eMedicine Specialties > Emergency Medicine > Psychosocial

Schizophrenia

Paul S Gerstein, MD, Attending Physician, Baystate Mary Lane Hospital Emergency Department

Updated: Aug 18, 2009

Introduction

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, glutamate, and muscarine 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.

Glutamatergic and, most recently, muscarinic systems have been shown in some studies to be related to both positive and negative schizophrenia symptoms. Modulation of these systems is at the forefront of research on schizophrenia medication treatment.

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."¹

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.

Total economic burden of schizophrenia in the United States was estimated at $62.7 billion in 2002.²

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

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.³ 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.
- Phencyclidine (PCP) and ketamine produce a wide range of schizophrenia-like symptoms supporting the hypoglutamatergic hypothesis of schizophrenia. Both drugs are NMDA/glutamate receptor antagonists. Although current antipsychotic medications do not significantly affect the brain's glutamate system, intensive research is ongoing to develop medications that will directly target these receptors.
According to the stress-diathesis model, inherited vulnerability combined with stressful circumstances results in development of overt schizophrenia.

Differential Diagnoses

Delirium, Dementia, and Amnesia	Toxicity, Acetaminophen
Depression and Suicide	Toxicity, Hallucinogen
Encephalitis	Toxicity, Mushroom - Hallucinogens
Neuroleptic Malignant Syndrome	Toxicity, Neuroleptic Agents
Panic Disorders	Toxicity, Phencyclidine
Personality Disorders	Toxicity, Sympathomimetic

Workup

Laboratory 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

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 it is necessary to correctly diagnose and/or safely treat a patient who is severely disturbed.

Emergency clinicians always should examine each patient personally, assessing their suicide risk or threat to others and documenting all reasoning.
The emergency clinician should speak directly with the crisis consultant and read his or her evaluation notes. Then, based on the evaluation and the information that was obtained, the crisis consultant's disposition proposals should be confirmed or modified.
Ultimately, the emergency clinician is medically and legally responsible for the patient until a psychiatrist or other provider assumes the responsibility for care. The ultimate decision-making role must not be abdicated to a 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 presedation assessment.

Medication

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. Some newer agents cause serious weight gain and may raise the risk of insulin resistance and diabetes mellitus. Studies show a slightly 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.

For further information, see the Practice Guideline for the Treatment of Patients with Schizophrenia.⁴

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.

Haloperidol (Haldol)

DOC for patients with acute psychosis when no contraindications exist. Haloperidol and droperidol (below) are of butyrophenone class and are noted for high potency and low potential for causing orthostasis. Downside is the high potential for EPS/dystonia.
Parenteral dosage form may be mixed in same syringe with 2 mg lorazepam for better anxiolytic effects. Added benztropine, 1 mg, reduces EPS risk.

Dosing

Adult

1-5 mg PO initial; some patients require up to 100 mg/d
2-5 mg IM initial; 5-20 mg usually is sufficient
Geriatric or debilitated patients: 0.5-2 mg

Pediatric

<3 years: Not established
3-12 years: 0.05-0.15 mg/kg/d or 0.25-0.5 mg/d PO
>12 years: Administer as in adults
Higher doses may be necessary

Interactions

May increase tricyclic antidepressant serum concentrations and hypotensive action of antihypertensive agents; phenobarbital or carbamazepine may decrease effects of haloperidol; coadministration with anticholinergics may increase intraocular pressure; concurrent administration of lithium and haloperidol is associated with encephalopathylike syndrome

Contraindications

Documented hypersensitivity; narrow-angle glaucoma; bone marrow suppression; severe cardiac or liver disease; severe hypotension; subcortical brain damage

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Severe neurotoxicity manifesting as rigidity or inability to walk or talk may occur in patients with thyrotoxicosis also receiving antipsychotics; if IV/IM, watch for hypotension; caution in CNS depression or cardiac disease; if history of seizures, benefits must outweigh risks; significant increase in body temperature may indicate intolerance to antipsychotics (discontinue if it occurs)

Droperidol (Inapsine)

Some experts believe it is DOC for control of severely disturbed and/or violent behavior. Somewhat faster-acting and more sedating than haloperidol but more likely to cause hypotension.
Can be mixed with 2 mg lorazepam for better anxiolysis. Added benztropine, 1 mg, reduces EPS risk.

