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Schizophrenia Research 126 (2011) 110–116

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Schizophrenia Research
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / s c h r e s

Schizophrenia patients at higher risk of diabetes, hypertension and


hyperlipidemia: A population-based study
Chun-Hui Liao a,b, Chen-Shu Chang c, Wan-Ching Wei b, Shih-Ni Chang b,d, Chien-Chang Liao b,d,
Hsien-Yuan Lane a, Fung-Chang Sung b,d,⁎
a
Department of Psychiatry, China Medical University and Hospital, Taichung 404, Taiwan
b
Department of Public Health, China Medical University and Hospital, Taichung 404, Taiwan
c
Department of Neurology, Changhua Christian Hospital, Changhua City 500, Taiwan
d
Management Office for Health Data, China Medical University and Hospital, Taichung 404, Taiwan

a r t i c l e i n f o a b s t r a c t

Article history: Objective: This study investigates risks of developing diabetes mellitus (DM), hypertension,
Received 10 March 2010 and hyperlipidemia in treating schizophrenia with first- and second-generation antipsychotics
Received in revised form 6 December 2010
(FGA and SGA, respectively).
Accepted 8 December 2010
Methods: We established two study sets, each consisting of patients with schizophrenia and
Available online 8 January 2011
without schizophrenia, from the insurance claims from 1997 to 2000. Study set I had 1631
Keywords: patients taking FGA and 6524 non-schizophrenia controls; the other had 1224 patients taking
Antipsychotics SGA and 4896 controls. Controls were selected frequency matched with sex, age and the index
Retrospective cohort study year. All subjects were free of the studied metabolic disorders at the baseline. We measured
Metabolic abnormality incidences of these disorders developed by the end of 2008 in each cohort and their respective
Schizophrenia hazard ratios (HRs) for these disorders.
Results: Schizophrenic patients taking FGA were older than those taking SGA. In the Cox
models, significance adjusted HRs associated with SGA were 1.82 (95% confidence interval (CI)
1.30–2.55) for DM and 1.41 (95% CI 1.09–1.83) for hyperlipidemia. For those on the FGA, the
risk was only significant in developing DM (HR 1.32, 95% CI 1.01–1.75). The age-specific
antipsychotics-associated risks for metabolic disorders were higher in young patients than in
older patients particularly for hypertension; the HRs in 10–19 years of age were 4.52 (95% CI
1.76–11.6) associated with FGA and 3.92 (95% CI 1.83–8.39) associated with SGA.
Conclusions: Patients with schizophrenia on SGA have higher risk of developing metabolic
disorders than those on FGA. It is likely that older patients have already gone through the age of
developing these side-effects and were free of them at the baseline.
© 2010 Elsevier B.V. All rights reserved.

1. Introduction disease are at a higher risk of mortality, with a life expectancy


approximately 20% shorter than the general population
Schizophrenia is a significant mental illness with preva- (Newman and Bland, 1991). Coronary artery disease and
lence rates ranging 1–17 per 1000 worldwide (Chien et al., other cardiovascular diseases are also the major disease
2009; Warner and de Girolamo, 1995). Patients with the associated with schizophrenia (Brown, 1997; Hennekens et
al., 2005). Individuals with schizophrenia commonly require
long-term antipsychotic treatment, and have an unhealthy
⁎ Corresponding author. China Medical University College of Public Health, lifestyle with poor diet selection. These patients are at an
91 Hsueh-Shih Road, Taichung 404, Taiwan. Tel.: + 886 4 2203 5740; fax:
+ 886 4 2201 9901.
elevated risk of weight gain, leading to obesity and metabolic
E-mail addresses: fcsung@mail.cmu.edu.tw, fcsung1008@yahoo.com syndrome (Bobes et al., 2007; Cohn et al., 2004; De Hert et al.,
(F.-C. Sung). 2006; Hagg et al., 2006; Huang et al., 2009; McEvoy et al.,

