World Psychiatry 10:1 - February 2011
A number of reviews and studies have shown that people
with severe mental illness (SMI), including schizophrenia, bi-
polar disorder, schizoaffective disorder and major depressive
disorder, have an excess mortality, being two or three times as
high as that in the general population (1-21). This mortality
gap, which translates to a 13-30 year shortened life expectancy
in SMI patients (4,5,22-27), has widened in recent decades
(11,28-30), even in countries where the quality of the health
care system is generally acknowledged to be good (11). About
60% of this excess mortality is due to physical illness (27,31).
Individuals with SMI are prone to many different physi-
cal health problems (Table 1). While these diseases are also
prevalent in the general population, their impact on indi-
viduals with SMI is significantly greater (31,32).
Although many factors contribute to the poor physical
health of people with SMI (33), the increased morbidity and
mortality seen in this population are largely due to a higher
prevalence of modifiable risk factors, many of which are re-
lated to individual lifestyle choices (31). However, this is not
the whole story. It seems that the somatic well being of peo-
ple with a (severe) mental illness has been neglected for de-
cades (15), and still is today (7,34-39,40,41). There is in-
creasing evidence that disparities not only in health care
Physical illness in patients with severe mental disorders.
I. Prevalence, impact of medications and disparities
in health care
WPA EDUCATIONAL MODULE
Marc De Hert1, cHristopH U. correll2, JUlio BoBes3, Marcelo cetkovicH-BakMas4, Dan coHen5,
itsUo asai6, JoHan DetraUx1, sHiv GaUtaM7, Hans-JUrGen Möller8, DaviD M. nDetei9,
JoHn W. neWcoMer10, ricHarD UWakWe11, stefan leUcHt12
1University Psychiatric Center, Catholic University Leuven, Leuvensesteenweg 517, 3070 Kortenberg, Belgium; 2Albert Einstein College of Medicine, Bronx, NY, USA;
3Department of Medicine - Psychiatry, University of Oviedo-CIBERSAM, Spain; 4Department of Psychiatry, Institute of Cognitive Neurology, and Department
of Psychiatry, Institute of Neurosciences, Favaloro University Hospital, Buenos Aires, Argentina; 5Department of Epidemiology, University of Groningen,
The Netherlands; 6Japanese Society of Transcultural Psychiatry; 7Psychiatric Centre, Medical College, Jaipur, India; 8Department of Psychiatry, University of Munich,
Germany; 9University of Nairobi and Africa Mental Health Foundation, Nairobi, Kenya; 10Department of Psychiatry, Washington University School of Medicine,
St. Louis, MO, USA; 11Faculty of Medicine, Nnamdi Azikiwe University, Nnewi Campus, Nigeria; 12Department of Psychiatry and Psychotherapy, Technische
Universität München, Munich, Germany
The lifespan of people with severe mental illness (SMI) is shorter compared to the general population. This excess mortality is mainly due
to physical illness. We report prevalence rates of different physical illnesses as well as important individual lifestyle choices, side effects
of psychotropic treatment and disparities in health care access, utilization and provision that contribute to these poor physical health
outcomes. We searched MEDLINE (1966 – August 2010) combining the MeSH terms of schizophrenia, bipolar disorder and major depres-
sive disorder with the different MeSH terms of general physical disease categories to select pertinent reviews and additional relevant
studies through cross-referencing to identify prevalence figures and factors contributing to the excess morbidity and mortality rates. Nu-
tritional and metabolic diseases, cardiovascular diseases, viral diseases, respiratory tract diseases, musculoskeletal diseases, sexual
dysfunction, pregnancy complications, stomatognathic diseases, and possibly obesity-related cancers are, compared to the general popu-
lation, more prevalent among people with SMI. It seems that lifestyle as well as treatment specific factors account for much of the in-
creased risk for most of these physical diseases. Moreover, there is sufficient evidence that people with SMI are less likely to receive
standard levels of care for most of these diseases. Lifestyle factors, relatively easy to measure, are barely considered for screening; baseline
testing of numerous important physical parameters is insufficiently performed. Besides modifiable lifestyle factors and side effects of
psychotropic medications, access to and quality of health care remains to be improved for individuals with SMI.
Key words: Physical illness, severe mental illness, bipolar disorder, depression, schizophrenia, psychotropic medication, health disparities
(World Psychiatry 2011;10:52-77)
access and utilization, but also in health care provision con-
tribute to these poor physical health outcomes (33-39). A
confluence of patient, provider, and system factors has cre-
ated a situation in which access to and quality of health care
is problematic for individuals with SMI (31). This is not to-
tally surprising as we are today in a situation in which the
gaps, within and between countries, in access to care are
greater than at any time in recent history (42). Therefore, this
growing problem of medical comorbidities and premature
death in people with SMI needs an urgent call to action.
This paper highlights the prevalence of physical health
problems in individuals with SMI. Furthermore, contributing
factors are considered that impact on the physical health of
these people, such as psychotropic medications (antipsychot-
ics, antidepressants and mood stabilizers), individual lifestyle
choices (e.g., smoking, diet, exercise), psychiatric symptoms,
as well as disparities in the health care. This is a selective,
rather than a systematic review of clinical data on physical
health problems in people with SMI, as we did not include
all physical diseases. We searched MEDLINE (1966 – August
2010) for epidemiological, morbidity and mortality data on
the association between physical illnesses and schizophre-
nia, bipolar disorder and major depressive disorder. We com-
bined the MeSH terms of these psychiatric disorders with the
different MeSH terms of major general physical disease cat-
egories. We included pertinent reviews to identify prevalence
figures and factors contributing to the excess morbidity and
mortality rates. Reference lists of reviews were searched
for additional relevant studies. Moreover, if necessary to ob-
tain more specific information, for some of the general phys-
ical disease categories (e.g., respiratory diseases), we also
used specific physical illnesses as a search term.
PhysIcal dIseases lInKed to sMI and/or
Obesity is becoming a significant and growing health crisis,
affecting both developed and developing countries (43,44).
People with obesity have shorter life spans and are at in-
creased risk for a number of general medical conditions,
including type 2 diabetes mellitus, DM (relative risk, RR >3),
cardiovascular disease, CVD (RR >2-3), dyslipidemia (RR
>3), hypertension (RR >2-3), respiratory difficulties (RR >3),
reproductive hormone abnormalities (RR >1-2) and certain
cancers (e.g., colon) (RR >1-2) (22,45-49,50).
Several methods are available to assess overweight and
obesity. Body mass index (BMI) is a direct calculation
based on height and weight (kg/m2). A BMI ≥25 kg/m2
corresponds to overweight, a BMI ≥30 kg/m2 to obesity
(31). BMIs ≥30kg/m2 are known to shorten life expectancy
(48,51). However, based on evidence for higher morbidity
and mortality risk at BMIs below 30 Kg/m2 in Asian popu-
lations, the threshold for the definition of overweight in
these populations is modified to a BMI ≥23 Kg/m2 and the
threshold for obesity to a BMI ≥25 Kg/m2. Waist circumfer-
ence (WC), measuring abdominal or central adiposity, is
emerging as a potentially more valid and reliable predictor
of risk for CVD, type 2 DM, and other metabolic risk-re-
lated conditions, compared with BMI (31). Accumulating
evidence argues that lower cutoff points for WC should be
used for Asians, as this population is prone to obesity-re-
lated morbidity and mortality at shorter WCs (52-56). The
International Diabetes Federation (IDF) provides sex-and
race-specific criteria in defining WC to identify people
with central obesity, thus adjusting this criterion to make
it also useful in non-Caucasian populations (Table 2).
However, long-term prospective studies are still required
to identify more reliable WC cut points for different ethnic
groups, particularly for women (57).
Obesity in SMI patients
SMI and obesity overlap to a clinically significant extent
(45). Increasing evidence suggests that persons with SMI are,
compared to the general population, at increased risk for
overweight (i.e., BMI =25-29.9, unless Asian: BMI =23-24.9),
obesity (i.e., BMI ≥30, unless Asian: BMI ≥25) and abdomi-
nal obesity (see Table 2) (63-75), even in early illness phase
and/or without medication (76-78). The risk of obesity in
persons with SMI, however, varies by diagnosis. People with
schizophrenia have a 2.8 to 3.5 increased likelihood of being
obese (79). Several Canadian and US studies reported rates
of obesity (BMI ≥30) in patients with schizophrenia of 42-
60% (63,79,80). On the other hand, those with major depres-
Table 1 Physical diseases with increased frequency in severe mental illness (from 15)
Disease categoryPhysical diseases with increased frequency
Bacterial infections and mycoses
Respiratory tract diseases
Urological and male genital diseases
Female genital diseases and pregnancy complications
Nutritional and metabolic diseases
HIV (++), hepatitis B/C (+)
Obesity-related cancer (+)
Osteoporosis/decreased bone mineral density (+)
Poor dental status (+)
Impaired lung function (+)
Sexual dysfunction (+)
Obstetric complications (++)
Stroke, myocardial infarction, hypertension, other cardiac and vascular
Obesity (++), diabetes mellitus (+), metabolic syndrome (++),
(++) very good evidence for increased risk, (+) good evidence for increased risk
Table 2 Ethnicity-specific cutoff values of waist circumference indicating abdominal obesity (see 57-62)
European, sub-Saharan Africans, Mediterranean
and Middle Eastern populations
South Asians, Chinese, and ethnic South
and Central Americans
World Psychiatry 10:1 - February 2011
sion or bipolar disorder have a 1.2 to 1.5 increased likelihood
of being obese (BMI ≥30) (44,69,70,81,82). Clinical research
has suggested that up to 68% of treatment-seeking bipolar
disorder patients are overweight or obese (83). One study
found an obesity rate (BMI ≥30) of 57.8% among those with
severe depression (84).
In patients with SMI, as in the general population, obe-
sity is associated with lifestyle factors (e.g., lack of exercise,
poor diet), but also with illness-related (negative, disorgan-
ized and depressive symptoms) and treatment-related fac-
tors, including weight liability of certain psychotropic
agents. Adverse effects, such as sedation, should also be
considered as potential contributors to weight gain in addi-
tion to, still not fully elucidated, medication induced effects
on appetite and food intake (45,73,50,85-87).
Obesity and psychotropics
Weight gain during acute and maintenance treatment of
patients with schizophrenia is a well established side effect of
antipsychotics (AP), affecting between 15 and 72% of patients
(26,50,77,88-98). There is growing evidence for similar effects
in patients with bipolar disorder (65,83,99). There is a hierar-
chy for risk of weight gain with AP that has been confirmed in
different studies and meta-analyses (88,92,100-106). Weight
gain is greatest with clozapine and olanzapine (107,108),
while quetiapine and risperidone have an intermediate risk.
Aripiprazole, asenapine, amisulpride and ziprasidone have
little effect on weight. A recent systematic review of random-
ized, placebo controlled trials of novel AP in children and
adolescents (<18 years old) identified the same hierarchy for
risk of weight gain for this vulnerable population (109). Among
the conventional AP, so-called low-potency agents, such as
chlorpromazine and thioridazine, have a higher risk than
high-potency drugs, such as haloperidol (110-112). No agent,
however, should be considered as truly weight-neutral, as the
proportion of individuals experiencing ≥7% weight gain is
greater with any atypical AP than with placebo (92), and all
AP have been found to cause significant weight gain in AP-
naïve or first-episode patients (113-115). Even amisulpride,
ziprasidone and low-dose haloperidol demonstrated notable
weight gain of 9.7 kg, 4.8 kg and 6.3 kg respectively at endpoint
in a 12-month trial of AP in first-episode patients (102). Equal-
ly, antidepressants (AD) such as paroxetine (116), and mood
stabilizers, such as lithium and valproate (117-119), have been
associated with weight gain (Table 3).
The high interindividual variability in medication-induced
weight gain suggests that genetic factors influence the risk to
gain weight (50,122). Studies of genetic predictors of weight
gain under AP therapy have mainly but not exclusively (131)
focused on HTR2C (132-135) and LEPR (135,136) gene
polymorphisms. Although the results are promising, the role
of genetic factors in predicting this severe side effect remains
an option for the future.
Obesity is also associated with the metabolic syndrome
(MetS), a clustering of abnormalities that confers a 5-6-fold
Table 3 Weight gain liability of psychotropic agents used in SMI (see 45,63-65,87,95,99,104,120,121-130)
Drug classWeight lossRelatively weight neutralWeight gain
AntipsychoticsAripiprazole (in pre-treated individuals)
Molindone (in pre-treated individuals)
Ziprasidone (in pre-treated individuals)
increased risk of developing type 2 DM and a 3-6 fold in-
creased risk of mortality due to coronary heart disease (137-
There is also evidence supporting the hypothesis that the
MetS or components of the MetS may be important etio-
logic factors for certain cancers (e.g., colon cancer) (145,146).
Although some controversy exists whether the MetS is a
true syndrome (57,147-149), and despite differences in spe-
cific criteria among the definitions (Table 4), there is agree-
ment that the major characteristics of the syndrome include
central obesity, hypertension, dyslipidemia, glucose intoler-
ance or insulin resistance (45,137,150). Studies show large
variations in prevalence estimates of the MetS across defini-
tions, countries or regions, gender, ethnicity, and age groups
(137). Countries in North and South America (151-154)
reported a relatively higher prevalence than other countries
or regions in the world (137).
MetS in SMI patients
The MetS is highly prevalent among treated patients with
schizophrenia. Depending on used MetS criteria, gender,
ethnicity, country, age groups and AP treatment, percentages
vary considerably (between 19.4% and 68%) (155-167).
However, there is little debate that people with schizophre-
nia exhibit a higher MetS prevalence than their peers in the
general population across the world (168). MetS rates in
patients with bipolar disorder and schizoaffective disorder
have been reported to be 22-30% (143,169,170) and 42%
Table 5 summarizes the potential of various AP medica-
tion to cause or exacerbate the metabolic syndrome. Never-
theless, lifestyle and behavioral patterns (smoking, physical
inactivity, dietary habits) also play important roles in the
prevalence of the MetS in SMI populations (118,168,176).
Disparities in health care
The proportion of SMI patients not receiving tests for as-
sessing metabolic risk factors, even for factors relatively
simple and easy to measure, such as obesity and blood pres-
sure, is high (141,177-181). At present, neither psychiatrists
nor primary care physicians carefully screen or monitor pa-
tients receiving AP medication for metabolic risk factors
(173). Even after FDA (Food and Drug Administration) and
ADA (American Diabetes Association)/APA (American
Psychiatric Association) recommendations for novel AP, the
frequency of baseline glucose and lipid testing showed little
change. Several large-scale pharmacoepidemiologic studies
of individuals initiating a novel AP (with non-psychiatric
large control groups) reported low mean baseline metabolic
testing rates, varying between 8% and less than 30% (181-
183) and follow-up assessments done in only 8.8% of pa-
tients. Likewise, most children starting treatment with novel
AP do not receive recommended glucose and lipid screen-
ing. In a related study in children receiving AP treatment,
similarly low metabolic monitoring rates were found (184).
The MetS remains, thus, widely underdiagnosed and under-
treated among patients with SMI.
Three to four percent of the world’s population have DM,
which leads to a markedly increased risk of blindness, renal
failure, amputation and cardiovascular disease, and reduces
life expectancy by 10 or more years. Currently, 70% of peo-
ple with DM live in developing countries, and while DM is
increasing across the world, its greatest increase will be in
these countries. By 2030 more than 80% of people with DM
will live in developing countries (195).
There are well-defined biological and behavioral risk fac-
tors for type 2 DM (195). The most important of these are
overweight and obesity (RR: 4.10-17.5)(196), particularly
abdominal obesity, and physical inactivity (RR: 1.12-2.18)
(196-205). Other behavioral risk factors include certain di-
etary patterns (over and above any effect on obesity), such
as diets low in whole grains and other sources of fibre, as
well as smoking (206).
Identifying people at high risk of DM is important be-
cause it has been demonstrated that intensive interventions
in this group can reduce the incidence of DM. In individuals
at high risk, a combination of moderate weight loss, in-
creased physical activity and dietary advice can lead to a
60% reduction in DM incidence (207,208).
DM in SMI patients
Evidence suggests that the prevalence of DM in people
with schizophrenia as well as in people with bipolar disor-
der and schizoaffective disorder is 2-3 fold higher compared
with the general population (103,209-216). The risk of DM
in people with depression or depressive symptoms is 1.2-2.6
times higher compared to people without depression (217-
The reason for the increased risk of DM in SMI patients
is multifactorial and includes genetic and lifestyle factors as
well as disease and treatment specific effects. An increase in
well-established DM risk factors in these patients partially
accounts for much of the increased risk (16,226). However,
additional factors (disease, treatment) are important as well,
and research suggests that, compared to the general popula-
tion, the prevalence of DM in schizophrenia patients is 4 to
5 times higher in different age groups (15-25: 2% vs. 0.4%;
25-35: 3.2% vs. 0.9%; 35-45: 6.1% vs. 1.1%; 45-55: 12.7%
vs. 2.4%; 44-65: 25% vs. 5.8%) (227).
World Psychiatry 10:1 - February 2011
DM and psychotropic medications
Atypical AP seem to have a stronger diabetogenic risk
than conventional AP (96,228,229), the risk being 1.3 fold
higher in people with schizophrenia taking atypical AP com-
pared with those receiving conventional AP (230). However,
the risk of DM-related adverse events differs between atypi-
cal AP. Of the atypical AP, specifically olanzapine (231-234)
and clozapine (232,234,235) and, to a lesser extent, quetiap-
ine (236) and risperidone (237), are associated with an in-
creased risk of DM (80) in people who have schizophrenia
or bipolar disorder (238,239). A recent large-scale pharma-
coepidemiologic study (including 345,937 patients who pur-
chased antipsychotics and 1,426,488 unexposed individuals)
Table 4 Working definitions of the MetS (see 57,185-194)
NCEP ATP III
IDF & AHA/NHLBI
IGT, IFG or DM type
2, and/or insulin
plus any 2 or more
of the following
Insulin resistance or
plus any 2 of the
but any 3 or more
of the following
At least one of the
factors (e.g., obesity,
plus 2 or more
of the following
plus any 2 of the
but any 3 or more
of the following
Obesity Waist-to-hip ratio
and/or BMI>30 kg/m2
WC≥94 cm (men)
WC≥80 cm (women)
WC≥102 cm (men)
WC≥88 cm (women)
BMI>25 kg/m2 or
WC>102 cm (men)
WC>89 cm (women)
(10-15% lower for
Elevated WC and
definitions as defined
by the IDF and AHA/
NHLBI until more
data are available
HDL - cholesterol
≥150 mg/dL (≥1.7
(<0.9 mmol/L) (men)
(<1.0 mmol/L) (women)
>177 mg/dL (>2.0
(men and women)
or on dyslipidemia Rx
or on elevated
<40 mg/dL (<1.03
<50 mg/dL (<1.29
or on reduced HDL-
<40 mg/dL (men)
<50 mg/dL (women)
(≥1.7 mmol/L) or
on lipid abnorma-
< 40 mg/dL
(women) or on lipid
≥150 mg/dL (≥1.7
mmol/L) (Rx for ele-
vated triglycerides is
an alternate indicator)
<40 mg/dL (<1.0
(Rx for reduced
HDL-cholesterol is an
≥160/90 mm Hg
(later modified as
≥140/90 mm Hg)
≥140/90 mm Hg
or on hypertension
≥130/85 mm Hg
or on hypertension
>130/85 mm Hg
≥130/85 mm Hg
≥130/85 mm Hg
(antihypertensive Rx in
a patient with a histo-
ry of hypertension is
an alternate indicator)
GlucoseIGT, IGF (≥110 mg/dL)
or DM type 2
IGT or IFG
(but not DM)
(later modified as
≥100 mg/dL) (≥5.6
mmol/L) or on
elevated glucose Rx
≥100 mg/dL (≥5.6
mmol/L) or pre-
type 2 DM
(Rx of elevated
glucose is an alternate
≥20 mg/min or albumin:
as ≥30 mg/g)
WHO: World Health Organization; EGIR: European Group for the Study of Insulin Resistance; NCEP ATP III: National Cholesterol Education Program Expert
Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III); AACE/ACE: American Association of Clinical
Endocrinologists/American College of Endocrinology; IDF: International Diabetes Federation; AHA/NHLBI: American Heart Association/National Heart, Lung,
and Blood Institute; IGT: impaired glucose tolerance; IFG: impaired fasting glucose; DM: diabetes mellitus; BMI: body mass index; WC: waist circumference; Rx:
treatment; HDL: high-density lipoprotein.
found low to moderate, but significantly increased rates of
incident DM compared with the general population for clo-
zapine (RR=1.45), olanzapine (RR=1.29) and risperidone
(RR=1.23). Rates increased two or more times with ziprasi-
done and sertindole. Aripiprazole, amisulpride and quetiap-
ine did not have a significantly increased rate (240).
