Green Tea Extract for Obesity of Psychiatric Patients
Green Tea Extract for Obesity of Psychiatric Patients
Obesity or metabolic syndrome is becoming a global epidemic and common health problem,
 leading to the increase of associated comorbidities such as type 2 diabetes, cardiovascular
 disease, and certain cancers. This phenomenon is also a serious problem among psychiatric
 patients due to the increase use of second generation antipsychotics and mood stabilizers
 such as lithium or valproic acid. These metabolic abnormalities can be regarded as medical
 comorbidities, and have an impact not only on physical health and increased hospital length
 of stay, but also on a lower functional outcome, low self-esteem and poorer quality of life
 and non-compliance to antipsychotics. Green tea is one of the most popular beverages in the
 world and is believed to have beneficial effects in prevention and treatment of many
 diseases, such as cancer-prevention, adjunct to chemotherapy for malignancy, to reduce mental
 and physical stress and improve memory function, to increase bone mineral density, and to
 decrease body weight. Since weight gain is a common and undesirable side effect with
 psychiatric medications, the management of it becomes an important issue in clinical
 practice. In this clinical trial, we will use decaffeinated green tea extract to treat
 overweight patients with schizophrenia or bipolar disorder in a double-blind,
 placebo-controlled study design.
Prevalence of obesity or metabolic syndrome and diabetes:

 Obesity or metabolic syndrome is becoming a global epidemic and common health problem. The
 rising prevalence of obesity and associated comorbidities such as type 2 diabetes,
 cardiovascular disease, and certain cancers represents a major threat to public health
 worldwide. In a recent study in Asian populations, the result showed a strong association
 between BMI and prevalence of diabetes. From the results of a general population survey in
 Taiwan, the overall prevalence of obesity (body mass index (BMI) ≧ 27 kg/m2) in men and women
 was 19.2% and 13.4%, respectively, while the age-standardized prevalence of MS was 15.7% by
 the modified Adult Treatment Panel III criteria, 14.3% by the International Diabetes
 Federation for Chinese criteria and 16.4% by the metabolic syndrome criteria for Taiwanese.
 Their data also showed that the prevalence of obesity and metabolic syndrome significantly
 increased with age (trend test, p < 0.0001) in men and women. The risk of metabolic syndrome
 and its components increased significantly with BMI, and showed a marked increase with BMI≧24
 kg/m2.

 Prevalence of obesity or metabolic syndrome and diabetes in psychiatric patients:

 The prevalence of MS among patients with schizophrenia or other psychotic disorder has been
 reported to be high, ranging from 24% to 43% in males and from 27% to 52% in females in
 previous large-scale investigations. These metabolic abnormalities can be regarded as medical
 comorbidities, and have an impact not only on physical health and increased hospital length
 of stay, but also on a lower functional outcome, low self-esteem and poorer quality of life
 and lead to non-compliant to antipsychotics.

 In Taiwan, a large scale survey on 650 patients with schizophrenia or schizoaffective
 disorder from 36 community psychiatric rehabilitation centers or hospital-affiliated day
 hospitals in Taipei area revealed an overall metabolic syndrome prevalence of 34.9%, with
 38.9% in female and 31.5% in male patients, respectively. The difference of metabolic
 syndrome prevalence between those patients and the general population was marked in male
 patients under 40 years of age and in female patients under 50. The authors suggested that
 BMI≧24 kg/m2 and age over 40 years old are two important risk factors of metabolic syndrome.
 Since the implementation of second generation antipsychotics (SGAs), especially clozapine,
 olanzapine or quetiapine, the metabolic syndrome prevalence exaggerated. Bai and her
 associates (2009) carried a large survey on 567 hospitalized of patients with schizophrenia
 under SGAs (clozapine =231, olanzapine n=94 and risperidone =242) for an average duration of
 45.8+/-27.8 months, and revealed the prevalence of metabolic syndrome among all subjects was
 23.8%. The clozapine group had a higher prevalence of metabolic syndrome (28.7%) than did the
 olanzapine (24.2%) and risperidone groups (19.5%) (P=0.039), and the clozapine group had
 lower levels of adiponectin (8.46+/-6.02 mg/mL) than did the olanzapine (10.26+/-4. 9 mg/mL)
 and risperidone groups (10.69+/-7.43 mg/mL) (P=0.001). The authors also found that
 adiponectin level was negatively correlated with BMI increase after initiation of SGAs
 treatment. Beside the increase use of SGAs, the use of mood stabilizers such as lithium or
 valproic acid in patients with bipolar disorder can also lead to body weight increment and
 metabolic syndrome.

