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Schizophrenia

Highlights

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 patients and their families. Patients 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:

  • Typical antipsychotics (“first-generation” antipsychotics) include haloperidol (Haldol), chlorpromazine (Thorazine), perphenazine (Trilafon), thioridazine (Mellaril), trifluoperazine (Stelazine), and fluphenazine (Prolixin). All of these drugs are available as generics.
  • Atypical antipsychotics (“second-generation” antipsychotics) include clozapine (Clozaril, generic), risperidone (Risperdal, generic), olanzapine (Zyprexa, generic), quetiapine (Seroquel), ziprasidone (Geodon), aripiprazole (Abilify), palperidone (Invega), iloperidone (Fanapt), asenapine (Saphris), and lurasidone (Latuda).

Drug Approvalsand Warnings

  • In 2011, the FDA approved a generic version of olanzapine.
  • In 2011, the FDA warned that serious allergic reactions have been reported in patients taking asenapine (Saphris). Symptoms include difficulty breathing; swelling of face, tongue or throat; feeling lightheaded; itching. Patients should immediately contact their doctors if they experience any of these symptoms.

Introduction

Schizophrenia is a group of psychotic disorders that interfere with thinking and mental or emotional responsiveness. It is a disease of the brain. The term schizophrenia, which means "split mind," was first used in 1911 by Swiss psychiatrist Eugen Bleuler to categorize patients whose thought processes and emotional responses seemed disconnected. Despite its name, the condition does not cause a split personality.

Schizophrenia
Schizophrenia is a group of psychotic disorders characterized by disturbances in perception, behavior, and communication that last longer than 6 months. (This includes psychotic behavior.) A person with schizophrenia has deteriorated occupational, interpersonal, and self-supportive abilities.

Types of Schizophrenia

Schizophrenia includes the following subtypes:

  • Paranoid-type schizophrenia is marked by delusions of persecution or conspiracy and is often accompanied by auditory hallucinations.
  • Disorganized-type schizophrenia is marked by disordered thought processes, manifested in disorganized speech and behavior, and includes flat affect (absence of appropriate emotional responsiveness).
  • Catatonic-type schizophrenia is marked by extremes in movement and behavior ranging from hyperactive agitation to complete lethargy and immobility.
  • Undifferentiated-type schizophrenia is a category used when symptoms do not clearly fall into one of the above subtypes.
  • Residual-type schizophrenia is used to describe patients who have had a history of schizophrenia but whose symptoms have diminished or become less severe.

Symptoms

Doctors often group symptoms of schizophrenia into three categories: Positive, negative, and cognitive.

Positive Symptoms

Positive symptoms include the psychotic symptoms that are most often associated with schizophrenia. Psychotic symptoms usually occur every now and then, alternating with periods of remission. These symptoms include:

  • Hallucinations. A hallucination is the experience of seeing, hearing, tasting, smelling, or feeling something that doesn't really exist. Auditory hallucinations are false senses of sound such as hearing voices that can't be heard by others. Auditory hallucinations are the most common psychotic symptoms experienced by people with schizophrenia.
  • Delusions. A delusion is a fixed, false belief. It can be bizarre (such as invisible aliens have entered the room through an electrical socket) or more conventional (such as unwarranted jealousy or the paranoid belief in being persecuted or watched).
  • Thought Disorders. Thought disorders are manifestations of disorganized speech and thinking. People with schizophrenia may have incoherent or garbled speech patterns or have difficulty expressing themselves in a logical manner.
  • Movement Disorders. Movement disorders span a spectrum from agitated or repetitive body movements to complete lack of motion or responsiveness (catatonia).

Negative Symptoms

Negative symptoms indicate an absence of normal emotional responses. They include:

  • Emotional flatness (“lack of affect”) often characterized by a dull empty facial expression
  • Limited or monotone speech
  • A general loss of interest in life and the ability to experience pleasure
  • Lack of ability to plan or initiate activities

Cognitive Symptoms

Cognitive symptoms are associated with thinking processes. They include:

  • Difficulty focusing or paying attention
  • Difficulty understanding information or following instructions
  • Poor memory and concentration

Causes

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

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, brother) with the disease to about 40 - 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. There is also evidence that schizophrenia may share genetic pathways with other psychotic and psychiatric disorders, such as bipolar disorder and autism.

