AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Commonly known as insanity or madness, schizophrenia is a chronic psychotic disorder with onset typically occurring in adolescence or young adulthood. Schizophrenia results in fluctuating, gradually deteriorating, or relatively stable disturbances in thinking, behavior, and perception. Severity can range from mild and subtle with very good adaptation to everyday life, to severely disabling requiring constant supervision in a restricted environment. The illness is marked by the presence of "positive" symptoms, such as delusions, hallucinations, and disorganized speech and behavior, and "negative" symptoms, such as poverty of speech, flattened affect, social withdrawal, and avolition.

To satisfy the diagnostic requirements of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), the syndrome must continue for at least 6 months, with at least 1 month of active symptoms present much of the time, and must result in significant impairment of occupational and social functioning.

Other schizophrenia-related disorders may have a less severe, less global, or more transient course but can share strong familial associations with schizophrenia. Certain psychotic disorders such as bipolar disorder in a manic phase and delusive disorder share some of the positive symptoms of schizophrenia but can have distinctly different courses and prognosis. Easily confused with schizophrenia in their acute presentations, time is required to observe for differences between these disorders in order to make a secure diagnosis, unless the patient's past psychiatric history is already known. Autistic disorders, as well, share superficial similarities to schizophrenia and can be easily misdiagnosed in the acute setting.

It is essential in the emergency department not to confuse the thought and behavioral disturbances of organically based acute delirium with any of the psychotic disorders. The avoidance of this confusion is the primary reason for "medical clearance" examinations and drugs-of-abuse screening.

Because of the variability of symptom expression, diagnostic requirements of chronicity, and lack of pathognomonic features, an ED diagnosis of schizophrenia should be provisional at best. As a diagnosis-by-exclusion, schizophrenia must be distinguished from the numerous psychiatric and organic disorders that also can lead to psychotic disturbances in thinking and behavior (see Delirium, Dementia, and Amnesia).

For additional reading, see Schizophrenia.

Pathophysiology

Schizophrenia currently is conceptualized as a broad syndrome expressed by a heterogeneous group of brain disorders rather than as a single disease entity. In addition, schizophrenia is viewed as the most severe end of a spectrum of schizophrenia-related disorders. Although placed in the category of "functional" psychiatric disorders, schizophrenia is associated primarily with abnormalities of brain neurochemistry, neuroanatomy, and development.

Genetics and intrauterine events likely play the major etiologic role in schizophrenia, with psychosocial stressors serving as precipitating or exacerbating factors. This view is a move away from the psychodynamic theories of the mid-twentieth century and a return to some of the earliest conceptions of the disease.

This modern biopsychiatric model has a firm foundation in twin concordance studies and research into the actions of antipsychotic medications on the dopamine systems, and, more recently, serotonin systems in the brain. As a result, antipsychotic medications are now the primary treatment for schizophrenia, with counseling and behavioral therapies playing supportive, but secondary, roles.

The dopamine hypothesis suggests that the hallmark neurochemical disturbance is an overactivity of the dopamine system in the brain, particularly that involving the D2 receptors, which are blocked by all antipsychotic drugs (with the possible exception of the newest atypical antipsychotic drugs). Dopamine overactivity is thought to cause the positive symptoms of the disease. Diminished activity in the prefrontal cortex (ie, hypofrontality) related to serotonin transmission is associated with the negative symptoms. The efficacy of the new atypical antipsychotics in reversing negative symptoms may be owing to their blockage of specific serotonin receptors.

Frequency

United States

The approximate lifetime incidence is 1% or 3 million individuals. In 1990, direct and indirect costs were estimated to be $33 billion, accounting for 2.5% of the healthcare dollar. Patients with schizophrenia occupy as many as 25% of all hospital beds at any given time.

International

A remarkably constant 1% worldwide lifetime incidence exists across all cultural, geographic, and socioeconomic boundaries.

Mortality/Morbidity

Schizophrenia in its full expression is usually a devastating disorder and has a profound impact on family, social, and occupational life. According to Kaplan, "To patients, schizophrenia threatens the loss of what almost everyone takes for granted: selfhood, the ontological sense of being someone and something. Only when that sense is missing is its importance, its survival value, and its function of endorsing people as sentient creatures, appreciated."

