Schizophrenia

The term schizophrenia was first used in 1911 by Eugen Bleuler, a Swiss psychiatrist, to categorize patients whose thought processes and emotional responses seemed disconnected. The term schizophrenia literally means split mind and many people still believe incorrectly that the condition causes a split personality (which is an uncommon problem involving dissociation). Schizophrenia is now used to describe a cluster of symptoms that typically includes delusions, hallucinations, disordered thinking, and emotional unresponsiveness. Several definitions of schizophrenia still exist and no single cause has been found to explain all aspects of this devastating syndrome. Most likely, the symptoms are triggered by a number of disease processes coupled with genetic factors and environmental stresses.

HOW SERIOUS IS SCHIZOPHRENIA?

Schizophrenia has a devastating effect on all aspects of human thought, emotion, and expression. The course of the disease varies from one patient to the next. Treatments do not cure the disease, but they can reduce symptoms significantly and reduce the relapse rate by more than 50%. Newer drugs may be improving this rate. Early treatment of schizophrenia--shortly after the first symptoms occur--may result in remission rates as high as 80% to 85%.

Onset of schizophrenia is either gradual or sudden. The prognosis is slightly better for those whose symptoms come on suddenly. In up to a third of patients, the disease is unrelenting and progresses from the first episode onward. In others, schizophrenia follows a fluctuating course with psychotic flare-ups, followed by remissions. Women are more likely to have a remitting form and a better chance than men for a positive outcome, possibly because of estrogen's effects on the brain. Mental and social functioning each decline for a number of years. Memory is often impaired. After five to 10 years of deterioration, the illness tends to stabilize, and eventually some improvement may occur. Studies indicate that after 20 to 30 years, half of schizophrenic patients are capable of caring for themselves, working, and participating socially. Support services and appropriate housing improve this outcome.

Without care and adequate treatment, people with schizophrenia suffer. The consequences for work and relationships are usually severe and difficult to repair, even if symptoms improve. In spite of their sometimes frightening behavior, people with schizophrenia are no more likely to behave violently than are those in the general population, and, in fact, they are more apt to withdraw from others or to harm themselves. An estimated 15% of individuals with schizophrenia commit suicide; the risk may increase following shorter hospital stays and may be greater in younger, more paranoid, and delusional patients.

Studies also report that a large majority of people with schizophrenia has a history of substance and alcohol abuse. Substance abuse increases non-compliance with antipsychotic drugs in the schizophrenic patient, in addition to its other adverse effects. A genetic factor called P50 which researchers associate with schizophrenia is found in receptors in the brain that attach to nicotine, and may explain why schizophrenics tend to be heavy smokers. Nicotine use may be a form of self-medication that helps reduce psychotic symptoms, which may temporarily increase when patients stop smoking. New studies suggest that cigarette smoke inhibits the activity of a protein called monoamine oxidase B (MAO-B). Blocking this protein leads to an increase in the brain of phenylethylamine (PEA)--a compound linked to stress-related mania and hyperactivity (though not to aggression).

Schizophrenia damages individuals and society as a whole. In 1991, schizophrenia was estimated to cost the U.S. $65 billion, including direct health care costs, money paid to the criminal justice system for dealing with people with schizophrenia, and lost productivity at work and home by both patients and their caregivers. In the past, schizophrenia was generally treated with long-term stays in mental hospitals. After the introduction and widespread use of antipsychotic drugs in the 1950s and 60s, political pressure for cost reduction coincided with the hope that these drugs would be more effective than they were. In the 1970s, thousands of patients were released from custodial institutions into the community, a concept called deinstitutionalization. Most communities and families were ill-prepared to receive these individuals, and the incidence of homelessness dramatically increased. In spite of these attempts to reduce mental hospital costs, schizophrenia still accounts for 40% of all long-term hospitalization days. More than half of patients require public assistance within a year of their reentry into the community.

WHAT ARE THE SYMPTOMS OF SCHIZOPHRENIA?

Because symptoms of schizophrenia arise from various physical processes and respond differently to treatments, some experts recommend classifying them into two groups: positive and negative symptoms. Negative symptoms, e.g., low sociability, are probably due to loss of nerve cells resulting in a diminished ability to function. Positive symptoms are manifested as psychotic symptoms (e.g., hallucinations and delusions) or cognitive impairment (also called thought disorder). It is important to note that these symptoms overlap and interact with each other, so categorization may be misleading. A patient may have more than one symptom, but rarely does a patient with schizophrenia have all of them.