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 patients with schizophrenia have revealed structural abnormalities. Such problems may cause nerve damage and disconnections in the pathways that carry brain chemicals.

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 ages of 16 - 30 years. 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.

Family History

Schizophrenia often runs in families.

Environmental Factors

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

  • Viral infections. Factors that increase exposure to viruses (living in urban environments, large families, winter and spring births) have been associated with higher risk for schizophrenia.
  • Prenatal and Perinatal Problems. Maternal exposure to viruses, maternal malnutrition, and birth complications (such as a baby experiencing lack of oxygen during delivery) may be linked to schizophrenia.
  • Father’s age. According to some studies, the older a father is when a child is born, the greater the risk is for schizophrenia in his offspring, perhaps because of a greater chance of genetic mutations in the sperm that can be passed on.
  • Childhood trauma. Although parental influence is no longer believed to directly lead to the development of schizophrenia, certain types of childhood trauma (including sexual and physical abuse) may play a role.

Complications

Schizophrenia can have a devastating effect on both patients 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 patient 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 the schizophrenic patient increases the risk for violence.

Nicotine dependence is the most common form of substance abuse among people with schizophrenia. Most patients with schizophrenia smoke. Biologic and genetic factors associated with schizophrenia may play a role. Although smoking may be a form of self-medication in controlling symptoms, smoking can interfere with some types of antipsychotic medication.

Suicide. Patients with schizophrenia have an increased risk for suicide and suicidal behavior. About 10% of patients with schizophrenia commit suicide. Clinical depression is common among people with schizophrenia. The stresses of dealing with social isolation, discrimination, and stigma can also be factors.

Medical Illnesses

Patients with untreated schizophrenia are more likely to suffer from poverty, homelessness, and incarceration. If patients do not take their medication and symptoms recur, they can have difficulty caring for themselves. These conditions can increase the risk of the patient developing other medical illnesses. In addition, smoking and other forms of substance abuse can lead to medical problems (such as heart disease, cirrhosis, and malnutrition).

Diabetes is a particular concern for people with schizophrenia. In addition to a possible link to schizophrenia itself, many new antipsychotic medications can raise blood sugar levels. Patients 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 patients with schizophrenia. In addition to medical professionals and community resources, family members play a vital role in monitoring a patient’s mental status and helping the patient 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

A doctor will make a diagnosis of schizophrenia based on a patient’s symptoms and how long they have lasted.

Diagnostic Criteria

Psychiatrists use as diagnostic criteria:

  • If a patient has at least one active flare-up lasting a month or more. The flare-up consists of at least two characteristic symptoms (such as hallucinations, delusions, evidence of disorganized thinking and speaking, and emotional unresponsiveness with a flat speaking tone). If the patient has particularly bizarre delusions or hallucinations, these alone will qualify as a diagnostic sign of schizophrenia.
  • If major areas of functioning (work, school, interpersonal relations, self-care) have been significantly affected since the disturbance began
  • If certain symptoms are present for at least 6 months, even in the absence of active flare-ups. Such symptoms include marked social withdrawal, peculiar behavior (talking to oneself, severe superstitiousness), vague and incoherent speech, or other indications of disturbed thinking, as well as continued deterioration of the patient's social and personal relationships.

Ruling Out Other Conditions

The common hallmarks of schizophrenia are also symptoms that can occur in dozens of other psychologic 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:

  • Other Psychiatric Disorders. Bipolar disorder, schizoaffective disorder, and depression can all have psychotic elements that resemble schizophrenia. Autism and pervasive developmental disorder can share some characteristics of schizophrenia but are entirely different disorders.
  • Alcohol and Drug Abuse. Both substance abuse and withdrawal from drugs or alcohol can trigger psychosis.
  • Medical Illnesses. Other causes of psychotic symptoms include cancer in the central nervous system, infections such as encephalitis and syphilis, thyroid disorders, Alzheimer's disease, epilepsy, Huntington's disease, multiple sclerosis, stroke, Wilson's disease, and some B vitamin deficiencies..
  • Medication Reactions. Many medications may induce psychosis as a side effect, and some can precipitate delusions and severe confusion. Such medication-induced symptoms are most often observed in elderly patients.

