Guide

Schizophrenia
Patients to
Brenda Lumby, RN(EC), BScN, MN-ANP

chizophrenia occurs in approximately 1% of the popula-

S tion, affecting three million people in the United States. Peo-
ple with schizophrenia experience psychotic symptoms such as
delusions, hallucinations, and other disordered thoughts and feelings, which
tend to recur in a cyclical pattern with highly variable severity and frequency.
The need for treatment of psychotic symptoms, using a combination of medica-
tion and psychosocial interven-
tions,is well recognized and documented,
but presents considerable challenges. Peo-
ple with schizophrenia are at significantly
higher risk for a number of physical
health problems when compared
to the general population.1
Lifestyle plays an important

30 The Nurse Practitioner • Vol. 32, No. 7 www.tnpj.com

 2.0
CONTACT HOURS

Better Physical Health

role in this increased

risk, as do effects of the illness it-
self, the stigma associated with mental illness, and side ef-
fects of antipsychotic medications.
Brown et al. reported that mortality in people with schizophrenia from all causes occurs
at three times the rate of the general population.2 Rates are particularly high in males, the
unemployed, unmarried, and in lower socioeconomic classes. Many of these deaths, at-
tributed to failure of diagnosis, treatment refusal, poor treatment compliance, and lifestyle
are preventable. Suicides and accidents are 12 times more likely to occur in
people with schizophrenia than in the general public and accounted
for one-third of excess mortality among patients over 40 years
of age.2 Hennekens et al. found the suicide rate to be 10 to
20 times higher than average, accounting for 10% of deaths
among people with schizophrenia.3 Studies involving peo-
ple with schizophrenia who are in contact with a psychia-
trist indicate death from natural causes such as cardiovascular
disease (CVD), type-2 diabetes mellitus (T2DM), and epilepsy
occur at twice the rate of the general population, accounting for
two-thirds of excess mortality.3