Negative Symptoms.

Negative symptoms often occur early in the disease process and frequently go unnoticed. These symptoms are often not sufficient to motivate treatment. Negative symptoms may co-exist with positive symptoms and typically persist after positive symptoms have been treated. Negative symptoms reflect the diminishment of the self--lack of emotions, colorless speaking tones, and a general loss of interest in life. Patients with negative symptoms may also display emotionally inappropriate reactions, a condition known as inappropriate affect (e.g., laughing hysterically over a sad event). Negative symptoms may appear early in life. Lack of responsiveness and poor sociability have been observed in the childhood of many people who later develop full-blown symptoms of schizophrenia. In others, however, negative symptoms do not appear until after the positive symptoms develop. Negative symptoms tend to be more common in older patients than in younger ones.

Positive Symptoms.

Psychotic Symptoms. Psychotic events--particularly delusions and hallucinations--are the most widely recognized signs of schizophrenia. Hallucinations can take the form of either seeing or hearing things that don't exist. Auditory hallucinations, which are false senses of sound, such as hearing voices, are the most common symptoms. Delusions are fixed, false beliefs. Schizophrenic delusions can be bizarre (e.g., invisible aliens have entered the room through an electric socket) or nonbizarre (e.g., unwarranted jealousy, or the paranoid belief in being persecuted or watched). When psychotic symptoms occur, they usually begin in men between the ages of 17 and 30 and in women between the ages of 20 and 40. Most patients, however, display some evidence of schizophrenia before the first psychotic episode. After the initial event, psychotic symptoms usually occur episodically and are interspersed with periods of remission.

Cognitive Impairment. The symptoms of cognitive impairment include a lack of attention, disordered thoughts and information processing, and an aberrant association between words and sentences. Sometimes discontinuity between ideas is so extreme that speech becomes incoherent, a condition referred to as "word salad". Patients also occasionally connect words because of similarity of sound, rather than by meaning; these are known as "clang associations". The ability to abstract may also be impaired. Oddly enough, studies have shown that vocabulary and spatial abilities, such as map reading, are not damaged. Some cognitive impairment may occur long before full-blown symptoms develop. As with hallucinations, once symptoms appear they are usually episodic.

WHO GETS SCHIZOPHRENIA?

Intelligence.

Cultural and Geographic Factors.

No cultural group is immune, although the course of the disease seems to be more severe in developed than in developing countries. According to one study a similar percentage of positive (20%) and negative (80%) delusions were found in patients who lived in three culturally different cities (Tokyo, Vienna, and Tubinger, Germany). The content of the delusions varied, however. In Europe, patients were more apt to have delusions of poisoning or religious guilt while in Japan the delusions most often related to being slandered.

Socioeconomic Factors.

The disease occurs twice as often in unmarried and divorced people as in married or widowed ones, and people with schizophrenia are eight times more likely to be in the lowest socioeconomic groups. These two latter statistics, however, are likely to reflect the alienating effects of this disease rather than any causal relationship or risk factor associated with poverty or a single life.

Age and Gender.

Schizophrenia usually appears for the first time in late adolescence or early adulthood. Children who later develop schizophrenia often suffer from behavioral problems and excessive shyness; minor early physical and motor-control problems may go unnoticed by parents. Schizophrenia itself is sometimes evident in children; in such cases it is likely to be severe. Paranoid schizophrenia, in particular, may be more common in men. Paranoid patients usually have a normal developmental history and an intact personality. Men tend to develop schizophrenia between the ages of 15 and 24. The onset in women is usually slightly later--between 25 and 34--and the symptoms tend to be less severe. Although the risk of schizophrenia declines with age, some experts believe that there is another peak incidence at around 45 years, and another peak--mostly in women--in the mid-60s.

Inherited Risk.

Schizophrenia undoubtedly has a genetic component and new studies continue to offer support for this idea. According to some studies, individuals with a family predisposition to schizophrenia have several structural brain abnormalities, including reduced brain size and enlarged ventricles, that are similar to those in patients with schizophrenia. Heredity does not explain all cases of the disease, however. The risk for inheriting schizophrenia is 10% in those who have one immediate family member with the disease, and about 40% if the disease affects both parents or an identical twin. About 60% of people with schizophrenia have no close relatives with the illness. Eye tracking dysfunction is a genetic trait that appears to be associated with schizophrenia. Experts argue about whether these two conditions are genetically linked or if the eye disorder is simply a physical symptom of schizophrenia.