In the only study to date in first-episode patients, DM
development was promoted in patients with schizophrenia
by initial treatment with olanzapine (hazard ratio, HR=1.41)
and mid-potency conventional AP (HR=1.60), as well as by
current treatment with low-potency conventional AP (odds
ratio, OR=1.52), olanzapine (OR= 1.44) and clozapine
(OR=1.67). Current aripiprazole treatment reduced DM risk
(OR= 0.51) (241). An analysis of the FDA’s DM-related ad-
verse events database (ranging from new-onset hyperglyce-
mia to life-threatening ketoacidosis), found the following
adjusted reporting ratios for DM relative to all drugs and
events: olanzapine 9.6 (9.2-10.0); risperidone 3.8 (3.5-4.1);
quetiapine 3.5 (3.2-3.9); clozapine 3.1 (2.9-3.3); ziprasidone
2.4 (2.0-2.9); aripiprazole 2.4 (1.9-2.9); haloperidol 2.0 (1.7-
2.3) (242). However, a systematic review of 22 prospective,
randomized, controlled trials found no difference in the in-
cidence of glycaemic abnormalities between placebo co-
horts and AP medication cohorts, as well as no significant
difference between any of the AP medications studied in
terms of their association with glycaemic abnormalities
(243). Although the latter analysis was restricted to mostly
short-term trials, this inconsistency of findings suggests that
medication effects interact with patient, illness, cohort and
AD may also increase the risk of DM, probably partly due
to side effects such as sedation, increased appetite, and
weight gain (244-248). However, although increasing, spe-
cific data on the risk of DM associated with the use of AD
are sparse. Given the heterogeneity and small sample sizes
of the few currently available studies, it is unclear whether
or not specific AD themselves may increase the risk of DM.
Nevertheless, it seems that an increased risk of DM is associ-
ated with the concurrent use of tricyclic AD and serotonin
reuptake inhibitors (SSRIs) (OR=1.89) (249), the long-term
use of both tricyclic AD (incidence rate ratio, IRR=1.77) and
SSRIs (IRR=2.06) in at least moderate daily doses (250), as
well as the use of AD medication in high-risk patients (251).
Furthermore, although understudied, certain mood stabi-
lizers, especially valproate, have been associated with an
elevated risk for the development of insulin resistance
(252,253), conferring a risk for DM, which is possibly re-
lated to weight gain (254), and/or fatty liver infiltration
(255), but also to valproate itself (256).
Disparities in health care
There is evidence that diabetes patients with mental health
conditions are less likely to receive standard levels of diabe-
tes care (35,257,258). In the Clinical Antipsychotic Trials of
Intervention Effectiveness (CATIE) schizophrenia study,
non-treatment rate for DM was 45.3% (35). One study
(n=76,799), examining the impact of mental illness on DM
management, found the unadjusted OR to be 1.24 (1.22-
1.27) for no hemoglobin A(1c) testing, 1.25 (1.23-1.28) for no
low-density lipoprotein cholesterol testing, 1.05 (1.03-1.07)
for no eye examination, 1.32 (1.30-1.35) for poor glycemic
control, and 1.17 (1.15-1.20) for poor lipaemic control (257).
Despite clear guidance and a high prevalence of undiagnosed
DM, screening rates for metabolic abnormalities in people
with SMI remain low, which may lead to prolonged periods
of poor glycaemic control (259-263). Delayed diagnosis re-
sults in prolonged exposure to raised blood glucose levels,
which can, among other things, cause visual impairment and
blindness, damage to kidneys with the potential consequence
of renal failure, and nerve damage (264).
Although diabetic ketoacidosis (DKA), a potentially fatal
condition related to infection, trauma, myocardial infarction
or stroke (265), occurs most often in patients with type 1
DM, it may be the first obvious manifestation of type 2 DM.
Symptoms include: increased thirst and urination, nausea
and vomiting, abdominal pain, poor appetite, unintended
weight loss, lethargy, confusion and coma.
The incidence of DKA is nearly (266) or more (267) than
10-fold greater in those with schizophrenia compared to the
general population. Cases of DKA have been reported with
the atypical AP clozapine (235,268), olanzapine (233,269),
quetiapine (236), risperidone (237), aripiprazole (270-272)
and ziprasidone (242). However, not all atypical AP appear
to have the same propensity to cause this complication
(273). The incidence of DKA for each atypical AP over a
7-year period was as follows: clozapine, 2.2%; olanzapine,
0.8%; and risperidone, 0.2% (267). However, higher inci-
dence rates for clozapine and olanzapine can be due to re-
porting and detection biases (more DKA cases may be re-
Table 5 Approximate relative likelihood of metabolic distur-
bances with AP medication (172-175)
High (?, limited data)
Mild (?, limited data)
Low (?, limited data)
Low (?, limited data)
World Psychiatry 10:1 - February 2011
ported for these agents since doctors in general are more
careful about clozapine and olanzapine and therefore detect
and report such cases with these agents more frequently).
Within the class of conventional AP, cases of DKA have
been reported with chlorpromazine (274,275), but no such
cases have been reported for other conventional AP. The
mortality of reported cases of DKA varies between 15.4%
and 48% (233,235-237), which is up to ten times higher than
the 4% rate in the general population (276).
The term cardiovascular diseases (CVD) refers to any dis-
ease that affects the cardiovascular system. Coronary heart
disease and cerebrovascular disease are the principal com-
ponents of CVD and make the largest contribution to its
global burden (277,278). CVD accounts for 17.1 million or
29% of total worldwide deaths (279). While there are down-
ward trends in CVD mortality in most developed countries
due to successful secondary prevention, the mortality rates
in developing countries are rising (280). A staggering 82%
of worldwide CVD deaths take place in developing coun-
tries (279). Global trade and food market globalization have
led to a transition toward a diet that is energy dense and
nutrient poor. The resultant increases in obesity are accom-
panied by physical inactivity. In addition, tobacco consump-
tion is increasing at alarming rates in developing countries
(281). Finally, people in developing countries have less ac-
cess to effective and equitable health care services which
respond to their needs (279).
The conventional risk factors for CVD are smoking, obe-
sity, hypertension, raised blood cholesterol and DM. Many
other factors increase the risk of CVD, including unhealthy
diet, physical inactivity and low socioeconomic status (282,
283). Table 6 shows the summary prevalence of CVD risk
factors in developed and developing countries, based on the
World Health Organization (WHO) comparative risk factor
survey data. The risk of late detection of CVD risk factors
and consequent worse health outcomes is higher among
people from low socioeconomic groups due to poor access
to health care. This gradient exists in both rich and poor
CVD in SMI patients
The preponderance of evidence suggests that patients
with major depression, bipolar disorder and schizophrenia
are at significantly higher risk for cardiovascular morbidity
and mortality than are their counterparts in the general pop-
ulation (2,9,11,23,28,29,287-295). Moreover, in SMI pa-
tients, CVD is the commonest cause of death (2,25,33,
The prevalence of CVD in people with schizophrenia and
bipolar disorder is approximately 2- to 3-fold increased, par-
ticularly in younger individuals (5,16,25,29,297,299,301,302).
A recent review of all published larger (>100 patients) studies
between 1959 and 2007 found the mortality risk for CVD to
be 35% to 250% higher among persons with bipolar spectrum
disorders compared to the general population (6). People with
depression have a 50% greater risk of CVD (22). Besides the
fact that depression is an independent risk factor for aggravat-
ing morbidity and mortality in coronary heart disease (303),
the main factor mediating the link between depression and
coronary events seems to be lack of physical activity (304).
The aetiology of this excess CVD is multifactorial and
likely includes genetic and lifestyle factors as well as disease
specific and treatment effects (16). People with SMI have
significantly higher rates of several of the modifiable risk
factors compared with controls. They are more likely to be
overweight or obese, to have DM, hypertension, or dyslip-
idemia and to smoke (25,95,229,178,305-308). The excess
CVD mortality associated with schizophrenia and bipolar
disorder is widely attributed to the 1-5 fold RR of the modi-
fiable CVD risk factors in this group of patients compared
with the general population (Table 7).
Coronary heart disease in SMI patients
Coronary heart disease refers to the failure of coronary
Table 6 Economic development and risk factors for cardiovascular disease in WHO subregions (see 280,286)
Poorest countries in Africa, America,
South-East Asia, Middle East
Better-off countries in America, Europe,
South-East Asia, Middle East, Western Pacific
Developed countries of Europe,
North America, Western Pacific
Mean body mass index19.9 - 26.022.9 - 26.023.4 - 26.9
Physical inactivity (% with
no physical activity)
11 - 2315 - 2417 - 20
Low fruit and vegetable
intake: average intake
per day (grams)
240 - 360 190 - 350290 - 450
Blood pressure (mean
systolic pressure mmHg)
125 - 133124 - 133 127 - 138
Mean cholesterol (mmol/L)4.8 - 5.1 4.6 - 5.8 5.1 - 6.0
circulation to supply adequate circulation to cardiac muscle
and surrounding tissue, a phenomenon that can result in a
myocardial infarction. During the 21st century, coronary
heart disease will remain the leading cause of death in de-
veloped countries, will become the leading cause of death in
developing countries, and therefore, will emerge as the lead-
ing cause of death in the world (25). The risk of coronary
heart disease seems to be 2-3.6-fold higher in patients with
schizophrenia (25,299). One large study found that the ten-
year coronary heart disease risk was significantly elevated in
male (9.4% vs. 7.0%) and female (6.3% vs. 4.2%) patients
who have schizophrenia compared to controls (p=0.0001)
(101). People with bipolar disorder have a 2.1 fold higher
risk (299). The RR of myocardial infarction in people with
major affective disorder was found to be 1.7 to 4.5 (310-313).
Depression is an even stronger risk factor for cardiac events
in patients with established coronary heart disease: prospec-
tive studies have shown that depression increases the risk of
death or nonfatal cardiac events approximately 2.5-fold in
patients with coronary heart disease (314).
Cerebrovascular disease in SMI patients
Cerebrovascular disease is a group of brain dysfunctions
related to disease of the blood vessels supplying the brain,
and can result in a cerebrovascular accident or stroke. The
risk of cerebrovascular accident seems to be 1.5 to 2.9 fold
higher in patients with schizophrenia (40,41,299,302,315,
316) and 2.1 to 3.3 fold higher in patients with bipolar dis-
order (299,317). The RR of developing cerebrovascular ac-
cident for patients with major affective disorder was found
to be 1.22 to 2.6 (318,319). Obesity, DM, CVD as well as
depressive symptoms are recognized as risk factors for cere-
brovascular accident (317,320).
CVD and psychotropics
In addition to weight gain and obesity related mecha-
nisms, there appears to be a direct effect of AP that contrib-
utes to the worsening of CVD risk (96,97,121,321). A recent
publication demonstrated that atypical AP D2 antagonism
could have a direct effect on the development of insulin re-
sistance (322). Evidence was found that higher AP doses
predicted greater risk of mortality from coronary heart dis-
ease and cerebrovascular accident (299).
Overall, SSRIs appear safe in cardiac populations, with
few cardiac side effects (287,311), while studies have found
an increased risk of adverse cardiac events in patients using
tricyclic AD (311,323,324). Tricyclic AD commonly increase
heart rate by over 10%, induce orthostatic hypotension, slow
cardiac conduction, and increase the risk of arrhythmias. Al-
though it can have some cardiac conduction effects, in gen-
eral, lithium can be safely used in cardiac patients (287).
Sudden cardiac death and psychotropics
Patients with schizophrenia have been reported to be three
times as likely to experience sudden cardiac death as indi-
viduals from the general population (325,326). In patients
with AP monotherapy, a similar dose-related increased risk
of sudden cardiac death was found for both conventional and
atypical AP, with adjusted RRs of 1.31 vs. 1.59 (low dose,
chlorpromazine equivalents <100mg), 2.01 vs. 2.13 (moder-
ate dose, chlorpromazine equivalents 100-299mg) and 2.42
vs. 2.86 (high dose, chlorpromazine equivalents ≥300mg),
respectively (327). In large epidemiological studies, a dose
dependent increased risk of sudden cardiac death has been
identified in current users of tricyclic AD (328).
There is a consensus that QTc values >500 msec, or an
absolute increase of 60 msec compared with drug-free base-
line, puts a patient at significant risk of torsade de pointes,
ventricular fibrillation and sudden cardiac death (94,329,
330). Most AP and some AD may be associated with QTc
prolongation (331). Patients using AP have higher rates of
cardiac arrest or ventricular arrhythmias than controls, with
ratios ranging from 1.7 to 5.3 (332-335). AP associated with
a greater risk of QTc prolongation include pimozide, thio-
ridazine and mesoridazine among the conventional AP
(94,335,336) and sertindole and ziprasidone among the
atypical AP (94,337). However, the largest randomized study
to date (n=18,154) did not find a statistically significant dif-
ference in the risk of sudden cardiac death between ziprasi-
done and olanzapine treated patients with schizophrenia
Table 7 Estimated prevalence and relative risk (RR) of modifiable risk factors for cardiovascular disease in schizophrenia and bipolar
disorder compared to the general population (see 4,305,309)
Modifiable risk factorsSchizophreniaBipolar disorder
Prevalence (%)RRPrevalence (%)RR
World Psychiatry 10:1 - February 2011
(338,339). Similarly, another large randomized study
(n=9,858) observed no significant differences between
sertindole and risperidone recipients in cardiac events, in-
cluding arrhythmias, requiring hospitalization. However,
cardiac mortality in general was higher with sertindole
(337). These large randomized studies, which focused on a
low incidence serious side effect, suffer from the problem
that they did not enrich samples for cardiac risk, so that they
lack power and, possibly, generalizability. Cases of torsade
de pointes have been reported with thioridazine, haloperi-
dol, ziprasidone, olanzapine, and tricyclic AD. Although
SSRIs have been associated with QTc prolongation, no cases
of torsade de pointes have been reported with the use of
these agents. There are no reported cases of lithium-induced
torsade de pointes (328).
Disparities in health care
SMI patients have the highest CVD mortality but the least
chance of receiving many specialized interventions or circu-
latory medications. Evidence suggests that people with
schizophrenia are not being adequately screened and treat-
ed for dyslipidemia (up to 88% untreated) and hypertension
(up to 62% untreated) (35,306,340-343). The care of these
patients shows a significant deficit in the monitoring of cho-
lesterol values and the prescription of statins (25,35,40,344).
They also have low rates of surgical interventions, such as
stenting and coronary artery bypass grafting (40,41,291,
297,345). A poorer quality of medical care contributes to
excess mortality in older people with mental disorders after
heart failure (346). Another important barrier is the lack of
seeking medical care by SMI patients themselves, even dur-
ing acute cardiovascular syndromes (25).
Patients with SMI are at increased risk for a variety of
chronic viral infections, of which the most serious are the
diseases associated with human immunodeficiency virus
(HIV) and hepatitis C virus.
The prevalence of HIV positivity in people with SMI is
generally higher than in the general population, but varies
substantially (1.3-23.9%) (347-370). The high frequency of
substance abuse, sexual risk behaviors (e.g., sex without a
condom, trading sex for money and drugs), and a reduced
knowledge about HIV-related issues contribute to this high
HIV prevalence (364,371-376). Therefore, it is important
that patients with SMI are tested for HIV (377). However,
studies investigating HIV testing rates among individuals
with a SMI indicate that fewer than half of these patients
(percentages ranging from 17% to 47%) have been tested in
the past year (378-394).
Since many patients with SMI are exposed to atypical AP,
which have been associated with metabolic abnormalities,
and since patients infected with HIV and on highly active
antiretroviral therapy may also develop metabolic abnor-
malities, this group of patients is at particularly high risk for
developing MetS and ultimately CVD (395).
Across different continents, markedly elevated rates of
hepatitis virus infection have been reported in persons with
SMI compared to the general population (364,396-403).
The largest study to date found prevalence rates of hepatitis
B virus (23.4%) and hepatitis C virus (19.6%) in SMI pa-
tients to be approximately 5 and 11 times the overall esti-
mated population rates for these infections. Overall, an es-
timated 20-25% of persons with SMI are infected with
hepatitis C virus (360,404-407).
The most common transmission routes for persons with
SMI are drug-use behaviors and sexual behaviors related to
drug use (404-406). Therefore, especially patients with SMI
and substance use disorders (including dependency) should
have routine screening and treatment for hepatitis C virus
infection to prevent associated morbidity and mortality
(400,407,408). Interventions exist that are specifically de-
signed to facilitate integrated infectious disease program-
ming in mental health settings for people with SMI and to
overcome provider- and consumer-level barriers at a modest
and specified cost (409). A recent study showed that the as-
signment of people with SMI to the “STIRR” (Screening,
Testing, Immunization, Risk reduction counseling, medical
treatment Referral) intervention had high levels (over 80%)
of participation and acceptance of core services (testing for
hepatitis C, immunization against hepatitis, knowledge
about hepatitis) (407).
respiratory tract diseases
Up until 50 years ago, respiratory diseases, such as pneu-
monia and tuberculosis, accounted for the majority of deaths
amongst people with SMI who lived in institutions (2). To-
day, respiratory diseases are still more prevalent in people
with SMI (8,410-417).
Studies consistently show a higher incidence of tubercu-
losis among patients with schizophrenia compared with the
general population (422-426). In some countries, tuberculo-
sis still occurs so frequently that mental hospitals have spe-
cial wards for people with both tuberculosis and schizophre-
nia (15). If untreated, up to 65% of people with active tuber-
culosis will die of the disease. However, chemotherapy is
effective and the vast majority of people with drug-suscepti-
ble forms of tuberculosis are cured if properly treated (427).
A nationwide, population-based study found schizophre-
nia to be associated with a 1.37 times greater risk of acute
respiratory failure and a 1.34-fold greater risk of mechanical
ventilation (428). Filik et al (414) found that people with
SMI have a higher prevalence of angina and respiratory
symptoms and impaired lung function when compared with
the general population. Significant barriers to prompt and
appropriate medical care for pneumonia still persist for pa-
tients who have schizophrenia (428).
Chronic obstructive pulmonary disease
The prevalence of chronic obstructive pulmonary dis-
ease, i.e. chronic bronchitis and emphysema, is significantly
higher among those with SMI than comparison subjects
(429-433). In a study of 200 outpatients in the US, 15% of
those with schizophrenia and 25% of those with bipolar
disorder had chronic bronchitis, and 16% of people with
schizophrenia and 19% of people with bipolar disorder had
asthma. These rates were significantly higher than those of
the matched controls from the general population. The au-
thors also found that, even when smoking was controlled for
as a confounder, both people with schizophrenia and bipo-
lar disorder were more likely to suffer from emphysema
(430). Although the association remains unclear, a higher
incidence of chronic obstructive pulmonary disease in the
past two decades has been associated with the side effects of
phenothiazine conventional AP (434).