Dosing

Adult

0.625-5 mg IV/IM initial; 5 mg is standard dose for chemical restraint and can be doubled in 20-30 min if necessary for severe, resistant agitation

Pediatric

0.03-0.07 mg/kg IV/IM; may need 0.1-0.15 mg/kg initial over 2 min; not to exceed 2.5 mg

Interactions

May increase toxicity of CNS depressants

Contraindications

Documented hypersensitivity; prolonged QT interval

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hypovolemic patients may experience hypotension; may decrease pulmonary arterial pressure; tardive dyskinesia in patients receiving long-term droperidol therapy is 40%; elderly persons may experience high rate of EPS
Black box warning: Rarely, life-threatening arrhythmias may occur (eg, torsade de pointes), especially with high doses (>50 mg); ECG before administration is recommended to rule out prolonged QT interval

Thioridazine (Mellaril)

Medium potency antipsychotic with less EPS but more sedation than haloperidol. Previously first-line drug for treatment of evening psychosis (ie, sundowning) or multiple affective symptoms (eg, agitation, anxiety, depressed mood, tension, sleep disturbance, fears) in elderly and/or demented patients. Now supplanted by risperidone and other atypicals that have fewer anticholinergic adverse effects and are less likely to increase mortality. Not appropriate for rapid neuroleptization of acute psychosis in the ED.

Dosing

Adult

Psychosis: 50-100 mg PO tid initial; 200-800 mg PO divided bid/qid maintenance; not to exceed 800 mg/d
Sundowning, multiple affective symptoms: 25 mg PO tid initial; 25-50 mg PO hs maintenance

Pediatric

0.5-3 mg/kg/d PO

Interactions

Some anticholinergics may reduce effects of medication; thioridazine may increase toxicity of CNS depressants, tricyclic antidepressants, and antihypertensives (eg, propranolol, pindolol); may decrease effects of guanethidine

Contraindications

Documented hypersensitivity; severe depression

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Thermoregulatory changes and stomach upset may occur; orthostasis may lead to falls in elderly patients; caution in narrow-angle glaucoma and severe cardiac or liver disease

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.

Clozapine (Clozaril)

May inhibit serotonin, muscarinic, and dopamine effects. Revolutionized treatment of medication-resistant schizophrenia. Effective in 30% of patients in whom other medications have failed. May improve tardive dyskinesia resulting from long-term use of traditional antipsychotics. Major drawback of reversible agranulocytosis occurs in 1-2% and requires weekly CBC and enrollment in national patient registry.

Dosing

Adult

12.5 mg PO q12-24h initially; gradually increase dose by 25-50 mg/d over 14 d to achieve target dose of 300-450 mg/d by the end of 2 wk

Pediatric

Not established

Interactions

Epinephrine and phenytoin may decrease effects; tricyclic antidepressants, neuroleptics, CNS depressants, guanabenz, and anticholinergics may increase effects

Contraindications

Documented hypersensitivity; WBC <3500 cells/mm³ before or during therapy

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Do not abruptly stop the medication; to minimize risk of agranulocytosis, available only through a distribution system that ensures weekly WBC testing before delivery of next week's supply of medication; upon initiation of therapy, up to a 1-wk supply of additional clozapine tablets may be provided to be held for emergencies (eg, weather, holidays)

Risperidone (Risperdal)

Now considered a DOC for sundowning in elderly patients. Binds to dopamine D2 receptor with 20 times lower affinity than for serotonin 5-HT2 receptor. Improves negative symptoms of psychoses and reduces incidence of EPS. Also may have antidepressant effects, probably because of its serotonin activity.

