Emergent Treatment of Schizophrenia

Updated: Nov 26, 2018
  • Author: Melissa Kohn, MD, MS, FACEP, EMT-PHP; Chief Editor: Gil Z Shlamovitz, MD, FACEP  more...
  • Print


Schizophrenia is a severe, chronic psychotic disorder. Classic features may include delusions, hallucinations, disturbed thinking processes, flattening of affect, and abnormal behaviors. Symptoms can be either persistent or episodic, depending on how well the patient is managed. Affecting approximately 23 million person worldwide, schizophrenia is a catastrophically disabling illness with heavy burdens on both its sufferers and society. The effects are felt within the educational and occupational spheres as well as the medical field. 

During 2009–2011, an estimated 382,000 emergency department (ED) visits related to schizophrenia occurred each year among adults aged 18–64 years, with an overall ED visit rate of 20.1 per 10,000 adults. [1]  The trend has continued upwards in the years to follow. [2]  Schizophrenia is more common in men, and the diagnosis is made at a younger age in males. Patients with schizophrenia have a higher risk of death when compared to the general population. Interestingly, deaths are due to typical medical conditions such as cardiovascular, metabolic, and infectious diseases. [3]

It is essential in the ED not to confuse the thought and behavioral disturbances of organically based acute delirium with any of the psychotic disorders. Many medical conditions can cause the acute delirium that be confused with an acute schizophrenic psychotic episode. 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 made cautiously. 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. The diagnosis is best made by a psychiatrist who has throughly evaluated the patient, including historical episodes and corroborating information from family and friends.

Psychosis and schizophrenia are not equivalent, although they are 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). Psychosis is a major feature of schizophrenia, as it is in several other psychiatric disorders. Other psychiatric disorders with psychotic features 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

The most common etiologies for severe acute mental status changes in the ED are organic, not psychiatric. They include medications, drug intoxication, drug withdrawal syndromes, and general medical illnesses causing delirium.

Be sure to take a careful medication history as many commonly prescribed medicines can occasionally cause an acute psychotic reaction.

Medical clearance examinations can be risky from a medicolegal standpoint. In the ED these evaluations are typically brief and rarely sufficient to rule out all organic etiologies.

Go to Schizoaffective Disorder, Childhood-Onset Schizophrenia, and Schizophreniform Disorder for complete information on these topics.


Patient History

The onset of schizophrenia is insidious in approximately one half of all patients. The prodromal phase can begin years before the full-blown syndrome and is characterized by decreasing ability to function based on societal norms of one's home, social interactons, and occupation. Patients will potentially display poor school or work performance, deterioration of hygiene and appearance, decreasing emotional connections with others, and/or behaviors that would have been atypical or strange 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. Patients arriving in an acute psychotic crisis that requires immediate management may not have been previously diagnosed with a psychiatric illness. These patients 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 acute or chronic alcohol or drug use.

Often, the visit to the ED relates to a complication of treatment (medication adverse effects, noncompliance), a crisis arising from socioeconomic factors secondary to schizophrenia (poverty, homelessness, social isolation, failure of support systems), or intoxication from substance abuse (drugs or alcohol).

While the primary diagnosis of schizophrenia rarely is made de novo in the ED, several historical features can be helpful in distinguishing the illness from the many medical and psychiatric conditions that can mimic it. Typically, the first episode will present in the patient's early 20's.

Two or more of the following must have been present over the prior month for a significant period (less than a month if treated with medication). Only one is required if the patient has a delusion of a voice providing a running commentary or two voices conversing. [4]

  • Delusions — Bizarre or illogical false beliefs, which often have a paranoid, grandiose, persecutory, or religious flavor; beliefs that are held strong even when presented with evidence of the contrary; false interpretation of normal perceptions 

  • Hallucinations — Typically auditory (visual or tactile strongly suggest an organic etiology), often involving malevolent or taunting voices commenting on the patient's actions or character, often with sexual overtones; voices that give commands (ie, command hallucinations); 2 or more voices discussing or arguing with each other; audible thoughts; thought withdrawal (feeling that thoughts are being extracted from head), thought broadcasting, or thought interference by an outside agent

  • Disorganized speech —Tangential, incoherent, rambling speech; flight of ideas or derailments; neologisms (new word creation); loosening of associations

  • Behavior — Grossly disorganized or catatonic; wandering without a purpose; talking or laughing to one's self; self-neglect, especially with respect to hygiene

  • 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. They may be present, but only for a brief period of time and are not the majority of symptoms. Additionally, an organic etiology (eg, drug intoxication, medical illness, or medication side effect) must be ruled out.

