Schizophrenia

Highlights

What is Schizophrenia?

Schizophrenia is a long-term (chronic) psychiatric disorder that severely affects a person's thinking, mood, and behavior. It is a leading cause of disability and a major risk factor for alcohol and substance abuse as well as suicide.

Causes of Schizophrenia

The causes of schizophrenia are not known. Multiple factors such as genetics and brain chemistry may play a role.

Complications of Schizophrenia

Schizophrenia can have a devastating impact on people and their families. People with schizophrenia have increased risk for self-destructive behaviors and suicide. The antipsychotic drugs used to treat schizophrenia can have severe side effects, including increased risk of obesity and diabetes.

Medications

Schizophrenia is a chronic condition, which is usually treated with antipsychotic medication. There are two main classes of these drugs:

Introduction

Schizophrenia is a long-term (chronic) severe brain disorder that interferes with thinking and mental or emotional responsiveness. The term schizophrenia, which means "split mind," was first used in 1911 by Swiss psychiatrist Eugen Bleuler to categorize people whose thought processes and emotional responses seemed disconnected. Despite its name, the condition does not cause a split personality.

Schizophrenia affects people's ability to:

Schizophrenia is a lifelong condition that poses significant challenges to both people and their families. The severity and prognosis of the disease vary from person to person. With medication, therapy, and support services, many people are able to control their symptoms, prevent relapses, and cope well with their condition.

Schizophrenia

Schizophrenia is one condition in a group of psychotic disorders characterized by disturbances in perception, behavior, and communication.

Symptoms

Schizophrenia is part of a spectrum of psychotic disorders. Psychosis is the medical term for a loss of contact with reality.

The American Psychiatric Association assigns the following 5 features to psychotic disorders:

Psychiatrists often group the first four of these symptoms as positive symptoms to distinguish them from negative symptoms. Positive symptoms include the psychotic symptoms that are most often associated with schizophrenia.

Cognitive symptoms, which are associated with thinking processes, are also associated with schizophrenia. They include:

The American Psychiatric Association used to previously categorize subtypes of schizophrenia (such as paranoid and catatonic). The APA has eliminated these subtypes because they had not proven to be helpful or reliable for diagnosis or treatment decisions.

The signs and symptoms of schizophrenia can start abruptly or emerge subtly. For many people, schizophrenia initially develops slowly and gradually, and is often accompanied by symptoms of depression. As people with schizophrenia age, their psychotic symptoms often diminish over time.

Causes

The causes of schizophrenia are not yet understood. Scientists think that schizophrenia may develop from a combination of brain chemistry and genetic and environmental factors.

Brain Chemistry and Structure

Brain Chemistry

Schizophrenia is associated with an unusual imbalance of neurotransmitters (chemicals that act as messengers between nerve cells). In particular, brain chemicals such as dopamine and glutamine may be involved.

Brain Structure

Magnetic resonance imaging (MRI) scans of the brains of people with schizophrenia have revealed structural abnormalities. Such problems may cause nerve damage and disconnections in the pathways that carry brain chemicals.

Genetic Factors

Schizophrenia undoubtedly has a genetic component. The risk for inheriting schizophrenia ranges from about 10% for those who have one first-degree family member (mother, father, sister, or brother) with the disease to about 40% to 65% if the disease affects both parents or an identical twin.

However, heredity does not explain all cases of schizophrenia. About 60% of people with schizophrenia have no close relatives with the illness.

Researchers are seeking the specific genetic factors that may be responsible for schizophrenia. Genes under investigation include the neuregulin-1 gene, the OLIG2 gene, and the COMT gene. Researchers are also investigating how schizophrenia may be linked to abnormalities in genetic regions on specific chromosomes. There is increasing evidence that schizophrenia may share genetic pathways with other psychotic and psychiatric disorders, such as bipolar disorder and major depression.

Risk Factors

Schizophrenia is the most common psychotic condition, affecting about 1% of people worldwide.

Age

Schizophrenia can occur at any age. But it tends to first develop (or at least become evident) between adolescence and young adulthood, typically between the late teens and mid-30s. It rarely occurs before adolescence or after age 45.

Gender

Schizophrenia affects both men and women. Men are more likely than women to develop schizophrenia at an earlier age and to experience more severe symptoms. For men, the age of peak onset is in the early-to-mid 20s. Women are most likely to develop schizophrenia when they are in their late 20s.

Family History

Schizophrenia often runs in families.

Environmental Factors

Various environmental factors may play a role in the development of schizophrenia, such as for people who already have a genetic predisposition. Environmental factors possibly associated with schizophrenia include:

Complications

Schizophrenia can have a devastating effect on both people and their families.