Cancer risk in SMI patients
Given that obesity and unhealthy lifestyle behaviors are
known risk factors for a number of cancer types (149,435-
438), one would expect to see higher cancer rates in patients
with SMI. However, studies exploring the relationship be-
tween SMI and all cancer types together have shown con-
flicting results (30,439). Some studies have demonstrated a
decreased cancer risk in schizophrenia (440-448). On the
other hand, other studies found an increased (9,21,28,449-
451) or no different (292,419,452,453) overall risk of cancer
in patients with schizophrenia compared to the general
population. In the population of bipolar spectrum disorders,
deaths from cancer are not higher (8,288,416,417,454-456)
or only slightly elevated (417,418,456) compared with the
general population, despite the higher number of risk factors
for cancer (such as obesity) in this population. This discrep-
ancy of results may be a result of various confounding fac-
tors that could artificially lower the rates of diagnosed and
reported cancer in SMI populations. For example, people
with SMI are less likely to receive routine cancer screening
(457-460). Furthermore, patients with SMI have a shorter
life expectancy, so they may die from cardiovascular reasons
before reaching the expected age of death from cancer (30).
Another tentative hypothesis is that AP have antitumour
properties (448) or that the disease itself has a possible pro-
tective effect, including a tumor suppressor gene or en-
hanced natural killer cell activity (461,462). Nevertheless, a
problem with most of the existing data base analyses is that
etiologically disparate cancer types were lumped together.
An important analysis of cause-specific excess deaths asso-
ciated with underweight, overweight, and obesity in the gen-
eral population found that obesity was associated with an
increased mortality from cancers considered obesity-related
but not with mortality from other cancers (463).
Cancer risk and psychotropics
Because of the possible, but still controversial, role of pro-
lactin in breast cancer, the assumption has been made that
exposure to prolactin-raising dopamine antagonists could
result in breast cancer. The current study database on AP
and breast cancer risk is very limited (464). The majority of
the studies in which the risk of breast cancer has been inves-
tigated in patients treated with conventional AP (465-468)
did not uncover an increased risk of breast cancer, an excep-
tion being the cohort study by Wang et al (469).
Osteoporosis in SMI patients
Schizophrenia, schizoaffective states, major depression
and bipolar disorder are known to be associated with low
bone mineral density (BMD) (470). In comparison with the
general population, untreated patients with schizophrenia
appear to have an increased risk of developing osteoporosis.
On the one hand, this is because of the disease itself, on the
other hand, because of risk factors related to their lifestyle
(e.g., smoking, reduced physical activity, alcohol abuse,
vitamin D and calcium deficiency, polydipsia) (470-476). Al-
though the association between depression and loss of BMD
has been reported inconsistently, most studies have found
low BMD in patients with depressive symptoms or major
depressive disorder (477-483). Two recent meta-analyses
confirmed that depression is associated with low BMD and
should be considered as an important risk factor for osteo-
porosis, although this increased risk may be mediated by AD
(484,485). However, physiologic changes and the adoption
of poor health behaviors are two prominent ways in which
depression is hypothesized to directly affect BMD (486).
World Psychiatry 10:1 - February 2011
Osteoporosis and psychotropics
Although it has been suggested that raised prolactin lev-
els provoked by AP medication can lead to an increased
risk of osteoporosis in patients with schizophrenia (471,
487), clinical data implicating AP-induced hyperprolac-
tinemia as a possible major risk factor for bone loss are
limited and contradictory (488,489). Some studies (490-
493) found a relationship between the use of prolactin-rais-
ing medication and low BMD in patients with chronic
schizophrenia, while others (474,489,494-498) failed to
find a relationship between prolactin, AP and osteoporosis.
Nevertheless, the available data seem to indicate that hy-
perprolactinemia with associated hypogonadism may be a
risk factor (488), leading to bone mineral loss in women as
well as men (499).
The majority of studies directly examining the relation-
ship between AD and BMD in humans report that the use
of these medications is associated with low BMD (486).
However, this finding seems to be restricted to the SSRI
class of AD (500-502).
Data describing the epidemiology of osteoporotic fracture
and psychotropics in patients with SMI are limited. Regard-
ing AP, conflicting results exist (503). Some of these studies
have reported higher prevalence rates of osteoporotic frac-
tures in patients with chronic schizophrenia, entirely or
partly independent of the use of AP (504,505). Other studies
(506-510) have found significant increases (OR=1.2-2.6) in
the risk of fractures associated with AP. For AD, a dose-re-
sponse relationship was observed for fracture risk (504,508).
SSRIs seem to be associated with the highest adjusted odds
of osteoporotic fractures (OR=1.5) (504,505, 508). A meta-
analysis showed a 33% increased risk of fractures with SSRIs
compared to non-SSRI AD. The RR of fractures in this meta-
analysis was 1.60 for AD and 1.59 for AP (511). Although
lithium has a potentially negative impact on bone metabo-
lism (470), it is associated with lower fracture risk (OR=0.6)
and, thus, seems to be protective against fractures (504,505).
Urological, male/female genital diseases
and pregnancy complications
Sexual dysfunction in SMI patients
Sexual dysfunction in SMI patients has received little at-
tention from clinicians (512,513). This low awareness has a
significant negative impact on patients’ satisfaction with
treatment, adherence, quality of life and partner relation-
ships (450). Although there are relatively few systematic in-
vestigations concerning sexual disorders in schizophrenia
(514), sexual dysfunction in schizophrenia is, compared to
normal controls, estimated to be more frequent (515-519)
and to affect 30-80% of women and 45-80% of men (512,515,
520-523). This dysfunction can be secondary to the disease
itself and to comorbid physical disorders, or be an adverse
event of AP (520,524,525). Sexual dysfunction is also a com-
mon symptom of depression (526-530). Up to 70% of pa-
tients with depression may have sexual dysfunction (466).
Approximately 25% of patients with major depression may
experience problems with erection or lubrication (531).
Patients with SMI are likely to engage in high-risk sexual
behavior, putting them at risk of sexually transmitted dis-
eases. However, findings suggest that sexual health educa-
tion for these people tends to produce a reduction in sexual
risk behavior (532).
Sexual dysfunction and psychotropics
Psychotropic drugs are associated with sexual dysfunc-
tion (514). To date, only few studies (534-547) have directly
compared the sexual functioning associated with different
atypical AP. These studies suggest that the relative impact of
AP on sexual dysfunction can be summarized as: paliperi-
done = risperidone > haloperidol > olanzapine ≥ ziprasi-
done > clozapine ≥ quetiapine > aripiprazole (503,520,536).
Conventional AP cause less sexual dysfunction than risper-
idone but more than the other novel AP (520,522).
AD therapy (except for mirtazapine, nefazodone and bu-
propion) frequently induces or exacerbates sexual dysfunc-
tion, which occurs in approximately 50% of patients (548).
Although sexual dysfunction has been reported with all
classes of AD (549), SSRIs are associated with higher rates
(550-552). Published studies suggest that between 30% and
60% of SSRI-treated patients may experience some form of
treatment-induced sexual dysfunction (553,554).
Pregnancy complications, SMI and psychotropics
There is an extensive literature reporting an increased oc-
currence of obstetric complications among women who
have schizophrenia (15). During pregnancy, it is important
to evaluate the safety of psychotropic drugs. Most women
with a SMI cannot stop taking their medication, as this
would interfere with their activities of daily living, especially
taking care of an infant (555). There is a paucity of informa-
tion, with a lack of large, well designed, prospective com-
parative studies during pregnancy. However, no definitive
association has been found up to now between the use of AP
during pregnancy and an increased risk of birth defects or
other adverse outcomes (555,556). Among AD, SSRIs and,
possibly, serotonin and noradrenaline reuptake inhibitors
(SNRIs) have been associated with preterm labor, respira-
tory distress, serotonin rebound syndrome, pulmonary hy-
pertension and feeding problems in the neonate (557-559).
Furthermore, a number of mood stabilizers have been as-
sociated with fetal malformations, including carbamazepine
and valproate (560,561). Current evidence seems to suggest
that Fallot’s tetralogy is not considerably elevated with lith-
ium compared to the rate in the general population (560).
Oral health in SMI patients
Dental health has been consistently found to be poor in
people with SMI (562-573). A study using an overall dental
status index (DMF-T) in chronically hospitalized patients
with mental disorders (mostly schizophrenia) found a mean
score of 26.74 (out of a possible 32), one of the highest re-
ported in the literature (571). According to another study,
only 42% of patients with schizophrenia brush their teeth
regularly (at least twice a day) (573). This poor dental health
leads to functional difficulties. In one large study (n=4,769),
34.1% of the patients with SMI reported that oral health
problems made it difficult for them to eat (572).
Factors which influence oral health include: type, sever-
ity, and stage of mental illness; mood, motivation and self-
esteem; lack of perception of oral health problems; habits,
lifestyle (e.g., smoking), and ability to sustain self-care and
dental attendance; socio-economic factors; effects of medi-
cation (dry mouth, carbohydrate craving); and attitudes and
knowledge of dental health teams concerning mental health
Oral health and psychotropics
AP, AD and mood stabilizers all cause xerostomia (575).
This reduction in salivary flow changes the oral environment
and leads to caries, gingivitis and periodontal disease (576).
Disparities in health care
Oral health status is a frequently disregarded health issue
among SMI patients (498), with low rates of dental examina-
tion within the past 12 months (569,577-579). In one study
of a mixed psychiatric population, 15% had not been to a
dentist in the last 2 years (579), while in another only 31% of
schizophrenia patients had visited a dentist during a three
year period (577). In the latter study, non-adherence to an-
nual dental visits was predicted by substance abuse diagnosis,
involuntary legal status, living in an institution, admission to
a psychiatric facility for a minimum of 30 days, and male
gender, whereas clozapine treatment, novel AP treatment, at
least monthly outpatient visits, and age > 50 years were as-
sociated with a lower risk for inappropriate dental care.
Taken together, these findings confirm the urgent need for
an intervention program to improve oral health outcomes
among patients with SMI, by facilitating access to dental
care and addressing modifiable factors such as smoking and
medication side effects (571,572), especially because oral
diseases are preventable and social inequity in oral health
avoidable (580). Moreover, improving dental health status
and care are relevant, as poor dental status is associated with
endocarditis and reduces social and work opportunities.
other physical health conditions in people with sMI
This review is by no means exhaustive. We speculate that
perhaps most medical illnesses occur with greater frequency
in SMI, which in itself serves as a vulnerability factor (587).
Haematological diseases, which may in themselves be
primary problems in patients with SMI, have frequently
been described in the literature as potential serious compli-
cations of psychotropic medications. AP (e.g., clozapine,
haloperidol, olanzapine, phenothiazines, quetiapine, ris-
peridone, ziprasidone), AD (e.g., amitriptyline, clomip-
ramine, imipramine) as well as lithium are associated with
blood dyscrasias. Clozapine (approximately 0.8%) and phe-
nothiazines (chlorpromazine approximately 0.13%) are the
most common causes of drug-related neutropenia/agranu-
locytosis. AD are rarely associated with agranulocytosis.
With appropriate management, the mortality from drug-in-
duced agranulocytosis in Western countries is 5-10% (be-
fore the use of antibiotics this percentage was 80%) (582).
Some physical conditions, although important, are rarely
studied, underreported and not systematically assessed. Al-
though a common side effect of AP that can be severe and
lead to serious consequences and even death, constipation
has been given relatively little attention. The most reported
complications of this physical condition are paralytic ileus,
faecal impaction, bowel obstruction and intestine/bowel
perforations. Constipation has most widely been reported
for clozapine, although it can be associated with other AP
as well. Prevalence of constipation in randomized controlled
trials for different AP is: zotepine 39.6%, clozapine 21.3%,
haloperidol 14.6% and risperidone 12% (583). Next to med-
ication effects, lifestyle and diet factors can contribute to the
occurrence of constipation in people with SMI (sedentary
life, low physical activity, diet low in fibre, limited fluid in-
take) (584). Clinicians should actively and systematically
screen and monitor symptoms and possible complications
of constipation (585-588).
In summary, many physical disorders have been identified
that are more prevalent in individuals with SMI. In addition
to modifiable lifestyle factors and psychotropic medication
side effects, poorer access to and quality of received health
care remain addressable problems for patients with SMI.
Greater individual and system level attention to these physi-
cal disorders that can worsen psychiatric stability, treatment
adherence, and life expectancy as well as quality of life will
improve outcomes of these generally disadvantaged popula-
tions worldwide. The barriers to somatic monitoring and
interventions in persons with SMI will be summarized in the
second part of this educational module, where monitoring
and treatment guidelines as well as recommendations at the
system level (state and health care institutions) and individ-
ual level (clinicians, patients, family) will be provided.
World Psychiatry 10:1 - February 2011
The production of this educational module is part of the
WPA Action Plan 2008-2011 and has been supported by the
Lugli Foundation, the Italian Society of Biological Psychia-
try, Pfizer and Bristol Myers Squibb.
1. Harris EC, Barraclough B. Excess mortality of mental disorder. Br
J Psychiatry 1998;173:11-53.
2. Brown S. Excess mortality of schizophrenia. A meta-analysis. Br
J Psychiatry 1997;171:502-8.
3. Allebeck P. Schizophrenia: a life-shortening disease. Schizophr
4. Holt RIG, Peveler RC. Diabetes and cardiovascular risk in severe
mental illness: a missed opportunity and challenge for the future.
Pract Diab Int 2010;27:79-84.
5. Rössler W, Salize HJ, van Os J et al. Size of burden of schizophre-
nia and psychotic disorders. Eur Neuropsychopharmacol 2005;
6. Roshanaei-Moghaddam B, Katon W. Premature mortality from
general medical illnesses among persons with bipolar disorder: a
review. Psychiatr Serv 2009;60:147-56.
7. Tidemalm D, Waern M, Stefansson CG et al. Excess mortality in
persons with severe mental disorder in Sweden: a cohort study of
12 103 individuals with and without contact with psychiatric ser-
vices. Clin Pract Epidemol Ment Health 2008;4:23.
8. Laursen TM, Munk-Olsen T, Nordentoft M et al. Increased mor-
tality among patients admitted with major psychiatric disorders: a
register-based study comparing mortality in unipolar depressive
disorder, bipolar affective disorder, schizoaffective disorder, and
schizophrenia. J Clin Psychiatry 2007;68:899-907.
9. Brown S, Inskip H, Barraclough B. Causes of the excess mortality
of schizophrenia. Br J Psychiatry 2000;177:212-7.
10. Brown S, Kim M, Mitchell C et al. Twenty-five year mortality of a
community cohort with schizophrenia. Br J Psychiatry 2010;196:
11. Osby U, Correia N, Brandt L et al. Time trends in schizophrenia
mortality in Stockholm county, Sweden: cohort study. BMJ 2000;
12. Newman SC, Bland RC. Mortality in a cohort of patients with
schizophrenia: a record linkage study. Can J Psychiatry 1991;36:
13. Casadebaig F, Philippe A. Mortality in schizophrenia patients. 3
years follow-up of a cohort. Encephale 1999;25:329-37.
14. Beyer J, Kuchibhatla M, Gersing K et al. Medical comorbidity in
a bipolar outpatient clinical population. Neuropsychopharmacol-
15. Leucht S, Burkard T, Henderson J et al. Physical illness and schiz-
ophrenia: a review of the literature. Acta Psychiatr Scand
16. De Hert M, Dekker JM, Wood D et al. Cardiovascular disease and
diabetes in people with severe mental illness. Position statement
from the European Psychiatric Association (EPA), supported by
the European Association for the Study of Diabetes (EASD) and
the European Society of Cardiology (ESC). Eur Psychiatry
17. Widerlöv B, Borgå P, Cullberg J et al. Epidemiology of long-term
functional psychosis in three different areas in Stockholm County.
Acta Psychiatr Scand 1989;80:40-6.
18. Joukamaa M, Heliövaara M, Knekt P et al. Schizophrenia, neuro-
leptic medication and mortality. Br J Psychiatry 2006;188:122-7.
19. Marder SR, Essock SM, Miller AL et al. Physical health monitor-
ing of patients with schizophrenia. Am J Psychiatry 2004;161:
20. von Hausswolff-Juhlin Y, Bjartveit M, Lindström E, et al. Schizo-
phrenia and physical health problems. Acta Psychiatr Scand 2009;
21. Tran E, Rouillon F, Loze JY et al. Cancer mortality in patients with
schizophrenia: an 11-year prospective cohort study. Cancer
22. Mental and Physical Health Platform. Mental and physical health
charter. Bridging the gap between mental and physical health.
Bruxelles: Mental and Physical Health Platform, 2008.
23. Colton CW, Manderscheid RW. Congruencies in increased mortal-
ity rates, years of potential life lost, and causes of death among
public mental health clients in eight states. Prev Chronic Dis
24. Tiihonen J, Lönnqvist J, Wahlbeck K et al. 11-year follow-up of
mortality in patients with schizophrenia: a population-based co-
hort study (FIN11 study). Lancet 2009;374:620-7.
25. Hennekens CH, Hennekens AR, Hollar D et al. Schizophrenia
and increased risks of cardiovascular disease. Am Heart J 2005;
26. Newcomer JW. Antipsychotic medications: metabolic and cardio-
vascular risk. J Clin Psychiatry 2007;68:8-13.
27. Vreeland B. Treatment decisions in major mental illness: weighing
the outcomes. J Clin Psychiatry 2007;68:5-11.
28. Saha S, Chant D, McGrath J. A systematic review of mortality in
schizophrenia. Arch Gen Psychiatry 2007;64:1123-31.
29. Capasso RM, Lineberry TW, Bostwick JM et al. Mortality in
schizophrenia and schizoaffective disorder: an Olmsted County,
Minnesota cohort: 1950-2005. Schizophr Res 2008;98:287-94.
30. Robson D, Gray R. Serious mental illness and physical health
problems: a discussion paper. Int J Nurs Stud 2007;44:457-66.
31. Parks J, Svendsen D, Singer P et al (eds). Morbidity and mortality
in people with serious mental illness. Alexandria: National Asso-
ciation of State Mental Health Program Directors (NASMHPD)
Medical Directors Council, 2006.
32. Maj M. Physical health care in persons with severe mental illness:
a public health and ethical priority. World Psychiatry 2009;8:1-2.
33. Lawrence D, Stephen K. Inequalities in health care provision for
people with severe mental illness. J Psychopharmacol (in press).
34. McIntyre RS, Soczynska JK, Beyer JL et al. Medical comorbidity
in bipolar disorder: re-prioritizing unmet needs. Curr Opin Psy-
35. Nasrallah HA, Meyer JM, Goff DC et al. Low rates of treatment
for hypertension, dyslipidemia and diabetes in schizophrenia:
data from the CATIE schizophrenia trial sample at baseline.
Schizophr Res 2006;86:15-22.
36. Roberts L, Roalfe A, Wilson S et al. Physical health care of patients
with schizophrenia in primary care: a comparative study. Fam
37. Osborn DP, King MB, Nazareth I. Participation in screening for
cardiovascular risk by people with schizophrenia or similar men-
tal illnesses: cross sectional study in general practice. BMJ 2003;
38. Fagiolini A, Goracci A. The effects of undertreated chronic medi-
cal illnesses in patients with severe mental disorders. J Clin Psy-
39. Mitchell AJ, Malone D, Doebbeling CC. Quality of medical care
for people with and without comorbid mental illness and sub-
stance misuse: systematic review of comparative studies. Br J Psy-
40. Kisely S, Campbell LA, Wang Y. Treatment of ischaemic heart dis-
ease and stroke in individuals with psychosis under universal
healthcare. Br J Psychiatry 2009;195:545-50.
41. Kisely S, Smith M, Lawrence D et al. Inequitable access for men-
tally ill patients to some medically necessary procedures. CMAJ
42. Chan M. Equity, social determinants and public health pro-
grammes. In: Blas E, Sivasankara Kurup A (eds). Equity, social
determinants and public health programmes. Geneva: World
Health Organization, 2010:1-2.