To underscore the profound impact of this illness, an editorial in the journal Science described schizophrenia as the worst disease affecting mankind (not excepting AIDS) for the following reasons:

• Lost productivity in the United States costs an estimated $20 billion per year.
• The completed suicide rate is 10%.
• Premature death may result from poor health maintenance, substance abuse, poverty, and homelessness.

Sex

The lifetime risk is equal for both sexes, but onset is earlier and outcome is poorer in males than in females.

• Females have a better response than males to antipsychotic medications.
• Monozygotic twin concordance rates are higher for females than for males.

Age

The peak onset is age 18-25 years for males and age 26-45 years for females.

• Disease onset before puberty is rare.
• Disease onset in persons older than 45 years is uncommon.
• An individual's symptoms may improve gradually when they are middle aged and older. Rarely, full spontaneous recovery occurs after many years of chronic illness.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

The onset is insidious in approximately one half of all patients. The prodromal phase can begin years before the full-blown syndrome and is characterized by losses of functioning in home, society, and occupation (eg, poor school or work performance, deterioration of hygiene and appearance, decreasing emotional connections with others, behaviors that are odd for the individual in the past).

A gradual onset indicates a more severe and prolonged course of illness.

An abrupt onset of hallucinations and delusional, bizarre, or disorganized thinking in patients who previously functioned normally may result in a better intermediate and long-term outcome. Such patients arriving in a psychotic crisis that requires immediate management may not have been diagnosed with psychiatric illness previously. They often present diagnostic dilemmas involving organic versus psychiatric etiology and primary psychotic versus affective disorder diagnosis. Treatment may be complicated further by the presence of alcohol or drug intoxication.

Often, the history obtained in the ED relates to a complication of treatment (medication adverse effects) or crisis arising from socioeconomic factors secondary to schizophrenia (eg, poverty, homelessness, social isolation, failure of support systems).

While the primary diagnosis of schizophrenia rarely is made in the ED, several historical features can be helpful to distinguish the illness from the many medical and psychiatric conditions that can mimic it.

• Two or more of the following must have been present over the prior month for a significant period (unless treated with medication):
• • Delusions - Bizarre or illogical false beliefs, which often have a paranoid, grandiose, persecutory, or religious flavor; false interpretation of normal perceptions
  • Hallucinations - Typically auditory (visual or tactile strongly suggest organic etiology), often involving malevolent or taunting voices commenting on the patient's actions or character, often with sexual flavor; giving commands (ie, command hallucinations); 2 or more voices discussing or arguing with each other; audible thoughts; thought withdrawal (feeling that thoughts are being removed from head), thought broadcasting, or thought interference by outside agent
  • Disorganized speech - Tangential, incoherent, rambling speech; neologisms (new word creation); loosening of associations
  • Behavior - Grossly disorganized or catatonic
  • Negative symptoms - Poverty of speech (ie, alogia), emotional and/or social withdrawal, blunting of affect, avolition
• Loss of a previously held level of occupational, social, or self-care functioning must have occurred since the onset of illness.
• Presence of an affective disorder (eg, major depression, bipolar disorder, schizoaffective disorder) must be excluded; these conditions can be mistaken for schizophrenia and have very different prognoses and therapies. Additionally, an organic etiology (eg, drug intoxication, medical illness) must be ruled out.
• A problem with antipsychotic medications commonly is the chief complaint.
• • Acute dystonia (muscle rigidity and spasm), oculogyric crisis (bizarre and frightening upward gaze paralysis and contortion of facial and neck musculature), akathisia (dysphoric sense of motor restlessness)
  • Parkinsonian symptoms of stiffness, resting tremor, difficulty with gait, and feeling slowed-down
  • Orthostatic hypotension caused by alpha-adrenergic blockade
  • Dry mouth, fatigue, sedation, visual disturbance, inhibited urination, and sexual dysfunction, which can be adverse reactions to antipsychotic medication or to anticholinergic drugs taken for prophylaxis of dystonia
• Obtain the following information when an acutely psychotic patient presents to the ED.
• • Potential danger the patient presents to self or others
    • A paranoid schizophrenic, in response to delusions and command hallucinations, can be extremely dangerous and unpredictable.
    • Find out about threats made to others, expressions of suicidal intent, and possession of weapons at home or on the person.
  • Prior medical and psychiatric records, including past hospitalizations and medication therapy
  • Baseline level of functioning
  • Current or recent substance abuse
  • Current use of prescribed, over-the-counter (OTC), and herbal medications
  • Compliance with current psychiatric medications

Physical

Depending on the reason for ED presentation, the patient with schizophrenia may present wildly agitated, combative, withdrawn, or severely catatonic. Conversely, they may appear rational, cooperative, and well controlled (perhaps only with some blunting of affect). They also could be subtly odd, unkempt, or frankly bizarre in manner, dress, and/or affect.