Self-Destructive Behaviors

Substance Abuse

Many people with schizophrenia abuse alcohol and drugs. Substance abuse, in addition to its other adverse effects, increases the likelihood that a person will not take medication and will have more severe symptoms. Although people with schizophrenia are not usually violent (except possibly those who have severe paranoia), substance abuse in people with schizophrenia increases the risk for violence.

Nicotine dependence is the most common form of substance abuse among people with schizophrenia. Most people with schizophrenia smoke. Biologic and genetic factors associated with schizophrenia may play a role. For some people, smoking can be a form of self-medication that may help control symptoms.

Suicide

People with schizophrenia have an increased risk for suicide and suicidal behavior. Clinical depression is common among people with schizophrenia. The stresses of dealing with social isolation, discrimination, and stigma can also be factors.

Medical Illnesses

People with untreated schizophrenia are more likely to suffer from poverty, homelessness, and incarceration. If people do not take their medication and symptoms recur, they can have difficulty caring for themselves and be at risk for developing other medical illnesses.

People with schizophrenia often do not seek routine medical care and health screenings and have an increased risk for dying from heart disease and cancer. Smoking, drinking, and other forms of substance abuse can also lead to medical problems (such as heart disease, cirrhosis, and malnutrition). In addition, the antipsychotic medications used to treat schizophrenia can cause weight gain, metabolic disorders, and heart problems.

Diabetes is a particular concern for all people with schizophrenia, and especially for children, adolescents, and young adults. In addition to a possible link to schizophrenia itself, many antipsychotic medications can raise blood sugar levels. People taking atypical antipsychotics drugs -- such as clozapine, olanzapine, risperidone, aripiprazole, quetiapine fumarate, and ziprasidone -- should receive a baseline blood sugar level reading and be monitored for any increases in blood sugar levels. [See "Diabetes Risk and Atypical Antipsychotics" in Medications section.]

Effect on Family Members

A strong social support system is very important for people with schizophrenia. In addition to medical professionals and community resources, family members play a vital role in monitoring a person's mental status and helping the person receive and maintain treatment.

Schizophrenia produces enormous family stress. In addition to dealing with bewildering and frightening symptoms and personality changes, families often need to confront difficult bureaucratic obstacles in finding appropriate care for their loved ones. Support groups can help families realize they are not alone, and provide recommendations for resources and advocacy.

Diagnosis

There are no imaging or lab tests for diagnosing schizophrenia. A psychiatrist will make a diagnosis of schizophrenia based on a person's symptoms and how long they have lasted. The diagnosis uses specific criteria defined by the American Psychiatric Association.

Diagnostic Criteria

Psychiatrists use the following five symptoms as the basic diagnostic criteria for schizophrenia:

A diagnosis of schizophrenia is made when:

Ruling Out Other Conditions

The common hallmarks of schizophrenia are also symptoms that can occur in dozens of other psychological and medical conditions, as well as with certain medications. Shared symptoms include delusions, hallucinations, disorganized and incoherent speech, a flat tone of voice, and bizarrely disorganized or catatonic behavior (such as lack of speech, muscular rigidity, and unresponsiveness).

Conditions that may resemble schizophrenia include:

Treatment

Medication is the primary treatment for schizophrenia, but therapies that address psychological and functioning needs are also important components.

Treatment for schizophrenia often uses an integrated approach with a multidisciplinary health care team that may include a psychiatrist, psychotherapist, social worker, and substance abuse counselor. An integrated approach may include:

Research suggests that the earlier schizophrenia is diagnosed and treated, the better the outcome. There is strong evidence for the beneficial effects of early drug treatment in helping to control symptoms and avoid rehospitalization.

Antipsychotic Medications

Antipsychotic medications used for treating schizophrenia are generally categorized as either "typical antipsychotics" or "atypical antipsychotics." These drugs work in part by blocking receptors of the neurotransmitter (brain chemical) dopamine. Dopamine is thought to play a major role in psychotic symptoms.

Typical antipsychotics are the older medications, which were first developed in the 1950s. Atypical antipsychotics are newer medications that first became available in the 1990s; newer ones are still being developed. Typical antipsychotics are sometimes referred to as "first-generation" to distinguish them from the newer "second-generation" atypical antipsychotics. They include:

Side Effects

Although these drugs have important benefits, they can also cause many side effects. Among the most disturbing side effects are those known as extrapyramidal symptoms, which involve the nerves and muscles controlling movement and coordination.

Tremors, muscle stiffness, and restlessness are the most common extrapyramidal symptom associated with antipsychotic medications. Less common is tardive dyskinesia which causes involuntary muscle movements that can be severe and even permanent. Movement disorders are more frequent with typical antipsychotics but they can also occur with atypical antipsychotics.