www.tnpj.com The Nurse Practitioner • July 2007 31

 Mental Health
■ Physical Health Concerns
Smoking
Over 70% of people with schizophrenia smoke cigarettes,
compared with 20% of the general public.3 They are also
more likely to smoke more than 20 cigarettes per day. Ac-
cordingly, deaths from lung cancer among people with schiz-
ophrenia are twice that of the general population.2 In a study
of self-reported diagnosis of chronic obstructive pulmonary
disease, Himelhoch et al. found that people with serious
mental illness were significantly more likely to have chronic
bronchitis (19.5% versus 6.1%) and emphysema (7.9% ver-
sus 1.5%) than the general public.4 Cigarette smoking also
interferes with metabolism of some antipsychotic drugs, ne-
cessitating higher doses.5 Nevertheless, people with schizo-
phrenia who smoke are much less likely than smokers in
general to receive smoking cessation counseling.4
The self-medication theory suggests that individuals with
schizophrenia may actually use nicotine as a means to re-
duce some of the symptoms of schizophrenia. There is de-
bate in the literature about both beneficial and detrimental
effects of nicotine on a number of psychiatric conditions.
However, the known addictive properties of nicotine pre-
sent considerable ethical and legal barriers to clinical inves-
tigation (see Sidebar: “Substance Abuse”).
Obesity
Obesity has been called an epidemic in North America with
27% of the population meeting the World Health Organi-
Over 70% of people with schizophrenia
smoke cigarettes, compared with 20% of
the general public.
zation (WHO) definition of obesity (body mass index [BMI]
3,6
over 30). Of people with schizophrenia, 42% are obese.
There is an even higher prevalence among older women with
schizophrenia, 71% of whom are overweight or obese com-
pared with 38% of age-matched women in the general pub-
lic.6 Higher rates of obesity are due in large part to inactivity ble that in the general population, largely related to modi-
and diets high in fat and carbohydrates.
Conventional (typical) antipsychotics are associated with
an increased risk of obesity and metabolic disturbance, but
this is even more of a concern with newer (atypical) antipsy-
chotics. Clozapine (Clozaril, FazaClo) and olanzapine
(Zyprexa) in particular are associated with significant weight
gain. Risperidone (Risperdal) and quetiapine (Seroquel) are
atypical antipsychotics that appear to have moderate adverse
metabolic effects similar to conventional (typical) antipsy-
32 The Nurse Practitioner • Vol. 32, No. 7
chotic drugs. Aripiprazole (Abilify) and ziprasidone (Ge-
odon) have not been shown to increase rates of adverse meta-
bolic effects.7
Obesity has been associated with increased rates of os-
teoarthritis, sleep apnea, gallbladder disease, liver disease
(nonalcoholic steatohepatitis), polycystic ovarian disease, and
certain types of cancer, particularly esophageal, colon, en-
dometrial, kidney, and postmenopausal breast cancer.8 Psy-
chosocial consequences of obesity include low self-esteem
and discrimination. Of particular concern is the high rate of
obesity-related metabolic disease and CVD. Abdominal obe-
sity (female waist circumference (WC) over 35 inches/88 cen-
timeters; male WC over 40 inches/102 centimeters) indicates
increased visceral fat, which has been linked to increased risks
of coronary heart disease (CHD), hypertension, stroke, hy-
perlipidemia, metabolic syndrome, and T2DM.8,9
T2DM
People with schizophrenia are two to three times more likely
than average to develop impaired glucose metabolism or
T2DM1,3,10 and three times more likely to die from compli-
cations of T2DM.2 Macrovascular complications include
CVD, stroke, and peripheral vascular disease. Microvascular
complications of T2DM include retinopathy, nephropathy,
and neuropathy. There is also an increased risk of infection
with T2DM.
Sedentary lifestyles, poor diet, and obesity are important
risk factors for T2DM. It has been suggested that schizophre-
nia is also an independent risk factor for
T2DM.1,10-12 The relative contribution of
each antipsychotic to weight gain closely
matches its contribution to the develop-
ment of metabolic syndrome, dyslipi-
demia, impaired glucose metabolism,
and T2DM, suggesting the link is in-
creased body fat. There is some experi-
mental evidence, however, indicating a possible direct effect
on insulin resistance independent of weight gain.13
Cardiovascular Disease
The rate of CVD among people with schizophrenia is dou-
fiable risks such as smoking, obesity, inactivity, and
hyperlipidemia. This increase is less than the relative in-
crease in mortality caused by suicides. However, because
of the high overall prevalence of CVD, it is by far the most
significant cause of increased mortality in people with
schizophrenia, two-thirds of whom die from CHD.2,3 Early
platelet activation and increased platelet aggregation
may also play a role in the development of CVD in this
population.14
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Hyperlipidemia
Hyperlipidemia is an important modifiable risk factor for
CVD. Some antipsychotics (especially olanzapine and cloza-
pine), adversely affect lipid profiles, increasing low-density
lipoproteins and triglycerides, and decreasing high-density
lipoproteins, largely as an outcome of weight gain. Patients
with schizophrenia are considerably more likely than aver-