Obtain the following information when an acutely psychotic patient presents to the ED:

  • The potential danger the patient presents to him/herself or to others

  • 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

Patients with schizophrenia may also present with complaints of the side effects of antipsychotic medications: [5]

  • 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

Find out about threats made to others, expressions of suicidal intent, and possession of weapons at home or on the person. A paranoid schizophrenic, in response to delusions and command hallucinations, can be extremely dangerous and unpredictable.


Physical Examination

Depending on the reason for ED presentation, the patient with schizophrenia may present with wildly agitated, combative, withdrawn, or severely catatonic behavior. Conversely, the patient may appear rational, cooperative, and well controlled (perhaps with only some blunting of affect). The person 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, medication reaction, or drug intoxication may be the source of the mental status changes.

Pay particular attention to fever, tachycardia (which, in association with rigidity, can be a sign of neuroleptic malignant syndrome), heatstroke (antipsychotics inhibit sweating), and other medical illness.

Look for signs of medication side effects: 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.


Differential Diagnosis

Conditions to consider in the differential diagnosis of schizophrenia include the following: [6]

  • Delirium, dementia, and amnesia

  • Severe depressive episode with psychotic features

  • Neuroleptic malignant syndrome

  • Personality disorders

  • Bipolar affective disorder

  • Post-traumatic stress disorder

  • Acetaminophen toxicity

  • Hallucinogen toxicity

  • Hallucinogenic mushroom toxicity

  • Neuroleptic agent toxicity

  • Phencyclidine toxicity

  • Sympathomimetic toxicity


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.

Blood levels of certain psychiatric drugs, such as lithium and antiseizure medications used as mood-stabilizers (eg, valproic acid, carbamazepine), can be used to confirm compliance or rule out toxicity.

Serum alcohol levels and drugs-of-abuse screening (blood and/or urine) 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 to disclose hypoxia resulting in behavioral or central nervous system (CNS) disturbance.

Electrolyte measurements may reveal various abnormalities that can cause altered mental status. Additionally, it would evaluate for hyponatremia secondary to water intoxication (ie, psychogenic polydipsia). This is common in undertreated or refractory schizophrenia.

Laboratory abnormalities observed in neuroleptic malignant syndrome may include leukocytosis with left shift and elevated skeletal muscle creatinine kinase (CK) and aldolase levels. Some antipsychotics may also cause leukopenia with long-term use. 

Thyroid function testing may reveal an acute thyrotoxic event causing altered mental status or psychosis.

Urine pregancy test for female patients as some medications are not indicated during pregnancy.


Other Studies

Computed tomography (CT) scanning, magnetic resonance imaging (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. Various psychological and neurobiologic tests, such as absence of smooth eye-tracking, may be helpful in studying schizophrenia but are not useful in the ED setting. A CT scan can be helpful to evaluate after a trauma and for masses, lesions, or areas of ischemia that may present as acute psychosis. Electrocardiograph prior to the use of antipsychotics is helpful as some can cause QT prolongation.


Prehospital Care

Primary concern should be to the providers' and the patient's safety. [7]

Safe transport of a patient with acute psychosis may require physical or chemical restraints. Be familiar with restraint and sedation protocols in your local emergency medical service (EMS) area and hospitals.

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.

Assess the patient as best as possible with regard to the provider's safety.

File appropriate application for involuntary transport/treatment when indicated. Consent for treatment is often difficult with these pateints in acute psychosis or acute intoxication.