Treatment

Schizophrenia is categorized as a brain disease, not a psychological disorder, Drug treatment is the primary therapy. Studies indicate, however, that an integrated approach that includes psychosocial therapy is better at preventing relapses than routine care (medication, monitoring, and access to rehabilitation programs).

Integrated Approach. An integrated approach, which may help to ease psychotic symptoms, may include:

  • Motivational interviewing to encourage the patient's commitment to change
  • Use of antipsychotic medications with monitoring
  • Community-based rehabilitation and social skills training
  • Family psychotherapy
  • Cognitive-behavioral therapy to reduce delusions and hallucinations

Treatment of schizophrenia has traditionally focused on decreasing patients’ negative symptoms. Doctors are now broadening treatment to emphasize patients’ ability to function independently -- shop, eat, cook, clean, do laundry, and work.

Early Treatment. The earlier schizophrenia is detected and treated, the better the outcome. Patients who receive antipsychotic drugs and other treatments during their first episode are admitted to the hospital less often during the following 5 years and may require less time to control symptoms than those who do not seek help as quickly. In spite of strong evidence for the positive effects of early treatment, patients usually do not receive treatment until after 10 months of serious symptoms.

Drug Classes Used for Schizophrenia

Most drugs that treat schizophrenia work by blocking receptors of the brain chemical (neurotransmitter) dopamine. Dopamine is thought to play a major role in psychotic symptoms. Although the drugs used to treat schizophrenia have important benefits, they may also cause side effects. The most disturbing and common side effects are those known as extrapyramidal symptoms, which involve the nerves and muscles controlling movement and coordination.

The following drug classes are generally used for schizophrenia:

  • Typical antipsychotics. Until recently, these drugs were the mainstay treatments for schizophrenia. They include haloperidol (Haldol), chlorpromazine (Thorazine), perphenazine (Trilafon), thioridazine (Mellaril), trifluoperazine (Stelazine), and fluphenazine (Prolixin). Side effects involving the nerves and muscle movement and coordination occur in up to 70% of patients. Typical antipsychotics, which are all available as generics, are sometimes referred to as “first-generation” to distinguish them from newer “second-generation” atypical antipsychotics.
  • Atypical antipsychotics. These newer drugs may be better tolerated than the older antipsychotics. They include clozapine (Clozaril, generic), risperidone (Risperdal, generic), olanzapine (Zyprexa, generic), quetiapine (Seroquel), ziprasidone (Geodon), aripiprazole (Abilify), paliperidone (Invega), iloperidone (Fanapt), asenapine (Saphris), and lurasidone (Latuda).

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.

Most practicing psychiatrists feel that atypical antipsychotics may work better than the older drugs. However, the additional benefits may be modest for most patients. Large, high-quality studies have compared newer and older drugs and generally found that newer atypical antipsychotics are not any more effective than older typical antipsychotics such as haloperidol, at least for initial treatment of first-episode schizophrenia. Similarly, for treatment of children and adolescents with schizophrenia, both atypical and typical antipsychotics appear to be equally effective, but atypical antipsychotics, particularly clozapine and olanzapine, carry a higher risk for metabolic side effects.

Side effect profiles between typical and atypical antipsychotics are different. Both groups cause extrapyramidal side effects (including muscle stiffness, tremors, and abnormal movements), but the newer atypical drugs do not seem to cause them as often. However, the atypical antipsychotics pose a higher risk for weight gain, which can lead to diabetes as well as heart disease.

One problem with most of the studies that evaluate these medications is that often more than half the patients discontinue the drugs either because of side effects or because they do not feel the medications are helping them.