age to have hyperlipidemia, but are prescribed statins only
25% as often as the general population.3
Hypertension
Hypertensive risk factors are prevalent among people with
schizophrenia. Hypertension in this population is estimated
at 19% compared with 15% in the general population.3
They are, however, considerably less likely to be diagnosed
with and treated for hypertension. In clinical trials, anti-
hypertensive therapy has been associated with an average
reduction in stroke incidence of 35% to 40%; myocardial
infarction, 20% to 25%; and heart failure, more than 50%.7
The National Institute of Mental Health’s Clinical Antipsy-
chotic Trials of Intervention Efficacy (CATIE) reported hy-
pertension treatment rates for Hispanic patients with
schizophrenia of 21.4% and non-Hispanic patients of
39.2%.15
■ The Metabolic Syndrome
The metabolic syndrome is a constellation of factors which
combine to represent a significantly increased risk for
T2DM and CVD. Diagnostic criteria for the metabolic syn-
drome include central obesity plus any two of the follow-
ing four factors: elevated triglyceride level; reduced
high-density lipoprotein; elevated blood pressure or treat-
ment of previously diagnosed hypertension; or elevated
fasting plasma glucose (FPG).16 As previously illustrated,
all of these risk factors are prevalent among individuals
with schizophrenia.
■ Other Adverse Effects of Medication
Hyperprolactinemia
Hyperprolactinemia is a side effect of all typical antipsychotics,
as well as risperidone and amisulpride.Antipsychotic-induced
suppression of dopamine indirectly increases pituitary pro-
lactin production, and may present as menstrual irregularity,
amenorrhea, or galactorrhea in women and gynecomastia and
sexual dysfunction in men. Suppression of estrogens or testos-
terone may contribute to the development of osteoporosis.
Meaney and O’Keane reported higher rates of decreased bone
mineral density among premenopausal women receiving pro-
lactin-elevating antipsychotic drugs.17 Some concerns have
also been raised that hyperprolactinemia may promote growth
of breast and prostate tumors.
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Mental Health
Substance Abuse
Some people who abuse drugs show symptoms similar
to those of schizophrenia, and people with schizophrenia
may be mistaken for people who are high on drugs.
While most researchers do not believe that substance
abuse causes schizophrenia, people who have
schizophrenia abuse alcohol and/or drugs more often
than the general population.
Substance abuse can reduce the effectiveness of
treatment for schizophrenia. Stimulants (such as am-
phetamines or cocaine), phencyclidine, and marijuana
may make the symptoms of schizophrenia worse, and
substance abuse also makes it more likely that patients
will not follow their treatment plan.
Schizophrenia and Nicotine
The most common form of substance abuse in people
with schizophrenia is an addiction to nicotine. People
with schizophrenia are addicted to nicotine at three times
the rate of the general population (75% to 90% vs. 25%
to 30%).
Research has revealed that the relationship between
smoking and schizophrenia is complex. People with schiz-
ophrenia seem to be driven to smoke, and researchers are
exploring whether there is a biologic basis for this need. In
addition to its known health hazards, several studies have
found that smoking interferes with the action of antipsy-
chotic drugs. People with schizophrenia who smoke may
need higher doses of their medication.
Quitting smoking may be especially difficult for people
with schizophrenia since nicotine withdrawal may cause
their psychotic symptoms to temporarily worsen. Smok-
ing cessation strategies that include nicotine replacement
methods may be better tolerated. Practitioners who treat
people with schizophrenia should carefully monitor their
patient’s response to antipsychotic medication if the pa-
tient decides to either start or stop smoking.
Source: National Institute of Mental Health, 2006.
QTc Prolongation
Corrected QT interval (QTc) prolongation related to antipsy-
chotic monotherapy appears to be uncommon.However,com-
bining these drugs,particularly with antidepressants,may cause
significant QTc prolongation.17-19 QTc prolongation is a risk
factor for torsade de pointes (TdP), a rare ventricular tach-
yarrhythmia, which is fatal in approximately 20% of cases. The
view of QTc prolongation as a surrogate marker for TdP, how-
ever,has been questioned and research is ongoing.18-20 Increased
risk for QTc prolongation has been associated with congenital
long QT syndromes, heart failure, bradycardia, electrolyte im-
balance, female gender, overdose of a QTc prolonging drug,
hepatic or renal impairment, and slow metabolizer status.20-22
Myocarditis and Clozapine
Symptoms of myocarditis include unexplained fatigue, dysp-
nea, tachypnea, fever, chest pain, palpitations, other signs or
The Nurse Practitioner • July 2007 33
 Mental Health
New Insights from CATIE Trial
New information from the Clinical Antipsychotic Trials for
Intervention Effectiveness (CATIE) may help practitioners
when comparing treatment options. The new results are
published in the March 2007 issue of the American Jour-
nal of Psychiatry. CATIE, a $42.6 million, multisite study,
was funded by the National Institutes of Health’s National
Institute of Mental Health.