Dosing

Adult

2-8 mg/d PO
Usual initial dose for schizophrenia: 6 mg/d
Initial dosing for elderly persons with delirium or sundowning: 0.25 mg/d, titrated upwards

Pediatric

Not established

Interactions

Coadministration with carbamazepine may decrease effects; may inhibit effects of levodopa; clozapine may increase risperidone levels

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May cause EPS, orthostatic hypotension, tachycardia, and arrhythmias; increased risk for EPS with doses higher than 10 mg/d

Olanzapine (Zyprexa)

Inhibits serotonergic, muscarinic, and dopaminergic overactivity. Substantial risk for weight gain and initiation of diabetes mellitus.
A rapidly dissolving oral wafer, Zyprexa Zydis, is being successfully used for emergency sedation of patients with acute psychosis.

Dosing

Adult

Usual dose: 10-20 mg/d
Rapid neuroleptization: Zyprexa Zydis, 10-20 mg PO as single dose

Pediatric

Not established

Interactions

Fluvoxamine may increase effects; antihypertensives may increase risk of hypotension and orthostatic hypotension; levodopa, pergolide, bromocriptine, charcoal, carbamazepine, omeprazole, rifampin, and cigarette smoking may decrease effects

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in narrow-angle glaucoma, cardiovascular disease, cerebrovascular disease, prostatic hypertrophy, seizure disorders, hypovolemia, or dehydration

Aripiprazole (Abilify)

Improves positive and negative symptoms of schizophrenia. Mechanism of action unknown but hypothesized to work differently than other antipsychotics. Thought to antagonize serotonin (5HT_2A) and be a partial dopamine (D₂) and serotonin (5HT_1A) agonist. Additionally, no QTc interval prolongation noted in clinical trials. Generally thought to be less effective than other agents but with milder adverse effects including minimal weight gain.

Dosing

Adult

10-15 mg PO qd; may gradually increase dose q2wk prn; not to exceed 30 mg/d

Pediatric

Not established

Interactions

CYP3A4 and CYP2D6 isoenzyme substrate; thus, inhibitors (eg, ketoconazole, quinidine, fluoxetine, paroxetine) or inducers (eg, carbamazepine) may increase or decrease serum levels, respectively

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Common adverse effects include headache, anxiety, somnolence, and insomnia; rare reports of tardive dyskinesia and neuroleptic malignant syndrome; may cause orthostatic hypotension, seizure, dysphagia, or suicidal ideation

Quetiapine (Seroquel)

May act by antagonizing dopamine and serotonin effects.
Newer antipsychotic used for long-term management. Improvements over earlier antipsychotics include fewer anticholinergic effects and less dystonia, parkinsonism, and tardive dyskinesia. Substantial risk for weight gain and initiation of diabetes mellitus.

Dosing

Adult

Start with 25 mg PO bid/tid and increase by 25-50 mg bid/tid on second or third day to achieve range by fourth day of 300-400 mg divided bid/tid; adjust prn at intervals of at least 2 d with adjustments of 25-50 mg bid
Maintenance: 150-750 mg/d PO; not to exceed 800 mg/d

Pediatric

Not established

Interactions

May antagonize levodopa and dopamine agonists; phenytoin, thioridazine, and other liver enzyme inducers may reduce quetiapine levels; CYP3A inhibitors (eg, ketoconazole, fluconazole, erythromycin) increase quetiapine serum concentration

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May induce orthostatic hypotension associated with dizziness, tachycardia, and syncope; neuroleptic malignant syndrome and tardive dyskinesia have been associated with this treatment

Ziprasidone (Geodon)

Antagonizes dopamine D₂, D₃, 5-HT_2A, 5-HT_2C, 5-HT_1A, 5-HT_1D, alpha₁ adrenergic. Has moderate antagonistic effect for histamine H₁. Moderately inhibits reuptake of serotonin and norepinephrine. Like other atypicals, can cause weight gain and diabetes mellitus.

