Professional Documents
Culture Documents
DRUG CLASS AND MECHANISM: Clozapine is an anti-psychotic medication that works by blocking receptors in the
brain for several neurotransmitters (chemicals that nerves use to communicate with each other) including dopamine
type 4 receptors, serotonin type 2 receptors, norepinephrine receptors, acetylcholine receptors, and histamine
receptors. Unlike traditional anti-psychotic agents, such as chlorpromazine (Thorazine) and haloperidol (Haldol) as
well as the newer anti-psychotics, risperidone (Risperdal) and olanzapine (Zyprexa), clozapine only weakly blocks
dopamine type 2 receptors.
PRESCRIPTION: Yes
PRESCRIBED FOR: Clozapine is use in the management of psychotic disorders including schizophrenia. Because of
concern for the side effect of agranulocytosis (see side effects), clozapine should be reserved for patients who have
failed to respond to other standard medications or who are at risk for recurring suicidal behavior.
DOSING: Clozapine is given once, twice, or three times daily. The dose often is increased slowly until the optimal
dose is found. The full effects of clozapine may not be seen until several weeks after treatment is begun.
DRUG INTERACTIONS: Risperidone (Risperdal) may cause an increase in the amount of clozapine in the blood.
This could lead to an increased risk of side effects from clozapine.
PREGNANCY: There are no adequate studies of clozapine in pregnant women. Studies in animals suggest no
important effects on the fetus. Clozapine can be used in pregnancy if the physician feels that it is necessary.
NURSING MOTHERS: Animal studies suggest that clozapine is secreted in breast milk. Therefore, women taking
clozapine should not nurse their infants.
SIDE EFFECTS: Clozapine may cause a severe reduction in white blood cell count, a condition known as
agranulocytosis, in approximately1 in 100 patients who take it for at least one year. White blood cells fight infections,
and a severe reduction in white blood cells can result in severe infections. If not caught early, agranulocytosis can be
fatal. Therefore, the white blood cell countshould bemeasured (with a blood test) prior to starting treatment and
regularly (weekly) while patients receive this medication, and for 4 weeks after it is stopped.
Among elderly patients with dementia-related psychosis, treatment with clozapine is associated with an increased risk
of death for unclear reasons. Clozapine is not approved for use in dementia-related psychosis.
Seizures have occurred in approximately 1 of every 20 to 30 persons receiving clozapine. Patients receiving higher
doses seem to be at higher risk.
Dizziness may occur in 1 of 5 persons taking clozapine. In some cases this may be due to orthostatic hypotension, a
marked decrease in blood pressure that occurs when going from a lying or sitting position to a standing position. The
drop in blood pressure may lead to loss of consciousness or even cardiac and respiratory arrest.This reaction is more
common during the first few weeks of therapy while the dose is increasing, when drug is stopped briefly, or when
patients are taking benzodiazepinessuch asdiazepam (Valium) or other anti-psychotic drugs.
The most common side effect of clozapine is drowsiness. Other side effects include increased heart rate, increased
salivation, headache, tremor, low blood pressure, and fever. Clozapine has anticholinergic effects that interfere with
the function of smooth muscles. This can lead to blurred vision and difficulty urinating (when there isenlargement of
the prostate) due to effects on the muscles of the eye and bladder. Clozapine slows the intestine and leads to
constipation in approximately 14% of patients. Paralysis of the intestinal muscles can lead to paralytic ileus, a
conditionin which the intestine stops working.
CLOZAPINE
( kloe' za peen)
Clozaril
PREGNANCY CATEGORY B
Drug classes
Therapeutic actions
Indications
Contraindications and cautions
Available forms
Dosages
Adults
Pediatric patients
Pharmacokinetics
Adverse effects
Interactions
Drug-drug
Nursing considerations
CLINICAL ALERT!
Assessment
Interventions
Teaching points
Drug classes
Antipsychotic
Dopaminergic blocking agent
Therapeutic actions
Mechanism not fully understood: blocks dopamine receptors in the brain, depresses the RAS; anticholinergic,
antihistaminic (H 1), and alpha-adrenergic blocking activity may contribute to some of its therapeutic (and adverse)
actions. Clozapine produces fewer extrapyramidal effects than other antipsychotics.
Indications
• Management of severely ill schizophrenics who are unresponsive to standard
antipsychotic drugs.