Emergency Department Care

The deinstitutionalization of patients with schizophrenia has had a major impact on emergency medicine. This process developed from the efficacy of modern antipsychotic medications but also the subsequent widespread budget cutting of psychiatric services over the past 2 decades, Patients with schizophrenia are frequently seen in the emergency department. These patients present with problems ranging from exacerbation of symptoms to medication noncompliance, adverse effects to medications, or a socioeconomic crisis that arises from either substance abuse, poverty, homelessness, or a failed support system.

Patients with schizophrenia may require care that is limited to diagnosis and treatment of an urgent or nonurgent medical complaint. Other visits are a brief medical evaluation followed by consultation with psychiatric, crisis, or social service personnel. Many visits are for evaluation and treatment of an adverse reaction to a psychiatric drug. The more concerning visit is the one requiring physical and chemical restraint of a patient with acute psychosis in coordination with a workup to rule out organic etiologies.

Remember that psychiatric and organic illness can coexist at the same time in the same patient. An acute medical diagnosis may be clouding the diagnosis or excerbating underlying psychiatric symptoms. Furthermore, acute psychiatric symptoms may create difficulty in obtaining a reliable history from the patient and can mask serious organic illness. A brief medical clearance examination is limited in its usefulness and is insufficient to rule out organic etiologies.

Use of restraints and involuntary commitment

Failure to talk down or intimidate with a show of force a severely agitated patient may require physical restraint of the patient, followed by chemical restraint with sedation.

Proper physical restraints and individuals trained in their application should be available at all times. [8] Documentation should include reasons for restraining a patient such as patient/staff safety and protection, the type of restraint used (eg, locked room vs 4-point leather), the maximum duration of restraint, and reasons for involuntary commitment. [9]

Follow all Consolidated Omnibus Budget Reconciliation Act (COBRA) regulations when transferring patients to another facility for psychiatric care. Be familiar with hospital and ED specific regulations, Health Insurance Portability and Accountability Act (HIPAA) rules, regional statutes, and Emergency Medical Treatment and Labor Act (EMTALA) requirements regarding the use of medical screening exams, physical restraints, involuntary psychiatric commitment, and facility transfer. [10]

Restraints should not be ordered as a prn or "as needed" order. Specific reasons for applying and removing restraints should be included in the order. Personally ensure that restraints are applied safely. Use the least restrictive measures that are effective for that specific patient. The patient should be monitored continuously while restrained whether it is physically or chemically. [8] Restraint and seclusion orders should be renewed at regular intervals and should not exceed 4 hours. In most cases, chemical restraint (ie, sedation) is preferable to physical restraint when prolonged behavioral control is necessary or when the patient is severely combative. Any physical restraint of a combative patient can lead to serious injury or death (eg, from aspiration, sudden cardiac death, rhabdomyolysis). [8]


Rapid tranquilization or chemical restraint may be carried out using some of the examples shown here.

A commonly used combination of lorazepam (Ativan) 2 mg mixed in the same syringe with haloperidol (Haldol) 5 or 10 mg is administered intramuscularly or intravenously. Benztropine (Cogentin) 1 mg of diphenhydramine (Benadryl) 25 or 50 mg may be added to counteract dystonia. Elderly patients typically require lower doses. Repeat doses can be administered every 20–30 minutes as needed to control continued severe agitation. The 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 (Inapsine) at the same dosages. Droperidol is more sedating, faster in onset, and somewhat shorter acting. The downside is the black-box warning about prolonged QT syndrome, which rarely occurs at higher doses than those typically utilized for acute behavioral control. Cardiac monitoring is recommended, but some experts believe these warnings to be overly cautious. [11] Following the black-box warning, most physicians continuing to utilize droperidol for acute behavioral control reserve it for special situations requiring somewhat faster onset and greater sedation than would be achieved with similar doses of haloperidol. Droperidol, therefore, may be considered useful, yet second-line to haloperidol in the emergency department. Halperidol may also cause prolongation of the QT interval, but not at the rates seen using droperidol.

In cases where the patient is agitated but more redirectable, sedation can be administered orally. The medications are similiar and may consist of lorazepam 2 mg plus haloperidol 2–5 mg or risperidone 2 mg PO (by mouth). An alternative is olanzapine (Zyprexa), which is an oral, rapidly disintegrating tablet, 5–10 mg. If a patient is noncompliant with his/her medication, you might be able to give them their regularly prescribed doses of antipsychotics. 