43. Haslam DW, James WP. Obesity. Lancet 2005;366:1197-209.
44. Mather AA, Cox BJ, Enns MW et al. Associations of obesity with
psychiatric disorders and suicidal behaviors in a nationally repre-
sentative sample. J Psychosom Res 2009;66:277-85.
45. McElroy SL. Obesity in patients with severe mental illness: over-
view and management. J Clin Psychiatry 2009;70:12-21.
46. World Health Organization. Global strategy on diet, physical ac-
tivity and health. Geneva: World Health Organization, 2003.
47. Bray GA. Obesity: the disease. J Med Chem 2006;49:4001-7.
48. Bray GA, Wilson JF. In the clinic. Obesity. Ann Intern Med
49. National Institutes of Health, National Heart, Lung and Blood
Institute. Clinical guidelines on the identification, evaluation and
treatment of overweight and obesity in adults: the evidence report.
Bethesda: National Institutes of Health, 1998.
50. Holt R, Peveler R. Obesity, serious mental illness and antipsy-
chotic drugs. Diabetes Obes Metab 2009;11:665-79.
51. Allison DB, Fontaine KR, Manson JE et al. Annual deaths attribut-
able to obesity in the United States. JAMA 1999;282:1530-8.
52. McKeigue PM, Shah B, Marmot MG. Relation of central obesity
and insulin resistance with high diabetes prevalence and cardio-
vascular risk in South Asians. Lancet 1991;337:382-6.
53. Misra A, Vikram NK, Gupta R et al. Waist circumference cutoff
points and action levels for Asian Indians for identification of
abdominal obesity. Int J Obes 2006; 30:106-11.
54. Ko GT, Chan JC, Cockram CS et al. Prediction of hypertension,
diabetes, dyslipidaemia or albuminuria using simple anthropo-
metric indexes in Hong Kong Chinese. Int J Obes Relat Metab
55. Raji A, Seely EW, Arky RA et al. Body fat distribution and insulin
resistance in healthy Asian Indians and Caucasians. J Clin Endo-
crinol Metab 2001;86:5366-71.
56. Deurenberg-Yap M, Chew SK, Lin VF et al. Relationships be-
tween indices of obesity and its co-morbidities in multi-ethnic
Singapore. Int J Obes Relat Metab Disord 2001;25:1554-62.
57. Alberti KG, Eckel RH, Grundy SM et al. Harmonizing the meta-
bolic syndrome: a joint interim statement of the International
Diabetes Federation Task Force on Epidemiology and Prevention;
National Heart, Lung, and Blood Institute; American Heart As-
sociation; World Heart Federation; International Atherosclerosis
Society; and International Association for the Study of Obesity.
58. International Diabetes Federation. The IDF consensus worldwide
definition of the metabolic syndrome. www.idf.org.
59. Alberti KG, Zimmet P, Shaw J. Metabolic syndrome – a new
world-wide definition. A consensus statement from the Interna-
tional Diabetes Federation. Diabet Med 2006;23:469-80.
60. Oka R, Kobayashi J, Yagi K et al. Reassessment of the cutoff values
of waist circumference and visceral fat area for identifying Japa-
nese subjects at risk for the metabolic syndrome. Diabetes Res
Clin Pract 2008;79:474-81.
61. Examination Committee of Criteria for ‘Obesity Disease’ in Japan;
Japan Society for the Study of Obesity. New criteria for ‘obesity
disease’ in Japan. Circ J 2002;66:987-92.
62. Zhou BF; Cooperative Meta-Analysis Group of the Working
Group on Obesity in China. Predictive values of body mass index
and waist circumference for risk factors of certain related diseases
in Chinese adults. Study on optimal cut-off points of body mass
index and waist circumference in Chinese adults. Biomed Environ
63. McElroy SL, Guerdjikova A, Kotwal R. Severe mental illness and
obesity. In: Bermudes RA, Keck PE, McElroy SL (eds). Managing
metabolic abnormalities in the psychiatrically ill: a clinical guide
for psychiatrists. Arlington: American Psychiatric Publishing,
64. Wirshing DA. Schizophrenia and obesity: impact of antipsychotic
medications. J Clin Psychiatry 2004;65:13-26.
65. Keck PE, McElroy SL. Bipolar disorder, obesity, and pharmaco-
therapy-associated weight gain. J Clin Psychiatry 2003;64:1426-35.
66. Citrome L, Vreeland B. Schizophrenia, obesity, and antipsychotic
medications: what can we do? Postgrad Med 2008;120:18-33.
67. Saarni SE, Saarni SI, Fogelholm M et al. Body composition in
psychotic disorders: a general population survey. Psychol Med
68. McIntyre RS, McElroy SL, Konarski JZ et al. Substance use disor-
ders and overweight/obesity in bipolar I disorder: preliminary evi-
dence for competing addictions. J Clin Psychiatry 2007;68:1352-7.
69. Petry NM, Barry D, Pietrzak RH et al. Overweight and obesity are
associated with psychiatric disorders: results from the National
Epidemiologic Survey on Alcohol and Related Conditions. Psy-
chosom Med 2008;70:288-97.
70. Simon GE, Von Korff M, Saunders K et al. Association between
obesity and psychiatric disorders in the US adult population. Arch
Gen Psychiatry 2006;63:824-30.
71. Monteleone P, Martiadis V, Maj M. Management of schizophrenia
with obesity, metabolic, and endocrinological disorders. Psychiatr
Clin North Am 2009;32:775-94.
72. Pack S. Poor physical health and mortality in patients with schiz-
ophrenia. Nurs Stand 2009;23:41-5.
73. Wildes JE, Marcus MD, Fagiolini A. Obesity in patients with bipo-
lar disorder: a biopsychosocial-behavioral model. J Clin Psychia-
74. Krishnan KR. Psychiatric and medical comorbidities of bipolar
disorder. Psychosom Med 2005;67:1-8.
75. Gracious BL, Cook SR, Meyer AE et al. Prevalence of overweight
and obesity in adolescents with severe mental illness: a cross-
sectional chart review. J Clin Psychiatry 2010;71:949-54.
76. Ryan MC, Flanagan S, Kinsella U et al. The effects of atypical
antipsychotics on visceral fat distribution in first episode, drug-
naive patients with schizophrenia. Life Sci 2004;74:1999-2008.
77. Maina G, Salvi V, Vitalucci A et al. Prevalence and correlates of
overweight in drug-naïve patients with bipolar disorder. J Affect
78. Citrome L, Blonde L, Damatarca C. Metabolic issues in patients
with severe mental illness. South Med J 2005;98:714-20.
79. Coodin S. Body mass index in persons with schizophrenia. Can J
80. Strassnig M, Brar JS, Ganguli R. Body mass index and quality of
life in community-dwelling patients with schizophrenia. Schizophr
81. McIntyre RS, Konarski JZ, Wilkins K et al. Obesity in bipolar
disorder and major depressive disorder: results from a national
community health survey on mental health and well-being. Can J
82. Scott KM, McGee MA, Wells JE et al. Obesity and mental disor-
ders in the adult general population. J Psychosom Res 2008;64:
83. McElroy SL, Kotwal R, Malhotra S et al. Are mood disorders and
obesity related? A review for the mental health professional. J Clin
84. Simon GE, Ludman EJ, Linde JA et al. Association between obe-
sity and depression in middle-aged women. Gen Hosp Psychiatry
85. Kluge M, Schuld A, Himmerich H et al. Clozapine and olanzapine
are associated with food craving and binge eating: results from a
randomized double-blind study. J Clin Psychopharmacol
86. Gebhardt S, Haberhausen M, Krieg JC et al. Clozapine/olanzap-
ine-induced recurrence or deterioration of binge eating-related
eating disorders. J Neural Transm 2007;114:1091-5.
World Psychiatry 10:1 - February 2011
87. Vieweg WV, Levy JR, Fredrickson SK et al. Psychotropic drug
considerations in depressed patients with metabolic disturb-
ances. Am J Med 2008;121:647-55.
88. Allison DB, Mentore JL, Heo M et al. Antipsychotic-induced
weight gain: a comprehensive research synthesis. Am J Psychia-
89. Allison DB, Newcomer JW, Dunn AL et al. Obesity among those
with mental disorders: a National Institute of Mental Health
meeting report. Am J Prev Med 2009;36:341-50.
90. American Diabetes Association; American Psychiatric Associa-
tion; American Association of Clinical Endocrinologists; North
American Association for the Study of Obesity. Consensus de-
velopment conference on antipsychotic drugs and obesity and
diabetes. Diabetes Care 2004;27:596-601.
91. Bech P, Vendsborg PJ, Rafaelson OJ. Lithium maintenance treat-
ment of manic-melancholic patients: its role in the daily routine.
Acta Psychiatr Scand 1976;53:70-81.
92. Citrome L. Risk-benefit analysis of available treatments for schizo-
phrenia. Psychiatric Times 2007;1:27-30.
93. Falkai P, Wobrock T, Lieberman J et al. Guidelines for biological
treatment of schizophrenia, Part 1: Acute treatment of schizo-
phrenia. World J Biol Psychiatry 2005;6:132-91.
94. Haddad PM, Sharma SG. Adverse effects of atypical antipsy-
chotics; differential risk and clinical implications. CNS Drugs
95. Newcomer JW. Second-generation (atypical) antipsychotics and
metabolic effects. A comprehensive literature review. CNS Drugs
96. Scheen AJ, De Hert MA. Abnormal glucose metabolism in pa-
tients treated with antipsychotics. Diabetes Metab 2007;33:169-
97. Scheen A, van Winkel R, De Hert M. Traitement neuroleptique
et troubles metabolic. Med Mal Metabol 2008;2:593-9.
98. Stahl SM, Mignon L, Meyer JM. Which comes first: atypical an-
tipsychotic treatment or cardiometabolic risk? Acta Psychiatr
99. Torrent C, Amann B, Sánchez-Moreno J et al. Weight gain in
bipolar disorder: pharmacological treatment as a contributing
factor. Acta Psychiatr Scand 2008;118:4-18.
100. Daumit GL, Goff DC, Meyer JM et al. Antipsychotic effects on
estimated 10-year coronary heart disease risk in the CATIE
schizophrenia study. Schizophr Res 2008;105:175-87.
101. Goff DC, Sullivan LM, McEvoy JP et al. A comparison of ten-year
cardiac risk estimates in schizophrenia patients from the CATIE
study and matched controls. Schizophr Res 2005;80:45-53.
102. Kahn RS, Fleischhacker WW, Boter H et al.. Effectiveness of
antipsychotic drugs in first-episode schizophrenia and schizo-
phreniform disorder: an open randomised clinical trial. Lancet
103. Leucht S, Corves C, Arbter D et al. Second-generation versus
first-generation antipsychotic drugs for schizophrenia: a meta-
analysis. Lancet 2009;373:31-41.
104. Lieberman JA, Stroup TS, McEvoy JP et al. Effectiveness of an-
tipsychotic drugs in patients with chronic schizophrenia. N Engl
J Med 2005;353:1209-23.
105. Parsons B, Allison DB, Loebel A et al. Weight effects associated
with antipsychotics: a comprehensive database analysis. Schizo-
phr Res 2009;110:103-10.
106. Coccurello R, Moles A. Potential mechanisms of atypical anti-
psychotic-induced metabolic derangement: clues for under-
standing obesity and novel drug design. Pharmacol Ther
107. Leucht S, Burkard T, Henderson JH et al. Physical illness and
schizophrenia. A review of the evidence. Cambridge: Cambridge
University Press, 2007.
108. Bobes J, Rejas J, García-García M et al. Weight gain in patients
with schizophrenia treated with risperidone, olanzapine, quetia-
pine or haloperidol: results of the Eire Study. Schizophr Res 2003;
109. De Hert M, Dobbelaere M, Sheridan EM et al. Metabolic and
endocrine adverse effects of second-generation antipsychotics in
children and adolescents: a systematic review of randomized,
placebo controlled trials and guidelines for clinical practice. Eur
Psychiatry (in press).
110. Newcomer JW. Comparing the safety and efficacy of atypical an-
tipsychotics in psychiatric patients with comorbid medical ill-
nesses. J Clin Psychiatry 2009;70:30-6.
111. Newcomer JW. Medical risk in patients with bipolar disorder
and schizophrenia. J Clin Psychiatry 2006;67:25-30.
112. American Diabetes Association; American Psychiatric Associa-
tion; American Association of Clinical Endocrinologists; North
American Association for the Study of Obesity. Consensus de-
velopment conference on antipsychotic drugs and obesity and
diabetes. J Clin Psychiatry 2004;65:267-72.
113. Alvarez-Jiménez M, González-Blanch C, Crespo-Facorro B et
al. Antipsychotic-induced weight gain in chronic and first-epi-
sode psychotic disorders: a systematic critical reappraisal. CNS
114. Correll CU, Manu P, Olshanskiy V et al. Cardiometabolic risk of
second-generation antipsychotic medications during first-time
use in children and adolescents. JAMA 2009;302:1765-73.
115. Saddichha S, Ameen S, Akhtar S. Incidence of new onset meta-
bolic syndrome with atypical antipsychotics in first episode
schizophrenia: a six-week prospective study in Indian female
patients. Schizophr Res 2007;95:247.
116. Fava M, Judge R, Hoog SL et al. Fluoxetine versus sertraline and
paroxetine in major depressive disorder: changes in weight with
long-term treatment. J Clin Psychiatry 2000;61:863-7.
117. Vanina Y, Podolskaya A, Sedky K et al. Body weight changes
associated with psychopharmacology. Psychiatr Serv 2002;53:
118. Fagiolini A, Chengappa KN, Soreca I et al. Bipolar disorder and
the metabolic syndrome: causal factors, psychiatric outcomes
and economic burden. CNS Drugs 2008;22:655-69.
119. Bowden CL, Calabrese JR, McElroy SL et al. A randomized,
placebo-controlled 12-month trial of divalproex and lithium in
treatment of outpatients with bipolar I disorder. Divalproex
Maintenance Study Group. Arch Gen Psychiatry 2000;57:481-9.
120. Bray GA, Greenway FL. Pharmacological treatment of the over-
weight patient. Pharmacol Rev 2007;59:151-84.
121. Nasrallah HA. Atypical antipsychotic-induced metabolic side
effects: insights from receptor-binding profiles. Mol Psychiatry
122. Reynolds GP, Kirk SL. Metabolic side effects of antipsychotic
drug treatment – pharmacological mechanisms. Pharmacol Ther
123. Stein K. When essential medications provoke new health prob-
lems: the metabolic effects of second-generation antipsychotics.
J Am Diet Assoc 2010;110:992-1001.
124. Bostwick JM. A generalist’s guide to treating patients with de-
pression with an emphasis on using side effects to tailor antide-
pressant therapy. Mayo Clin Proc 2010;85:538-50.
125. Papakostas GI. The efficacy, tolerability, and safety of contem-
porary antidepressants. J Clin Psychiatry 2010;71:e03.
126. Citrome L. Iloperidone for schizophrenia: a review of the effi-
cacy and safety profile for this newly commercialised second-
generation antipsychotic. Int J Clin Pract 2009;63:1237-48.
127. Poyurovsky M, Pashinian A, Gil-Ad I et al. Olanzapine-induced
weight gain in patients with first-episode schizophrenia: a dou-
ble-blind, placebo-controlled study of fluoxetine addition. Am J
128. Tohen M, Vieta E, Calabrese J et al. Efficacy of olanzapine and
olanzapine-fluoxetine combination in the treatment of bipolar I
depression. Arch Gen Psychiatry 2003;60:1079-88.
129. Barak Y, Aizenberg D. Switching to aripiprazole as a strategy for
weight reduction: a meta-analysis in patients suffering from
schizophrenia. J Obes (in press).
130. Weiden PJ, Newcomer JW, Loebel AD et al. Long-term changes
in weight and plasma lipids during maintenance treatment with
ziprasidone. Neuropsychopharmacology 2008;33:985-94.
131. Vehof J, Al Hadithy AFY, Burger H et al. BMI and rs1455832
SNP of the ROBO1 gene: association analysis in patients using
antipsychotics. Schizophr Res 2010;117:552-3.
132. Mulder H, Franke B, van der Beek AA et al. The association
between HTR2C gene polymorphisms and the metabolic syn-
drome in patients with schizophrenia. J Clin Psychopharmacol
133. Mulder H, Cohen D, Scheffer H et al. HTR2C gene polymor-
phisms and the metabolic syndrome in patients with schizophre-
nia: a replication study. J Clin Psychopharmacol 2009;29:16-20.
134. Risselada AJ, Vehof J, Bruggeman R et al. Association between
HTR2C gene polymorphisms and the metabolic syndrome in
patients using antipsychotics: a replication study. Pharmaco-
genomics (in press)
135. Opgen-Rhein C, Brandl EJ, Müller DJ et al. Association of
HTR2C, but not LEP or INSIG2, genes with antipsychotic-in-
duced weight gain in a German sample. Pharmacogenomics
136. Gregoor JG, van der Weide J, Mulder W et al. Polymorphisms of
the LEP- and LEPR gene and obesity in patients using antipsy-
chotic medication. J Clin Psychopharmacol 2009;26:21-5.
137. Li C, Ford ES. Definition of the metabolic syndrome: what’s new
and what predicts risk? Metab Syndr Relat Disord 2006;4:237-
138. Bhargava A. A longitudinal analysis of the risk factors for diabe-
tes and coronary heart disease in the Framingham Offspring
Study. Popul Health Metr 2003;1:3.
139. Grundy SM. Metabolic syndrome: connecting and reconciling
cardiovascular and diabetes worlds. J Am Coll Cardiol 2006;47:
140. Grundy SM. Obesity, metabolic syndrome, and cardiovascular
disease. J Clin Endocrinol Metab 2004;89:2595-600.
141. Hanson RL, Imperatore G, Bennett PH et al. Components of the
“metabolic syndrome” and incidence of type 2 diabetes. Diabe-
142. Laaksonen DE, Lakka HM, Niskanen LK et al. Metabolic syn-
drome and development of diabetes mellitus: application and
validation of recently suggested definitions of the metabolic syn-
drome in a prospective cohort study. Am J Epidemiol 2002;156:
143. Fagiolini A, Frank E, Scott JA et al. Metabolic syndrome in bi-
polar disorder: findings from the Bipolar Disorder Center for
Pennsylvanians. Bipolar Disord 2005;7:424-30.
144. Katon W, Maj M, Sartorius N (eds). Depression and diabetes.
Chichester: Wiley-Blackwell, 2010.
145. Pothiwala P, Jain SK, Yaturu S. Metabolic syndrome and cancer.
Metab Syndr Relat Disord 2009;7:279-88.
146. Giovannucci E. Metabolic syndrome, hyperinsulinemia, and co-
lon cancer: a review. Am J Clin Nutr 2007;86:s836-42.
147. Gale EA. The myth of the metabolic syndrome. Diabetologia
148. Moebus S, Stang A. The metabolic syndrome – a controversial
diagnostic concept. Herz 2007;32:529-40.
149. Pacholczyk M, Ferenc T, Kowalski J. The metabolic syndrome.
Part I: definitions and diagnostic criteria for its identification.
Epidemiology and relationship with cardiovascular and type 2
diabetes risk. Postepy Hig Med Dosw 2008;62:530-42.
150. Grundy SM, Cleeman JI, Daniels SR et al. Diagnosis and man-
agement of the metabolic syndrome: an American Heart Asso-
ciation/National Heart, Lung, and Blood Institute Scientific
Statement. Circulation 2005;112:2735-52.
151. Pollex RL, Hanley AJ, Zinman B et al. Metabolic syndrome in
aboriginal Canadians: prevalence and genetic associations. Ath-
152. Ford ES. Prevalence of the metabolic syndrome defined by the
International Diabetes Federation among adults in the US. Dia-
betes Care 2005;28:2745-9.
153. Aguilar-Salinas CA, Rojas R, Gómez-Pérez FJ et al. Prevalence
and characteristics of early-onset type 2 diabetes in Mexico. Am
J Med 2002;113:569-74.