Complications Surrounding Birth.

Studies have indicated that people with schizophrenia have an increased incidence of problems surrounding birth. Complications during labor and delivery appear to increase the risk. According to one study, a short gestation period and low birth weight in newborns may be associated with adult-onset schizophrenia. (In the same study, the mothers of schizophrenics were twice as likely to report being depressed during their pregnancy as were mothers of nonschizophrenics.) Experts suggest that the risk for schizophrenia exists if the developing fetus or newborn is deprived of oxygen. If pregnant women suffer starvation or malnutrition (less than 1,000 calories a day) during the first trimester of pregnancy, their risk of having a child who will develop schizophrenia increases. One study suggests that some people may develop schizophrenia if abnormalities occur during the fetal life at critical points in brain development, which occur between the 34th and 35th weeks of gestation. One study indicated that babies who are not breast fed have an increased risk for schizophrenia.

Winter Births.

WHAT WILL CONFIRM A DIAGNOSIS OF SCHIZOPHRENIA?

Because no single symptom is specific to schizophrenia, a diagnosis depends on a person having at least one active flare-up lasting a month or less that consists of two characteristic symptoms (e.g., hallucinations, delusions, evidence of disorganized thinking, and emotional unresponsiveness with a flat speaking tone). A diagnosis may also be made on the basis of just one symptom, if the patient has delusions or hallucinations that are particularly bizarre. To make a diagnosis in the absence of active flare-ups, other symptoms, including marked social withdrawal, peculiar behavior (talking to oneself, severe superstitiousness), vague and incoherent speech, or other indications of disturbed thinking, must be present for at least six months. The patient's social and personal relationships would also have deteriorated since the onset of symptoms. Other medical conditions, including bipolar disorder, should, of course, be ruled out.

A number of brain imaging techniques are becoming useful when determining if parts of the brain are damaged and if these abnormal structures relate to specific sets of symptoms. The usefulness of each of these techniques varies according to the power of the technology, the amount of radiation used, the clarity of the image, and the areas in the brain viewed. Magnetic resonance imaging (MRI) has become a particularly valuable tool for revealing parts of the brain inaccessible by other scanning methods. MRI does not use radiation and can show the brain from a number of different perspectives. Other new imaging techniques are single photon emission computed tomography (SPECT) and positron emission tomography (PET), which can provide information on blood flow and metabolism in the brain.

WHAT OTHER CONDITIONS RESEMBLE SCHIZOPHRENIA?

Over 70 conditions, including mood disorders such as depression and mania, can cause delusions. Delusions that focus on a physical abnormality or disease that isn't real, known as somatic delusions, sometimes occur in people with depression. Delusions of grandeur--the belief that one has a special power or mission--can occur in people with mania; people with mania may also become paranoid.

There are a number of schizophrenia-like psychoses that do not meet the criteria for schizophrenia and may be variations of entirely different diseases. Until more is known about schizophrenia, these variations are classified at this time as schizoaffective disorder, schizophreniform psychosis, and atypical and brief reactive schizophrenia. In schizoaffective disorder, for example, people have psychotic episodes between full manic or depressed periods.

Alcohol and drug abuse or withdrawal can also cause psychosis. Because of the high risk for substance abuse among people with schizophrenia, it is important that the health professional distinguish psychosis triggered by drugs or alcohol from a schizophrenic episode. Usually, the diagnosis is confirmed if psychosis ends after withdrawal from drugs or alcohol, and returns if the patient returns to alcohol or substance abuse.

WHAT CAUSES SCHIZOPHRENIA?

Brain Structure and Chemical Abnormalities.

Abnormalities of Brain Shape and Activity . In some patients, imaging techniques have revealed less brain activity in the prefrontal cortex and, in some cases, actual loss of tissue, particularly in the hippocampo-amygdala on the left side of the brain. The prefrontal cortex of the brain affects memory, reasoning, aggression, and meaningful speech; reduced activity in this area may cause negative symptoms. Decreased area of the temporal lobes of the brain (located close to the ears) and limbic areas (located deep in the brain) which are related to emotions, appear to be linked to positive symptoms, such as hearing voices. Magnetic resonance imaging (MRI) scans have also revealed that in some cases of schizophrenia the grooves of the brain, or sulci, are enlarged, as is a small cavity called the cavum septi pellucidi (CSP) that lies between the lateral ventricles, which are two structures that contain the brain's cerebrospinal fluid. During development in the womb, the CSP starts as a single layer, then splits into two, and before birth fuses again. In some people with schizophrenia, however, the final stage is incomplete and the CSP is enlarged. One study found high blood volume in the brains of people with schizophrenia suggesting that their brain blood vessels were abnormal. It is important to note that brain abnormalities have not been consistently found in all patients with schizophrenia. In addition, similar structural abnormalities have been found in people who have no indications of schizophrenia.