If the patient has haloperidol or droperidol sensitivity, ziprasidone 10–20 mg (administered intramuscularly) can be substituted (20 mg is the 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. [12]

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 administered orally or sublingually.

Consider giving the medicaions by intranasal administration. The lack of a needle may be safer for the provider but also requires more close contact. Not all medications may be given via intranasal methods, but there are many medications that would be helpful for the acutely psychotic patient. Midzaolam (Versed) and lorazepam (Ativan) may be given via the intranasal route. Most medications require higher doses when given intranasally instead of intramuscularly. [13]


Antipsychotic medications have revolutionized the treatment of and prognosis for schizophrenia. All these medications block dopamine (especially D2) receptors in the brain.

The newer, atypical agents also affect serotonin transmission. These newer agents include risperidone (Risperdal), clozapine (Clozaril), olanzapine (Zyprexa), quetiapine (Seroquel), ziprasidone (Geodon), and aripiprazole (Abilify). The medications are less likely to produce dystonia and tardive dyskinesia and are more likely to improve negative symptoms. However, these medications are not more effective than traditional agents (eg, haloperidol, droperidol, fluphenazine) in the treatment-resistant patient. The possible exception would be clozapine, which may be more effective but comes with the risk of agranulocytosis. [14]  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.

A retrospective analysis found that in relapsed schizophrenia patients, atypical long-acting injectable antipsychotics (LATs) were associated with lower rehospitalization rates than oral APs. [15]  Unfortunately, the 2-year rate of ED visits did not improve. The LAT medications included were risperidone (Risperdal) and paliperidone (Invega). Some patients also received oral medication in additiont to the LATs. [16]

Benzodiazepines also have a role in schizophrenia, especially in the emergency care of a patient with acute psychosis. Long-term use can develop dependence and put the patient at risk if they are noncompliant.

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. [17]



When available, consult with a psychiatrist when assistance is needed with proper diagnosis and/or management of acute symptoms or severe behavioral disturbances. Ideally there is a psychiatrist who can immediately and personally evaluate the patient in the ED. [18]

Crisis liaison teams, typically made up of clinical social workers, psychologists, and/or psychiatric nurses, are available in many EDs 24 hours a day either through the hospital or local psychiatric agencies. Their primary role is assessment for appropriateness of psychiatric hospitalization and to determine availability of inpatient beds in compliance with the patient's insurance coverage. Such clinicians can also assist in arranging prompt outpatient follow-up when hospitalization is not necessary.

Emergency clinicians always should examine each patient personally, assessing their suicide risk or threat to others, and documenting all reasoning. A medical clearance evaluation must be performed in order to rule out organic illness that may be causing psychiatric symptoms or will preclude admission to a psychiatric bed.

The emergency clinician should speak directly with the crisis consultant and read the notes following his/her evaluation. Then, based on the evaluation and the information obtained, the crisis consultant's disposition proposals should be confirmed or modified. The final decision as to patient disposition should always be confirmed by the emergency physician. Disposition decision-making should never be revoked or overruled by a crisis liaison worker. Ultimately, the emergency clinician is medically and legally responsible for the patient and his or her disposition until a psychiatrist or other provider assumes the primary responsibility for care.

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 and can increase morbidity and worsen prognosis. In these situations, the crisis consultant must rely on the presedation assessment.



Psychiatric transfers from the ED to other hospitals are common because of bed shortages, facility resources, and insurance considerations. These transfers should be treated as medical transfers by documenting the patient's stability, the reason for transfer, and other factors required to meet COBRA obligations.

Patient destination should be determined by the emergency physician in conjunction with the consulting resources available, such as a psychiatrist or a crisis liasion worker. The destination facility should also be appropriate for the patient's diagnosis, substance abuse history, or medical co-morbidities.

Transport should be coordinated with local agencies in order to ensure a safe transport. Making the agency aware of the patient's diagnosis and treatment provided is essential for a good handoff. Sedating patients with severe agitation and/or acute psychosis is essential to prevent potential injury to the patient and staff en route.