Dosing

Adult

20 mg PO bid initially; may increase gradually (q2-3d) to 80 mg PO bid; not to exceed 160 mg/d
Alternatively, administer 10-20 mg IM for rapid tranquilization (20 mg typical for severe agitation), as required, to maximum 40 mg/d; doses of 10 mg may be administered q2h; doses of 20 mg may be administered q4h to maximum 40 mg/d; IM administration for > 3 d has not been studied; if long-term therapy indicated, replace IM with PO administration as soon as possible

Pediatric

Not established

Interactions

CYP3A4 inhibitors (eg, erythromycin, ketoconazole) may increase serum levels; CYP3A4 inducers (eg, carbamazepine, rifampin) may decrease serum levels; coadministration with drugs that increase QT/QTc interval (eg, amiodarone, fluoroquinolones) increases risk of life-threatening arrhythmias; amphetamines may decrease efficacy; may decrease efficacy of levodopa

Contraindications

Documented hypersensitivity; history of prolonged QT

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Prolongs QT/QTc (caution in patients with known risk factors, eg, hypomagnesemia, hypokalemia); caution in seizure disorders; may cause hypotension, extrapyramidal symptoms, and somnolence

Paliperidone (Invega)

Major active metabolite of risperidone and first oral agent allowing once-daily dosing. Indicated for treatment of acute schizophrenia. Mechanism of action not completely understood but thought to mediate central receptor antagonism of dopamine type 2 (D₂) and serotonin type 2 (5HT_2A). Also elicits antagonist activity at adrenergic alpha1 and alpha2 receptors and histamine-1 receptors. Has no affinity for cholinergic, muscarinic, or beta-adrenergic receptors. Available as extended-release drug delivery system via osmotic pressure.

Dosing

Adult

6 mg PO qd initially; if needed, may increase by 3-mg increments after at least 5 d; not to exceed 12 mg/d; some patients respond to lower doses of 3 mg/d
CrCl >50 to <80 mL/min: Do not exceed daily dose of 6 mg
CrCl 10 to <50 mL/min: Do not exceed daily dose of 3 mg

Pediatric

<18 years: Not established

Interactions

Not substantially metabolized by cytochrome P450 isoenzymes and does not inhibit P-glycoprotein; may increase arrhythmia risk when coadministered with other drugs known to prolong QTc (eg, class IA [quinidine, procainamide] or class III [amiodarone, sotalol] antiarrhythmics, antipsychotics [chlorpromazine, thioridazine], antibiotics [gatifloxacin, moxifloxacin]); coadministration with other CNS depressants, including alcohol, may cause additive effects; coadministration with other drugs causing orthostatic hypotension (eg, alpha-blockers, diuretics) may increase hypotension risk; may antagonize effect of dopamine agonists (eg, levodopa, pramipexole)

Contraindications

Documented hypersensitivity to paliperidone or risperidone

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs have increased risk of CVA and TIA (some resulting in death) compared with placebo; decrease dose with renal impairment; causes modest QTc prolongation (caution with other drugs that prolong QTc, congenital long QT syndrome, or history of cardiac arrhythmias); other adverse effects include tachycardia, neuroleptic malignant syndrome, tardive dyskinesia, hyperglycemia (some with associated ketoacidosis, hyperosmolar coma, or death), orthostatic hypotension and syncope, hyperprolactinemia, sedation, priapism, thrombotic thrombocytopenia purpura, disrupted body temperature regulation, and antiemetic effector dysphagia; avoid with preexisting gastrointestinal narrowing (eg, esophageal motility disorders, small bowel inflammatory disease, short gut syndrome, peritonitis, cystic fibrosis, chronic pseudoobstruction, Meckel diverticulum) because tab is nondeformable and does not appreciably change in shape or size through gut
and is eliminated intact in feces; swallow tab whole (do not chew or split); suicidality is inherent in psychotic illnesses and close supervision of high-risk patients should accompany therapy

Iloperidone (Fanapt)

Atypical antipsychotic agent indicated for acute treatment of schizophrenia. Precise mechanism of action unknown. Antagonizes receptors for dopamine-2 and serotonin type 2 (5-HT2).