Abnormalities of Brain Circuitry . Of particular interest in brain circuitry research is a circuit that filters information entering the brain and sends on necessary or relevant information to other parts of the brain for determining action. A defect in this circuit can result in a bombardment of unfiltered information that can cause both negative and positive symptoms. Overwhelmed by unorganized data, positive symptoms occur--the mind makes errors in perception and hallucinates, draws incorrect conclusions and becomes delusional, and makes odd behavioral choices. To compensate for this barrage, the mind withdraws, causing negative symptoms.

Abnormal Brain Chemicals. Some experts believe that schizophrenia stems from an unusual imbalance of neurotransmitters (chemical messengers between nerve cells). One possible link between abnormalities in the brain and the development of schizophrenia involves the pathways of the neurotransmitter dopamine. Dopamine has been under investigation for years since researchers first observed that certain drugs that reduce the action of dopamine in the brain also reduce psychotic symptoms. On the other hand, drugs that increase dopamine activity increase psychotic symptoms or aggravate schizophrenia. This research focuses on receptors (molecules on cells that attach and bind to other molecules) of dopamine, particularly those known as dopamine D1 and D2. Imaging studies have now reported a hyperactivity of dopamine in parts of the brain that seem to be the site of psychotic symptoms. The left side of the brain tends to have higher concentrations of dopamine than the right in schizophrenia, which is probably not due to an overproduction of dopamine, but to an increase in chemical receptors that attract and lock dopamine to the parts of the brain that have been damaged. Research has also revealed low activity of dopamine D1 receptors occurring in the prefrontal cortex of the brain, which may be related to negative symptoms. Experts now suggest that an abnormal balance of dopamine--not just overactivity--triggers the schizophrenic syndrome. Other neurotransmitters and chemicals in the brain are also being studied. Low levels of the amino acid glycine is found in the brains of people with schizophrenia, which is leading to research on possible mechanisms and treatments related to this substance. New studies indicate that patients tend to have abnormalities in proteins that effect the repair, structure, and function of nerve cells; two such proteins being investigated are called SNAP-25 and alpha-fodrin.

Genetic Factors.

Scientists may be close to pinpointing the genetic locations of schizophrenia, which are believed to be on human chromosomes 13 and possibly 8. One hypothesis, common to a number of neurologic diseases, is that a defective gene causes the healthy cells in people to be susceptible to attack by their own immune system, a condition called autoimmunity. In schizophrenia, these include the nerve cells in the brain. One study found that mothers of schizophrenic patients had a high incidence of the gene type HLA-B44. Similar genes are found in other autoimmune diseases that predispose the immune system to attack its own cells and tissues when a virus invades.

Viruses.

The case for viruses as a cause of this disease rests mainly on circumstantial evidence: the high rate of winter births among people with schizophrenia; the higher rate of the disease in cities than in nonurban areas; and a higher incidence of schizophrenia reported in populations that have had flu epidemics. For example, a study in Finland showed a high rate of schizophrenia in people whose mothers were in their second trimester of pregnancy during a major flu epidemic 20 years earlier. Some experts have postulated that if a pregnant woman with a genetic susceptibility has a flu in the second trimester when the brain cells of the fetus are developing, her immune system reacts to the invasion of the virus by attacking these vulnerable brain cells as well. Recently, Borna disease virus, which triggers a neurologic disorder in animals, was found in the blood of a schizophrenic patient. Extensive research needs to be done before an actual connection between the virus and the onset of schizophrenia can be made.

Psychologic Factors.

Although genetic and neurologic factors almost certainly play major roles in schizophrenic disorders, it would be irresponsible to ignore outside pressures and influences that may exacerbate or trigger symptoms. The brain is a complex learning system that responds not only to internal physical mechanisms but also to stimuli from the world. Research has shown that the prefrontal lobes of the brain, which are often affected in people with schizophrenia, are extremely responsive to environmental stress. Given the fact that schizophrenic symptoms naturally elicit negative responses from the sufferer's circle of family and acquaintances, it is safe to assume that negative feedback can intensify the already vulnerable neurologic state and perhaps even trigger and exacerbate existing symptoms.