Other serious side effects associated more with atypical antipsychotics are weight gain and metabolic changes, which can increase the risk for developing diabetes, high cholesterol levels, and heart problems.

There are many other antipsychotic side effects that people (and parents) need to be aware of, especially for children and adolescents. Specific concerns for pediatric people in addition to weight gain and diabetes include increased prolactin levels, which can result in milk secretion from breasts (galactorrhea) and development of male breasts (gynecomastia). Not all antipsychotic medications are approved for children and adolescents.

Which Type of Drug to Choose

Doctors have debated whether newer atypical antipsychotics carry a treatment advantage over the older typical antipsychotics, which are much less expensive.

Large, high-quality studies that have compared newer and older drugs have generally found that newer atypical antipsychotics are not any more effective than older typical antipsychotics for controlling symptoms of psychosis such as hallucinations, delusions, and agitation.

Side effect profiles between typical and atypical antipsychotics are different. Both drug classes can cause movement disorders such as tardive dyskinesia, but the newer atypical second-generation drugs do not seem to cause them as often as the older typical first-generation drugs. However, the atypical antipsychotics pose a higher risk for weight gain and metabolic problems, which can lead to diabetes as well as heart disease. As mentioned above, there are additional concerns when treating children and adolescents.

APA's "Choosing Wisely" Antipsychotics

In 2015, the American Psychiatric Association (APA) updated their "Choosing Wisely" recommendations for doctors and people regarding antipsychotics medications. In addition to warning against prescribing antipsychotics for non-psychotic disorders (such as dementia or insomnia), the APA advises:

Treating an Acute or Initial Phase

For the severe, active phase of schizophrenia, people are often hospitalized. Injections of an antipsychotic drug are usually given every few hours until the person is calm. Anti-anxiety drugs may also be administered at the same time. In people who are being treated for the first time, improvement in psychotic symptoms usually becomes evident within the first few weeks of treatment, although the full benefit of the drug usually manifests over several more weeks and months.

Maintenance Treatment

Once a person has recovered from a psychotic episode, the psychiatrist will adjust the medication to continue to keep symptoms under control. This is referred to as maintenance treatment.

Most people with schizophrenia need to continue to take medication on a lifelong basis. People who stop medication usually experience relapse of psychotic symptoms and often require rehospitalization.

The choice of an antipsychotic medication needs to be individually determined and depends on many factors including a person's overall health condition and response to side effects. Side effects and effectiveness vary from individual to individual. Some trial and error adjustments may be necessary when prescribing dosage amounts so that the benefits of treatment outweigh the side effects of the therapy.

The doctor must monitor the drug effects carefully including regularly checking a person's blood sugar (glucose) and cholesterol levels, as well as measuring any weight gain or changes in blood pressure or heart rate. If a single antipsychotic medication does not work, the doctor may prescribe a second one. Due to increased risk of side effects and drug interactions, the American Psychiatric Association does not recommend that people use more than two antipsychotic medications at one time.

A psychiatrist may also prescribe other types of medication, such as antidepressants or antianxiety drugs, if necessary.

Medications

Antipsychotic medications for schizophrenia are divided into two classes:

Large-scale studies have not found much difference between these classes of drugs when it comes to controlling psychotic symptoms. But there are some differences between typical and atypical antipsychotics in terms of side effects. Specific side effects vary from drug to drug, and a person's reaction to a drug.

Typical Antipsychotic Drugs

Typical ("first-generation") antipsychotics include:

Certain types of side effects are more likely with some of these drugs. Haloperidol, trifluoperazine, and fluphenazine are considered "high-potency" in terms of their dopamine receptor blocking effects compared to "low-potency" drugs like chlorpromazine and thioridazine. (Perphenazine is considered in intermediate potency.)

High-potency typical antipsychotics tend to cause more problems with extrapyramidal symptoms and increased prolactin levels than low-potency drugs. Low-potency typical antipsychotics tend to cause more side effects like dry mouth, sedation, sexual dysfunction, and drop in blood pressure when standing (postural hypotension).

Atypical Antipsychotic Drugs

Twelve atypical antipsychotic drugs ("second-generation antipsychotics") are currently approved in the United States:

Clozapine was the first atypical drug approved (in 1989) and lumateperone the most recently approved (in 2019).

Clozapine and olanzapine appear to have more side effects than the other atypical antipsychotics, particularly in terms of causing weight gain, insulin resistance, and unhealthy cholesterol levels. Clozapine can also cause agranulocytosis, a dangerous drop in white blood cell count. For this reason, many doctors recommend against using clozapine or olanzapine as first-line drugs. However, clozapine may have specific benefits for controlling positive symptoms, as well as violent, hostile, or suicidal behaviors.