• Reduction of the risk of recurrent suicidal behavior in patients with schizophrenia
or schizoaffective disorder.
Available forms
Tablets—25, 100 mg
Dosages
Adults
Initial: 25 mg PO daily or bid; then gradually increase with daily increments of 25–50
mg/day, if tolerated, to a dose of 300–450 mg/day by the end of second week.
Adjust later dosage no more often than twice weekly in increments < 100 mg. Do
not exceed 900 mg/day.
Maintenance: Maintain at the lowest effective dose for remission of symptoms.
Discontinuation: Gradual reduction over a 2-wk period is preferred. If abrupt
discontinuation is required, carefully monitor patient for signs of acute psychotic
symptoms.
Reinitiation of treatment: Follow initial dosage guidelines, use extreme care;
increased risk of severe adverse effects with re-exposure.
Pediatric patients
Safety and efficacy in patients < 16 yr not established.
Pharmacokinetics
Adverse effects
Adverse effects in Italics are most common; those in Bold are life-threatening.
Interactions
Drug-drug
• Increased therapeutic and toxic effects with cimetidine
• Decreased therapeutic effect with phenytoin, mephenytoin, ethotoin
Nursing considerations
CLINICAL ALERT!
Name confusion has occurred with Clozaril (clozapine) and Colazal (balsalazide);
dangerous effects could occur. Use extreme caution.
Assessment
• History: Allergy to clozapine, myeloproliferative disorders, history of clozapine-
induced agranulocytosis or severe granulocytopenia, severe CNS depression,
comatose states, history of seizure disorders, CV disease, prostate enlargement,
narrow-angle glaucoma, lactation, pregnancy
• Physical: T, weight; reflexes, orientation, intraocular pressure, ophthalmologic
exam; P, BP, orthostatic BP, ECG; R, adventitious sounds; bowel sounds, normal
output, liver evaluation; prostate palpation, normal urine output; CBC, urinalysis,
liver and kidney function tests, EEG
Interventions
• Use only when unresponsive to conventional antipsychotic drugs.
• Obtain clozapine through the Clozaril Patient Management System.
• Dispense only 1 wk supply at a time.
• Monitor WBC carefully prior to first dose.
• Weekly monitoring of WBC during treatment and for 4 wk thereafter. Dosage may
be adjusted based on WBC count.
• Monitor T. If fever occurs, rule out underlying infection, and consult physician for
comfort measures.
• Monitor elderly patients for dehydration. Institute remedial measures promptly;
sedation and decreased thirst related to CNS effects can lead to dehydration.
• Encourage voiding before taking drug to decrease anticholinergic effects of
urinary retention.
• Follow guidelines for discontinuation or reinstitution of the drug.
Teaching points
• Weekly blood tests will be taken to determine safe dosage; dosage will be
increased gradually to achieve most effective dose. Only 1 wk of medication can be
dispensed at a time. Do not take more than your prescribed dosage. Do not make
up missed doses, instead contact care provider. Do not stop taking this drug
suddenly; gradual reduction of dosage is needed to prevent side effects.
• These effects may occur as a result of drug therapy: drowsiness, dizziness,
sedation, seizures (avoid driving or performing tasks that require concentration);
dizziness, faintness on arising (change positions slowly); increased salivation
(reversible); constipation (consult care provider for correctives); fast heart rate
(rest, take your time).
• This drug cannot be taken during pregnancy. If you think you are pregnant or wish
to become pregnant, contact your care provider.
• Report lethargy, weakness, fever, sore throat, malaise, mouth ulcers, and flu-like
symptoms.
Health
Top of Form
Search
Bottom of Form
Share
In-Depth Reports
Home
In This Report
Highlights
Introduction
Causes
Risk Factors
Complications
Symptoms
Diagnosis
Treatment
Medications
Psychotherap
y
Other
Treatments
Resources
References
Encyclopedia
Schizophrenia
Schizophrenia -
disorganize...
Schizophrenia -
paranoid ty...
More Features
Printer-friendly
version
Schizophrenia
Highlights
Causes of Schizophrenia
The causes of schizophrenia are unknown. Multiple factors may play a role such as
genetics and brain chemistry.
Age. Schizophrenia can occur at any age, but it tends to first develop (or at least
become evident) between adolescence and young adulthood.