Dosing

Adult

1 mg PO bid initially on day 1; to reach target dose of 12-24 mg/d, adjust dose daily by smallest possible increments (ie, 2 mg bid on day 2; 4 mg bid on day 3; 6 mg bid on day 4) to avoid orthostatic hypotension

Pediatric

<18 years: Not established

Interactions

CYP3A4 and CYP2D6 substrate; CYP3A4 inhibitors (eg, ketoconazole) or CYP2D6 inhibitors (eg, fluoxetine, paroxetine) may inhibit elimination and increase blood levels; do not use with other drugs that prolong QT interval (eg, class 1A antiarrhythmics [quinidine, procainamide], class III antiarrhythmics [amiodarone, sotalol], antipsychotics [chlorpromazine, thioridazine], antibiotics [moxifloxacin, erythromycin]); additive CNS effects may occur when coadministered with other centrally acting drugs or alcohol

Contraindications

Documented hypersensitivity; coadministration with other drugs that prolong QT interval

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Boxed warning: Increased risk of TIAs, CVA, and death with off-label use to treat dementia-related psychosis in elderly individuals
Common dose-related adverse effects include dizziness, xerostomia, fatigue, nasal congestion, orthostatic hypotension and syncope, tachycardia, and weight gain; serious adverse effects include QT interval prolongation, neuroleptic malignant syndrome, tardive dyskinesia, hyperglycemia, seizures, leukopenia, neutropenia, agranulocytosis, hyperprolactinemia, disruption of body temperature, and dysphagia; avoid with hepatic impairment

Asenapine (Saphris)

Mechanism of action unknown. Efficacy thought to be mediated through a combination of antagonist activity at dopamine 2 and serotonin (5-HT2) receptors. Exhibits high affinity for serotonin 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT5, 5-HT6, and 5-HT7 receptors; dopamine D2, D3, D4, and D1 receptors; alpha1- and alpha2-adrenergic receptors; and histamine H1 receptors, with moderate affinity for H2 receptors. In vitro assays suggest antagonistic activity elicited at these receptors. Indicated for acute treatment of schizophrenia.

Dosing

Adult

5 mg SL bid; if patient responds favorably, continue beyond initial acute phase (currently no recommendations for duration of therapy)

Pediatric

Not established

Interactions

Metabolized via UGT1A4 and CYP450 (predominantly isoenzyme 1A2); weak inhibitor of CYP2D6; coadministration with other drugs that prolong QTc interval may result in life-threatening arrhythmias (eg, class 1A antiarrhythmics [quinidine, procainamide], class 3 antiarrhythmics [amiodarone, sotalol], antipsychotics [ziprasidone, chlorpromazine, thioridazine], and antibiotics [gatifloxacin, moxifloxacin]); concurrent use of CNS-acting drugs or alcohol may increase toxicity

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Common adverse effects while treating schizophrenia include akathisia, oral hypoesthesia, and dizziness; common adverse effects while treating bipolar disorder include drowsiness, dizziness, and movement disorders other than akathisia; may cause neuroleptic malignant syndrome, tardive dyskinesia, hyperglycemia (monitor patients with diabetes mellitus for worsening of glucose control), and weight gain; may cause hypotension and syncope, especially early in treatment because of its alpha1-antagonistic activity; may cause leukopenia, neutropenia, and agranulocytosis; may prolong QTc interval (avoid with history of cardiac arrhythmias and other conditions that increase risk for torsade de pointes [eg, bradycardia, hypokalemia, hypomagnesemia]); may increase risk of hyperprolactinemia, seizures, cognitive/motor impairment, and dysphagia; may disrupt body temperature regulation; not recommended with severe hepatic impairment (ie, Child-Pugh C); inherent suicide risk with population treated warrants close supervision when changing drug therapy
Boxed warning: Use of antipsychotic drugs to treat elderly patients with dementia-related psychosis has been found to increase risk of death (not approved for dementia-related psychosis)

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).

Lorazepam (Ativan)

Sedative hypnotic with short onset of effects and relatively long half-life. By increasing the action of GABA, a major inhibitory neurotransmitter in the brain, may depress all levels of CNS, including limbic and reticular formation. Benzodiazepine of choice in the ED. Can be given PO, SL (for rapid effect in panic attack), and IV/IM (mixed in the same syringe with the antipsychotic). Has longer CNS effects than diazepam and is preferred over antipsychotics for treatment of psychosis secondary to acute intoxication with hallucinogens, cocaine, PCP, and stimulants. Can be used as adjunctive therapy in nonorganic acute psychosis in which DOC is a high-potency antipsychotic.

