of psychiatric disorders, 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 a preoccupation 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

Schizoaffective disorder is about one-third as prevalent as schizophrenia.³³ It is characterized by Criterion A of schizophrenia (see Table 290-5) occurring concurrently with a major mood episode (major depressive or manic). 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 Patients with schizophrenia and schizoaffective 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 associated with 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 often includes stupor, and therefore patients often have their first clinical contact in the ED. It is therefore important to recognize that catatonia is frequently associated with an organic cause.³⁷