Gender. Schizophrenia affects both men and women, although males tend to
develop it at a slightly younger age (teens and 20s) than females (20s and 30s).
Family History. Schizophrenia often runs in families. Older paternal age is also being
investigated as a risk factor for schizophrenia.
Complications of Schizophrenia
Medications
Introduction
Delusions
Hallucinations
Disordered thinking
Emotional unresponsiveness
Psychotic symptoms
Disordered thinking
Some psychiatrists group psychotic and disordered thinking into a single category
called positive symptoms.
The disease is complicated by the fact that although a schizophrenic patient may
have more than one symptom, the patient rarely has all of them. Symptoms also
often go into remission.
Causes
No single cause can account for schizophrenia. Rather, it appears to be the result of
multiple causes such as genetic factors, environmental and psychological assaults,
and possible hormonal changes that alter the brain's chemistry.
Brain scans using magnetic resonance imaging (MRI) have shown a number of
abnormalities in the brain's structure associated with schizophrenia. Such problems
can cause nerve damage and disconnections in the pathways that carry brain
chemicals.
Because these problems tend to show up on brain scans of people with chronic
schizophrenia rather than newly diagnosed patients, some doctors believe they may
be a result of the disease and its treatments rather than a cause. (Medications used
for schizophrenia can also cause brain shrinkage over time.)
Genetic Factors
Researchers are seeking the specific genetic factors that may be responsible for
schizophrenia in such cases. Current evidence suggests that there are a multitude
of genetic abnormalities involved in schizophrenia, possibly originating from one or
two changes in genetic expression. Scientists are beginning to discover the ways in
which specific genes affect particular brain functions and cause specific symptoms.
Genes that have been studied include the neuregulin-1 gene, the OLIG2 gene, and
the COMT gene.
Heredity does not explain all cases of the disease. About 60% of people with
schizophrenia have no close relatives with the illness.
Infectious Factors
Winter and Spring Births. The risk for schizophrenia worldwide is 5 - 8% higher for
those born during winter and spring, when colds and viruses are more prevalent.
Large Families. The risk for schizophrenia is also greater in large families in which
there are short intervals between siblings (2 or fewer years). Such observations
suggest that exposure to infection early in infancy may help set the stage for later
development of the disease.
Researchers are trying to identify specific viruses that may be responsible for some
cases. Of particular interest is research finding evidence of a virus that belongs to
the HERV-W retrovirus family in 30% of people with acute schizophrenia.
Some research has found an association between some cases of schizophrenia and
toxoplasmosis, a parasite carried by cats and other domestic animals. Several
studies suggest that patients with schizophrenia have an increased prevalence of
antibodies to toxoplasmosis. Toxoplasmosis can lie dormant in the nervous system
and migrate to the brain over many years.
Psychologic Factors
Age
Schizophrenia can occur at any age, but it tends to first develop (or at least become
evident) between adolescence and young adulthood. Schizophrenia in children is
likely to be severe. Although the risk of schizophrenia declines with age, its
incidence has been known to peak in those who are about 45 years old, and again
in people who are in their mid-60s (mostly women). Late-onset schizophrenia that
develops in the 40s is most likely to be the paranoid subtype with fewer negative
symptoms or learning impairment. Such patients usually have functioned at a near-
normal level until structural deficits in the brain break down.
Gender
Although schizophrenia affects both men and women, there are some differences:
The onset in women is usually slightly later, between ages 25 - 34, and the
symptoms tend to be less severe. The earlier a girl starts menstruation, the longer
she is protected against schizophrenia. Schizophrenia is more severe during a
woman's menstrual cycle when estrogen levels are low. Such findings and other
evidence suggest that estrogen may have nerve-protecting properties. For example,
the higher the estrogen levels in female patients with schizophrenia, the better their
mental functions.
Intelligence
People with schizophrenia span the full range of intelligence. In fact, one study
reported that a higher than expected number of people who develop schizophrenia
had been intellectually gifted children. Research suggests, however, that a decline
in IQ scores during childhood may be a sign of potential psychotic symptoms in
adults.