Most antipsychotic medications are approved only for adult patients. Some atypical antipsychotics (such as risperidone, aripiprazole, olanzapine, and quetapine) are approved for treatment of schizophrenia in adolescents (ages 13 - 17 years). Because olanzapine (Zyprexa, generic) has particularly high risks for causing weight gain and unhealthy cholesterol levels, doctors should first try other atypical antipsychotics when treating adolescent patients. Doctors caution that more research is needed to determine the long-term safety and efficacy of these drugs for pediatric patients.

Treating an Acute or Initial Phase

For the severe, active phase of schizophrenia, injections of an antipsychotic drug are typically given every few hours until the patient is calm. Anti-anxiety drugs may also be administered at the same time. In patients who are being treated for the first time, improvement in psychotic symptoms may be evident within 1 - 2 days of treatment, although the full benefit of the drug usually manifests over about 6 - 8 weeks. Thought disturbances tend to abate more gradually.

Maintenance

To reduce the risk of relapse, many doctors recommend that drugs be given daily for at least 1 year. Atypical drugs are increasingly being used as maintenance for those with new-onset psychosis, although the choice of the drug depends on many factors. 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.

Keeping patients on maintenance therapy is very difficult, however, and many patients stop their medication. Factors that may contribute to poor compliance include:

  • A history of alcohol or drug abuse
  • Delusions of persecution
  • A history of stopping medications within the first 6 months after diagnosis

Stopping Medications

Nearly all patients experience some relapse or worsening of symptoms within 2 years of stopping maintenance medication. Recognizing signs of relapse and starting medications immediately can help prevent rehospitalization for these patients.

Supportive Drugs

Antidepressants and anti-anxiety drugs may also be used in schizophrenia treatment, particularly given the high rates of depression and suicide among these patients.

General Guidelines for Psychological Treatments

Psychiatrists generally agree that patients with schizophrenia should be offered both medical and psychological treatment. Cognitive-behavioral approaches are showing promise. Support to the family or other caregiver is also important for the long-term improvement of people with schizophrenia.

Medications

Atypical Antipsychotic Drugs

Ten atypical antipsychotic drugs are currently approved in the United States:

  • Clozapine (Clozaril, generic)
  • Risperidone (Risperdal, generic)
  • Olanzapine (Zyprexa, generic)
  • Quetiapine (Seroquel)
  • Aripiprazole (Abilify)
  • Ziprasidone (Geodon)
  • Paliperidone (Invega)
  • Iloperidone (Fanapt)
  • Asenapine (Saphris)
  • Lurasidone (Latuda)

Clozapine was the first atypical drug approved (in 1989), and lurasidone the most recently approved (in 2010). 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. 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.

Most atypical antipsychotics come in pill form, but some may come in liquid form or as an injection. In general, it may take up to 6 months before an atypical drug has an effect.

The atypical antipsychotics zotepine (Zoleptil) and amisulpride (Solian) are not approved for use in the United States.

Benefits of Atypical Antipsychotics.

  • Affect both dopamine receptors and other neurotransmitters responsible for psychotic symptoms
  • Improve negative and positive symptoms
  • May improve working memory and mental functioning
  • May reduce depression and hostility
  • May reduce the risk for suicide
  • Have fewer extrapyramidal side effects than the typical antipsychotics (see "Extrapyramidal Symptoms" below)

Atypical antipsychotics have some significant limitations and complications, and their benefits compared to each other and to other antipsychotics are not always clear-cut.

Side Effects of Atypical Antipsychotics.