154. Florez H, Silva E, Fernández V et al. Prevalence and risk factors
associated with the metabolic syndrome and dyslipidemia in
White, Black, Amerindian and Mixed Hispanics in Zulia State,
Venezuela. Diabetes Res Clin Pract 2005;69:63-77.
155. De Hert MA, van Winkel R, Van Eyck D et al. Prevalence of the
metabolic syndrome in patients with schizophrenia treated with
antipsychotic medication. Schizophr Res 2006;83:87-93.
156. Saari KM, Lindeman SM, Viilo KM et al. A 4-fold risk of meta-
bolic syndrome in patients with schizophrenia: the Northern Fin-
land 1966 Birth Cohort study. J Clin Psychiatry 2005;66:559-63.
157. Cohn T, Prud’homme D, Streiner D et al. Characterizing coro-
nary heart disease risk in chronic schizophrenia: high prevalence
of the metabolic syndrome. Can J Psychiatry 2004;49:753-60.
158. McEvoy JP, Meyer JM, Goff DC et al. Prevalence of the meta-
bolic syndrome in patients with schizophrenia: baseline results
from the Clinical Antipsychotic Trials of Intervention Effective-
ness (CATIE) schizophrenia trial and comparison with national
estimates from NHANES III. Schizophr Res 2005;80:19-32.
159. Meyer J, Loh C, Leckband SG et al. Prevalence of the metabolic
syndrome in veterans with schizophrenia. J Psychiatr Pract
160. Correll CU, Frederickson AM, Kane JM et al. Metabolic syn-
drome and the risk of coronary heart disease in 367 patients
treated with second-generation antipsychotic drugs. J Clin Psy-
161. Hägg S, Lindblom Y, Mjörndal T et al. High prevalence of the
metabolic syndrome among a Swedish cohort of patients with
schizophrenia. Int Clin Psychopharmacol 2006;21:93-8.
162. Lamberti JS, Olson D, Crilly JF et al. Prevalence of the meta-
bolic syndrome among patients receiving clozapine. Am J Psy-
163. Mackin P, Bishop D, Watkinson H et al. Metabolic disease and
cardiovascular risk in people treated with antipsychotics in the
community. Br J Psychiatry 2007;191:23-9.
164. Tirupati S, Chua LE. Obesity and metabolic syndrome in a psy-
chiatric rehabilitation service. Aust N Z J Psychiatry 2007;41:
165. Srisurapanont M, Likhitsathian S, Boonyanaruthee V et al.
Metabolic syndrome in Thai schizophrenic patients: a naturalis-
tic one-year follow-up study. BMC Psychiatry 2007;7:14.
166. Rejas J, Bobes J, Arango C et al. Concordance of standard and
modified NCEP ATP III criteria for identification of metabolic
syndrome in outpatients with schizophrenia treated with anti-
psychotics: a corollary from the CLAMORS study. Schizophr
167. Arango C, Bobes J, Aranda P et al. A comparison of schizophre-
nia outpatients treated with antipsychotics with and without
metabolic syndrome: findings from the CLAMORS study. Schiz-
ophr Res 2008;104:1-12.
168. Meyer JM, Stahl SM. The metabolic syndrome and schizophre-
nia. Acta Psychiatr Scand 2009;119:4-14.
169. Garcia-Portilla MP, Sáiz PA, Benabarre A et al. The prevalence
of metabolic syndrome in patients with bipolar disorder. J Affect
170. Bobes J, Arango C, Aranda P et al. Cardiovascular and meta-
bolic risk in outpatients with schizoaffective disorder treated
with antipsychotics: results from the CLAMORS study. Eur Psy-
chiatry (in press).
World Psychiatry 10:1 - February 2011
171. Basu R, Brar JS, Chengappa KN et al. The prevalence of the
metabolic syndrome in patients with schizoaffective disorder -
bipolar subtype. Bipolar Disord 2004;6:314-8.
172. Rummel-Kluge C, Komossa K, Schwarz S et al. Head-to-head
comparisons of metabolic side effects of second generation an-
tipsychotics in the treatment of schizophrenia: a systematic re-
view and meta-analysis. Schizophr Res (in press).
173. Hasnain M, Fredrickson SK, Vieweg WV et al. Metabolic syn-
drome associated with schizophrenia and atypical antipsychot-
ics. Curr Diab Rep 2010;10:209-16.
174. De Hert M, Mittoux A, He Y et al. Metabolic parameters in the
short- and long-term treatment of schizophrenia with sertindole
or risperidone. Eur Arch Psychiatry Clin Neurosci (in press).
175. De Hert M, Mittoux A, He Y et al. A head-to-head comparison
of sertindole and risperidone on metabolic parameters. Schi-
zophr Res 2010;123:276-7.
176. Vancampfort D, Knapen J, Probst M et al. Considering a frame
of reference for physical activity research related to the cardio-
metabolic risk profile in schizophrenia. Psychiatry Res 2010;
177. Buckley PF, Miller DD, Singer B et al. Clinicians’ recognition of
the metabolic adverse effects of antipsychotic medications.
Schizophr Res 2005;79:281-8.
178. Newcomer JW, Nasrallah HA, Loebel AD. The Atypical Antip-
sychotic Therapy and Metabolic Issues National Survey: prac-
tice patterns and knowledge of psychiatrists. J Clin Psychophar-
179. Cavanagh MR, Hancock E, Taylor DM et al. A UK audit of
screening for the metabolic side effects of antipsychotics in com-
munity patients. Schizophr Bull 2007;33:1397-403.
180. Lambert TJ, Newcomer JW. Are the cardiometabolic complica-
tions of schizophrenia still neglected? Barriers to care. Med J
181. Morrato EH, Druss B, Hartung DM et al. Metabolic testing rates
in 3 state Medicaid programs after FDA warnings and ADA/
APA recommendations for second-generation antipsychotic
drugs. Arch Gen Psychiatry 2010;67:17-24.
182. Morrato EH, Newcomer JW, Kamat S et al. Metabolic screening
after the American Diabetes Association’s consensus statement on
antipsychotic drugs and diabetes. Diabetes Care 2009;32:1037-42.
183. Morrato EH, Cuffel B, Newcomer JW et al. Metabolic risk status
and second-generation antipsychotic drug selection: a retro-
spective study of commercially insured patients. J Clin Psycho-
184. Morrato EH, Nicol GE, Maahs D et al. Metabolic screening in
children receiving antipsychotic drug treatment. Arch Pediatr
Adolesc Med 2010;164:344-51.
185. Alberti KG, Zimmet PZ. Definition, diagnosis and classification
of diabetes mellitus and its complications. Part 1: diagnosis and
classification of diabetes mellitus: provisional report of a WHO
consultation. Diabet Med 1998;15:539-53.
186. World Health Organization Department of Noncommunicable
Disease Surveillance. Definition, diagnosis and classification of
diabetes mellitus and its complications: report of a WHO con-
sultation. Part 1: diagnosis and classification of diabetes melli-
tus. Geneva: World Health Organization, 1999.
187. Balkau B, Charles MA. Comment on the provisional report from
the WHO consultation. European Group for the Study of Insulin
Resistance (EGIR). Diabet Med 1999;16:442-3.
188. Expert Panel on Detection, Evaluation, and Treatment of High
Blood Cholesterol in Adults. Executive summary of the third
report of the National Cholesterol Education Program (NCEP)
(Adult Treatment Panel III). JAMA 2001;285:2486-97.
189. Ford ES, Giles WH, Mokdad AH. Increasing prevalence of the
metabolic syndrome among U.S. adults. Diabetes Care 2004;27:
190. Grundy SM, Brewer HB Jr, Cleeman JI et al. Definition of meta-
bolic syndrome: report of the National Heart, Lung, and Blood
Institute/American Heart Association conference on scientific
issues related to definition. Arterioscler Thromb Vasc Biol
191. Grundy SM, Hansen B, Smith SC Jr et al. Clinical management
of metabolic syndrome: report of the American Heart Associa-
tion/National Heart, Lung, and Blood Institute/American Dia-
betes Association conference on scientific issues related to man-
agement. Circulation 2004;109:551-6.
192. Einhorn D, Reaven GM, Cobin RH et al. American College of
Endocrinology position statement on the insulin resistance syn-
drome. Endocr Pract 2003;9:237-52.
193. Bloomgarden ZT. Definitions of the insulin resistance syndrome:
the 1st World Congress on the Insulin Resistance Syndrome.
Diabetes Care 2004;27:824-30.
194. Alberti KG, Zimmet P, Shaw J; IDF Epidemiology Task Force
Consensus Group. The metabolic syndrome – a new worldwide
definition. Lancet 2005;366:1059-62.
195. Whiting D, Unwin N, Roglic G. Diabetes: equity and social de-
terminant. In: Blas E, Sivasankara Kurup A (eds). Equity, social
determinant and public health programmes. Geneva: World
Health Organization, 2010:77-94.
196. Qin L, Knol MJ, Corpeleijn E et al. Does physical activity mod-
ify the risk of obesity for type 2 diabetes: a review of epidemio-
logical data. Eur J Epidemiol 2010;25:5-12.
197. Jeon CY, Lokken RP, Hu FB et al. Physical activity of moderate
intensity and risk of type 2 diabetes: a systematic review. Dia-
betes Care 2007;30:744-52.
198. Rana JS, Li TY, Manson JE et al. Adiposity compared with phys-
ical inactivity and risk of type 2 diabetes in women. Diabetes
199. Weinstein AR, Sesso HD, Lee IM et al. Relationship of physical
activity vs body mass index with type 2 diabetes in women.
200. Siegel LC, Sesso HD, Bowman TS et al. Physical activity, body
mass index, and diabetes risk in men: a prospective study. Am J
201. Hu G, Lindström J, Valle TT et al. Physical activity, body mass
index, and risk of type 2 diabetes in patients with normal or
impaired glucose regulation. Arch Intern Med 2004;164:892-6.
202. Hartemink N, Boshuizen HC, Nagelkerke NJ et al. Combining
risk estimates from observational studies with different exposure
cutpoints: a meta-analysis on body mass index and diabetes type
2. Am J Epidemiol 2006;163:1042-52.
203. Alberti KG, Zimmet P, Shaw J. International Diabetes Federa-
tion: a consensus on Type 2 diabetes prevention. Diabet Med
204. Hu FB, Leitzmann MF, Stampfer MJ et al. Physical activity and
television watching in relation to risk for type 2 diabetes mellitus
in men. Arch Intern Med 2001;161:1542-8.
205. Hu FB, Sigal RJ, Rich-Edwards JW et al. Walking compared with
vigorous physical activity and risk of type 2 diabetes in women:
a prospective study. JAMA 1999;282:1433-9.
206. Patja K, Jousilahti P, Hu G et al. Effects of smoking, obesity and
physical activity on the risk of type 2 diabetes in middle-aged
Finnish men and women. J Intern Med 2005;258:356-62.
207. Knowler WC, Barrett-Connor E, Fowler SE et al. Reduction in
the incidence of type 2 diabetes with lifestyle intervention or
metformin. N Engl J Med 2002;346:393-403.
208. Tuomilehto J, Lindström J, Eriksson JG et al. Prevention of type
2 diabetes mellitus by changes in lifestyle among subjects with
impaired glucose tolerance. N Engl J Med 2001;344:1343-50.
209. Holt RI, Peveler RC. Association between antipsychotic drugs
and diabetes. Diabetes Obes Metab 2006;8:125-35.
210. Bushe C, Holt R. Prevalence of diabetes and impaired glucose
tolerance in patients with schizophrenia. Br J Psychiatry 2004;
211. McIntyre RS, Konarski JZ, Misener VL et al. Bipolar disorder
and diabetes mellitus: epidemiology, etiology, and treatment im-
plications. Ann Clin Psychiatry 2005;17:83-93.
212. van Winkel R, De Hert M, Van Eyck D et al. Screening for dia-
betes and other metabolic abnormalities in patients with schizo-
phrenia and schizoaffective disorder: evaluation of incidence
and screening methods. J Clin Psychiatry 2006;67:1493-500.
213. Barnett AH, Mackin P, Chaudhry I et al. Minimising metabolic
and cardiovascular risk in schizophrenia: diabetes, obesity and
dyslipidaemia. J Psychopharmacol 2007;21:357-73.
214. van Winkel R, De Hert M, Van Eyck D et al. Prevalence of dia-
betes and the metabolic syndrome in a sample of patients with
bipolar disorder. Bipolar Disord 2008;10:342-8.
215. Regenold WT, Thapar RK, Marano C et al. Increased prevalence
of type 2 diabetes mellitus among psychiatric inpatients with
bipolar I affective and schizoaffective disorders independent of
psychotropic drug use. J Affect Disord 2002;70:19-26.
216. De Hert M, Mauri M, Shaw K et al. The METEOR study of dia-
betes and other metabolic disorders in patients with schizophre-
nia treated with antipsychotic drugs. I. Methodology. Int J Meth-
ods Psychiatr Res (in press).
217. Arroyo C, Hu FB, Ryan LM et al. Depressive symptoms and risk
of type 2 diabetes in women. Diabetes Care 2004;27:129-33.
218. Brown LC, Majumdar SR, Newman SC et al. History of depres-
sion increases risk of type 2 diabetes in younger adults. Diabetes
219. Carnethon MR, Kinder LS, Fair JM et al. Symptoms of depres-
sion as a risk factor for incident diabetes: findings from the Na-
tional Health and Nutrition Examination Epidemiologic Fol-
low-up Study, 1971-1992. Am J Epidemiol 2003;158:416-23.
220. Eaton WW, Armenian H, Gallo J et al. Depression and risk for
onset of type II diabetes. A prospective population-based study.
Diabetes Care 1996;19:1097-102.
221. Everson-Rose SA, Meyer PM, Powell LH et al. Depressive symp-
toms, insulin resistance, and risk of diabetes in women at midlife.
Diabetes Care 2004;27:2856-62.
222. Golden SH, Williams JE, Ford DE et al. Depressive symptoms
and the risk of type 2 diabetes: the Atherosclerosis Risk in Com-
munities study. Diabetes Care 2004;27:429-35.
223. Kawakami N, Takatsuka N, Shimizu H et al. Depressive symp-
toms and occurrence of type 2 diabetes among Japanese men.
Diabetes Care 1999;22:1071-6.
224. Palinkas LA, Lee PP, Barrett-Connor E. A prospective study of
type 2 diabetes and depressive symptoms in the elderly: the Ran-
cho Bernardo Study. Diabet Med 2004;21:1185-91.
225. van den Akker M, Schuurman A, Metsemakers J et al. Is depres-
sion related to subsequent diabetes mellitus? Acta Psychiatr
226. Gough S, Peveler R. Diabetes and its prevention: pragmatic solu-
tions for people with schizophrenia. Br J Psychiatry 2004;47:
227. De Hert M, van Winkel R, Van Eyck D et al. Prevalence of dia-
betes, metabolic syndrome and metabolic abnormalities in
schizophrenia over the course of the illness: a cross-sectional
study. Clin Pract Epidemiol Ment Health 2006;2:14.
228. Okumura Y, Ito H, Kobayashi M et al. Prevalence of diabetes
and antipsychotic prescription patterns in patients with schizo-
phrenia: a nationwide retrospective cohort study. Schizophr Res
229. Citrome LL, Holt RI, Zachry WM et al. Risk of treatment-emer-
gent diabetes mellitus in patients receiving antipsychotics. Ann
230. Smith M, Hokins D, Peveler R et al. First versus second genera-
tion antipsychotics and risk for diabetes in schizophrenia: system-
atic review and meta-analysis. Br J Psychiatry 2008;192:406-11.
231. Ramaswamy K, Masand PS, Nasrallah HA. Do certain atypical
antipsychotics increase the risk of diabetes? A critical review of
17 pharmacoepidemiologic studies. Ann Clin Psychiatry 2006;
232. Yood MU, DeLorenze G, Quesenberry CP Jr et al. The incidence
of diabetes in atypical antipsychotic users differs according to
agent – results from a multisite epidemiologic study. Pharmaco-
epidemiol Drug Saf 2009;18:791-9.
233. Koller EA, Doraiswamy PM. Olanzapine-associated diabetes
mellitus. Pharmacotherapy 2002;22:841-52.
234. Starrenburg FC, Bogers JP. How can antipsychotics cause diabe-
tes mellitus? Insights based on receptor-binding profiles, hu-
moral factors and transporter proteins. Eur Psychiatry 2009;24:
235. Koller E, Schneider B, Bennett K et al. Clozapine-associated
diabetes. Am J Med 2001;111:716-23.
236. Koller EA, Weber J, Doraiswamy PM et al. A survey of reports of
quetiapine-associated hyperglycemia and diabetes mellitus. J
Clin Psychiatry 2004;65:857-63.
237. Koller EA, Cross JT, Doraiswamy PM et al. Risperidone-associ-
ated diabetes mellitus: a pharmacovigilance study. Pharmaco-
238. Guo JJ, Keck PE Jr, Corey-Lisle PK et al. Risk of diabetes mellitus
associated with atypical antipsychotic use among Medicaid pa-
tients with bipolar disorder: a nested case-control study. Phar-
239. Guo JJ, Keck PE Jr, Corey-Lisle PK et al. Risk of diabetes mellitus
associated with atypical antipsychotic use among patients with
bipolar disorder: a retrospective, population-based, case-control
study. J Clin Psychiatry 2006;67:1055-61.
240. Kessing LV, Thomsen AF, Mogensen UB et al. Treatment with
antipsychotics and the risk of diabetes in clinical practice. Br J
241. Nielsen J, Skadhede S, Correll CU. Antipsychotics associated with
the development of type 2 diabetes in antipsychotic-naïve schizo-
phrenia patients. Neuropsychopharmacology 2010;35:1997-2004.
242. Baker RA, Pikalov A, Tran QV et al. Atypical antipsychotic
drugs and diabetes mellitus in the US Food and Drug Adminis-
tration Adverse Event Database: a systematic Bayesian signal
detection analysis. Psychopharmacol Bull 2009;42:11-31.
243. Bushe C, Leonard B. Association between atypical antipsychot-
ic agents and type 2 diabetes: review of prospective clinical data.
Br J Psychiatry 2004;47:S87-93.
244. Sussman N, Ginsberg DL, Bikoff J. Effects of nefazodone on
body weight: a pooled analysis of selective serotonin reuptake
inhibitor- and imipramine-controlled trials. J Clin Psychiatry
245. Sachs GS, Guille C. Weight gain associated with use of psycho-
tropic medications. J Clin Psychiatry 1999;60:16-9.
246. Frank E, Kupfer DJ, Buhari A et al. Imipramine and weight gain
during the long-term treatment of recurrent depression. J Affect
247. Fernstrom MH, Kupfer DJ. Antidepressant-induced weight gain:
a comparison study of four medications. Psychiatry Res 1988;26:
248. Garland EJ, Remick RA, Zis AP. Weight gain with antidepres-
sants and lithium. J Clin Psychopharmacol 1988;8:323-30.
249. Brown LC, Majumdar SR, Johnson JA. Type of antidepressant
therapy and risk of type 2 diabetes in people with depression.
Diabetes Res Clin Pract 2008;79:61-7.
250. Andersohn F, Schade R, Suissa S et al. Long-term use of antide-
pressants for depressive disorders and the risk of diabetes mel-
litus. Am J Psychiatry 2009;166:591-8.
251. Rubin RR, Ma Y, Marrero DG et al. Diabetes Prevention Pro-
gram Research Group. Elevated depression symptoms, antide-
pressant medicine use, and risk of developing diabetes during
the diabetes prevention program. Diabetes Care 2008;31:420-6.
252. Verrotti A, la Torre R, Trotta D et al. Valproate-induced insulin
resistance and obesity in children. Horm Res 2009;71:125-31.
World Psychiatry 10:1 - February 2011
253. Pylvänen V, Pakarinen A, Knip M et al. Insulin-related meta-
bolic changes during treatment with valproate in patients with
epilepsy. Epilepsy Behav 2006;8:643-8.