Dosing

Adult

0.5-2 mg PO/SL
2-4 mg IM
1-2 mg IV initial; not to exceed 10 mg (more may be needed when tolerance is factor, such as in alcoholism) and >30 mg for short-term treatment of delirium tremens

Pediatric

0.02-0.05 mg/kg PO/IV/IM; not to exceed 4 mg/dose

Interactions

Toxicity of benzodiazepines in CNS increases when used concurrently with alcohol, phenothiazines, barbiturates, and MAOIs

Contraindications

Documented hypersensitivity; preexisting CNS depression; hypotension; narrow-angle glaucoma

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in renal or hepatic impairment, myasthenia gravis, organic brain syndrome, or Parkinson disease

Diazepam (Valium)

Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA.
Individualize dosage and increase cautiously to avoid adverse effects.
2 mg of lorazepam is approximately equal to 5 mg of diazepam.

Dosing

Adult

5-10 mg PO/IM/IV q3-4h, repeat q2-4h prn; not to exceed 30 mg in 8 h

Pediatric

Not established

Interactions

Increases toxicity of benzodiazepines in CNS with coadministration of phenothiazines, barbiturates, alcohols, and MAOIs

Contraindications

Documented hypersensitivity; narrow-angle glaucoma

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution with other CNS depressants, low albumin levels, or hepatic disease (may increase toxicity)

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).

Diphenhydramine (Benadryl)

DOC for initial treatment of acute dystonia or akathisia. (Lorazepam is also effective for akathisia.) IV is best dosing route for treatment of acute EPS.

Dosing

Adult

25-50 mg PO/IV/IM initial; may repeat doses up to 100 mg total; 25-50 PO bid/qid maintenance

Pediatric

1 mg/kg PO/IV/IM

Interactions

Potentiates effect of CNS depressants; because of alcohol content, do not give syrup dosage form to patients taking medications that can cause disulfiramlike reactions

Contraindications

Documented hypersensitivity; MAOIs

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

May exacerbate angle-closure glaucoma, hyperthyroidism, peptic ulcer, and urinary tract obstruction

Benztropine (Cogentin)

By blocking striatal cholinergic receptors, may help balancing cholinergic and dopaminergic activity in striatum. Alternative first-line drug for acute treatment of dystonia and EPS. DOC for long-term prophylaxis of EPS. Often given IM in combination with conventional antipsychotic and lorazepam for acute sedation of psychotic agitation (ie, haloperidol 5 mg, lorazepam 2 mg, benztropine 1 mg—mixed in one syringe: "5-2-1").

Dosing

Adult

1-2 mg IV/IM; repeat prn; 1-4 mg PO qd/bid maintenance

Pediatric

<3 years: Not established
>3 years: 0.02-0.05 mg/kg/dose PO qd/bid

Interactions

Decreases effects of levodopa; increases effects of narcotic analgesics, phenothiazines, quinidine, tricyclic antidepressants, and anticholinergics

Contraindications

Documented hypersensitivity; angle-closure glaucoma; stenosing peptic ulcers; prostatic hypertrophy or bladder neck obstructions; myasthenia gravis; pyloric or duodenal obstruction; achalasia (megaesophagus); megacolon

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May exacerbate hypertension, tachycardia, cardiac arrhythmias, liver or kidney disorders, hypotension, prostatic hypertrophy urinary retention, and obstructive disease of GI/GU tract; toxic psychosis may occur in EPS, resulting from phenothiazine treatment in psychiatric patients

Follow-up

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 more recent 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.⁵
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