  • Nasal congestion or runny nose
  • Drooling
  • Dizziness
  • Headache
  • Drowsiness -- although, sometimes the drugs may cause restlessness and insomnia
  • Constipation
  • Rapid heart beat
  • Difficulty urinating
  • Skin rash
  • Increased body temperature
  • Confusion, short-term memory problems, disorientation, and impaired attention

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

  • Diabetes
  • Weight gain and metabolic problems. The risk appears to be highest for olanzapine and clozapine, and lowest for aripiprazole and ziprasidone.
  • Unhealthy cholesterol levels. Particularly with olanzapine and clozapine, increased risk for high levels of trigylcerides and total cholesterol.
  • Seizures
  • Extreme and very serious increases in body temperature
  • Sudden drop in blood pressure (hypotension)
  • A significant drop in white blood cell count (neutropenia), which can be severe, occurs in 1% or more of patients, generally in the first 6 months after starting treatment. Patients should have their white blood count and absolute neutrophil count regularly monitored.
  • Extrapyramidal side effects
  • Cataracts and worsening of existing glaucoma
  • Increased prolactin levels -- prolactin is a hormone associated with infertility and erectile dysfunction. High levels can cause menstrual abnormalities and may increase the risk for osteoporosis and possibly breast cancer.
  • Heart problems, including sudden death
  • Severe allergic reactions have occurred with asenapine (Saphris)

Diabetes Risk and Atypical Antipsychotics

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

The U.S. Food and Drug Administration (FDA) recommends that:

  • Patients with an established diagnosis of diabetes who begin atypical antipsychotic treatment should be regularly monitored for worsening of blood sugar control.
  • Patients with risk factors for diabetes (obesity, family history of diabetes) should undergo fasting blood sugar testing at the beginning of atypical antipsychotic treatment and periodically during treatment.
  • All patients treated with atypical antipsychotics should be monitored for high blood sugar (hyperglycemia) symptoms.
  • Patients who develop hyperglycemia symptoms should undergo fasting blood sugar testing.

There may also be an increased background risk of diabetes in patients with schizophrenia. As a precaution, many doctors advise that all patients treated with atypical antipsychotics receive a baseline blood sugar level reading and be monitored for any increases in blood sugar levels during drug treatment. Patients should also have their cholesterol and other lipid levels monitored. [For more information, see In-Depth Report #60: Diabetes - type 2.]

Typical Antipsychotic Drugs

The standard typical antipsychotic drug used for schizophrenia is haloperidol (Haldol, generic). Others include:

  • Chlorpromazine (Thorazine, generic)
  • Perphenazine (Trilafon, generic)
  • Thioridazine (Mellaril, generic)
  • Trifluoperazine (Stelazine, generic)
  • Fluphenazine (Prolixin, generic)

Studies have not shown any significant difference in the benefits these drugs provide.

The beneficial impact of these drugs is greatest on psychotic symptoms, particularly hallucinations and delusions in the early and midterm stages of the disorder. They are not very successful in reducing negative symptoms. Because of their significant side effects, many patients stop taking these drugs.

Depot therapy (long-lasting monthly injections, usually of haloperidol or fluphenazine) has been used with success in people who have difficulty complying with a daily regimen of these drugs. Researchers are studying low-dose regimens to see if they can be effective and cause fewer side effects.

Side Effects of Typical Antipsychotics. These drugs can have adverse side effects related to many organs and systems in the body. These drugs are also known as neuroleptics, a name that comes from the severe neurological side effects that these medications can cause. Side effects may include:

  • Extrapyramidal symptoms (see below)
  • Sleepiness and lethargy -- common in the beginning but usually decreases over time
  • Insomnia and agitation
  • Dulling of the mind
  • Nausea, vomiting, diarrhea, constipation, and heartburn
  • Dry mouth and blurred vision
  • Allergic reactions
  • Sexual dysfunction
  • Neuroleptic malignant syndrome -- rare, but can be fatal without prompt treatment
  • Increased prolactin levels -- prolactin is a hormone associated with infertility and erectile dysfunction. High levels can cause menstrual abnormalities and may increase the risk for osteoporosis and possibly breast cancer
  • A sudden drop in blood pressure (hypotension)
  • An increased risk of sudden cardiac death

Extrapyramidal Symptoms

Nearly every antipsychotic drug used to treat schizophrenia can cause extrapyramidal side effects to some degree. These side effects involve the nerves and muscles controlling movement and coordination.