Socioeconomic Factors
Schizophrenia occurs twice as often in unmarried and divorced people as in married
or widowed individuals. Furthermore, people with schizophrenia are eight times
more likely to be in the lowest socioeconomic groups. However, these findings are
likely to be a result of schizophrenia rather than a cause. Nevertheless, low income
and poverty increases the risk for delayed diagnosis and treatment, and such delays
could lead to more severe disease in patients with fewer resources.
Fathers 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. In one
study, children of fathers who were 50 years old or more faced a three-fold risk for
schizophrenia compared to children of fathers who were 25 or younger.
Epilepsy. A family history of epilepsy increases the chance for developing
schizophrenia or similar psychosis. Scientists think that epilepsy and schizophrenia
may share similar genetic or environmental factors.
Complications
Medical Illnesses
Studies have reported that people with severe mental illnesses suffer more from
serious health problems than those without mental disorders, and they are less
likely to receive medical help. Substance abuse is a significant factor in this higher
risk.
Depression
Depression is common later in adulthood. Although this mood disorder can certainly
be a result of the negative social impact of schizophrenia, some doctors believe that
depression is part of the disease process itself.
Studies indicate that after 20 - 30 years, half of patients are able to care for
themselves, work, and participate socially. Support services and appropriate
housing improve this outcome. Unsurprisingly, the decline in status, including the
inability to earn a living, is less steep when there are more financial resources and
fewer emotional disorders at the outset of symptoms. Also, on average, the later
the onset of the disease, the milder the social impact. The long-term effects on work
and relationships, however, are usually severe and difficult to repair, even if
symptoms improve.
Effect on Intelligence
In one study, about half of patients experienced some decline in IQ (10 points or
more), but intelligence scores remained the same in the other half. Researchers
believe that a decline in IQ reflects early nerve damage but that it is not an
inevitable consequence of the disease process.
Suicide
The general risk for suicide is higher at certain times in the course of the disease:
The widespread use of antipsychotic drugs over the past decade does not appear to
have had much effect on suicide rates. In fact, evidence suggests that the use of
these drugs as a way of reducing hospitalization time is increasing the incidence of
suicide. Depression, not delusions, appears to be the most important motive for
suicide in these patients. Suicide risk is also associated with prior suicide attempts,
drug abuse, agitation, poor treatment compliance, fear of mental deterioration, and
personal loss.
Self-Destructive Behaviors
Smoking and Other Addictions. Most people with schizophrenia abuse nicotine,
alcohol, and other substances. Substance abuse, in addition to its other adverse
effects, increases non-compliance with antipsychotic drugs in the schizophrenic
patient and may worsen symptoms.
Family members suffer from grief, long-term guilt, and many emotional issues when
faced with a schizophrenic loved one. If these patients commit suicide, the effects
can be devastating.
In the 1970s, tens of thousands of patients were put on antipsychotic drugs and
released from institutions into the community, a concept called
deinstitutionalization. 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 with schizophrenia require public assistance within a year of their
reentry into the community.
Symptoms
Impairments in gross motor skills (the child's ability to control different parts of the
body)
Attention deficits
Most often, early warning signs go unnoticed, and schizophrenia usually becomes
evident for the first time in late adolescence or early adulthood. Schizophrenia that
starts in childhood or adolescence tends to be severe. It should be strongly noted
that the traits discussed above, even combinations of them, can be present without
schizophrenia.
Negative Symptoms
Lack of emotions
Colorless speaking tones
Lack of responsiveness and poor sociability often appear in childhood as the first
indications of schizophrenia. Certain imaging techniques suggest that these findings
are based on biologic changes in specific parts of the brain. In many patients,
however, negative symptoms do not appear until after positive symptoms develop.
Negative symptoms tend to be more common than positive symptoms in older
patients and typically persist after positive symptoms have been treated.
Psychotic Symptoms
Psychotic symptoms, particularly delusions and hallucinations, are the most widely
recognized manifestations of schizophrenia.
Psychotic symptoms usually occur every now and then, alternating with periods of
remission. They typically occur in men ages 17 - 30 and in women ages 20 - 40.
The symptoms of cognitive impairment and disordered thinking may occur before
other symptoms of schizophrenia. They include:
A lack of attention.
Other Symptoms
The course of the disease varies from one patient to the next. Symptoms of
psychosis can become gradually or suddenly evident.
In up to a third of patients, the disease is unrelenting and progresses from the first
episode onward.