0920-9964/$ – see front matter © 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.schres.2010.12.007
C.-H. Liao et al. / Schizophrenia Research 126 (2011) 110–116 111

2005; Suvisaari et al., 2007). The prevalence of metabolic comprehensive medical services, including outpatient and
syndrome among patients with schizophrenia may range inpatient cares, Chinese medicine, dental care, childbirth,
from 24% to 43% in males and 27%–52% in females. A recent physical therapy, preventive cares, home care, and rehabil-
population-based period-prevalence study in Canada showed itation for chronic mental illness. Using the electronic claims
that patients with schizophrenia have an elevated prevalence database, the NHRI randomly selected from the insured
of diabetes mellitus (DM), hypertension, hyperlipidemia and population to establish a representative reimbursement
cardiovascular diseases (Bresee et al., 2010). Lin et al. (2008) claims dataset of a sample of one million insured persons in
even found that patients with schizophrenia have a higher 2000. We were able to use scrambled patient identifications
risk of stroke. Hypertension, DM and hyperlipidemia are to link files, including the information on patient gender,
known risk factors of stroke. Chien et al. (2009) also found birth date, and other demographic data. The scrambled
that the prevalence of DM in patients with schizophrenia was identification system safeguards the insured population
around 7.90% in Taiwan. Central obesity, hypertension, against the violation of personal privacy and confidentiality.
hyperglycemia and dyslipidemia are the core problems of The codes of health care received, codes of health care
metabolic syndrome that contribute to the high prevalence of providers, and medical costs covered by the insurance
cardiovascular disease (Grundy et al., 2004; Laaksonen et al., program were also available. The diagnoses were coded
2004; Mokdad et al., 2003). using the International Classification of Diseases 9th Revision
The association between metabolic abnormalities and of the Clinical Modification (ICD-9-CM).
schizophrenia has reached new developments in recent years
after the use of second-generation antipsychotics (SGA). 2.2. Study samples
Studies have suggested that the medication may contribute to
metabolic abnormalities, particularly the risk of diabetes From the dataset, the claims data for 837,810 insured aged
(Hennekens et al., 2005; Newcomer, 2007; Scheen and De 10 years and above defined in 1997 were extracted, approx-
Hert, 2007; Tschoner et al., 2007). Two well-designed multi- imately equivalent to 3.6% of all enrollees in the insurance
city clinical trials in adults (Lieberman et al., 2005) and youth system. Based on this sub-dataset, patients with histories of
(Sikich et al., 2008) with schizophrenia revealed that DM (ICD-9-CM codes 250), hypertension (ICD-9-CM codes
olanzapine can most likely increase weight gain and 401–405) and/or hyperlipidemia (ICD-9-CM codes 272.0–
measures of other metabolic abnormalities. In a meta- 272.4) identified were excluded from the study samples
analysis, Smith et al. (2008) found that SGA are associated selection. Patients newly diagnosed with schizophrenia (ICD-
with slightly increased risk of diabetes, compared with the 9-CM 295) in 1997–2000 that were prescribed with FGA and
first-generation antipsychotics (FGA). Most of these studies SGA were identified and defined separately as two treatment
were limited by small sample sizes. In a retrospective chart cohorts, the FGA cohort and SGA cohort, respectively, in two
review study for patients with three-year treatment expo- study sets, set I and set II. For comparison, two cohorts of non-
sure, De Hert et al. (2008) found a more than three-fold schizophrenia controls were also established by random
higher risk of metabolism syndrome for patients started with selection from the insured population without the history of
SGA than those started with FGA. Most studies appeared to schizophrenia or other psychiatric illness. These controls
lack of comparison with the general population in measuring were frequency-matched with age, sex and index year of the
the effectiveness of medications and were limited by short cases in the corresponding schizophrenia cohort, with a
follow-up time. control sample size four-fold of the corresponding schizo-
We conducted a 12-year follow-up, population-based phrenia cohort. Each study subject was followed until a
cohort study to estimate the risks of developing DM, diagnosis of DM, hypertension or hyperlipidemia was made,
hypertension and hyperlipidemia in schizophrenic patients or until the time the subject was censored for loss to follow-
prescribed with FGA and SGA and compared them with their up, death, or termination of insurance, or up to 31 December
corresponding non-schizophrenia controls. The results de- 2008, the end of the follow-up. We followed these cohorts as
rived from this study can provide an evidence-based data fixed groups for this study. To ensure the validity of the
plan for a more comprehensive approach in the long-term diagnoses of the three major follow-up outcomes, we
care of schizophrenic patients taking into consideration the identified the patients through both ICD-9-CM disease
prevention of metabolic syndrome and related cardiovascular codes and medications prescribed. Medications of FGAs and
diseases. SGAs were listed in the Appendix A.