• Perform a general physical examination on all patients, with attention to vital signs, pupillary findings, hydration status, and mental status.
• A comprehensive physical examination and laboratory evaluation is required when an organic etiology or drug intoxication may be related to mental status changes (see Delirium, Dementia, and Amnesia).
• • Pay particular attention to fever, tachycardia (in association with rigidity, can be a sign of neuroleptic malignant syndrome), heatstroke (antipsychotics inhibit sweating), and other medical illness.
  • Look for signs of dystonia, akathisia, tremor, and muscle rigidity.
  • Tardive dyskinesia is a common and often irreversible sequela of long-term (and sometimes brief) antipsychotic use. It involves uncontrollable tongue thrusting, lip smacking, and facial grimacing.
• Mental status testing should typically reveal clear sensorium and orientation to person, place, and time. Assess attention, language, memory, constructions, and executive functions. Absence of clear sensorium and/or orientation may indicate the presence of acute delirium, a medical condition.

Causes

• The causes of schizophrenia are multifactorial, including genetically inherited brain abnormalities and/or embryonic developmental insult, perhaps in concert with psychosocial stressors.
• • Hallucinogenic or sympathomimetic drug abuse is a frequent precipitating or contributing factor. Marijuana use in teenagers has been statistically associated with a higher risk of chronic psychosis.
  • Psychosocial stressors often interact with the etiology and expression of the disorder.
  • The final common pathway of these various factors is sustained hyperactivity of dopamine neurotransmission in the brain in association with decreased frontal lobe functioning, likely involving serotonin-mediated neurons.
  • "Hypofrontality" (flat affect and other negative symptoms is thought to be secondary to overactivity of specific serotonin subreceptors possibly in concert with dopamine overactivity. Specific serotonin receptors may also be involved with hallucinations and delusions (Note: LSD and other psychotomimetics act upon brain serotonin receptors.). The newer atypical antipsychotic medications, especially clozapine, affect both dopaminergic and serotonergic transmission and improve both positive (dopamine and, possibly, serotonin) and negative (serotonin) symptoms. Older antipsychotic medications (haloperidol and others) do not affect serotonin and fail to improve negative symptoms.
• In a retrospective study of the medical records of 87,907 people born in Jerusalem, Israel, it was found that older men were more likely than younger men to father children who later developed schizophrenia. The study concluded that 26.6% of cases were related to the father's age, whereas the mother's age was unrelated to schizophrenia risk (Malaspina, 2001). Other studies show increased risk of autism as well (father's age 35 years old and older).
• • Men aged 45-49 years were twice as likely as men younger than 25 years to father children who developed schizophrenia.
  • Men older than 50 years were 3 times as likely as men younger than 25 years to father children who developed schizophrenia.
  • These findings support the remarkably persistent 1% incidence of schizophrenia worldwide, in spite of the reduced reproduction rate of individuals with schizophrenia (lowered mating secondary to social deficits resulting from the illness). Apparently, fresh genetic mutations in aging sperm replenish schizophrenia genes in the population, allowing incidence to remain stable.
• Findings from twin concordance, adoption, and family tree studies suggest a strong genetic contribution independent of environmental or child-rearing factors.
• • Monozygotic twins are 65% concordant, and dizygotic twins are 12% concordant.
  • The risk of occurrence is 5-10% in persons who have 1 parent with schizophrenia and 46% or more in persons who have 2 parents with schizophrenia.
  • Among second-degree relatives, the risk of any schizophrenia spectrum disorder is twice that of the general population.
• Other factors supporting the fundamental role of brain abnormalities include the following:
• • Preponderance of winter and early spring births (60%) suggesting that intrauterine insult may be of viral etiology (unproven)
  • High prevalence of ventricular enlargement and other neuroanatomical abnormalities on imaging and postmortem examination
  • Impaired smooth eye-tracking in most patients
• Factors supporting neurochemical theories include the following:
• • Paranoid psychosis resulting from prolonged amphetamine or cocaine abuse is often indistinguishable from schizophrenia. This lends support to the dopamine hypothesis.
  • Lysergic acid diethylamide (LSD) and cannabis, particularly with long-term abuse, may precipitate persistent psychotic states that can be indistinguishable from schizophrenia. Acutely, LSD is a serotonin receptor agonist and can cause hallucinations distinct from schizophrenia—predominantly visual rather than auditory.
• According to the stress-diathesis model, inherited vulnerability combined with stressful circumstances results in development of overt schizophrenia.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• No specific laboratory findings are diagnostic of schizophrenia. However, performing some studies may be necessary to rule out possible organic etiologies for psychosis or to uncover complications of schizophrenia and its treatment (see Delirium, Dementia, and Amnesia).
• • Blood levels of certain psychiatric drugs, specifically lithium and the mood-stabilizing antiseizure medications (eg, valproic acid, carbamazepine), can be used to confirm compliance or rule out toxicity.
  • Serum alcohol levels and drugs-of-abuse screening can be useful when substance abuse is suspected.
  • Interpreting the results of a fingerstick blood glucose determination is a rapid and inexpensive method of ruling out a diabetic emergency masquerading as an exacerbation of a psychotic illness; similarly, measuring oxygen saturation levels can help disclose hypoxia resulting in behavioral or CNS disturbance.
  • Electrolyte measurements may reveal hyponatremia secondary to water intoxication (ie, psychogenic polydipsia). This is common in undertreated or refractory schizophrenia.
  • Laboratory abnormalities observed in neuroleptic malignant syndrome (NMS) may include leukocytosis with left shift and elevated skeletal muscle creatinine kinase (CK) and aldolase levels.