Side Effects

Side effects of both typical and atypical antipsychotics vary depending on the specific drug but can include:

The following are more severe side effects or complications that may occur with these drugs:

Diabetes Risk and Atypical Antipsychotics

All atypical antipsychotic drugs can increase the risk of high blood sugar (hyperglycemia) and type 2 diabetes. (Olanzapine is more likely to cause high blood sugar levels than other atypical antipsychotic medications.)

The US Food and Drug Administration (FDA) recommends that:

There may also be an increased background risk of diabetes in people with schizophrenia. As a precaution, many doctors advise that all people treated with atypical antipsychotics receive a baseline blood sugar level reading and be monitored for any increases in blood sugar levels during drug treatment. People should also have their cholesterol and other lipid levels monitored. In addition to diabetes, atypical antipsychotics are associated with increased risk for heart problems.

Extrapyramidal Side Effects

Extrapyramidal side effects are movement disorders that resemble some of the symptoms of Parkinson disease. They include the following conditions:

Nearly every antipsychotic drug used to treat schizophrenia can cause extrapyramidal side effects to some degree. The risk seems to be higher with typical antipsychotics than atypical antipsychotics, but these side effects can also occur with the newer drugs.

Who is at Risk?

Extrapyramidal side effects develop in about a third of people who take antipsychotic medication. They usually develop within long-term use, but can develop after 3 or more months. Anyone who takes these drugs can develop these symptoms but people at higher risk include:

Treatment of Extrapyramidal Side Effects

Prevention is the best treatment for tardive dyskinesia and other extrapyramidal side effects. Health care providers recommend prevention because extrapyramidal side effects are extremely difficult to treat once they occur. It is very important that people report to their providers any emerging signs of these symptoms.

In their early stages, extrapyramidal side effects can often be reversed or stopped by reducing a medication's dosage. If switching to a different medication is considered, the doctor must be careful to monitor for worsening of psychosis. Switching to a different medication can also sometimes worsen extrapyramidal side effects instead of improve them.

Milder extrapyramidal side effects such as dystonia and akathisia may be successfully treated with medications like benztropine (Cogentin). Unfortunately, these anticholinergic medications may increase the risk of tardive dyskinesia.

Once symptoms become severe, they become much more difficult to treat. There is insufficient evidence to recommend a standard treatment for extrapyramidal side effects. There is moderate evidence to support effectiveness of the benzodiazepine anti-anxiety drugs clonazepam (Klonopin, generic) and lorazepam (Ativan, generic).

There is weak evidence to support drugs used to treat other movement disorders, such as tetrabenazine (Xenazine), which is used to treat Huntington's chorea, and amantadine (Symadine, generic), which is used to treat Parkinson disease. Researchers are studying other types of treatments, such as deep brain stimulation. Beta blockers such as propranolol are also used.

Antidepressants

Anti-depressants such as selective serotonin reuptake inhibitors (SSRIs) or selective norepinephrine reuptake inhibitors (SNRIs) may be added to anti-psychotic therapy sometimes in what is called adjunctive or augmentation therapy. Antidepressants may help with depressive or negative symptoms in people who are not at risk for psychosis worsening.

Psychotherapy and Support Services

Psychological, psychosocial, and rehabilitative support can help people achieve skills to function better at home and in the community.

Psychotherapy and Cognitive-Behavioral Therapies

While talking to a therapist may not be a substitute for antipsychotic medication, psychotherapy is an important part of an integrated treatment approach for schizophrenia. Psychotherapy can offer people an opportunity to discuss their feelings about living with schizophrenia, and ways that they can emotionally cope better with the condition. It may also be helpful in complying with consistent taking of antipsychotic medications.

The use of cognitive-behavioral therapy is showing particular promise for improving symptoms of schizophrenia, such as delusions and hallucinations. This approach helps strengthen the person's capacity for normal thinking, using mental exercises and self-observation. People with schizophrenia are taught to critically analyze and develop techniques for dealing with specific symptoms, such as hearing voices.

Psychosocial therapies can also help address alcohol and substance abuse, smoking, and weight gain.

Rehabilitation Programs

Rehabilitation services can include counseling to help with:

Family Education

Family support is critical for people with schizophrenia. Families or other caregivers can be very helpful in a number of ways:

Support Groups

Support groups can provide valuable shared advice, resources, and a sense of community, comfort, and advocacy for people and their families. Support groups can help people and families become better educated about schizophrenia, and learn more about the illness so they can better manage it.

Resources

References

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Review Date: 11/7/2020
Reviewed By: Fred K. Berger, MD, addiction and forensic psychiatrist, Scripps Memorial Hospital, La Jolla, CA. Also reviewed by David Zieve, MD, MHA, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team.
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