Diagnosis
The doctor will use one or more verbal screening tests to help determine whether a
patient's symptoms meet the criteria for schizophrenia. Because no single symptom
is specific to schizophrenia, a diagnosis may be made when one or more of the
following conditions is present:
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 emotional unresponsiveness with a flat
speaking tone).
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. The patient's social and personal
relationships would also have deteriorated since the onset of symptoms.
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).
Among the conditions that may resemble schizophrenia are the following:
Depression. Delusions that focus on a physical abnormality or disease that isn't real,
known as somatic delusions, sometimes occur in people with depression.
Bipolar Disorder. Paranoia and delusions of grandeur (the belief that one has a
special power or mission) can occur in people with bipolar disorder during the manic
phase. Sometimes it is difficult even for doctors to differentiate between these two
disorders. Evidence suggests that they may share certain genetic factors that make
some families vulnerable to either one.
Alcohol and Drug Abuse. Either substance abuse itself or withdrawal from drugs or
alcohol can trigger 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 the psychosis ends after withdrawal from drugs or alcohol,
and returns if the patient returns to alcohol or substance abuse.
Medical Illnesses. Other causes of psychotic symptoms include cancer in the central
nervous system, encephalitis, neurosyphilis, thyroid disorders, Alzheimer's disease,
epilepsy, Huntington's disease, multiple sclerosis, stroke, Wilson's disease, some
vitamin B deficiencies, and systemic lupus erythematosus.
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.
Imaging Techniques
Many brain imaging techniques can detect changes in the brain structure that relate
to specific sets of symptoms in schizophrenia. These imaging techniques include
magnetic resonance imaging (MRI), single photon emission computed tomography
(SPECT), and positron emission tomography (PET). Such techniques are used as
research tools. However, research continues in evaluating whether they may be
useful for identifying candidates for early treatment among high-risk young people
with early warnings signs of schizophrenia and brain damage.
Treatment
Family psychotherapy
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.
Typical antipsychotics. Until recently, these drugs were the mainstay treatments for
schizophrenia. They include haloperidol (Haldol), chlorpromazine (Thorazine),
perphenazine (Trilafon), thioridazine (Mellaril), mesoridazine (Serentil),
trifluoperazine (Stelazine), and fluphenazine (Prolixin). Side effects involving the
nerves and muscle movement and coordination occur in up to 70% of patients.
Typical antipsychotics 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 but new research contradicts the belief that they are safer for the
heart. They include clozapine (Clozaril), risperidone (Risperdal), olanzapine
(Zyprexa), quetiapine (Seroquel), ziprasidone (Geodon), aripiprazole (Abilify), and
palperidone (Invega).
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 work no better 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 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.
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.
Delusions of persecution
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 play an important role in treating
the patient with schizophrenia, particularly given the role of depression in the high
rates of suicide among these patients.
Psychiatrists generally agree that current treatment should offer both medical and
psychological treatment to the patient. 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
Seven atypical antipsychotic drugs are currently approved in the United States:
Clozapine (Clozaril)
Risperidone (Risperdal)
Olanzapine (Zyprexa)
Quetiapine (Seroquel)
Aripiprazole (Abilify)
Ziprasidone (Geodon)
Paliperidone (Invega)
Clozapine was the first atypical drug approved (in 1989), and paliperodine the most
recent approved (in 2007). Clozapine appears to have more side effects than the
other atypical antipsychotics. Most of these drugs 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.
May reduce the risk for suicide (clozapine may be particularly helpful for suicide
prevention).
These drugs, particularly the newer atypicals, have fewer extrapyramidal side
effects than the typical antipsychotics.
Drooling
Dizziness
Headache
Drowsiness -- although, sometimes the drugs may cause restlessness and insomnia
Constipation
Difficulty urinating
Skin rash
The following are more severe side effects or complications that may occur with
these drugs:
Diabetes
Weight gain and metabolic problems. The risk is highest for olanzapine, and lowest
for aripiprazole and ziprasidone.
Unhealthy cholesterol levels. Particularly with olanzapine, increased risk for high
levels of trigylcerides and total cholesterol.
Seizures.
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 if they take clozapine.
All atypical antipsychotic drugs carry a black box warning on their prescribing labels
advising that these 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 medicines.) The U.S. Food and Drug Administration (FDA)
recommends that:
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 lipid and cholesterol levels monitored. [For more information,
see In-Depth Report #60: Diabetes - type 2.]