 Introduction of green tea:

 Green tea is one of the most popular beverages in the world. It is made solely with the
 leaves of Camellia Sinensis that have undergone minimal oxidation during processing. Green
 tea is believed to have beneficial effects in prevention and treatment of many diseases, such
 as cancer-prevention and adjunct to chemotherapy for malignancy, to reduce mental and
 physical stress and improve memory function, to increase bone mineral density, and to
 decrease body weight. An epidemiological human study also showed that consumption of tea for
 more than 10 years led to a lower percentage of total body fat and smaller waist
 circumfluence. The anti-obesity effects of green tea are mainly attributed to its polyphenol
 content, in particular, epigallocatechin gallate (EGCG), which is most abundant in green tea
 and has been found to inhibit adipocyte proliferation and differentiation in in vitro
 studies.

 Green Tea Extract studies in Taiwan:

 In Taiwan, green tea extract (GTE) has been used to explore the effect on obese women by
 randomized, double-blind, placebo-controlled study design. Though the result showed that
 there was only a 0.3% reduction in body weight (0.15 kg) after 12 weeks of treatment with GTE
 in the study group, the GTE group had significant reduction in low-density lipoprotein
 (LDL)-cholesterol and triglyceride, and marked increase in the level of high-density
 lipoprotein (HDL)-cholesterol, adiponectin and ghrelin. In another study investigating
 insulin resistance type 2 diabetics patients, with no statistical difference was found in any
 measured variable between the decaffeinated GTE and placebo groups. However, there were some
 statistically significant within-group changes detected in items of reduction of waist
 circumference (WC), insulin resistance (HOMA-IR) index [fasting glucose (mmol/l) X fasting
 insulin (UI/l)/22.5], and insulin level, and a significant increase in the level of ghrelin.
 In an open label study, Tsai and his associates reported that more weight loss was found in
 the treatment group than the control (6.8 versus 2.3 kg; P <0.001) after 12-week use of green
 tea meal replacement formula product. Also, the treatment group had a greater changes in
 total cholesterol (185.2 versus 215.2 mg/dl; P=0.011) and low-density lipoprotein cholesterol
 (106.7 versus 127.6 mg/dl; P<0.005). Among completers only, the treatment group again lost
 more weight (6.8 kg; n=54 versus 0.8 kg; n=56; P =0.001) and had a greater reduced total body
 fat mass (7.6%; n=37 versus 0.5%; P=0.005). The authors concluded that green tea meal
 replacement formula contributes to the lower body weight and reduced low-density lipoprotein
 cholesterol level. Wu and his colleagues have carried out a cross-sectional survey of 1,210
 epidemiologically sampled adults (569 men and 641 women) and found that habitual tea drinkers
 for more than 10 years showed a 19.6% reduction in body fat percentage (BF%) and a 2.1%
 reduction in waist-to-hip ratio (WPR) compared with non-habitual tea drinkers. The multiple
 stepwise regression models revealed that men, older age, higher BMI, and current smokers were
 positive factors for BF% and WHR. In contrast, longer duration of habitual tea consumption
 and higher total physical activity were negative factors for BF%. Longer duration of habitual
 tea consumption, higher socioeconomic status, and premenopausal status were negative factors
 for WHR.

 Previous Study of GTE in Psychiatric patients:

 Though there were a lot of researches regarding the use of GTE to treat metabolic syndrome or
 to decrease body weight across many countries, no one was focusing on the psychiatric
 patients. Katzman and his associates published a paper reporting 4 patients with resistant
 mood and anxiety disorder taking quetiapine and antidepressants, and used GTE by themselves
 for overweight and found that each patient had an unexpected decrease in total body fat mass,
 body fat percentage, and increase in lean body mass. Since weight gain is a common and
 undesirable side effect with psychiatric medications, especially the SGAs, the authors
 suggested the need for conducting controlled clinical trial using these agents to ameliorate
 these unwanted consequences.

 In this clinical trial, the investigator will use decaffeinated green tea extract to treat
 overweight patients with schizophrenia or bipolar disorder in a double-blind,
 placebo-controlled study design.
Inclusion Criteria:

 -  Male or female patients with schizophrenia or mood disorders, followed at Taipei City
 Psychiatric Center will be the targeted study population. The subjects should fulfill
 the following criteria:

 1. Age between 20 to 65 years.

 2. Currently taking antipsychotics or mood stabilizers.

 3. BMI should be ≥ 27 kg/m2.

 4. Good adherence to medications as recorded by chart.

 5. Competent to understand the informed consent and have motivation to decrease
 their body weight.

 Exclusion Criteria:

 1. Unstable psychiatric symptoms or physical condition that may interfere the adherence
 of medication.

 2. Medical conditions such as endocrine disease, heart disease, allergy or immunology
 disease, or impaired liver function (high aminotransferases, alanine, aspartate >80
 IU/L or serum creatinine >2.5 mg/dl.

 3. Pregnant or lactating women.

 4. Childbirth within 6 months.

 5. Management for weight control within 3 months.

 6. Any other conditions deemed unsuitable for trial as evaluated by the
 physician-in-charge.