WHAT ARE THE GENERAL GUIDELINES FOR TREATING SCHIZOPHRENIA?

The National Institute of Mental Health and the Agency for HealthCare Policy and Research have organized their treatment recommendations into seven categories: (1) antipsychotic medications; (2) additional medications for depression, anxiety or hostility; (3) electroconvulsive therapy; (4) psychological treatments; (5) family interventions; (6) vocational rehabilitation; and (7) assertive community treatment. The earlier schizophrenia is detected and treated, the better the outcome. Studies indicate that patients who receive antipsychotic drugs and other treatments during their first episode are hospitalized less frequently during the following five years and may require less time to fully control symptoms than those who do not seek help as quickly. One study found that intervention with monitoring, low dose medication, and therapy in patients with very early signs of schizophrenia reduced the diagnosis of full-blown schizophrenia by tenfold. Patients usually endure, however, an average of 10 months of serious symptoms before they receive treatment, and research shows that more than half of individuals with schizophrenia receive inadequate care. In particular African Americans are less likely to receive good treatment.

WHAT ARE THE DRUG TREATMENTS FOR SCHIZOPHRENIA?

Typical Antipsychotic (or Neuroleptic) Drugs.

The typical antipsychotic drugs have been, until recently, the mainstay of treatment for schizophrenia. They work by blocking receptors of the neurotransmitter dopamine, which is thought to play a role in psychotic symptoms. These medications are also referred to as neuroleptic drugs, because they can cause a number of neurologic side effects [ see below ]. The first drug of this type used for treating schizophrenia was chlorpromazine (Thorazine). Many other antipsychotic drugs are now available, the most popular being haloperidol (Haldol). Others include perphenazine (Trilafon), thioridazine (Mellaril), mesoridazine (Serentil), trifluoperazine (Stelazine), and fluphenazine (Prolixin). Studies have not shown any significant difference in benefits among these drugs. The beneficial impact of these drugs is greatest on psychotic symptoms, particularly hallucinations and delusions in the early and midterm stages of the disorder. Typical antipsychotic drugs are not very successful in reducing negative symptoms, although people often show less withdrawal and apathy because of the reduction in psychotic episodes. Between one-fifth and one-third of all patients with schizophrenia do not respond adequately to drug treatment. One major study reported that only about a third of patients receive correct dosages.

Treating an Acute or Initial Phase. For the severe, active phase of schizophrenia, injections of an antipsychotic drug are often given every four to eight hours until the patient is calm. If possible, however, physicians prefer administering a drug orally or at least switching to an oral drug as soon as possible. Generally, higher doses are used to treat acute episodes and lower doses are given during periods of remission. In patients who do not to respond to haloperidol within three weeks, boosting the dosage does not appear to be effective and may be counter productive. One study indicated that for patients with a first episode, lower than standard doses, which have less risk for side effects, may be effective. In patients who are being treated for the first time, improvement in psychotic symptoms may be evident within one or two days of treatment, although the full benefit of the drug usually evolves over about six to eight weeks. Thought disturbances tend to abate more gradually.

Relapse and Maintenance. To reduce the risk of relapse, many physicians recommend that antipsychotic drugs be given daily for at least one year. About 75% of patients will relapse within two years after withdrawing from medication. If two or more episodes occur, some experts recommend maintenance treatment for at least five years--possibly indefinitely. Up to 75% of patients, however, stop using the drugs within two years. Compliance with an ongoing maintenance regimen is a problem for a number of reasons: side effects can be debilitating; the life of a patient with schizophrenia is usually unstable; and many people are reluctant to accept the concept of life-long treatment. To avoid side effects and to improve compliance, physicians try to keep dosages (and, therefore, side effects) as low as possible. The drug effects must be monitored carefully by the physician. Effectiveness varies from individual to individual, and 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. Depot therapy (long-lasting forms of neuroleptics, usually Haldol or Prolixin, that are administered as monthly injections) have been used with success in people who have difficulty complying with the daily regimen. In Europe, injection regimens have reduced the relapse rate of symptoms by more than 50%. Some experts recommend that depot therapy be used routinely in people who have shown they could tolerate short-acting forms. One disadvantage of this therapy is that side effects, if they occur, are prolonged.