254. Masuccio F, Verrotti A, Chiavaroli V et al. Weight gain and insu-
lin resistance in children treated with valproate: the influence of
time. J Child Neurol 2010;25:941-7.
255. Luef GJ, Waldmann M, Sturm W et al. Valproate therapy and
nonalcoholic fatty liver disease. Ann Neurol 2004;55:729-32.
256. Pylvänen V, Knip M, Pakarinen A et al. Serum insulin and leptin
levels in valproate-associated obesity. Epilepsia 2002;43:514-7.
257. Frayne SM, Halanych JH, Miller DR et al. Disparities in diabe-
tes care: impact of mental illness. Arch Intern Med 2005;165:
258. Desai MM, Rosenheck RA, Druss BG et al. Mental disorders and
quality of diabetes care in the veterans health administration.
Am J Psychiatry 2002;159:1584-90.
259. Subramaniam M, Chong SA, Pek E. Diabetes mellitus and im-
paired glucose tolerance in patients with schizophrenia. Can J
260. Taylor D, Young C, Mohamed R et al. Undiagnosed impaired
fasting glucose and diabetes mellitus amongst inpatients receiv-
ing antipsychotic drugs. J Psychopharmacol 2005;19:182-6.
261. Cohen D, Stolk RP, Grobbee DE et al. Hyperglycemia and dia-
betes in patients with schizophrenia or schizoaffective disorders.
Diabetes Care 2006;29:786-91.
262. Voruganti LP, Punthakee Z, Van Lieshout RJ et al. Dysglycemia
in a community sample of people treated for schizophrenia: the
Diabetes in Schizophrenia in Central-South Ontario (DiSCO)
study. Schizophr Res 2007;96:215-22.
263. Holt RI, Abdelrahman T, Hirsch M et al. The prevalence of un-
diagnosed metabolic abnormalities in people with serious men-
tal illness. J Psychopharmacol 2010;24:867-73.
264. Department of Health. Diabetes national service framework.
London: Department of Health, 2001.
265. Jin H, Meyer JM, Jeste DV. Atypical antipsychotics and glucose
dysregulation: a systematic review. Schizophr Res 2004;71:195-
266. Cohen D, Correll CU. Second-generation antipsychotic-associ-
ated diabetes mellitus and diabetic ketoacidosis: mechanisms,
predictors, and screening need. J Clin Psychiatry 2009;70:765-6.
267. Henderson DC, Cagliero E, Copeland PM et al. Elevated hemo-
globin A1c as a possible indicator of diabetes mellitus and dia-
betic ketoacidosis in schizophrenia patients receiving atypical
antipsychotics. J Clin Psychiatry 2007;68:533-41.
268. Nihalani ND, Tu X, Lamberti JS et al. Diabetic ketoacidosis
among patients receiving clozapine: a case series and review of
socio-demographic risk factors. Ann Clin Psychiatry 2007;19:105-
269. Wong JO, Fu JC, Hung GB. Olanzapine-induced diabetic keto-
acidosis in a Chinese man. Hong Kong Med J 2007;13:73-4.
270. Reddymasu S, Bahta E, Levine S et al. Elevated lipase and dia-
betic ketoacidosis associated with aripiprazole. JOP 2006;7:303-5.
271. Makhzoumi ZH, McLean LP, Lee JH et al. Diabetic ketoacidosis
associated with aripiprazole. Pharmacotherapy 2008;28:1198-202.
272. Church CO, Stevens DL, Fugate SE. Diabetic ketoacidosis as-
sociated with aripiprazole. Diabet Med 2005;22:1440-3.
273. Ramaswamy K, Kozma CM, Nasrallah H. Risk of diabetic keto-
acidosis after exposure to risperidone or olanzapine. Drug Saf
274. Aruna PAP. Chlorpromazine induced diabetes mellitus. J Assoc
Physicians India 1995;43:146.
275. de Boer C, Gaete HP. Neuroleptic malignant syndrome and dia-
betic keto-acidosis. Br J Psychiatry 1992;161:856-8.
276. Henriksen OM, Røder ME, Prahl JB et al. Diabetic ketoacidosis
in Denmark. Incidence and mortality estimated from public
health registries. Diabetes Res Clin Pract 2007;76:51-6.
277. World Health Organization. The world health report 2003: shap-
ing the future. Geneva: World Health Organization, 2003.
278. Mackin P. Cardiac side effects of psychiatric drugs. Hum Psycho-
279. World Health Organization. Cardiovascular diseases (CVDs).
Geneva: World Health Organization, 2009.
280. Mendis S, Banerjee A. Cardiovascular disease: equity and social
determinants. In: Blas E, Sivasankara Kurup A (eds). Equity,
social determinants and public health programmes. Geneva:
World Health Organization, 2010:31-48.
281. Hennekens CH. Increasing global burden of cardiovascular dis-
ease in general populations and patients with schizophrenia. J
Clin Psychiatry 2007;68:4-7.
282. Smith SC Jr, Amsterdam E, Balady GJ et al. Prevention Confer-
ence V: Beyond secondary prevention: identifying the high-risk
patient for primary prevention: tests for silent and inducible
ischemia: Writing Group II. Circulation 2000;101:E12-6.
283. Lindholm LH, Mendis S. Prevention of cardiovascular disease
in developing countries. Lancet 2007;370:720-2.
284. Walker RW, McLarty DG, Kitange HM et al. Stroke mortality in
urban and rural Tanzania. Adult Morbidity and Mortality Proj-
ect. Lancet 2000;355:1684-7.
285. Hetemaa T, Manderbacka K, Reunanen A et al. Socioeconomic
inequities in invasive cardiac procedures among patients with
incident angina pectoris or myocardial infarction. Scand J Public
286. World Health Organization. The world health report 2002: re-
ducing risks, promoting healthy life. Geneva: World Health Or-
287. Sowden GL, Huffman JC. The impact of mental illness on car-
diac outcomes: a review for the cardiologist. Int J Cardiol 2009;
288. Angst F, Stassen HH, Clayton PJ et al. Mortality of patients with
mood disorders: follow-up over 34-38 years. J Affect Disord
289. Brown AD, Barton DA, Lambert GW. Cardiovascular abnor-
malities in patients with major depressive disorder: autonomic
mechanisms and implications for treatment. CNS Drugs 2009;
290. Casey DE, Haupt DW, Newcomer JW et al. Antipsychotic-in-
duced weight gain and metabolic abnormalities: implications for
increased mortality in patients with schizophrenia. J Clin Psy-
291. Lawrence DM, Holman CD, Jablensky AV et al. Death rate from
ischaemic heart disease in Western Australian psychiatric pa-
tients 1980-1998. Br J Psychiatry 2003;182:31-6.
292. Osby U, Correia N, Brandt L et al. Mortality and causes of death
in schizophrenia in Stockholm county, Sweden. Schizophr Res
293. Surtees PG, Wainwright NW, Luben RN et al. Depression and
ischemic heart disease mortality: evidence from the EPIC-Nor-
folk United Kingdom prospective cohort study. Am J Psychiatry
294. Glassman A, Maj M, Sartorius N (eds). Depression and heart
disease. Chichester: Wiley-Blackwell, 2011.
295. Garcia-Portilla MP, Saiz PA, Bascaran MT et al. Cardiovascular
risk in patients with bipolar disorder. J Affect Disord 2009;115:
296. Carnethon MR, Biggs ML, Barzilay JI et al. Longitudinal asso-
ciation between depressive symptoms and incident type 2 diabe-
tes mellitus in older adults. The Cardiovascular Health Study.
Arch Intern Med 2007;167:801-8.
297. Laursen TM, Munk-Olsen T, Agerbo E et al. Somatic hospital
contacts, invasive cardiac procedures, and mortality from heart
disease in patients with severe mental disorder. Arch Gen Psy-
298. Nicol G, Haupt D, Flavin K et al. Preliminary results of the
MEAC study: metabolic effects of antipsychotics in children.
Schizophr Bull 2009;35(Suppl. 1):32.
299. Osborn DP, Levy G, Nazareth I et al. Relative risk of cardiovas-
cular and cancer mortality in people with severe mental illness
from the United Kingdom’s General Practice Research Data-
base. Arch Gen Psychiatry 2007;64:242-9.
300. Bouza C, López-Cuadrado T, Amate JM. Hospital admissions
due to physical disease in people with schizophrenia: a national
population-based study. Gen Hosp Psychiatry 2010;32:156-63.
301. Kilbourne AM, Brar JS, Drayer RA et al. Cardiovascular disease
and metabolic risk factors in male patients with schizophrenia,
schizoaffective disorder, and bipolar disorder. Psychosomatics
302. Bresee LC, Majumdar SR, Patten SB et al. Prevalence of cardio-
vascular risk factors and disease in people with schizophrenia: a
population-based study. Schizophr Res 2010;117:75-82.
303. Ruo B, Rumsfeld JS, Hlatky MA et al. Depressive symptoms and
health-related quality of life: the Heart and Soul Study. JAMA
304. Whooley MA, de Jonge P, Vittinghoff E et al. Depressive symp-
toms, health behaviors, and risk of cardiovascular events in pa-
tients with coronary heart disease. JAMA 2008;300:2379-88.
305. Correll CU, Frederickson AM, Kane JM et al. Equally increased
risk for metabolic syndrome in patients with bipolar disorder
and schizophrenia treated with second-generation antipsychot-
ics. Bipolar Disord 2008;10:788-97.
306. De Hert M, Falissard B, Mauri M et al. Epidemiological study for
the evaluation of metabolic disorders in patients with schizo-
phrenia: the METEOR Study. Eur Neuropsychopharmacol
307. De Hert M, Schreurs V, Sweers K et al. Typical and atypical an-
tipsychotics differentially affect long-term incidence rates of the
metabolic syndrome in first-episode patients with schizophre-
nia: a retrospective chart review. Schizophr Res 2008;101:295-
308. Meyer JM, Davis VG, Goff DC et al. Change in metabolic syn-
drome parameters with antipsychotic treatment in the CATIE
Schizophrenia Trial: prospective data from phase 1. Schizophr
309. De Hert M, Schreurs V, Vancampfort D et al. Metabolic syn-
drome in people with schizophrenia: a review. World Psychiatry
310. Rugulies R. Depression as a predictor for coronary heart disease.
A review and meta-analysis. Am J Prev Med 2002;23:51-61.
311. Khawaja IS, Westermeyer JJ, Gajwani P et al. Depression and
coronary artery disease: the association, mechanisms, and thera-
peutic implications. Psychiatry 2009;6:38-51.
312. Pratt LA, Ford DE, Crum RM et al. Depression, psychotropic
medication, and risk of myocardial infarction. Prospective data
from the Baltimore ECA follow-up. Circulation 1996;94:3123-9.
313. Barefoot JC, Schroll M. Symptoms of depression, acute myocar-
dial infarction, and total mortality in a community sample. Cir-
314. Blumenthal JA. Depression and coronary heart disease: associa-
tion and implications for treatment. Cleve Clin J Med 2008;75:
315. Lin HC, Hsiao FH, Pfeiffer S et al. An increased risk of stroke
among young schizophrenia patients. Schizophr Res 2008;101:
316. Curkendall SM, Mo J, Glasser DB et al. Cardiovascular disease
in patients with schizophrenia in Saskatchewan, Canada. J Clin
317. Lin HC, Tsai SY, Lee HC. Increased risk of developing stroke
among patients with bipolar disorder after an acute mood epi-
sode: a six-year follow-up study. J Affect Disord 2007;100:49-54.
318. Nilsson FM, Kessing LV. Increased risk of developing stroke for
patients with major affective disorder – a registry study. Eur Arch
Psychiatry Clin Neurosci 2004;254:387-91.
319. Larson SL, Owens PL, Ford D et al. Depressive disorder, dysthy-
mia, and risk of stroke: thirteen-year follow-up from the Baltimore
epidemiologic catchment area study. Stroke 2001;32:1979-83.
320. Everson SA, Roberts RE, Goldberg DE et al. Depressive symp-
toms and increased risk of stroke mortality over a 29-year peri-
od. Arch Intern Med 1998;158:1133-8.
321. Tschoner A, Engl J, Laimer M et al. Metabolic side effects of
antipsychotic medication. Int J Clin Pract 2007;61:1356-70.
322. García-Tornadú I, Ornstei A, Chamson-Reig A et al. Disruption
of the dopamine D2 receptor impairs insulin secretion and
causes glucose intolerance. Endocrinology 2010;151:1441-50.
323. Witchel HJ, Hancox JC, Nutt DJ. Psychotropic drugs, cardiac
arrhythmia, and sudden death. J Clin Psychopharmacol 2003;23:
324. Cohen HW, Gibson G, Alderman MH. Excess risk of myocardial
infarction in patients treated with antidepressant medications: as-
sociation with use of tricyclic agents. Am J Med 2000;108:2-8.
325. Appleby L, Thomas S, Ferrier N et al. Sudden unexplained death
in psychiatric in-patients. Br J Psychiatry 2000;176:405-6.
326. Ruschena D, Mullen PE, Burgess P et al. Sudden death in psy-
chiatric patients. Br J Psychiatry 1998;172:331-6.
327. Ray WA, Chung CP, Murray KT et al. Atypical antipsychotic
drugs and the risk of sudden cardiac death. N Engl J Med 2009;
328. Alvarez PA, Pahissa J. QT alterations in psychopharmacology:
proven candidates and suspects. Curr Drug Saf 2010;5:97-104.
329. Pies RW. Antipsychotics: the heart of the problem. Psychiatric
330. Elbe D, Savage R. How does this happen? Part I: mechanisms
of adverse drug reactions associated with psychotropic medica-
tions. J Can Acad Child Adolesc Psychiatry 2010;19:40-5.
331. Glassman AH, Bigger JT. Antipsychotic drugs: prolonged QTc
interval, torsade de pointes, and sudden death. Am J Psychiatry
332. Mehtonen OP, Aranko K, Mälkonen L et al. A survey of sudden
death associated with the use of antipsychotic or antidepressant
drugs: 49 cases in Finland. Acta Psychiatr Scand 1991;84:58-64.
333. Ray WA, Meredith S, Thapa PB et al. Antipsychotics and the risk
of sudden cardiac death. Arch Gen Psychiatry 2001;58:1161-7.
334. Hennessy S, Bilker WB, Knauss JS et al. Cardiac arrest and ven-
tricular arrhythmia in patients taking antipsychotic drugs: co-
hort study using administrative data. BMJ 2002;325:1070.
335. Reilly JG, Ayis SA, Ferrier IN et al. Thioridazine and sudden
unexplained death in psychiatric in-patients. Br J Psychiatry
336. Ames D, Camm J, Cook P et al. Comment minimiser les risques
associés à un allongement significatif de l’intervalle QTc chez les
personnes souffrant de schizophrénie. Recommandations consen-
suelles du Cardiac Safety in Schizophrenia Group (CSISG).
337. Thomas SH, Drici MD, Hall GC et al. Safety of sertindole versus
risperidone in schizophrenia: principal results of the sertindole
cohort prospective study (SCoP). Acta Psychiatr Scand 2010;122:
338. Strom BL, Faich GA, Reynolds RF et al. The Ziprasidone Obser-
vational Study of Cardiac Outcomes (ZODIAC): design and base-
line subject characteristics. J Clin Psychiatry 2008;69:114-21.
339. Strom BL, Eng SM, Faich G et al. Comparative mortality associ-
ated with ziprasidone and olanzapine in real-world use among
18,154 patients with schizophrenia: the Ziprasidone Observa-
tional Study of Cardiac Outcomes (ZODIAC). Am J Psychiatry
340. Kilbourne AM, Welsh D, McCarthy JF et al. Quality of care for
cardiovascular disease-related conditions in patients with and
without mental disorders. J Gen Intern Med 2008;23:1628-33.
341. Weiss AP, Henderson DC, Weilburg JB et al. Treatment of car-
diac risk factors among patients with schizophrenia and diabe-
World Psychiatry 10:1 - February 2011
tes. Psychiatr Serv 2006;57:1145-52.
342. Morrato EH, Newcomer JW, Allen RR et al. Prevalence of base-
line serum glucose and lipid testing in users of second-genera-
tion antipsychotic drugs: a retrospective, population-based study
of Medicaid claims data. J Clin Psychiatry 2008;69:316-22.
343. Raedler TJ. Cardiovascular aspects of antipsychotics. Curr Opin
344. Hippisley-Cox J, Parker C, Coupland C et al. Inequalities in the
primary care of patients with coronary heart disease and serious
mental health problems: a cross-sectional study. Heart 2007;
345. Druss BG, Bradford DW, Rosenheck RA et al. Mental disorders
and use of cardiovascular procedures after myocardial infarc-
tion. JAMA 2000;283:506-11.
346. Rathore SS, Wang Y, Druss BG et al. Mental disorders, quality
of care, and outcomes among older patients hospitalized with
heart failure: an analysis of the national heart failure project.
Arch Gen Psychiatry 2008;65:1402-8.
347. Sacks M, Dermatis H, Looser-Ott S et al. Undetected HIV infec-
tion among acutely ill psychiatric inpatients. Am J Psychiatry
348. Volavka J, Convit A, Czobor P et al. HIV seroprevalence and risk
behaviors in psychiatric inpatients. Psychiatry Res 1991;39:109-14.
349. Lee HK, Travin S, Bluestone H. HIV-1 in inpatients. Hosp Com-
mun Psychiatry 1992;43:181-2.
350. Empfield M, Cournos F, Meyer I et al. HIV seroprevalence
among homeless patients admitted to a psychiatric inpatient
unit. Am J Psychiatry 1993;150:47-52.
351. Meyer I, McKinnon K, Cournos F et al. HIV seroprevalence
among long-stay patients in a state psychiatric hospital. Hosp
Commun Psychiatry 1993;44:282-4.
352. Susser E, Valencia E, Conover S. Prevalence of HIV infection
among psychiatric patients in a New York City men’s shelter. Am
J Public Health 1993;83:568-70.
353. Stewart DL, Zuckerman CJ, Ingle JM. HIV seroprevalence in a
chronically mentally ill population. J Natl Med Assoc 1994;86:
354. Cournos F, Horwath E, Guido JR et al. HIV-1 infection at two
public psychiatric hospitals in New York City. AIDS Care 1994;
355. Naber D, Pajonk FG, Perro C et al. Human immunodeficiency
virus antibody test and seroprevalence in psychiatric patients.
Acta Psychiatr Scand 1994;89:358-61.
356. Dasananjali T. The prevalence of HIV infection among mentally
ill offenders in Thailand. J Med Assoc Thai 1994;77:257-60.
357. Chen CH. Seroprevalence of human immunodeficiency virus
infection among Chinese psychiatric patients in Taiwan. Acta
Psychiatr Scand 1994;89:441-2.
358. Schwartz-Watts D, Montgomery LD, Morgan DW. Seropreva-
lence of human immunodeficiency virus among inpatient pre-
trial detainees. Bull Am Acad Psychiatry Law 1995;23:285-8.
359. Ayuso-Mateos JL, Montañés F, Lastra I et al. HIV infection in
psychiatric patients: an unlinked anonymous study. Br J Psy-
360. Rosenberg SD, Goodman LA, Osher FC et al. Prevalence of HIV,
hepatitis B, and hepatitis C in people with severe mental illness.
Am J Publ Health 2001;91:31-7.
361. Blank MB, Mandell DS, Aiken L et al. Co-occurrence of HIV
and serious mental illness among Medicaid recipients. Psychiatr
362. Baillargeon J, Ducate S, Pulvino J et al. The association of psy-
chiatric disorders and HIV infection in the correctional setting.
Ann Epidemiol 2003;13:606-12.
363. Chafetz L, White MC, Collins-Bride G et al. The poor general
health of the severely mentally ill: impact of schizophrenic diag-
nosis. Commun Ment Health J 2005;41:169-84.