Quetiapine (Seroquel), and to some extent olanzapine
(Zyprexa), may be more effective than risperidone
(Risperdal) among patients who were originally taking,
but had to discontinue, perphenazine (Trilafon)—an older,
first-generation antipsychotic medication. However, pa-
tient responses varied considerably.
Of the 257 patients who were initially randomized to
perphenazine in the CATIE study, 192 discontinued the
medication for various reasons, including ineffectiveness
and intolerable side effects. Among those who discontin-
ued, 114 agreed to be rerandomized to one of three newer
antipsychotic medications—olanzapine, quetiapine, or
risperidone.
The effectiveness of the medications was compared by
determining how long patients stayed on their assigned
medication. Those taking quetiapine stayed on the
longest—averaging about 10 months before discontinu-
ing. Those taking olanzapine discontinued after an average
of about 7 months, and those taking risperidone discon-
tinued after an average of 4 months.
Although the discontinuation results suggest that olan-
zapine was generally on par with quetiapine, patients tak-
ing olanzapine experienced more side effects. While none
of those taking quetiapine discontinued use due to weight
gain or metabolic side effects, 13% of those assigned to
olanzapine discontinued it due to weight gain or meta-
bolic problems, and 5% of those on risperidone did so.
Source: National Institute of Mental Health, 2007.
symptoms of heart failure, or electrocardiogram (ECG) find-
ings such as ST abnormalities and T-wave inversion. Patients
being treated with clozapine should be monitored for signs
and symptoms of myocarditis and should be educated to re-
port any such symptoms to their healthcare provider
promptly.23 If myocarditis is suspected, an ECG, white blood
cell count and serum troponin level or CK-MB should be eval-
uated.23 If evidence of myocarditis is found, clozapine should
be stopped and the patient referred urgently to an internist.
Cataracts
Development of cataracts observed in beagle dogs receiving
four times the therapeutic dose of quetiapine has led to con-
cern about the possibility of quetiapine-associated cataract
development in humans. Reports of quetiapine-associated
cataracts showed no characteristic pattern in lens changes,
and the rate of occurrence does not exceed that of the general
public.24 Fraunfelder concluded that age-related lens changes
would likely account for the 32 cases of cataracts in over 3 mil-
34 The Nurse Practitioner • Vol. 32, No. 7
lion patients taking quetiapine and,using WHO criteria,found
a causal relationship unlikely.24 Risk of cataracts may be in-
creased in young people and with concomitant statin use.25
Although there is no clear link between use of quetiapine and
development of cataracts, the manufacturer has issued rec-
ommendations for eye examinations at baseline and at 6-
month intervals in patients treated with quetiapine.26
Need for Medication
The CATIE study, which compared the effectiveness of vari-
ous antipsychotic drugs, confirmed the existence of signifi-
cant individual differences in both positive and negative
response to antipsychotic medications (see Table: “Summary
of Novel Antipsychotics’ Long-term Adverse Effcts”).27
Schizophrenia is a severely disabling and potentially
life-threatening disease. Overall quality of life and tolerabil-
ity afforded by atypical antipsychotics must be weighed
against potential health risks of weight gain and metabolic
problems. Typical antipsychotics are effective in relieving
positive symptoms (hallucinations, delusions), but are inad-
equate to treat negative symptoms (flattened affect, poverty
of speech, and social withdrawal). They are associated with
a high risk for debilitating extrapyramidal side effects (EPS)
such as Parkinsonism, akathisia, and tardive dyskinesia.
Atypical antipsychotics, effective in treating both positive
and negative symptoms, are far less likely to cause EPS and
are now considered first-line treatment for schizophrenia.
Primary care providers should be aware of side effects of the
specific antipsychotic medications their patients are using.
■ Comprehensive Primary Care
Preventive Care
Tobacco. Brief counseling for smoking cessation is a cost-
effective, life-saving intervention. During each visit, patients
who smoke should be asked about smoking behavior and
be advised to quit; readiness to quit should be assessed, and
support and assistance offered. Because nicotine interferes
with the metabolism of some antipsychotic medications, the
effects of those medications should be more closely moni-
tored in patients who are quitting or starting smoking.
Diet and exercise. The potential for weight gain and
strategies for prevention should be discussed with patients,
and both WC and BMI should be measured frequently dur-
ing the first 3 to 6 months of treatment with a novel antipsy-
chotic. Regular, ongoing preventive counseling regarding
diet and physical activity should be offered and patients
should be encouraged to self-monitor weight. All manifes-
tations of metabolic syndrome can be improved through
lifestyle modifications that include a high-fiber, low-fat diet,
and exercise aimed at weight reduction.28 If an increase in
BMI or WC is noted, additional interventions should in-
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 Mental Health