Side Effects of Neuroleptics. Neuroleptics can have adverse side effects related to many organs and systems in the body. Sleepiness and lethargy commonly occur in the beginning of therapy, but they usually decrease over time. Other side effects include dry mouth, eye problems, allergic reactions, weight gain, and menstrual irregularities in women. Sexual dysfunction resulting from treatments is a common reason for noncompliance, although the drug amantadine may help offset this side effect. A much more serious but rare side effect is the neuroleptic malignant syndrome, in which dangerously high body temperatures occur. Without prompt and expert treatment, this side effect can be fatal in 20% of those who develop it. Sometimes the effects of the drugs mimic schizophrenic symptoms, such as agitation, slow speech, and retarded movement, and so the physician may be tempted to increase the dosage.

The most disturbing common side effects of typical antipsychotic drugs are those known as extrapyramidal symptoms, which involve the nerves and muscles controlling movement and coordination. Women face a higher risk for these symptoms, and the risk increases with length of therapy and age. So-called high potency drugs (e.g., haloperidol, and fluphenazine) cause less drowsiness and drops in blood pressure but pose a higher risk for extrapyramidal side effects; low-potency drugs (e.g., chlorpromazine, thioridazine) are more sedating but side effects are not as acute. Nearly every neuroleptic drug can cause extrapyramidal side effects, which occur in up to 70% of patients taking these medications. A condition known as acute dystonia can develop shortly after taking antipsychotic drugs. This syndrome includes abnormal muscle spasms, particularly sustained contortions of the neck, jaw, trunk, and eye muscles. The most serious effect of antipsychotic therapy is tardive dyskinesia , which is often manifest by repetitive and involuntary movements, or tics, most often of the mouth, lips, or of the legs, arms, or trunk. Symptoms range from mild to severe, and sometimes interfere with eating and walking. They can appear months or even years after taking the drugs. After the drug is withdrawn, symptoms can sometimes persist for weeks or months. Some cases of tardive dyskinesia may be permanent although they can go into remission, or remit completely.

Treatment of Extrapyramidal Side Effects. In general, if extrapyramidal side effects occur from neuroleptic drugs, the physician may first try to reduce the dosage or switch to an atypical drug [ see below ]. Extrapyramidal side effects may actually mimic those of Parkinson's disease (caused by too little dopamine), and so physicians may prescribe anti-parkinsonism drugs known as anticholinergics which increase dopamine levels and help to restore balance. Among the anticholinergics most commonly used in the U.S. are trihexyphenidyl (Artane, Trihexy) and benztropine (Congentin). Some of these drugs may also be helpful in managing negative symptoms of schizophrenia. The use of anticholinergics, however, adds to the cost and complicates management: they have their own, sometimes serious, side effects. They commonly cause dryness of the mouth and may cause nausea, blurred vision, increased heart rate, constipation, and urinary retention in men with enlarged prostates. People with glaucoma should use these drugs cautiously. Anticholinergics may even cause significant mental problems, including memory loss, confusion, and hallucinations, which can mimic schizophrenia. They also interact with alcohol and antihistamines.

Most experts oppose the routine use of anti-parkinsonism drugs for schizophrenia and recommend them only for patients who cannot be monitored regularly and for those who need very high doses of powerful antipsychotic drugs and are at risk for severe side effect. Experts recommend they be withdrawn after three or four months if possible. If symptoms recur, the drugs can be reinstituted. It should be noted that withdrawal from anticholinergics can cause depression that can exacerbate schizophrenia.

Atypical Drugs.

Although antipsychotics also affect dopamine levels, the actions of medications known as atypical drugs appear to occur in areas of the brain that are different from those affected by the older, typical, neuroleptic drugs. Clozapine (Clozaril) was the first of these drugs; newer ones include risperidone, olanzapine, and quetiapine. With the exception of clozapine, which has severe side effects, many experts now recommend atypical drugs for patients who are first diagnosed with schizophrenia and for patients who fail to respond to antipsychotics or who relapse. The most successful atypical drugs are able to simultaneously affect dopamine receptors and other neurotransmitters responsible for psychotic symptoms. Unlike the standard antipsychotics (also known as neuroleptics) the atypical drugs have some effect on negative as well as positive symptoms and may help prevent relapse. They are also rarely associated with severe extrapyramidal side effects caused by the antipsychotics.