Imaging Studies

• CT, MRI, and positron emission tomography (PET) scanning can disclose abnormalities of brain structure and function in schizophrenia. Although these studies are of interest for research, they have limited clinical relevance.

Other Tests

• Various psychological and neurobiological tests, such as absence of smooth eye-tracking, may be helpful in studying schizophrenia but are not useful in the ED setting.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Prehospital Care

• Safe transport of a patient with acute psychosis may require physical or chemical restraints.
• • Be familiar with restraint and sedation protocols in your emergency medical service (EMS) area and hospital.
  • Know your state's regulations or statutes regarding involuntary transport, treatment, and hospitalization of psychiatric patients.
  • Document your concerns regarding imminent risk to the patient or others resulting from the patient's psychiatric condition.
  • File appropriate application for involuntary transport/treatment when indicated.

Emergency Department Care

Evolving from the efficacy of modern antipsychotic medications and the subsequent widespread budget cutting of psychiatric services over the past 2 decades, deinstitutionalization of patients with schizophrenia has had a major impact on emergency medicine. Patients with schizophrenia now are frequent visitors to the ED, presenting with problems ranging from symptom exacerbation, medication noncompliance, adverse effects to medications, and socioeconomic crises arising from substance abuse, poverty, homelessness, and failed support systems.

Depending on the reason for the patient's ED visit, care may be limited to diagnosis and treatment of an urgent or nonurgent medical complaint; a brief medical evaluation followed by consultation with psychiatric, crisis, or social service personnel; evaluation and treatment of a psychiatric drug adverse reaction; or physical and chemical restraining of a patient with acute psychosis in coordination with a workup, when indicated, to rule out organic etiologies.