clude intensified counseling about spe-

cific dietary modifications and plans for
increasing physical activity. Cognitive
behavioral therapy has been shown to
be effective in preventing or reducing
adverse metabolic effects associated
with schizophrenia and psychotropic
medications.29
Monitoring.Measurement of blood
pressure, WC, fasting plasma glucose,
and lipids are cost-effective screening
tests for obesity, diabetes, and metabolic
syndrome (see Table:“Schedule for Rou-
tine Screening and Follow-up for Pa-
tients Using Antipsychotic Drugs”).28 All
primary care providers should be famil-
iar with best practice guidelines such as
the Seventh Report of the Joint National
Committee on Prevention, Detection,
Evaluation, and Treatment of High
Blood Pressure and American Diabetes
Association Practice Guidelines.10,30
Early detection of persistent diseases
helps to ensure appropriate preventive
action can be taken to reduce or delay the
onset of complications. Lipid-lowering
and antihypertensive drugs should be
used as required to achieve lipid targets
(using Framingham projections of 10-
year absolute CHD risk) and blood pres-
sure levels according to Adult Treatment
Panel III guidelines.9
■ Primary Healthcare
Considerations
Many lifestyle factors contributing to
excessive rates of chronic disease and
premature deaths among people with
severe mental illness are modifiable.
Schedule for Routine Screening and Follow-up for Patients
Using Antipsychotic Drugs10
Schedule Assessment/Intervention
Baseline workup • Personal and family history of obesity,
(on initiation or switching diabetes, dyslipidemia, hypertension, or
of antipsychotic medication) cardiovascular disease
• Smoking assessment/counseling
• Nutrition and physical activity counseling
• BMI
• Waist circumference (at the level of the
umbilicus)
• Blood pressure
• Fasting plasma glucose (FPG)
• Fasting lipid profile (low-density lipoprotein,
high-density lipoprotein, triglycerides)
• ECG
4, 8, and 12 weeks after • Smoking assessment/counseling
initiating antipsychotic • BMI
medication and quarterly • Waist circumference (at the level of the
umbilicus)
12 weeks after initiation • BMI
or switching of antipsychotic • Waist circumference (at the level of the
medication umbilicus)
• Blood pressure
• FPG
• Fasting lipid profile
• Smoking assessment/counseling
• Nutrition and physical activity counseling
• ECG
Annually • FPG
(more frequently in those with • Lipid profile*
increased baseline lipids, risks • Blood pressure
of diabetes or hypertension) • Smoking assessment/counseling
• Nutrition and physical activity counseling
• ECG
Adapted from American Diabetes Association; American Psychiatric Association; American Association
of Clinical Endocrinologists; North American Association for the Study of Obesity: Consensus
Development Conference on Antipsychotic Drugs and Obesity and Diabetes.
Schedule is additional to routine screening for a member of the general public.
*Annual lipid profile for persons with CVD risk factors. In patients with diagnosed dyslipidemia, monitor
response and adherence to therapy every 4 to 6 months as per the National Cholesterol Education
Program’s Adult Treatment Panel III recommendation.9