Clozapine. Clozapine (Clozaril) has been of benefit in up to half of the patients with schizophrenia who did not respond to standard treatments. It is particularly useful in younger people, although side effects are common, and newer atypical drugs may prove to be better choices. Positive effects may not be evident for up to nine months. Clozapine has improved negative symptoms in short-term trials; longer ones are needed to see if the benefit is sustained. Studies continue to report that it also reduces aggressive behavior and suicidal impulses. Although the drug does not appear to cause tardive dyskinesia, it does have other side effects including nasal congestion, drooling, low blood pressure, headache, sleeplessness, and significant weight gain. Serious side effects include seizures and, in up to 1% of cases, agranulocytosis--a potentially life-threatening decrease in the patient's white blood cells. When agranulocytosis develops, it usually does so within three months of treatment, peaking in the third month; if it hasn't appeared within six months, it most likely will not develop. Older women are at higher risk for this side effect. Agranulocytosis can be reversed if treatment with clozapine is stopped at once. It is important that people taking clozapine have their serum glucose level count monitored frequently, especially those with diabetes or a family history of diabetes. The potency of clozapine can be effected by fluctuations in caffeine intake; patients who drink caffeinated beverages should be monitored by a doctor, particularly if their drinking habits change. Although clozapine is more expensive than haloperidol, this extra expense may be offset by its greater efficacy, which results in fewer hospitalizations.

Risperidone. Risperidone (Risperdal) is a dopamine receptor blocker that has shown benefits and even superiority in comparison to antipsychotics. Like clozapine, risperidone may have a beneficial effect on negative symptoms. Risperidone may also improve verbal working memory, a common problem in schizophrenics. In general, it has few extrapyramidal effects, although these effects can occur at higher doses. Common side effects include sleepiness, weight gain, and dizziness.

Olanzapine. Olanzapine (Zyprexa) may be more effective in blocking the serotonin and dopamine neurotransmitters than clozapine is and it has a much lower risk for seizures and agranulocytosis. Studies indicate it is at least as effective for acute symptoms and possibly more effective for negative ones than the typical neuroleptic drugs and that it has a very low risk for causing extrapyramidal symptoms. The drug may also be beneficial for patients who do not respond to neuroleptic drugs. A new study suggests that olanzapine also may be more effective than risperidone, particularly in its effect on negative symptoms, but more research is needed to confirm result. Like risperidone, olanzapine can cause sleepiness, weight gain, and dizziness.

Other Useful Drugs.

Antidepressants. Antidepressants are recommended along with antipsychotics to alleviate the depression that is so common in people with schizophrenia. One study indicates that taking antidepressants may even help prevent relapse. In spite of their benefits, less than half of all patients are given these useful medications. (African Americans are even less likely to receive antidepressants.)

Anti-Anxiety Drugs . Benzodiazepines are drugs normally used to treat anxiety; they have been found to reduce psychotic symptoms, although not as effectively as standard antipsychotic therapy, and they may have a strong sedative effect. Some physicians use them first during an attack to reduce the need for a higher dose of the more potent antipsychotic drugs. They may be useful in the early stages of a psychotic relapse for preventing a full attack and are sometimes used to treat the restlessness and agitation that can occur with the use of neuroleptics. Severe side effects, including respiratory arrest, very low blood pressure, and loss of consciousness, have been reported in a few people taking antianxiety medication and clozapine but there is no evidence yet of a clear danger associated with the use of these two drugs. In any case, prolonged use of anti-anxiety drugs is generally not recommended in schizophrenia and withdrawal must be gradual.

WHAT ARE NON-DRUG THERAPIES FOR SCHIZOPHRENIA?

Schizophrenia is now officially categorized as a brain disease, not a psychologic disorder, and drug treatment is the primary therapy. Between one-fifth and one-third of all patients with schizophrenia, however, do not respond adequately to drug treatment. The effects of the disease are profoundly emotional, and experts generally agree that current treatment should be an integrated approach using both drugs and some form of psychosocial therapy. Many patients who have been successfully treated with medications experience the "awakenings" phenomena, which are painful reactions that are manifested as inner emotions and the recognition of real losses. In such cases, psychotherapy is certainly an essential support. Other treatments may also be useful.

Electroconvulsive Therapy (ECT).

Electroconvulsive therapy (ECT), often called shock treatment, has received bad press since it was introduced in the 1940s, but refined techniques have recently revived its use, particularly for severe depression. Imaging studies have not found that current ECT techniques cause any damage to the brain's structure, and some physicians feel it is safer than drug therapy. One study found that ECT was helpful in a small group of adolescents with schizophrenia and other disorders.