2. Methods 2.3. Statistical analysis

2.1. Databases of Taiwan National Health Insurance Demographic factors, including age, sex, occupation,
population density, and income between each treatment
This study used claims data of the National Health cohort and the controls were compared. We categorized the
Insurance (NHI) obtained from the National Health Research ages into four groups (10–19, 20–39, 40–59, and 60 or more
Institute (NHRI) in Taiwan from 1996 to 2008. The Depart- years), and occupations into three groups (white collar, blue
ment of Health in Taiwan incorporated 13 insurance collar and others). All the insured were grouped into four-
programs to launch the universal NHI program in March quartile groups from high to low based on the population
1995. This insurance program has covered 99% of all 23 density in the areas the subjects lived. The subjects' incomes
million citizens and contracted with 97% of hospitals and for insurance premium estimation were classified into three
clinics in Taiwan (Cheng, 2009). The NHI program provides groups with monthly pay of b15,000, 15,000–29,999, and
112 C.-H. Liao et al. / Schizophrenia Research 126 (2011) 110–116

≥30,000 New Taiwan Dollars (1.0 USD is about 31–34 NTD). Table 2 shows that the incidence density rates of DM,
The Chi-square test was used to examine the differences. hypertension and hyperlipidemia by sex in study set II tended
The sex-specific and age-specific incidence density rates of to be higher in the schizophrenia cohort on SGA than in the
the studied disorders were calculated for each cohort. The non-schizophrenia controls. The incidence density rates of
case cohort to the control cohort rate ratios with 95% DM, hypertension and hyperlipidemia were 1.90, 1.19 and
confidence intervals (CI) were calculated by sex. Cox 1.56 times higher in patients taking SGA than in their
proportional hazard regressions were used to measure the corresponding controls, respectively. The incidence of DM
risk of developing DM, hypertension or hyperlipidemia was the highest in the SGA cohort, followed by FGA cohort,
associated with schizophrenia for each study set. The hazard control cohort I, and the lowest in the control cohort II. The
ratio (HR) was presented with 95% CI, controlling for socio- hierarchy was particularly true among female subjects, with
demographic variables used for adjustment in the multivar- incidence density rates of 6.29, 5.40, 3.94 and 2.65 per 1000
iable Cox analyses. This study used the SAS statistical package person-years, respectively. Comparing the incidences of DM,
(SAS Institute Inc., Cary, NC. Version 9.1) to perform all hypertension and hyperlipidemia between the cohorts of
analyses, with the statistical adopted significance level at study set I, only the incidence of hyperlipidemia in females
0.05. was significantly higher in the FGA cohort than in the
controls.
Table 3 presents the age-specific HRs of DM, hypertension
3. Results and hyperlipidemia associated with schizophrenia control-
ling for the socio-demographic variables. The results indicate
Study set I consisted of 1631 newly diagnosed schizo- that younger schizophrenic patients had higher risk of
phrenia cases in the FGA cohort and 6524 non-schizophrenia developing DM and hypertension for both study sets, and
controls during the period of 1997–2001 (Table 1). The developing hyperlipidemia for study set II. The HR of
corresponding sample sizes in study set II were 1224 cases developing hypertension in teens with schizophrenia was
and 4896 controls. Cases in both schizophrenia cohorts had even greater for those taking FGA (HR 4.52, 95% CI 1.76–11.6)
lower income, and higher un-employment, low income and than for SGA (HR 3.92, 95% CI 1.83–8.39).
retired rates, and resided in less urbanized areas compared Table 4 shows that, in the multivariable Cox proportional
with the respective controls. However, the two cohorts in hazard analyses, schizophrenic patients taking FGA had a
study set I were older than the two cohorts in study set II. significant association with developing diabetes (HR 1.32,