Medicolegal 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

Kaplan HI, Sadock BJ, eds. Schizophrenia. In: Comprehensive Textbook of Psychiatry. Williams & Wilkins; 1995:889-997.
Wu EQ, Birnbaum HG, Shi L, Ball DE, Kessler RC, Moulis M, et al. The economic burden of schizophrenia in the United States in 2002. J Clin Psychiatry. Sep 2005;66(9):1122-9. [Medline].
Malaspina D, Harlap S, Fennig S, et al. Advancing paternal age and the risk of schizophrenia. Arch Gen Psychiatry. Apr 2001;58(4):361-7. [Medline].
[Guideline] American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia. 2nd ed. Feb 2004;114.
Zammit S, Allebeck P, Dalman C, et al. Paternal age and risk for schizophrenia. Br J Psychiatry. Nov 2003;183:405-8. [Medline].
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].
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.
Braff DL. Schizophrenic disorders. In: Harrison's Principles of Internal Medicine. 17^th ed. McGraw-Hill; 1996:2414-17.
Carpenter WT Jr, Buchanan RW. Schizophrenia. N Engl J Med. Mar 10 1994;330(10):681-90. [Medline].
Chambers RA, Druss BG. Droperidol: efficacy and side effects in psychiatric emergencies. J Clin Psychiatry. Oct 1999;60(10):664-7. [Medline].
Freedman R. Schizophrenia. N Engl J Med. Oct 30 2003;349(18):1738-49. [Medline].
Gabbard GO, ed. Schizophrenia and other psychotic disorders. In: Treatments of Psychiatric Disorders. 2^nd ed. American Psychiatric Press; 1995:944-1089.
Kane JM. Schizophrenia. N Engl J Med. Jan 4 1996;334(1):34-41. [Medline].
Lagomasino I, Daly R, Stoudemire A. Medical assessment of patients presenting with psychiatric symptoms in the emergency setting. Psychiatr Clin North Am. Dec 1999;22(4):819-50, viii-ix. [Medline].
[Best Evidence] Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. Sep 22 2005;353(12):1209-23. [Medline].
Lucke WC. Thought and affective disorders. In: Emergency Medicine - Concepts and Clinical Practice. Mosby-Year Book; 1992:2073-80.
Marder SR, Ames D, Wirshing WC, Van Putten T. Schizophrenia. Psychiatr Clin North Am. Sep 1993;16(3):567-87. [Medline].
Powchik P, Schulz SC, eds. Schizophrenia. Psychiatr Clin North Am;1993.
Reus VI. Schizophrenia. In: Harrison's Principles of Internal Medicine. 18^th ed. McGraw-Hill; 1998:2499-2501.

Keywords

schizophrenia, schizophrenia symptoms, schizophrenia treatment, hallucinations, schizophrenia drugs, delusions, psychosis, psychotic disorder, psychotic disorders, acute psychiatric emergencies, insanity, madness, dementia praecox, schizophrenic disorder, delusive disorder, thought disorder, chronic psychotic disorder, schizophrenia-related disorders, schizophrenia spectrum disorder

Contributor Information and Disclosures

Author

Paul S Gerstein, MD, Attending Physician, Baystate Mary Lane Hospital Emergency Department
Paul S Gerstein, MD is a member of the following medical societies: American Academy of Emergency Medicine and Massachusetts Medical Society
Disclosure: Nothing to disclose.

Medical Editor

Joseph A Salomone III, MD, EMS Medical Director, Kansas City, Missouri; Associate Professor and Staff Physician, Truman Medical Centers/UMKC School of Medicine
Joseph A Salomone III, MD is a member of the following medical societies: American Academy of Emergency Medicine, National Association of EMS Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Robert Harwood, MD, MPH, FACEP, FAAEM, Program Director, Department of Emergency Medicine, Advocate Christ Medical Center; Assistant Professor, Department of Emergency Medicine, University of Illinois at Chicago College of Medicine
Robert Harwood, MD, MPH, FACEP, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, Council of Emergency Medicine Residency Directors, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Pamela L Dyne, MD, Professor of Clinical Medicine/Emergency Medicine, David Geffen School of Medicine at UCLA; Attending Physician, Department of Emergency Medicine, Olive View-UCLA Medical Center
Pamela L Dyne, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Further Reading

Clinical guidelines

Practice guideline for the treatment of patients with schizophrenia. Second edition. American Psychiatric Association. Arlington (VA): American Psychiatric Association; 2004 Feb. 114 p. [1391 references]