Psychosocial Therapy.

Because so much is now known about the physical basis for schizophrenia, psychotherapy is no longer recommended as an alternative to drug treatment. One study reported, however, that patients were more likely to take their drugs if they meet with a therapist for as short a time as 15 minutes per month. Most experts believe that an integrated program that offers both medical and psychological treatment of the patient and support to the family or other caregiver is important for the long-term improvement of people with schizophrenia. Rather than the classic psychoanalytic approach that uncovers and analyzes childhood events, the use of cognitive-behavioral methods of therapy are showing particular promise in helping patients . Commonly used for depression, this approach attempts to strengthen the patient's capacity for normal thinking using mental exercises and self-observation. In one study, patients who combined cognitive therapy with routine care (using medications) reported nearly eight times the chance for improvement compared to routine care alone. Cognitive therapy teaches patients to change their negative patterns of thought and behavior by helping them learn problem solving techniques and other strategies to reduce the risks for relapse. One method is to retrain the patient in basic living skills to make up for the mental impairment. Patients are trained in social skills, such as good hygiene, cooking, and traveling, in improving thinking, and learning techniques to achieve a basic quality of life. This approach should also include methods for stress reduction, intervention to maintain compliance with drug therapy, and general emotional support.

Family and Outside Support Structures.

Family Support . In any treatment of a mental disorder, it is unwise to view the patient as if he or she existed in a vacuum. The people closest to the patient play too great a role in the course of a disease to be ignored. It is deeply painful for anyone to interact with a loved one whose behavior is determined not by a healthy and immediate response to the real world, but by a mysterious internal mechanism that has gone awry. Nevertheless, fewer than 10% of families of patients with schizophrenia receive support and education, even though many studies have shown the benefits of such programs for both the patient and the family. Studies are showing that when families become involved in a positive way, particularly with other families who share similar difficulties, the relapse rates for patients is significantly lower than for patients simply receiving medication and treatment. For example, families or other caregivers can be taught to recognize impending symptoms of or stressful situations that might trigger a schizophrenic event, help patients comply with drug treatments, and to recognize early signs of serious side effects of these treatments. Both physicians and family members should be on the lookout for signs of relapse. Such symptoms may include feeling distant from family and friends, being increasingly bothered by persistent thoughts, and having an increased interest in religion.

In addition to helping the patient, however, family members and caregivers usually need support as well. Often their own mental health is threatened. When affection and reason have failed to bring a loved one back to reality, family members often react with anger and frustration, which only makes the situation worse. Out of despair and fear, they may reject the patient completely. Numerous studies have shown that schizophrenic patients do worse in families who are overly emotional--either hostile, critical, or overly involved. The problem is a two way street, critical families generate anxiety and depression in patients and conversely, anxiety and depression in patients may induce criticism from families. Studies indicate that once the patient receives appropriate treatment and support, the family's over-emotional state also recedes. Support groups can be very helpful, and some studies show that patients improve when families are in self-help groups. Short-term residential care and other services can also help protect the patient and offer relief to the family [ see Where Else Can Someone Get Help For Schizophrenia?, below].

Vocational Rehabilitation. Up to 90% of patients with severe mental problems are unemployed. Paid work is very important in the health of the patient. One study reported that after one year, 40% of workers with schizophrenia who were paid for their labor reported much improvement in all symptoms and 50% reported much improvement in positive symptoms. Those who were not paid for their work did considerably less well. At this time, less than a quarter of patients with schizophrenia are in programs that assist them in finding and keeping jobs.

Alternative Treatments.

In a few studies, the common amino acid glycine has been used in large doses to treat negative symptoms, resulting in a small, but significant, improvement in some patients. There were few side effects. In one study, when glycine was added to an antipsychotic drug regimen, patients experienced a 7% reduction in negative symptoms, less depression, and better mental function. Glycine is available in health food stores, but between 60 to 120 over-the-counter pills would have to be taken daily to match the strength of the glycine currently being tested in trials. Physicians do not recommend purchasing glycine for this purpose, but more research would be worth while. According to the results of a recent study, the consumption of omega-3 fatty acids found in fish oils was associated with improvement in patients with schizophrenia.

WHERE ELSE CAN SOMEONE GET HELP FOR SCHIZOPHRENIA?

RECENT LITERATURE

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