• Remember that psychiatric and organic illness can coexist and interact at the same time in the same patient. Furthermore, acute psychiatric symptoms and difficulties obtaining a reliable history from the patient can mask serious organic illness.
• A brief medical clearance examination is limited in usefulness and insufficient to rule out organic etiologies.
• Failure to talk down or intimidate (with a show of force) a severely agitated patient may require physical restraining, followed by chemical restraining (ie, sedation).
• • Proper physical restraints and individuals trained in their application should be available at all times. Document the reason for restraint (eg, patient and/or staff safety), the type of restraint (eg, locked room vs 4-point leather), and the maximum duration of restraint.
  • Any physical restraining of a combative patient can lead to serious injury or death (eg, aspiration, sudden cardiac death, rhabdomyolysis). Therefore, the use of physical restraint should be minimized in favor of chemical restraint (ie, sedation).
• Rapid tranquilization (chemical restraining) may consist of the following:
• • Typically, a combination of lorazepam 2 mg mixed in the same syringe with haloperidol 5 or 10 mg is administered intramuscularly or intravenously. Benztropine (Cogentin), 1 mg, may be added to counteract dystonia ("5-2-1"). Elderly patients typically require lower doses. Repeat doses can be administered in 20-30 minutes as needed to control continued severe agitation. Haloperidol dose can be doubled each time up to 20 mg if prior dosing is inadequate for severe agitation.
  • An alternative to the haloperidol component is droperidol at the same dosages. Droperidol is more sedating, faster, and somewhat shorter acting. The downside is the black box warning about prolonged QT syndrome, which usually only occurs at high doses greater than 25 mg. Cardiac monitoring is recommended, but some experts believe these warnings to be overly cautious.
  • In certain cases, sedation can be administered orally and may consist of lorazepam 2 mg plus haloperidol 2-5 mg or risperidone 2 mg PO. An alternative is Zyprexa Zydis, which is an oral rapid disintegrating tablet, 5-10 mg.
  • If the patient has haloperidol or droperidol sensitivity, ziprasidone 10-20 mg IM can be substituted (20 mg is typical dose). Exercise caution regarding prolonged QT syndrome and multiple drug-drug interactions. Ziprasidone may be somewhat slower in onset than haloperidol and droperidol but has excellent sedating qualities with less propensity for dystonia. A single repeat dose of 20 mg in 4 hours may be necessary (maximum 40 mg/d IM). A 10 mg dosing can be repeated in 2 hours. Reduced pricing now makes ziprasidone an excellent first-line alternative to the older conventional antipsychotics, especially in younger patients who are more likely to develop dystonic reactions.
  • Lorazepam alone is sometimes sufficient for lesser degrees of agitation or anxiety and can be given sublingually for more rapid onset. The recommended dose for anxiety and mild agitation is 1-2 mg PO or SL.

Consultations

Crisis liaison teams, typically made up of clinical social workers, psychologists, and/or psychiatric nurses, are available in many EDs 24 hours a day through the hospital or local psychiatric agencies. Consulting with a psychiatrist by phone or physically in the ED may be more difficult, but this should be done whenever the emergency physician believes it is necessary to correctly diagnose and/or safely treat a patient who is severely disturbed.

• Emergency physicians always should examine each patient personally, assessing their suicide risk or threat to others and documenting all reasoning.
• The emergency physician should speak directly with the crisis consultant and read his or her evaluation notes. Then, the emergency physician should confirm or modify the crisis consultant's disposition proposals based on his or her own evaluation and the information that was obtained.
• Ultimately, the emergency physician is medically and legally responsible for the patient until a psychiatrist or other physician assumes the responsibility for care. The ultimate decision-making role must not be abdicated to a nonphysician consultant.
• Do not delay necessary sedation of a patient with acute psychosis for the diagnostic benefit of psychiatric crisis consultants not yet present in the ED. Treatment delays can lead to injuries, increase morbidity, and worsen prognosis. In these situations, the crisis consultant must rely on the emergency physician's presedation assessment.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Antipsychotic medications (previously referred to as neuroleptics or major tranquilizers) have revolutionized the treatment of and prognosis for schizophrenia. All block dopamine (especially D2) receptors in the brain.

The newer atypical agents also affect serotonin transmission. These newer agents (eg, risperidone, clozapine, olanzapine, quetiapine, ziprasidone, aripiprazole) are less likely to produce dystonia and tardive dyskinesia and more likely to improve negative symptoms. However, they are not more effective than traditional agents (eg, haloperidol, droperidol, fluphenazine), with the possible exception of clozapine in the treatment-resistant patient. A recent study shows a slight increased death rate in elderly patients with dementia using atypical agents. However, the risk was even higher with the older conventional agents.

Benzodiazepines also have a role in schizophrenia, especially in the emergency care of a patient with acute psychosis.

Anticholinergic medications (ie, benztropine, diphenhydramine) are used to counteract the dystonic and parkinsonian adverse effects (extrapyramidal symptoms [EPS]) of the antipsychotics, particularly the higher-potency agents that are less sedating but more EPS-producing.