Table 1
Comparison of socio-demographic characteristics between schizophrenic patients on first-generation antipsychotics (FGA) and non-schizophrenia controls, and
between schizophrenic patients on second-generation antipsychotics (SGA) and non-schizophrenia controls identified in 1997–2001.

Variables Non-schizophrenia Schizophrenia with FGA Non-schizophrenia Schizophrenia with SGA

N = 6524 N = 1631 N = 4896 N = 1224

n (%) n (%) n (%) n (%)

Age(years)
10–19 752 (11.5) 188 (11.5) 740 (15.1) 185 (15.1)
20–39 3176 (48.7) 794 (48.7) 2968 (60.6) 742 (60.6)
40–59 1780 (27.3) 445 (27.3) 1036 (21.2) 259 (21.2)
≥60 816 (12.5) 204 (12.5) 152 (3.1) 38 (3.1)
p value a 1.00 1.00
Sex
Female 3008 (46.1) 752 (46.1) 2168 (44.3) 542 (44.3)
Male 3516 (53.9) 879 (53.9) 2728 (55.7) 682 (55.7)
p-value a 1.00 1.00
Occupation
White collar 3610 (55.3) 629 (38.6) 2909 (59.4) 483 (39.5)
Blue collar 2080 (31.9) 500 (30.7) 1384 (28.3) 281 (23.0)
Others b 834 (12.8) 502 (30.8) 603 (12.3) 460 (37.6)
p value a b0.0001 b 0.0001
Urbanization c
1 1930 (29.6) 436 (26.7) 1570 (32.1) 336 (27.5)
2 1925 (29.5) 425 (26.1) 1414 (28.9) 358 (29.3)
3 1224 (18.8) 316 (19.4) 958 (19.6) 254 (20.8)
4 1444 (22.1) 454 (27.8) 953 (19.5) 276 (22.6)
p value a b0.0001 0.007
Income
b15,000 2163 (33.2) 852 (52.2) 1534 (31.3) 710 (58.0)
15,000–29,999 3218 (49.3) 680 (41.7) 2454 (50.1) 472 (38.6)
≥30,000 1143 (17.5) 99 (6.1) 908 (18.6) 42 (3.4)
p value a b0.0001 b 0.0001
a
Chi-square test.
b
Others: including un-employment, low income and retired.
c
1 indicates the highest degree of urbanization of residential areas and 4 the lowest.
C.-H. Liao et al. / Schizophrenia Research 126 (2011) 110–116 113

Table 2
Incidences of diabetes mellitus, hypertension and hyperlipidemia occurred during the follow-up period compared between cohorts with and without
schizophrenia by sex and medication.

Variables Non-schizophrenia FGA cohort FGA-to-controls Non-schizophrenia SGA cohort SGA-to-controls


a b a b a b a b
Cases Rate Cases Rate RR (95% CI) Cases Rate Cases Rate RR (95% CI)