Description of Extrapyramidal Side Effects. These effects resemble some of the symptoms of Parkinson's disease and include the following conditions:

  • Tardive dyskinesia is the most serious extrapyramidal side effect. It typically involves repetitive and involuntary movements, or tics, most often of the mouth, lips, or of the legs, arms, or torso. Symptoms range from mild to severe, and sometimes interfere with eating and walking. They may appear months or even years after taking the drugs. After the drug is stopped, symptoms can sometimes persist for weeks or months and may even be permanent. Some people are more likely to develop these symptoms, including older patients, women, smokers, people with diabetes, and patients with movement disorders.
  • Acute dystonia typically develops shortly after taking an antipsychotic drug. This syndrome includes abnormal muscle spasms, particularly sustained contortions of the neck, jaw, torso, and eye muscles.
  • Other extrapyramidal symptoms. Other effects are agitation, slow speech, tremor, and retarded movement. Sometimes these symptoms mimic schizophrenia itself.

Treatment of Extrapyramidal Side Effects. In general, if extrapyramidal side effects occur from neuroleptic drugs, the doctor may first try to reduce the dosage or switch to an atypical drug.

Another approach is to use anti-parkinsonism drugs known as anticholinergics, which increase dopamine levels and help to restore balance. Among the anticholinergics sometimes used are trihexyphenidyl (Artane, Trihexy, generic) and benztropine (Cogentin, generic). They are not helpful for tardive dyskinesia. Some of these drugs may also help in managing negative symptoms of schizophrenia.

However, these medicines also have their own, sometimes serious, side effects. Most doctors recommend them only for patients who cannot be monitored regularly, need very high doses of powerful antipsychotic drugs, and are at risk for severe side effects. They should be stopped after 3 or 4 months, if possible. If symptoms recur, the drugs can be restarted. Withdrawal from anticholinergics can cause depression that can worsen schizophrenia

Supportive Add-On Drugs

Antidepressants. Antidepressants may be given along with antipsychotics to treat depression associated with schizophrenia.

Anti-Anxiety Drugs. Benzodiazepines are drugs normally used to treat anxiety. They also have some modest effect on psychotic symptoms. They also are sometimes used to treat the restlessness and agitation that can occur with the use of neuroleptics. Prolonged use of anti-anxiety drugs is generally not recommended in schizophrenia.

Lithium. Lithium, the main drug treatment for bipolar disorder, may be useful for some patients with schizophrenia. However, there are no reliable criteria to predict who will benefit.

Anti-Epileptic Drugs. Drugs ordinarily prescribed for epilepsy -- such as carbamazepine (Tegretol, generic), gabapentin (Neurontin, generic), lamotrigine (Lamictal, generic), or others -- are occasionally used in combination with antipsychotic drugs for patients who do not respond to standard drugs. However, these drugs may cause an increased risk for suicide.

Psychotherapy

Psychosocial and rehabilitative therapies may be helpful for patients with schizophrenia.

Cognitive-Behavioral and Other Psychosocial Therapies

The use of cognitive-behavioral therapy is showing particular promise for improvement of both positive and negative symptoms in some patients, and the benefits may persist after treatment has stopped. This approach attempts to strengthen the patient's capacity for normal thinking, using mental exercises and self-observation. Improving patients' abilities to learn, remember, and pay attention may allow them to better cope with ongoing positive symptoms and lead independent lives. Patients with schizophrenia are taught to critically analyze hallucinations and examine underlying beliefs in them.

Psychosocial therapies can also be helpful for addressing alcohol and substance abuse, smoking, and weight gain. In addition to psychosocial techniques, patients can benefit from nutritional counseling for weight management, and bupropion (Zyban) for smoking cessation.

Family and Outside Support Structures

Positive social interaction is extremely important for people with schizophrenia and may help reduce symptoms, including the number of delusional moments.