Chlorpromazine (Thorazine)
Perphenazine (Trilafon)
Thioridazine (Mellaril)
Mesoridazine (Serentil)
Trifluoperazine (Stelazine)
Fluphenazine (Prolixin)
Studies have not shown any significant difference in benefits among these drugs.
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 include:
Extrapyramidal symptoms
Sleepiness and lethargy -- common in the beginning but usually decreases over
time
Allergic reactions
Sexual dysfunction -- a common reason why patients stop taking the drug;
amantadine may help offset this side effect
Neuroleptic malignant syndrome -- rare, but can be fatal without prompt treatment
In general, higher potency drugs cause less drowsiness and drops in blood pressure
but pose a higher risk for extrapyramidal side effects. Lower-potency drugs (such as
chlorpromazine, thioridazine) are more sedating and have milder side effects.
Extrapyramidal Symptoms
Nearly every drug used to date for schizophrenia can cause extrapyramidal side
effects to some degree. These side effects involve the nerves and muscles
controlling movement and coordination.
Tardive dyskinesia is the most serious extrapyramidal side effect. It often manifests
itself 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 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 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, trunk, and eye muscles.
Other extrapyramidal symptoms. Other effects are agitation, slow speech, tremor,
and retarded movement. It should be noted that sometimes these symptoms mimic
schizophrenia itself. In response, the doctor may be tempted erroneously to
increase the dosage.
Anti-Anxiety Drugs. Benzodiazepines are drugs normally used to treat anxiety. They
also have some modest effect on psychotic symptoms. They may be useful in the
early stages of a psychotic relapse for preventing a full attack. They also 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 anti-
anxiety medication and clozapine. There is no evidence, however, 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. Withdrawal from
these drugs should occur gradually.
Lithium. Lithium, ordinarily used for bipolar disorder, is useful for some
schizophrenic patients. It appears to help those with fewer negative symptoms and
without a family history of schizophrenia. However, there are no reliable criteria to
predict who will benefit.
Psychotherapy
Positive social interaction is extremely important for people with schizophrenia and
may help reduce symptoms, including the number of delusional moments.
Family Support. It is deeply painful for anyone to interact with a loved one whose
behavior is determined by a mysterious internal mechanism that has gone awry.
Given support and direction, however, 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, being
increasingly bothered by persistent thoughts, and having an increased interest in
religion.)
Unfortunately, the family's own mental health is often threatened. As a result,
caretakers also need help. Numerous studies have shown that patients with
schizophrenia do worse in families who are too emotional, hostile, critical, or even
overly involved. The problem is an emotional loop:
When affection and reason have failed to bring a loved one back to reality, overly
critical or emotional family members typically react with anger and frustration.
The subsequent expression of these emotions by the patient triggers yet more
criticism or acting out. So the cycle continues.
Eventually, out of despair and fear, the family may reject the patient completely.
Studies indicate that once the patient receives appropriate treatment and support,
the family's over-emotional state also recedes. Some studies have reported that
when families receive help for themselves (group support or cognitive therapy) the
relapse rates for the related patients are significantly lower than for patients whose
families did not seek help. Still, only a small number of families of patients with
schizophrenia receive the support and education needed not only for the patient but
also for themselves.
Vocational Rehabilitation. Paid work may help the mental health of the patient. One
study reported that after 1 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. (The arts and crafts activities that are often used to
enhance self-esteem in rehabilitation programs offer few real benefits to the
patient.)
Unfortunately, at this time, few patients with schizophrenia are in programs that
help them find and keep jobs, and up to 90% of patients with severe mental
problems are unemployed.
Other Treatments
Electroconvulsive therapy (ECT), often called shock treatment, has received bad
press since it was introduced in the 1940s. However, refined techniques have
revived its use, particularly for those with severe depression. Imaging studies have
not found that current ECT techniques cause any damage to the brain's structure,
and some doctors feel it is safer than drug therapy. A recent review of many clinical
trials indicated that ECT combined with antipsychotic medication can provide rapid
improvements for patients who are suicidal or severely psychotic. The review found
that the combined treatment worked better than antipsychotics alone for these
patients. ECT treatments are usually given 2 - 3 times a week, for a total of 8 - 12
sessions.