Drug Category: Antipsychotics, conventional

These drugs are used for short- and long-term treatment of psychosis. The high-potency agents (eg, haloperidol, droperidol) provide rapid, predictable, and effective sedation in the ED treatment of patients with acute psychosis. They are less sedating and more easily titrated but more likely to cause EPS than the lower-potency agents. They often are combined in the same syringe with a benzodiazepine (eg, lorazepam, diazepam) with or without benztropine (Cogentin) for better sedation and anxiolysis, less dystonia, or akathisia; this is administered IM, IV, or, in less immediate settings, PO (haloperidol only). Fluphenazine (Prolixin) is a commonly used depot antipsychotic, which is administered intramuscularly only once per month. Haloperidol also has a monthly depot form (ie, haloperidol decanoate—not to be used acutely or intravenously). Depot antipsychotics are not intended for use in the emergency setting.

Lower-potency agents are more sedating than high-potency agents and less likely to cause dystonia, but they are more likely to cause orthostatic hypotension. Their primary role is for evening sedation in elderly patients with sundowning (disorientation and psychosis at night) or for patients who cannot tolerate the dystonia associated with the high-potency agents. The atypical antipsychotics have largely supplanted lower-potency agents for this use.

Chlorpromazine (Thorazine) was the original groundbreaking antipsychotic. Now, it is rarely used in favor of newer, less-sedating medications.

Drug Category: Antipsychotics, atypical

For acute sedation—IM: ziprasidone (10-20 mg); PO: Zyprexa Zydis, a rapid-dissolving oral wafer. Risperidone, 0.25-3 mg PO, is useful for sedation of elderly persons who are experiencing sundowning (lowest doses), milder psychotic agitation in younger patients, and acute sedation of bipolar mania in cooperative patients. The atypical antipsychotics offer major improvements over the traditional agents, including fewer anticholinergic adverse effects, less dystonia and parkinsonism, lower risk of tardive dyskinesia, and potential reversal of many negative symptoms with long-term use (eg, affective blunting, alogia, withdrawal, avolition). Recent studies show slight increased mortality risk in elderly persons with dementia. However, the older conventional antipsychotics have an even higher mortality risk in this population.

These agents affect both dopamine D2 receptors and serotonin receptors involved with frontal lobe functions. Atypical antipsychotics include clozapine (Clozaril), risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), ziprasidone (Geodon, now available in IM formulation), and aripiprazole (Abilify). Some significant adverse effects have emerged as a result of increasing experience with this class of medications; these include severe weight gain, hyperglycemia, diabetes mellitus, and increased death rate in elderly persons.

Drug Category: Benzodiazepines

These agents are useful as adjunctive agents in the treatment of acute psychosis. They can be given PO or mixed in same syringe with high-potency antipsychotic for rapid tranquilization when given IM or IV. They are also useful in the acute treatment of akathisia (eg, motor restlessness secondary to antipsychotics).

Drug Category: Anticholinergics

These agents are used in the treatment of acute dystonic reactions and in chronic prophylaxis of dystonia, akathisia, and parkinsonian symptoms (EPS) secondary to antipsychotics (especially high-potency agents).

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Transfer

• Psychiatric transfers from the ED to other hospitals are common because of bed shortages and insurance considerations. These transfers should be treated as medical transfers by documenting the patient's stability, reason for transfer, and other factors required to meet the Consolidated Omnibus Budget Reconciliation Act (COBRA) obligations.
• Sedating patients with severe agitation and/or acute psychosis is essential to prevent potential injury to the patient and staff en route.

Deterrence/Prevention

• One of the latest theories on the etiology of schizophrenia holds that the normal "pruning" of brain synapses that occurs in adolescence and young adulthood—a remodeling of brain connections to create a mature, efficient organ of thought—is overly exuberant in patients with schizophrenia. This explains the onset of the illness among individuals in this age range. Stress and genetics, perhaps associated with viral illness during the prenatal period, are thought to be primary causes of the abnormal pruning process. Studies are now underway to evaluate regimens to abort the abnormal pruning and, thereby, prevent or ameliorate schizophrenia in vulnerable individuals, such as those with a family history of the disease who are showing possible early symptoms. Regimens include early administration of the newer atypical antipsychotics, even before definitive symptoms appear, in association with psychotherapy to reduce stress.
• Studies strongly suggest a relationship between increasing paternal age and schizophrenia risk. Schizophrenia risk seems to increase by 30% per 10-year increase in paternal age. This is believed to be due to accumulating germ cell mutations (Zammit, 2003).
• Early and vigorous use of antipsychotic medication during acute psychotic episodes speeds recovery and may lessen the long-term severity of the illness.