364. Cournos F, McKinnon K, Sullivan G. Schizophrenia and comor-
bid human immunodeficiency virus or hepatitis C virus. J Clin
365. Sewell DD. Schizophrenia and HIV. Schizophr Bull 1996;22:
366. Carey MP, Carey KB, Kalichman SC. Risk for human immuno-
deficiency virus (HIV) infection among persons with severe
mental illnesses. Clin Psychol Rev 1997;17:271-91.
367. Carey M, Weinhardt L, Carey K. Prevalence of infection with
HIV among the seriously mentally ill: review of the research and
implications for practice. Prof Psychol Res Pr 1995;26:262-8.
368. Cournos F, McKinnon K. HIV seroprevalence among people
with severe mental illness in the United States: a critical review.
Clin Psychol Rev 1997;17:259-69.
369. McKinnon K, Cournos F. HIV infection linked to substance use
among hospitalized patients with severe mental illness. Psychi-
atr Serv 1998;49:1269.
370. De Hert M, Trappeniers L, Wampers M et al. Knowledge about
HIV in people with schizophrenia. A general population com-
parison. Clinical Schizophrenia & Related Psychoses (in press).
371. Dixon L, Haas G, Weiden PJ et al. Drug abuse in schizophrenic
patients: clinical correlates and reasons for use. Am J Psychiatry
372. Drake RE, Wallach MA. Substance abuse among the chronic
mentally ill. Hosp Commun Psychiatry 1989;40:1041-6.
373. Coverdale JH, Turbott SH. Risk behaviors for sexually transmit-
ted infections among men with mental disorders. Psychiatr Serv
374. Goldberg RW, Tapscott SL, Calmes CA et al. HIV and hepatitis
C knowledge among individuals with serious mental illness. Psy-
chiatr Rehabil J 2009;33:47-9.
375. Aruffo JF, Coverdale JH, Chacko RC et al. Knowledge about
AIDS among women psychiatric outpatients. Hosp Commun
376. Kalichman SC, Kelly JA, Johnson JR, et al. Factors associated
with risk for HIV infection among chronic mentally ill adults.
Am J Psychiatry 1994;151:221-7.
377. Senn TE, Carey MP. HIV testing among individuals with a severe
mental illness: review, suggestions for research, and clinical im-
plications. Psychol Med 2009;39:355-63.
378. Blumberg SJ, Dickey WC. Prevalence of HIV risk behaviors, risk
perceptions, and testing among US adults with mental disorders.
J Acquir Immune Defic Syndr 2003;32:77-9.
379. Desai MM, Rosenheck RA. HIV testing and receipt of test results
among homeless persons with serious mental illness. Am J Psy-
380. Desai MM, Rosenheck RA, Desai RA. Prevalence and correlates
of human immunodeficiency virus testing and posttest coun-
seling among outpatients with serious mental illness. J Nerv
Ment Dis 2007;195:776-80.
381. Goldberg RW, Himelhoch S, Kreyenbuhl J et al. Predictors of
HIV and hepatitis testing and related service utilization among
individuals with serious mental illness. Psychosomatics 2005;46:
382. Goldberg RW. Hepatitis and HIV screening, education, and
treatment for adults with serious mental illness. Gen Hosp Psy-
383. Grassi L, Pavanati M, Cardelli R et al. HIV-risk behaviour and
knowledge about HIV/AIDS among patients with schizophre-
nia. Psychol Med 1999;29:171-9.
384. Katz RC, Watts C, Santman J. AIDS knowledge and high risk
behaviors in the chronic mentally ill. Commun Ment Health J
385. Kelly JA, Murphy DA, Bahr GR et al. AIDS/HIV risk behavior
among the chronic mentally ill. Am J Psychiatry 1992;149:886-9.
386. Knox MD, Boaz TL, Friedrich MA et al. HIV risk factors for
persons with serious mental illness. Commun Ment Health J
387. Levounis P, Galanter M, Dermatis H et al. Correlates of HIV
transmission risk factors and considerations for interventions in
homeless, chemically addicted and mentally ill patients. J Addict
388. Meade CS, Sikkema KJ. Voluntary HIV testing among adults
with severe mental illness: frequency and associated factors.
AIDS Behav 2005;9:465-73.
389. Miller LJ, Finnerty M. Sexuality, pregnancy, and childrearing
among women with schizophrenia-spectrum disorders. Psychi-
atr Serv 1996;47:502-6.
390. Pirl WF, Greer JA, Weissgarber C et al. Screening for infectious
diseases among patients in a state psychiatric hospital. Psychiatr
391. Thompson SC, Checkley GE, Hocking JS et al. HIV risk behav-
iour and HIV testing of psychiatric patients in Melbourne. Aust
N Z J Psychiatry 1997;31:566-76.
392. Walkup J, McAlpine DD, Olfson M et al. Recent HIV testing
among general hospital inpatients with schizophrenia: findings
from four New York City sites. Psychiatr Q 2000;71:177-93.
393. Weinhardt LS, Carey MP, Carey KB. HIV-risk behavior and the
public health context of HIV/AIDS among women living with a
severe and persistent mental illness. J Nerv Ment Dis 1998;186:
394. Hughes E, Gray R. HIV prevention for people with serious men-
tal illness: a survey of mental health workers’ attitudes, knowl-
edge and practice. J Clin Nurs 2009;18:591-600.
395. Vergara-Rodriguez P, Vibhakar S, Watts J. Metabolic syndrome
and associated cardiovascular risk factors in the treatment of
persons with human immunodeficiency virus and severe mental
illness. Pharmacol Ther 2009;124:269-78.
396. Mistler LA, Brunette MF, Marsh BJ et al. Hepatitis C treatment
for people with severe mental illness. Psychosomatics 2006;47:
397. Said WM, Saleh R, Jumaian N. Prevalence of hepatitis B virus
among chronic schizophrenia patients. East Mediterr Health J
398. Chaudhury S, Chandra S, Augustine M. Prevalence of Australia
antigen (HBsAg) in institutionalised patients with psychosis. Br
J Psychiatry 1994;164:542-3.
399. Cividini A, Pistorio A, Regazzetti A et al. Hepatitis C virus infec-
tion among institutionalised psychiatric patients: a regression
analysis of indicators of risk. J Hepatol 1997;27:455-63.
400. Matthews AM, Huckans MS, Blackwell AD et al. Hepatitis C test-
ing and infection rates in bipolar patients with and without comor-
bid substance use disorders. Bipolar Disord 2008;10:266-70.
401. Kalkan A, Ozdarendeli A, Bulut Y et al. Prevalence and geno-
typic distribution of hepatitis GB-C/HG and TT viruses in blood
donors, mentally retarded children and four groups of patients
in eastern Anatolia, Turkey. Jpn J Infect Dis 2005;58:222-7.
402. Kilbourne AM. The burden of general medical conditions in pa-
tients with bipolar disorder. Curr Psychiatry Rep 2005;7:471-7.
403. Nakamura Y, Koh M, Miyoshi E et al. High prevalence of the
hepatitis C virus infection among the inpatients of schizophrenia
and psychoactive substance abuse in Japan. Prog Neuropsy-
chopharmacol Biol Psychiatry 2004;28:591-7.
404. Loftis JM, Matthews AM, Hauser P. Psychiatric and substance
use disorders in individuals with hepatitis C: epidemiology and
management. Drugs 2006;66:155-74.
405. Meyer JM. Prevalence of hepatitis A, hepatitis B, and HIV
among hepatitis C-seropositive state hospital patients: results
from Oregon State Hospital. J Clin Psychiatry 2003;64:540-5.
406. Klinkenberg WD, Caslyn RJ, Morse GA et al. Prevalence of hu-
man immunodeficiency virus, hepatitis B, and hepatitis C among
homeless persons with co-occurring severe mental illness and
substance use disorders. Compr Psychiatry 2003;44:293-302.
407. Rosenberg SD, Goldberg RW, Dixon LB et al. Assessing the
STIRR model of best practices for blood-borne infections of cli-
ents with severe mental illness. Psychiatr Serv 2010;61:885-91.
408. Essock SM, Dowden S, Constantine NT et al. Risk factors for
HIV, hepatitis B, and hepatitis C among persons with severe
mental illness. Psychiatr Serv 2003;54:836-41.
409. Osher FC, Goldberg R, Goodman LA et al. Hepatitis C and in-
dividuals with serious mental illness. Psychiatr Ann 2003;33:394-
410. Rosenberg SD, Swanson JW, Wolford GL et al. Blood-borne in-
fections and persons with mental illness: the five-site health and
risk study of blood-borne infections among persons with severe
mental illness. Psychiatr Serv 2003;54:827-35.
411. Freedman K, Nathanson J. Interferon-based hepatitis C treat-
ment in patients with pre-existing severe mental illness and sub-
stance use disorders. Expert Rev Anti Infect Ther 2009;7:363-76.
412. Huckans M, Mitchell A, Pavawalla S et al. The influence of an-
tiviral therapy on psychiatric symptoms among patients with
hepatitis C and schizophrenia. Antivir Ther 2010;15:111-9.
413. Rosenberg S, Brunette M, Oxman T et al. The STIRR model of
best practices for blood-borne diseases among clients with seri-
ous mental illness. Psychiatr Serv 2004;55:660-4.
414. Filik R, Sipos A, Kehoe PG et al. The cardiovascular and res-
piratory health of people with schizophrenia. Acta Psychiatr
415. Kendrick T. Cardiovascular and respiratory risk factors and
symptoms among general practice patients with long-term men-
tal illness. Br J Psychiatry 1996;169:733-9.
416. Kisely S, Smith M, Lawrence D et al. Mortality in individuals
who have had psychiatric treatment: population-based study in
Nova Scotia. Br J Psychiatry 2005;187:552-8.
417. Osby U, Brandt L, Correia N et al. Excess mortality in bipolar
and unipolar disorder in Sweden. Arch Gen Psychiatry 2001;
418. Høyer EH, Mortensen PB, Olesen AV. Mortality and causes of
death in a total national sample of patients with affective disor-
ders admitted for the first time between 1973 and 1993. Br J
419. Saku M, Tokudome S, Ikeda M et al. Mortality in psychiatric
patients, with a specific focus on cancer mortality associated
with schizophrenia. Int J Epidemiol 1995;24:366-72.
420. Nilsson A. Mortality in recurrent mood disorders during periods
on and off lithium. A complete population study in 362 patients.
421. Bobes J, Saiz J, Montes JM et al. Consenso español de salud
física del paciente con trastorno bipolar. Revista de Psiquiatría y
Salud Mental 2008;1:26-37.
422. Ohta Y, Nakane Y, Mine M et al. The epidemiological study of
physical morbidity in schizophrenics – 2. Association between
schizophrenia and incidence of tuberculosis. Jpn J Psychiatry
423. Baldwin JA. Schizophrenia and physical disease. Psychol Med
424. Zeenreich A, Gochstein B, Grinshpoon A et al. Recurrent tuber-
culosis in a psychiatric hospital, recurrent outbreaks during
1987-1996. Harefuah 1998;134:168-72.
425. Fisher II, Bienskii AV, Fedorova IV. Experience in using sero-
logical tests in detecting tuberculosis in patients with severe
mental pathology. Probl Tuberk 1996;1:19-20.
426. Mishin VIu, Shevchuk EIu, Tsygankov BD et al. New-onset pul-
monary tuberculosis patients with schizophrenia: course and
efficiency of treatment. Probl Tuberk Bolezn Legk 2008;6:6-10.
427. Lönnroth K, Jaramillo E, Williams B et al. Tuberculosis: the role
of risk factors and social determinants. In: Blas E, Sivasankara
Kurup A (eds). Equity, social determinants and public health
programmes. Geneva: World Health Organization, 2010:219-41.
428. Chen YH, Lin HC, Lin HC. Poor clinical outcomes among pneu-
monia patients with schizophrenia. Schizophr Bull (in press).
429. Himelhoch S, Lehman A, Kreyenbuhl J et al. Prevalence of
World Psychiatry 10:1 - February 2011
chronic obstructive pulmonary disease among those with seri-
ous mental illness. Am J Psychiatry 2004;161:2317-9.
430. Sokal J, Messias E, Dickerson FB et al. Comorbidity of medical
illnesses among adults with serious mental illness who are re-
ceiving community psychiatric services. J Nerv Ment Dis 2004;
431. Carney CP, Jones L, Woolson RF. Medical comorbidity in wom-
en and men with schizophrenia: a population-based controlled
study. J Gen Intern Med 2006;21:1133-7.
432. Batki SL, Meszaros ZS, Strutynski K et al. Medical comorbidity
in patients with schizophrenia and alcohol dependence. Schizo-
phr Res 2009;107:139-46.
433. Copeland LA, Mortensen EM, Zeber JE et al. Pulmonary disease
among inpatient decedents: impact of schizophrenia. Prog Neu-
ropsychopharmacol Biol Psychiatry 2007;31:720-6.
434. Volkov VP. Respiratory diseases as a cause of death in schizo-
phrenia. Probl Tuberk Bolezn Legk 2009;6:24-7.
435. Fuemmeler BF, Pendzich MK, Tercyak KP. Weight, dietary be-
havior, and physical activity in childhood and adolescence: im-
plications for adult cancer risk. Obes Facts 2009;2:179-86.
436. Fair AM, Montgomery K. Energy balance, physical activity, and
cancer risk. Methods Mol Biol 2009;472:57-88.
437. Pan SY, DesMeules M. Energy intake, physical activity, energy
balance, and cancer: epidemiologic evidence. Methods Mol Biol
438. Hammerschmidt S, Wirtz H. Lung cancer: current diagnosis and
treatment. Dtsch Arztebl Int 2009;106:809-18.
439. Kisely S, Sadek J, MacKenzie A et al. Excess cancer mortality in
psychiatric patients. Can J Psychiatry 2008;53:753-61.
440. Mortensen PB. The incidence of cancer in schizophrenic pa-
tients. J Epidemiol Commun Health 1989;43:43-7.
441. Gulbinat W, Dupont A, Jablensky A et al. Cancer incidence of
schizophrenic patients. Results of record linkage studies in three
countries. Br J Psychiatry 1992;18:75-83.
442. Dupont A, Jensen OM, Strömgren E et al. Incidence of cancer
in patients diagnosed as schizophrenic in Denmark. In: Ten
Horn GHMM, Giel R, Gulbinat W et al (eds). Psychiatric case
registries in public health. Amsterdam: Elsevier, 1986:229-39.
443. Mortensen PB. The occurrence of cancer in first admitted schiz-
ophrenic patients. Schizophr Res 1994;12:185-94.
444. Lawrence D, Holman CD, Jablensky AV et al. Excess cancer
mortality in Western Australian psychiatric patients due to high-
er case fatality rates. Acta Psychiatr Scand 2000;101:382-8.
445. Dalton SO, Mellemkjaer L, Thomassen L et al. Risk for cancer
in a cohort of patients hospitalized for schizophrenia in Den-
mark, 1969-1993. Schizophr Res 2005;75:315-24.
446. Grinshpoon A, Barchana M, Ponizovsky A et al. Cancer in
schizophrenia: is the risk higher or lower? Schizophr Res 2005;
447. Barak Y, Achiron A, Mandel M et al. Reduced cancer incidence
among patients with schizophrenia. Cancer 2005;104:2817-21.
448. Cohen M, Dembling B, Schorling J. The association between
schizophrenia and cancer: a population-based mortality study.
Schizophr Res 2002;57:139-46.
449. Lichtermann D, Ekelund J, Pukkala E et al. Incidence of cancer
among persons with schizophrenia and their relatives. Arch Gen
450. Hippisley-Cox J, Vinogradova Y, Coupland C et al. Risk of malig-
nancy in patients with schizophrenia or bipolar disorder: nested
case-control study. Arch Gen Psychiatry 2007;64:1368-76.
451. Mortensen PB, Juel K. Mortality and causes of death in schizo-
phrenic patients in Denmark. Acta Psychiatr Scand 1990;81:372-7.
452. Goldacre MJ, Kurina LM, Wotton CJ et al. Schizophrenia and
cancer: an epidemiological study. Br J Psychiatry 2005;187:334-8.
453. Catts VS, Catts SV, O’Toole BI et al. Cancer incidence in patients
with schizophrenia and their first-degree relatives – a meta-anal-
ysis. Acta Psychiatr Scand 2008;117:323-36.
454. Dutta R, Boydell J, Kennedy N et al. Suicide and other causes of
mortality in bipolar disorder: a longitudinal study. Psychol Med
455. Zilber N, Schufman N, Lerner Y. Mortality among psychiatric pa-
tients – the groups at risk. Acta Psychiatr Scand 1989;79:248-56.
456. Weeke A, Vaeth M. Excess mortality of bipolar and unipolar
manic-depressive patients. J Affect Disord 1986;11:227-34.
457. Xiong GL, Bermudes RA, Torres SN et al. Use of cancer-screen-
ing services among persons with serious mental illness in Sacra-
mento County. Psychiatr Serv 2008;59:929-32.
458. Carney CP, Jones LE. The influence of type and severity of men-
tal illness on receipt of screening mammography. J Gen Intern
459. Martens PJ, Chochinov HM, Prior HJ et al. Are cervical cancer
screening rates different for women with schizophrenia? A Man-
itoba population-based study. Schizophr Res 2009;113:101-6.
460. Chochinov HM, Martens PJ, Prior HJ et al. Does a diagnosis of
schizophrenia reduce rates of mammography screening? A Man-
itoba population-based study. Schizophr Res 2009;113:95-100.
461. Catts VS, Catts SV. Apoptosis and schizophrenia: is the tumour
suppressor gene, p53, a candidate susceptibility gene? Schizo-
phr Res 2000;41:405-15.
462. Yovel G, Sirota P, Mazeh D et al. Higher natural killer cell activ-
ity in schizophrenic patients: the impact of serum factors, medi-
cation, and smoking. Brain Behav Immun 2000;14:153-69.
463. Flegal KM, Graubard BI, Williamson DF et al. Cause-specific
excess deaths associated with underweight, overweight, and
obesity. JAMA 2007;298:2028-37.
464. Harvey PW, Everett DJ, Springall CJ. Adverse effects of prolactin
in rodents and humans: breast and prostate cancer. J Psycho-
465. Wagner S, Mantel N. Breast cancer at a psychiatric hospital be-
fore and after the introduction of neuroleptic agents. Cancer Res
466. Kanhouwa S, Gowdy JM, Solomon JD. Phenothiazines and
breast cancer. J Natl Med Assoc 1984;76:785-8.
467. Kelly JP, Rosenberg L, Palmer JR et al. Risk of breast cancer ac-
cording to use of antidepressants, phenothiazines, and antihis-
tamines. Am J Epidemiol 1999;150:861-8.
468. Dalton SO, Johansen C, Poulsen AH et al. Cancer risk among
users of neuroleptic medication: a population-based cohort
study. Br. J Cancer 2006;95:934-9.
469. Wang PS, Walker AM, Tsuang MT et al. Dopamine antagonists
and the development of breast cancer. Arch Gen Psychiatry
470. Misra M, Papakostas GI, Klibanski A. Effects of psychiatric dis-
orders and psychotropic medications on prolactin and bone me-
tabolism. J Clin Psychiatry 2004;65:1607-18.
471. Lean M, de Smedt G. Schizophrenia and osteoporosis. Int Clin
472. Naidoo U, Goff DC, Klibanski A. Hyperprolactinemia and bone
mineral density: the potential impact of antipsychotic agents.
473. Abraham G, Friedman RH, Verghese C et al. Osteoporosis and
schizophrenia: can we limit known risk factors? Biol Psychiatry
474. Malik P. Cross-sectional study of bone density in patients with
schizophrenic or schizophreniform disease. Dissertation, Leop-
old-Franzens University, Innsbruck, 2001.