Diabetes
Female 116 3.94 35 5.40 1.37 (0.94–2.00) 56 2.65 31 6.29 2.37 (1.53–3.68)
Male 131 3.85 31 4.30 1.12 (0.76–1.65) 73 2.78 27 4.32 1.55 (1.00–2.41)
Total 247 3.89 66 4.82 1.24 (0.94–1.63) 129 2.72 58 5.18 1.90 (1.40–2.60)
Hypertension
Female 664 25.2 145 24.7 0.98 (0.82–1.17) 370 19.1 91 19.3 1.01 (0.80–1.27)
Male 755 24.8 166 25.1 1.01 (0.86–1.20) 387 15.6 124 21.2 1.35 (1.11–1.66)
Total 1419 25.0 311 24.9 1.00 (0.88–1.13) 757 17.2 215 20.3 1.19 (1.02–1.38)
Hyperlipidemia
Female 196 6.76 59 9.39 1.39 (1.04–1.86) 109 5.21 39 7.93 1.52 (1.06–2.19)
Male 241 7.20 42 5.87 0.81 (0.59–1.13) 138 5.32 52 8.42 1.58 (1.15–2.18)
Total 437 7.00 101 7.51 1.07 (0.87–1.33) 247 5.27 91 8.20 1.56 (1.22–1.98)

FGA, first-generation antipsychotics; SGA, second-generation antipsychotics; RR, rate ratio; CI, confidence interval.
a
Cases, incident cases of diabetes, hypertension or hyperlipidemia.
b
Per 1000 person-years.

95% CI 1.01–1.755). The effects seemed greater with patients et al., 1989; Thakore et al., 2002). Although the study design
taking SGA for developing DM (HR 1.82, 95% CI 1.30–2.55), could not control and adjust all these potential confounding
hypertension (HR 1.14, (95% CI 0.97–1.34), and hyperlipid- factors, we also found that the occurrence of DM is higher
emia (HR 1.41, 95% CI 1.09–1.83). The overall risks of among schizophrenic patients than those without schizo-
developing DM, hypertension and hyperlipidemia increased phrenia, from our insurance claims data. The schizophrenia
with age (p for trend b0.0001). There were strong relation- association is stronger for DM than for hypertension and
ships among these three disorders. hyperlipidemia. Antipsychotics are associated with the
increased risk for metabolic abnormalities.
4. Discussion This is the first nature course study using a population-
based retrospective cohort design to measure the risk of
Schizophrenia has been associated with metabolic abnor- metabolic abnormalities in schizophrenic patients between
malities such as DM. Previous prevalence studies estimated taking typical and atypical antipsychotics, using the general
the ratios of DM among those with schizophrenia to be 1.5 to population as controls. The major findings in our present
2-fold higher than in the general population (Bresee et al., study indicate that, compared with the non-schizophrenia
2010; Chien et al., 2009; Mukherjee et al., 1996). Factors controls, schizophrenic patients prescribed with SGA had a
associated with the increased incidence of diabetes among higher risk of developing DM, hypertension, and hyperlipid-
schizophrenic patients are obesity, genetic factors, lifestyle emia after adjusting for demographic factors and comorbid-
factors, and medication effects (Dixon et al., 2000; Mukherjee ities. We further analyzed whether schizophrenic patients
prescribed with FGA also had higher risks for these effects.
Table 3 Interestingly, schizophrenic patients taking FGA were older,
Age-specific Cox's proportional regression estimated hazard ratio for with 12.5% of patients aged 60 and above; whereas only 3.1%
diabetes, hypertension and hyperlipidemia in association with schizophrenia
taking first- and second-generation antipsychotics controlling for sex,
of patients prescribed with the SGA were aged 60 and above.
occupation, urbanization level and income. This is why the incidence rates of hypertension were higher
in the study set I cohorts than in the study set II cohorts.
Variables Diabetes Hypertension Hyperlipidemia
Additional analysis was focused on comparing the incidence
HR (95% CI) HR (95% CI) HR (95% CI) of developing DM, hypertension, and hyperlipidemia for
FGA patients taking specific SGA. Most patients (as high as 65.3%)
Age (years) were prescribed with risperidone (data not shown). How-
10–19 4.86 (0.64–37.1) 4.52 (1.76–11.6)** 2.15 (0.52–8.87) ever, quetiapine had higher risk than risperidone associated
20–39 2.28 (1.31–3.98)** 1.48 (1.16–1.88)** 1.34 (0.89–2.01) with developing DM (9.3 vs. 5.7 per 1000 person-years),
40–59 0.98 (0.66–1.47) 0.99 (0.81–1.20) 1.15 (0.85–1.57)
hypertension (23.6 vs. 17.4 per 1000 person-years) and
≥60 0.97 (0.52–1.81) 0.67 (0.52–0.86)** 0.73 (0.41–1.29)
hyperlipidemia (9.0 vs. 6.9 per 1000 person-years). Cloza-
SGA pine also had high risk in association with DM (6.8 per 1000
Age (years) person-years) and hyperlipidemia (14.2 per 1000 person-
10–19 – – 3.92 (1.83–8.39)** 3.02 (0.59–15.5)
years).
20–39 1.98 (1.23–3.17)** 1.63 (1.28–2.06)*** 2.38 (1.69–3.36)***
40–59 1.68 (0.99–2.85) 0.83 (0.63–1.09) 1.02 (0.65–1.60) Studies have also found a higher prevalence of hypertension
≥60 2.41 (0.76–7.64) 0.78 (0.48–1.26) 0.17 (0.02–1.27) in schizophrenic patients than in controls (Dixon et al., 1999;
HR, hazard ratio; CI, confidence interval; FGA, first-generation antipsychotics;
Nasrallah et al., 2006; Osborn et al., 2008). This study found a
SGA, second-generation antipsychotics. moderate risk of developing hypertension in schizophrenic
*p b 0.05, **p b 0.01, ***p b 0.0001. patients after adjusting for socioeconomic status and
114 C.-H. Liao et al. / Schizophrenia Research 126 (2011) 110–116