Broad social determinants of health

such as autonomy, education, social status, poverty, and
access to healthcare, which have significant impacts on
morbidity and mortality of people with schizophrenia, are
also modifiable. Healthcare professionals can work toward
increasing public awareness and understanding of mental
health issues and be advocates for healthy public policies re-
garding issues such as adequate housing, employment, and
strengthened community health services. Health promotion
interventions, when incorporated into mental health prac-
tice, can be effective and can improve patients’ quality of life
and life expectancy.
In interviews of people with schizophrenia regarding
satisfaction with primary care, Lester, Tritter and England
found that they considered kindness, patience, and ability
to inspire confidence to be important interpersonal compe-
tencies.31 Access to a stable primary care provider facilitates
the gradual development of trust through a long-term rela-
tionship. Most patients described the importance of being
treated as partners in care and felt empowered by informa-
tion.31 However, most also reported they did not feel they
had significant influence on the course of their healthcare.
The inability to affect outcomes or influence management

www.tnpj.com The Nurse Practitioner • July 2007 35

 Mental Health
Summary of Novel Antipsychotics’ Long-term Adverse Effects
Medication Weight gain FPG Total cholesterol/
triglycerides
Clozapine ++ ++
Olanzapine ++ ++
Risperidone + +
Quetiapine + +
Aripiprazole 0 0
Ziprasidone 0 0
++Significant increase
+Moderate increase
*Increased potential when used in combination with antidepressants
plans impedes future participation and leads to a sense of
hopelessness.
The term ”psychological recovery” describes a concep-
tual model of recovery from mental illness. It is not synony-
mous with cure,32 but is considered as a process that includes
the development of a sense of hope, establishment of an
identity beyond that of psychiatric patient, finding meaning
in life, and taking responsibility for recovery.33 Lester, Trit-
ter, and Sorohan found that most healthcare professionals
see serious mental illnesses as a lifelong, chronic illness, while
most patients with schizophrenia prefer an optimistic ap-
proach that acknowledges the possibility of recovery.34 The
concept of hope is a central theme of psychological recovery
and is understood by both rehabilitation professionals and
patients as essential to recovery from mental illness. It is a
growing belief in one’s ability to reach goals; it is a trigger
for recovery and sustains recovery. Andresen, Oades, and
Caputi contend that hope is essential to promoting self-care
and responsible management of wellness.33 Individuals who
are experiencing severe psychotic symptoms may not be ca-
pable of making informed choices. However, as symptoms
subside, the locus of control should gradually shift towards
the recovering individual so that they develop a sense of con-
trol over their lives.
Barriers to Healthcare
Patient factors such as cognitive impairment, lifestyle choices,
lack of motivation, and a sense of hopelessness contribute to
the high prevalence of physical health problems and relatively
low rates of prevention, recognition, and follow-up among
people with schizophrenia. Some of these factors are wors-
ened by antipsychotic medications and by stigmatization.
Healthcare providers may lack knowledge about comorbid
health risks in people with schizophrenia or may hold nega-
tive attitudes toward mental illness. Healthcare systems often
do not provide integrated services capable of providing com-
36 The Nurse Practitioner • Vol. 32, No. 7
Prolactin Prolonged Other
QTc
++ 0 * Myocarditis (rare)
++ 0 *
+ ++ *
+ 0 * Cataracts—inconclusive
0 0 *
0 0 *
prehensive healthcare. Financial concerns may be an addi-
tional barrier to access. All of these factors are modifiable.
■ Conclusion
People with schizophrenia have a higher-than-average preva-
lence of preventable physical health problems, which result
in a shortened life-expectancy, but they are also less likely to
receive routine screening and treatment than the average
person. Interdisciplinary teams with NPs, physicians, and
psychiatrists working collaboratively to provide broad med-
ical and psychiatric expertise could increase access to com-
prehensive primary healthcare for people with schizophrenia
and minimize the negative impact mental health has on phys-
ical health and lifespan. Reducing the stigma of mental ill-
ness and encouraging patients with schizophrenia to become
partners in their own healthcare can promote empowerment
and hope for recovery.
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INSTRUCTIONS
Guide Schizophrenia Patients to Better Physical Health
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Mental Health
23. Shahzad S, Suleman MI, Shahab H, et al. Cataract occurrence with antipsy-
chotic drugs. Psychosomatics. 2002;43(5):354-359.
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AUTHOR DISCLOSURE
The author has disclosed that she has no significant relationship or financial in-
terest in any commercial companies that may pertain to this educational activity.
ABOUT THE AUTHOR
Brenda Lumby is a Primary Care Nurse Practitioner at Whitby Mental Health
Centre, Ontario, Canada.
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