475. Haddad PM, Wieck A. Antipsychotic-induced hyperprolacti-
naemia: mechanisms, clinical features and management. Drugs
476. Javaid MK, Holt RI. Understanding osteoporosis. J Psychophar-
477. Michelson D, Stratakis C, Hill L et al. Bone mineral density in
women with depression. N Engl J Med 1996;335:1176-81.
478. Eskandari F, Martinez PE, Torvik S et al. Premenopausal, Osteo-
porosis Women, Alendronate, Depression (POWER) Study
Group. Low bone mass in premenopausal women with depres-
sion. Arch Intern Med 2007;167:2329-36.
479. Schweiger U, Deuschle M, Körner A et al. Low lumbar bone
mineral density in patients with major depression. Am J Psy-
480. Kahl KG, Rudolf S, Dibbelt L et al. Decreased osteoprotegerin
and increased bone turnover in young female patients with ma-
jor depressive disorder and a lifetime history of anorexia nervo-
sa. Osteoporos Int 2005;16:424-9.
481. Schweiger U, Weber B, Deuschle M et al. Lumbar bone mineral
density in patients with major depression: evidence of increased
bone loss at follow-up. Am J Psychiatry 2000;157:118-20.
482. Yazici KM, Akinci A, Sütçü A et al. Bone mineral density in
premenopausal women with major depressive disorder. Psychia-
try Res 2003;117:271-5.
483. Robbins J, Hirsch C, Whitmer R et al. The association of bone
mineral density and depression in an older population. J Am
Geriatr Soc 2001;49:732-6.
484. Mezuk B, Eaton WW, Golden SH. Depression and osteoporosis:
epidemiology and potential mediating pathways. Osteoporos Int
485. Wu Q, Magnus JH, Liu J et al. Depression and low bone mineral
density: a meta-analysis of epidemiologic studies. Osteoporos
486. Wu Q, Liu J, Gallegos-Orozco JF et al. Depression, fracture risk,
and bone loss: a meta-analysis of cohort studies. Osteoporos Int
487. Halbreich U, Palter S. Accelerated osteoporosis in psychiatric
patients: possible pathophysiological processes. Schizophr Bull
488. Byerly M, Suppes T, Tran QV et al. Clinical implications of anti-
psychotic-induced hyperprolactinemia in patients with schizo-
phrenia spectrum or bipolar spectrum disorders: recent develop-
ments and current perspectives. J Clin Psychopharmacol 2007;
489. Bergemann N, Parzer P, Mundt C et al. High bone turnover but
normal bone mineral density in women suffering from schizo-
phrenia. Psychol Med 2008;38:1195-201.
490. Meaney AM, Smith S, Howes OD et al. Effects of long-term
prolactin-raising antipsychotic medication on bone mineral
density in patients with schizophrenia. Br J Psychiatry 2004;
491. O’Keane V, Meaney AM. Antipsychotic drugs: a new risk factor
for osteoporosis in young women with schizophrenia? J Clin
492. Meaney AM, O’Keane V. Bone mineral density changes over a
year in young females with schizophrenia: relationship to medi-
cation and endocrine variables. Schizophr Res 2007;93:136-43.
493. Bilici M, Cakirbay H, Guler M et al. Classic and atypical neuro-
leptics, and bone mineral density, in patients with schizophre-
nia. Int J Neurosci 2002;112:817-28.
494. Abraham G, Paing WW, Kaminski J et al. Effects of elevated se-
rum prolactin on bone mineral density and bone metabolism in
female patients with schizophrenia: a prospective study. Am J
495. Becker D, Liver O, Mester R et al. Risperidone, but not olanza-
pine, decreases bone mineral density in female premenopausal
schizophrenia patients. J Clin Psychiatry 2003;64:761-6.
496. Howes OD, Wheeler MJ, Meaney AM et al. Bone mineral den-
sity and its relationship to prolactin levels in patients taking an-
tipsychotic treatment. J Clin Psychopharmacol 2005;25:259-61.
497. Keely E, Reiss JP, Drinkwater DT et al. Bone mineral density, sex
hormones, and long-term use of neuroleptic agents in men. En-
docr Pract 1997;3:209-13.
498. Hummer M, Malik P, Gasser RW et al. Osteoporosis in patients
with schizophrenia. Am J Psychiatry 2005;162:162-7.
499. O’Keane V. Antipsychotic-induced hyperprolactinaemia, hypo-
gonadism and osteoporosis in the treatment of schizophrenia. J
500. Cauley JA, Fullman RL, Stone KL et al. Factors associated with
the lumbar spine and proximal femur bone mineral density in
older men. Osteoporos Int 2005;16:1525-37.
501. Diem SJ, Blackwell TL, Stone KL et al. Use of antidepressants
and rates of hip bone loss in older women: the study of oste-
oporotic fractures. Arch Intern Med 2007;167:1240-5.
502. Haney EM, Chan BK, Diem SJ et al. Association of low bone
mineral density with selective serotonin reuptake inhibitor use
by older men. Arch Intern Med 2007;167:1246-51.
503. Peuskens J, Pani L, de Hert M et al. Antipsychotics and hyper-
prolactinemia. Unpublished paper.
504. Bolton JM, Metge C, Lix L et al. Fracture risk from psychotropic
medications: a population-based analysis. J Clin Psychopharma-
505. Vestergaard P. Varying effects of psychotropic medications on
fracture risk in older people. Evid Based Ment Health 2009;12:25.
506. Howard L, Kirkwood G, Leese M. Risk of hip fracture in pa-
tients with a history of schizophrenia. Br J Psychiatry 2007;
507. Hugenholtz GW, Heerdink ER, van Staa TP et al. Risk of hip/
femur fractures in patients using antipsychotics. Bone 2005;37:
508. Vestergaard P, Rejnmark L, Mosekilde L. Anxiolytics, sedatives,
antidepressants, neuroleptics and the risk of fracture. Osteopo-
ros Int 2006;17:807-16.
509. Jacqmin-Gadda H, Fourrier A, Commenges D et al. Risk factors
for fractures in the elderly. Epidemiology 1998;9:417-23.
510. Woolcott JC, Richardson KJ, Wiens MO, et al. Meta-analysis of
the impact of 9 medication classes on falls in elderly persons.
Arch Intern Med 2009;169:1952-60.
511. Takkouche B, Montes-Martínez A, Gill SS et al. Psychotropic
medications and the risk of fracture: a meta-analysis. Drug Saf
512. Kelly DL, Conley RR. Sexuality and schizophrenia: a review.
Schizophr Bull 2004;30:767-79.
513. Schöttle D, Kammerahl D, Huber J et al. Sexual problems in
patients with schizophrenia. Psychiatr Prax 2009;36:160-8.
514. Kasperek-Zimowska B, Brodniak WA, Sarol-Kulka A. Sexual
disorders in schizophrenia – overview of research literature. Psy-
chiatr Pol 2008;42:97-104.
515. Macdonald S, Halliday J, MacEwan T et al. Nithsdale Schizo-
phrenia Surveys 24: sexual dysfunction. Case-control study. Br J
516. Smith SM, O’Keane V, Murray R. Sexual dysfunction in patients
taking conventional antipsychotic medication. Br J Psychiatry
517. Aizenberg D, Zemishlany Z, Dorfman-Etrog P et al. Sexual dys-
function in male schizophrenic patients. J Clin Psychiatry 1995;
518. Peuskens J, Sienaert P, De Hert M. Sexual dysfunction: the un-
spoken side effect of antipsychotics. Eur Psychiatry 1998;13:23s-
519. Harley EW, Boardman J, Craig T. Sexual problems in schizo-
phrenia: prevalence and characteristics. A cross sectional survey.
Soc Psychiatry Psychiatr Epidemiol 2010;45:759-66.
520. Baggaley M. Sexual dysfunction in schizophrenia: focus on re-
cent evidence. Hum Psychopharmacol 2008;23:201-9.
521. Dossenbach M, Hodge A, Anders M et al. Prevalence of sexual
dysfunction in patients with schizophrenia: international varia-
tion and underestimation. Int J Neuropsychopharmacol 2005;8:
522. Cutler AJ. Sexual dysfunction and antipsychotic treatment. Psy-
523. Olfson M, Uttaro T, Carson WH et al. Male sexual dysfunction
World Psychiatry 10:1 - February 2011
and quality of life in schizophrenia. J Clin Psychiatry 2005;66:331-
524. Malik P. Sexual dysfunction in schizophrenia. Curr Opin Psy-
525. Gabay PM, Fernández Bruno M, Roldan E. Sexual behavior in
patients with schizophrenia: a review of the literature and survey
in patients attending a rehabilitation program. Vertex 2006;17:
526. Laurent SM, Simons AD. Sexual dysfunction in depression and
anxiety: conceptualizing sexual dysfunction as part of an inter-
nalizing dimension. Clin Psychol Rev 2009;29:573-85.
527. Kennedy SH, Rizvi S. Sexual dysfunction, depression, and the
impact of antidepressants. J Clin Psychopharmacol 2009;29:157-
528. Zemishlany Z, Weizman A. The impact of mental illness on
sexual dysfunction. Adv Psychosom Med 2008;29:89-106.
529. Kinzl JF. Major depressive disorder, antidepressants and sexual
dysfunction. Neuropsychiatry 2009;23:134-8.
530. Werneke U, Northey S, Bhugra D. Antidepressants and sexual
dysfunction. Acta Psychiatr Scand 2006;114:384-97.
531. Williams K, Reynolds MF. Sexual dysfunction in major depres-
sion. CNS Spectr 2006;11:19-23.
532. Higgins A, Barker P, Begley CM. Sexual health education for
people with mental health problems: what can we learn from the
literature? J Psychiatr Ment Health Nurs 2006;13:687-97.
533. Berner MM, Hagen M, Kriston L. Management of sexual dys-
function due to antipsychotic drug therapy. Cochrane Database
Syst Rev 2007;1:CD003546.
534. Konarzewska B, Wołczyski S, Szulc A et al. Effect of risperidone
and olanzapine on reproductive hormones, psychopathology
and sexual functioning in male patients with schizophrenia. Psy-
535. van Bruggen M, van Amelsvoort T, Wouters L et al. Sexual dys-
function and hormonal changes in first episode psychosis pa-
tients on olanzapine or risperidone. Psychoneuroendocrinology
536. Hanssens L, L’Italien G, Loze JY et al. The effect of antipsychotic
medication on sexual function and serum prolactin levels in com-
munity-treated schizophrenic patients: results from the Schizo-
phrenia Trial of Aripiprazole (STAR) study (NCT00237913). BMC
537. Knegtering H, van den Bosch R, Castelein S et al. Are sexual side
effects of prolactin-raising antipsychotics reducible to serum
prolactin? Psychoneuroendocrinology 2008;33:711-7.
538. Knegtering H, Boks M, Blijd C et al. A randomized open-label
comparison of the impact of olanzapine versus risperidone on
sexual functioning. J Sex Marital Ther 2006;32:315-26.
539. Dossenbach M, Dyachkova Y, Pirildar S et al. Effects of atypical
and typical antipsychotic treatments on sexual function in pa-
tients with schizophrenia: 12-month results from the Interconti-
nental Schizophrenia Outpatient Health Outcomes (IC-SOHO)
study. Eur Psychiatry 2006;21:251-8.
540. Byerly MJ, Nakonezny PA, Bettcher BM et al. Sexual dysfunc-
tion associated with second-generation antipsychotics in outpa-
tients with schizophrenia or schizoaffective disorder: an empi-
rical evaluation of olanzapine, risperidone, and quetiapine.
Schizophr Res 2006;86:244-50.
541. Kelly D., Conley RR. A randomized double-blind 12-week study
of quetiapine, risperidone or fluphenazine on sexual functioning
in people with schizophrenia. Psychoneuroendocrinology 2006;
542. Melkersson K. Differences in prolactin elevation and related
symptoms of atypical antipsychotics in schizophrenic patients. J
Clin Psychiatry 2005;66:761-7.
543. Dossenbach M, Erol A, el Mahfoud Kessaci M et al. IC-SOHO
Study Group. Effectiveness of antipsychotic treatments for schizo-
phrenia: interim 6-month analysis from a prospective observa-
tional study (IC-SOHO) comparing olanzapine, quetiapine, ris-
peridone, and haloperidol. J Clin Psychiatry 2004;65:312-21.
544. Knegtering R, Castelein S, Bous H et al. A randomized open-
label study of the impact of quetiapine versus risperidone on
sexual functioning. J Clin Psychopharmacol 2004;24:56-61.
545. Bobes J, Garcia-Portilla MP, Rejas J et al. Frequency of sexual
dysfunction and other reproductive side-effects in patients with
schizophrenia treated with risperidone, olanzapine, quetiapine,
or haloperidol: the results of the EIRE study. J Sex Marital Ther
546. Kim KS, Pae CU, Chae JH et al. Effects of olanzapine on prolac-
tin levels of female patients with schizophrenia treated with ris-
peridone. J Clin Psychiatry 2002;63:408-13.
547. Conley RR, Mahmoud R. A randomized double-blind study of
risperidone and olanzapine in the treatment of schizophrenia or
schizoaffective disorder. Am J Psychiatry 2001;158:765-74.
548. Lee KU, Lee YM, Nam JM et al. Antidepressant-induced sexual
dysfunction among newer antidepressants in a naturalistic set-
ting. Psychiatry Investig 2010;7:55-9.
549. Montgomery SA, Baldwin DS, Riley A. Antidepressant medica-
tions: a review of the evidence for drug-induced sexual dysfunc-
tion. J Affect Disord 2002;69:119-40.
550. Clayton AH, Pradko JF, Croft HA et al. Prevalence of sexual
dysfunction among newer antidepressants. J Clin Psychiatry 2002;
551. Montejo AL, Llorca G, Izquierdo JA et al. Incidence of sexual
dysfunction associated with antidepressant agents: a prospective
multicenter study of 1022 outpatients. J Clin Psychiatry 2001;62:
552. Ginsberg LD. Impact of drug tolerability on the selection of an-
tidepressant treatment in patients with major depressive disor-
der. CNS Spectr 2009;14:8-14.
553. Fava M, Rankin M. Sexual functioning and SSRIs. J Clin Psy-
554. Gregorian RS, Golden KA, Bahce A et al. Antidepressant-in-
duced sexual dysfunction. Ann Pharmacother 2002;36:1577-
555. Einarson A, Boskovic R. Use and safety of antipsychotic drugs
during pregnancy. J Psychiatr Pract 2009;15:183-92.
556. Trixler M, Gáti A, Fekete S et al. Use of antipsychotics in the
management of schizophrenia during pregnancy. Drugs 2005;65:
557. Lund N, Pedersen LH, Henriksen TB. Selective serotonin reup-
take inhibitor exposure in utero and pregnancy outcomes. Arch
Pediatr Adolesc Med 2009;163:949-54.
558. Tuccori M, Testi A, Antonioli L et al. Safety concerns associated
with the use of serotonin reuptake inhibitors and other seroto-
nergic/noradrenergic antidepressants during pregnancy: a re-
view. Clin Ther 2009;31:1426-53.
559. Oberlander TF, Warburton W, Misri S et al. Neonatal outcomes
after prenatal exposure to selective serotonin reuptake inhibitor
antidepressants and maternal depression using population-
based linked health data. Arch Gen Psychiatry 2006;63:898-906.
560. Yonkers KA, Wisner KL, Stowe Z et al. Management of bipolar
disorder during pregnancy and the postpartum period. Am J Psy-
561. Gentile S. Neurodevelopmental effects of prenatal exposure to
psychotropic medications. Depress Anxiety 2010;27:675-86.
562. Kenkre AM, Spadigam AE. Oral health and treatment needs in
institutionalized psychiatric patients in India. Indian J Dent Res
563. Thomas A, Lavrentzou E, Karouzos C et al. Factors which influ-
ence the oral condition of chronic schizophrenia patients. Spec
Care Dentist 1996;16:84-6.
564. Velasco E, Machuca G, Martinez-Sahuquillo A et al. Dental
health among institutionalized psychiatric patients in Spain.
Spec Care Dentist 1997;17:203-6.
77 Download full-text
565. Velasco-Ortega E, Monsalve-Guil L, Velasco-Ponferrada C et al.
Temporomandibular disorders among schizophrenic patients. A
case-control study. Med Oral Patol Oral Cir Bucal 2005;10:315-
566. Lewis S, Jagger RG, Treasure E. The oral health of psychiatric
in-patients in South Wales. Spec Care Dentist 2001;21:182-6.
567. Clark DB. Dental care for the patient with bipolar disorder. J
Can Dent Assoc 2003;69:20-4.
568. Friedlander AH, Birch NJ. Dental conditions in patients with
bipolar disorder on long-term lithium maintenance therapy.
Spec Care Dentist 1990;10:148-51.
569. McCreadie RG, Stevens H, Henderson J et al. The dental health
of people with schizophrenia. Acta Psychiatr Scand 2004;110:
570. Tang WK, Sun FC, Ungvari GS et al. Oral health of psychiatric
in-patients in Hong Kong. Int J Soc Psychiatry 2004;50:186-91.
571. Ramon T, Grinshpoon A, Zusman SP et al. Oral health and treat-
ment needs of institutionalized chronic psychiatric patients in
Israel. Eur Psychiatry 2003;18:101-5.
572. Kilbourne AM, Horvitz-Lennon M, Post EP et al. Oral health in
Veterans Affairs patients diagnosed with serious mental illness.
J Public Health Dent 2007;67:42-8.
573. Hede B. Dental health behavior and self-reported dental health
problems among hospitalized psychiatric patients in Denmark.
Acta Odontol Scand 1995;53:35-40.
574. British Society for Disability and Oral Health. Oral health care
for people with mental health problems – guidelines and recom-
575. Friedlander AH, Friedlander IK, Marder SR. Bipolar I disorder:
psychopathology, medical management and dental implications.
J Am Dent Assoc 2002;133:1209-17.
576. Friedlander AH, Marder SR. The psychopathology, medical ma-
nagement and dental implications of schizophrenia. J Am Dent
577. Nielsen J, Munk-Jørgensen P, Skadhede S et al. Determinants of
poor dental care in patients with schizophrenia: a historical,
prospective database study. J Clin Psychiatry (in press).
578. Mackell JA, Harrison DJ, McDonnell DD. Relationship between
preventative physical health care and mental health in individu-
als with schizophrenia: a survey of caregivers. Ment Health Serv
579. Persson K, Axtelius B, Söderfeldt B et al. Monitoring oral health
and dental attendance in an outpatient psychiatric population. J
Psychiatr Ment Health Nurs 2009;16:263-71.
580. Kwan S, Petersen PE. Oral health: equity and social determi-
nants. In: Blas E, Sivasankara Kurup A (eds). Equity, social de-
terminants and public health programmes. Geneva: World
Health Organization, 2010:159-76.
581. Adamis D, Ball C. Physical morbidity in elderly psychiatric in-
patients: prevalence and possible relations between the major
mental disorders and physical illness. Int J Geriatr Psychiatry
582. Flanagan RJ, Dunk L. Haematological toxicity of drugs used in
psychiatry. Hum Psychopharmacol 2008;23:27-41.
583. Ozbilen M, Adams CE. Systematic overview of Cochrane re-
views for anticholinergic effects of antipsychotic drugs. J Clin
584. De Hert M, Hudyana H, Dockx L et al. Second-generation an-
tipsychotics and constipation: a review of the literature. Eur Psy-
chiatry (in press).
585. Buscema CA, Abbasi QA, Barry DJ et al. An algorithm for the
treatment of schizophrenia in the correctional setting: the Fo-
rensic Algorithm Project. J Clin Psychiatry 2000;61:767-83.
586. Dennison C, Prasad M, Lloyd A et al. The health-related quality
of life and economic burden of constipation. Pharmacoeconom-
587. Hayes G, Gibler B. Clozapine-induced constipation. Am J Psy-
588. Palmer SE, McLean RM, Ellis PM et al. Life-threatening clozap-
ine-induced gastrointestinal hypomotility: an analysis of 102
cases. J Clin Psychiatry 2008;69:759-68.