Table 4
Multivariable Cox proportional model measuring hazard ratios of developing diabetes mellitus, hypertension and hyperlipidemia in schizophrenic patients taking
first- and second-generation antipsychotics controlling for sex, occupation, urbanization and income.

Diabetes Hypertension Hyperlipidemia

HR (95% CI) HR (95% CI) HR (95% CI)

1st generation antipsychotics


Age, years
10–19 1.00 (Reference) 1.00 (Reference) 1.00 (Reference)
20–39 2.72 (0.97–7.65) 6.11 (3.78–9.88)*** 3.13 (1.57–6.26)**
40–59 6.81 (2.45–18.9)** 20.2 (12.6–32.5)*** 5.36 (2.69–10.7)***
≥60 6.30 (2.25–17.6)** 44.7 (27.9–71.8)*** 4.30 (2.13–8.69)***
p for trend b 0.0001 b0.0001 0.0001
Schizophrenia 1.32 (1.00–1.75)* 0.98 (0.86–1.11) 1.16 (0.93–1.45)
Diabetes – – 1.85 (1.57–2.17)*** 5.65 (4.62–6.90)***
Hypertension 2.88 (2.19–3.78)*** – – 3.90 (3.19–4.78)***
Hyperlipidemia 7.11 (5.58–9.05)*** 2.59 (2.27–2.96)*** – –

2nd generation antipsychotics


Age, years
10–19 1.00 (Reference) 1.00 (Reference) 1.00 (Reference)
20–39 16.9 (2.31–123)** 3.21 (2.16–4.77)*** 1.41 (1.09–1.83)**
40–59 26.9 (3.67–198)** 10.8 ( 7.30–16.1)*** 4.82 (2.09–11.1)**
≥60 28.3 (3.68–218)** 27.5 (18.1–41.8)*** 7.03 (3.01–16.4)***
p for trend b 0.0001 b0.0001 0.0001
Schizophrenia 1.82 (1.30–2.55)** 1.14 (0.97–1.34) 1.41 (1.09–1.83)**
Diabetes – – 1.90 (1.53–2.37)*** 5.29 (4.05–6.92)***
Hypertension 3.16 (2.26–4.43)*** – – 4.57 (3.59–5.83)***
Hyperlipidemia 6.90 (5.01–9.49)*** 3.14 (2.64–3.74)*** – –