Complications

• Hallucinations and delusions can lead to acts of violence.
• Severe impact of disease on the family unit is common.
• The completed suicide rate is 10%.
• Life expectancy is decreased (by approximately 10 y) because of poor self-care, poverty, suicide, and diseases of institutionalization.
• Long-term morbidity may result from antipsychotic medication use (eg, tardive dyskinesia, parkinsonian symptoms) and persistence of negative symptoms in spite of improvement in positive ones.
• In the United Stated, loss of productivity is greater than $30 billion per year.

Prognosis

• Schizophrenia is generally a chronic and disabling illness. However, milder forms of the illness in concert with newer medications and diligent outpatient care can have a good long-term prognosis regarding independent living and social adjustment.
• • Fewer than 20% of patients recover fully from a single psychotic episode. A few patients have little or no recovery from the first episode and chronic pervasive psychotic illness that persists.
  • The most frequent illness pattern is an undulating course of recurrent episodes of acute psychosis with return to a gradually worsening baseline in-between state.
• Often, a plateau in severity occurs after approximately 5 years of worsening functioning (rarely, full spontaneous recovery occurs after many years of illness).
• • Approximately 60% of patients recover sufficiently to lead functional lives, with 50% of them being employed.
  • Approximately 30% of patients remain severely and permanently handicapped.
  • Approximately 10% of patients undergo long-term hospitalization.
• A better prognosis is associated with good premorbid adjustment, marriage, florid symptoms of acute onset, fewer and briefer episodes, supportive home and community environment, continued medication, and the female sex.
• • Rapid and aggressive medication therapy of acute psychotic episodes is correlated with a better overall prognosis.
  • Intensive research by drug companies promises newer antipsychotics with improved efficacy, fewer adverse effects, and better outcome.

Patient Education

• For excellent patient education resources, visit eMedicine's Mental Health and Behavior Center. Also, see eMedicine's patient education article Schizophrenia.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• The most common etiologies for severe mental status changes in the ED are organic, not psychiatric. They include medications, drug intoxication, drug withdrawal syndromes, and general medical illnesses causing delirium.
• • Remember that schizophrenia is a diagnosis by exclusion. Medical illness can cause or complicate a psychotic process.
  • Take a careful medication history; many commonly prescribed medicines can occasionally cause psychotic reactions.
  • Medical clearance examinations are medicolegally risky. These evaluations are typically brief and rarely sufficient to rule out organic etiologies.
• Be familiar with ED and hospital regulations, HIPAA rules, regional statutes, and EMTALA requirements regarding the use of physical restraints, involuntary psychiatric commitment, and transfer.
• • Document reasons for restraining a patient (mention patient/staff safety and protection) and for involuntary commitment; follow all COBRA regulations when transferring patients to another facility for psychiatric care.
  • Do not order "restrain prn." Give specific reasons for applying and removing restraints. Personally ensure that restraints are applied safely. Use the least restrictive measures that are effective. The patient should be monitored continuously while restrained either physically or chemically. Restraint and seclusion orders should be renewed at regular intervals not to exceed 4 hours.
  • In most cases, chemical restraint is preferable to physical restraint when prolonged behavioral control is necessary or when the patient is severely combative. Injury, including rhabdomyolysis or death, can result from intense or prolonged struggle against restraints.

Special Concerns

• Psychosis and schizophrenia are not equivalent, although commonly mistaken as such. Psychosis is a disorder of thinking and perception in which information processing and reality testing are impaired, resulting in an inability to distinguish fantasy from reality (delusions and hallucinations). Schizophrenia is one of several psychiatric disorders for which psychosis is a major feature. Other psychiatric disorders that can be mistaken for schizophrenia include the following:
• • Bipolar disorder in a manic phase
  • Delusional disorders
  • Brief psychotic disorder
  • Schizophreniform illness, schizoid and schizotypal personality disorder
  • Borderline personality disorder
  • Posttraumatic stress disorder (PTSD)
  • Transient drug-induced psychosis, alcoholic hallucinosis, and drug or alcohol withdrawal syndromes
  • Major depression with psychotic features
  • Delirium and dementia

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• APA Task Force. Schizophrenia and other psychotic disorders. In: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). American Psychiatric Association;1994:273-315.
• Andreasen NC, Arndt S, Alliger R, et al. Symptoms of schizophrenia. Methods, meanings, and mechanisms. Arch Gen Psychiatry. May 1995;52(5):341-51. [Medline].
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Article Last Updated: Jan 23, 2007