Family Support. Families or other caregivers can be very helpful in a number of ways:

  • They can encourage patients to comply with drug treatments and to recognize early signs of serious treatment side effects.
  • They can be taught to recognize impending symptoms of relapse and help the patient avoid situations that might trigger them. (Symptoms for an impending relapse after remission may include feeling distant from family and friends or being increasingly bothered by persistent thoughts.)

Rehabilitation Programs. Rehabilitation services include job counseling and training, social rehabilitation services (to improve patients’ abilities to interact socially with others), and other programs to help patients live independent lives within their communities. Substance abuse counseling and treatment programs are also very important for many patients.

Support Groups. Support groups can provide shared advice, resources, and a sense of community and comfort for patients and their families.

Resources

References

Buchanan RW, Kreyenbuhl J, Kelly DL, Noel JM, Boggs DL, Fischer BA, et al. The 2009 schizophrenia PORT psychopharmacological treatment recommendations and summary statements. Schizophr Bull. 2010 Jan;36(1):71-93. Epub 2009 Dec 2.

Dixon LB, Dickerson F, Bellack AS, Bennett M, Dickinson D, Goldberg RW, et al. The 2009 schizophrenia PORT psychosocial treatment recommendations and summary statements. Schizophr Bull. 2010 Jan;36(1):48-70. Epub 2009 Dec 2.

Komossa K, Rummel-Kluge C, Hunger H, Schmid F, Schwarz S, Duggan L, et al. Olanzapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev. 2010 Mar 17;(3):CD006654.

Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet. 2009 Jan 3;373(9657):31-41. Epub 2008 Dec 6.

Leucht S, Komossa K, Rummel-Kluge C, Corves C, Hunger H, Schmid F, et al. A meta-analysis of head-to-head comparisons of second-generation antipsychotics in the treatment of schizophrenia. Am J Psychiatry. 2009 Feb;166(2):152-63. Epub 2008 Nov 17.

Lieberman JA. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia: efficacy, safety and cost outcomes of CATIE and other trials. J Clin Psychiatry. 2007 Feb;68(2):e04.

Marshall M, Rathbone J. Early intervention for psychosis. Cochrane Database Syst Rev. 2011 Jun 15;(6):CD004718.

Newcomer JW. Metabolic considerations in the use of antipsychotic medications: a review of recent evidence. J Clin Psychiatry. 2007;68 Suppl 1:20-7.

Schultz SH, North SW, Shields CG. Schizophrenia: a review. Am Fam Physician. 2007 Jun 15;75(12):1821-9.

Sikich L, Frazier JA, McClellan J, Findling RL, Vitiello B, Ritz L, et al. Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizo-affective disorder: findings from the treatment of early-onset schizophrenia spectrum disorders (TEOSS) study. Am J Psychiatry. 2008 Nov;165(11):1420-31. Epub 2008 Sep 15.

Smith T, Weston C, Lieberman J. Schizophrenia (maintenance treatment). Am Fam Physician. 2010 Aug 15;82(4):338-9.

Swartz MS, Perkins DO, Stroup TS, et al. Effects of antipsychotic medications on psychosocial functioning in patients with chronic schizophrenia: findings from the NIMH CATIE study. Am J Psychiatry. 2007 Mar;164(3):428-36.

Thornicroft G, Brohan E, Rose D, Sartorius N, Leese M; INDIGO Study Group. Global pattern of experienced and anticipated discrimination against people with schizophrenia: a cross-sectional survey. Lancet. 2009 Jan 31;373(9661):408-15. Epub 2009 Jan 21.

van Os J, Kapur S. Schizophrenia. Lancet. 2009 Aug 22;374(9690):635-45.

Van Snellenberg JX, de Candia T. Meta-analytic evidence for familial coaggregation of schizophrenia and bipolar disorder. Arch Gen Psychiatry. 2009 Jul;66(7):748-55.

Wykes T, Huddy V, Cellard C, McGurk SR, Czobor P. A meta-analysis of cognitive remediation for schizophrenia: methodology and effect sizes. Am J Psychiatry. 2011 May;168(5):472-85. Epub 2011 Mar 15.


Review Date: 2/8/2012
Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.
The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997- A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.
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