*p b 0.05, **p b 0.01, ***p b 0.0001; HR, hazard ratio; CI, confidence interval.

comorbidities. Our definition of hypertension developed in the risk than females in developing hypertension and hyperlip-
follow-up period was based on the antihypertensive drug idemia. Since our findings were from an observational study
therapy and treatment for hypertension in patients with and limited by some unavailable data, further studies are
schizophrenia. The hypertension risk might be underestimated. needed to examine the sex-specific issues in schizophrenic
Schizophrenia-related hypertension has been associated with patients.
body weight gain and metabolic syndrome because of the Obesity and older age are highly related to DM, hyper-
sedentary life style in patients. (Goff et al., 2005; Nasrallah et al., tension and hyperlipidemia, (Flegal et al., 2002). However,
2006; Susce et al., 2005). studies regarding schizophrenia with age-specific analysis
Our study also showed a higher risk of developing found that younger patients had higher incidences of
hyperlipidemia associated with schizophrenia. Obesity in developing these metabolic comorbidities (Kato et al., 2005;
people with an unhealthy lifestyle with reduced physical Suvisaari et al., 2007). Bresee et al. (2010) also found that the
activity and poor diet selection is more common in schizo- adjusted risk of DM in schizophrenic patients was greater in
phrenic patients than in the general population, and this women than in men for all age groups, with the greatest risk
could also be related with hyperlipidemia. Studies on both in women ages 20–29 (aOR 2.49; 95% CI: 1.78–3.49). Our age-
adults and children have indicated the important role of specific analysis also demonstrated, the hazards of develop-
antipsychotics in the risk for obesity and DM in schizophrenic ing DM and hypertension or hyperlipidemia in schizophrenic
patients (Hennekens et al., 2005; Newcomer, 2007; Scheen patients taking either FGA or SGA were significantly elevated
and De Hert, 2007; Tschoner et al., 2007) The findings could in the 20–39 year old group, but not in the older age group.
be underestimated because of inequalities in recognizing and The patients on FGA aged 10–19 had the highest risk of
managing cholesterol in schizophrenic patients (Hippisley- developing hypertension among all age groups in this study.
Cox et al., 2007). Our findings reflect the greater vulnerability of younger
Sex and age differences associated with schizophrenia and patients in developing DM, hypertension and hyperlipidemia.
the risk of DM, hypertension and hyperlipidemia deserve Patients on FGA in the oldest group had a 33% less risk
attention. Previous studies have found women with schizo- compared with their controls. It is likely that the older
phrenia are at a higher risk for metabolic syndrome (Pilote et patients have already gone through the age of developing
al., 2007; Saari et al., 2005; Suvisaari et al., 2007). We also these metabolic disorders and free of them at the baseline.
found in the sex-specific analysis that the schizophrenia The elevated risk for younger patients and the protective
cohort of SGA are at a greater risk than the non-schizophrenia effect of age deserve further investigation.
controls for these three disorders. The incident DM was even The longitudinal design is the strength of the present
greater for females than for males (6.29 vs. 4.32 per 1000 study, which aims to evaluate the relationship between
person-years) in the schizophrenia cohort taking SGA. On the schizophrenia with antipsychotics and DM, hypertension, and
other hand, in the SGA cohort, males were at a slightly greater hyperlipidemia using population-based data. The technique
C.-H. Liao et al. / Schizophrenia Research 126 (2011) 110–116 115

to define both exposure and outcomes by using medication Second-generation antipsychotics


prescriptions, instead of only clinical diagnoses, is the other
strength. We only included patients who have received the Risperidone, ziprasidone, clozapine, olanzapine, quetia-
FGA or SGA therapy in the two schizophrenia cohorts. The pine, amisulpride, aripiprazole, and paliperidone.
sample size and the power for measuring the risk of DM,
hypertension and hyperlipidemia were accordingly reduced.
However, we were still able to observe the effects of References
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