Critical Analysis: Outcomes of Obese Schizophrenic Patients Report

This report critically analyzes a randomized controlled study investigating the impact of a six-month diet and physical activity program on obese schizophrenic inpatients treated with clozapine. The study addresses the issue of weight gain, a common side effect of clozapine, which can lead to metabolic complications and non-compliance with medication. The research found that the intervention program, involving dietary control and mild physical exercise, significantly decreased body weight, waist and hip circumference, and BMI, while also improving metabolic profiles such as IGFBP-3 levels and the IGF-1 to IGFBP-3 molar ratio. The study included 56 patients, with specific inclusion and exclusion criteria, and used ANCOVA and SPSS statistical software for data analysis. The findings highlight the importance of weight management in this patient population and suggest that lifestyle interventions can improve health outcomes and reduce the risk of metabolic syndromes. The study also points out the need for future research to explore long-term effects and the impact of other lifestyle changes, and other lipid lowering medication on the weight loss regime of the obese schizophrenic patients.

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CRITICAL ANALYSIS
Paper Selected: Outcomes of Obese, Clozapine-Treated InpatientsWith Schizophrenia
Placed on a Six-Month Diet and Physical Activity Program
Overview of the Paper
Issues addressed in the paper
Increased level of appetite along with consequent gaining of weight is a common
phenomenon among the schizophrenic patients who are under antipsychotic medication
(Deng, 2013). One of the most recommended antipsychotic drugs which is recommended for
the treatment of schizophrenia is Clozapine. This second-generation antipsychotic drug
belongs to the class of dibenzodiazepine derivative and has low risk of extra-pyramidal side
effects (Deng, Weston-Green & Huang, 2010).However, Clozapine has greatest potential to
induce weight gain. The antipsychotic drug induced weight gain occurs through histamine H3
receptors. Drug induced decrease in the activity of the histamine H1 receptors decrease the
specificity of the H3 autoreceptors, resulting in weight gain (Deng, Weston-Green & Huang,
2010). The increase in weight gain causes increase in the concentration of glucose, insulin,
cholesterol and triglycerides in blood (Deng, 2013). In case of patient who are under long-
term therapy under Clozaoine, significant decrease in the insulin like growth factor (IGF-1)
has been observedleading to cardiac complications (Henderson, Vincenzi, Andrea, Ulloa&
Copeland, 2015). This increase in weight gain arising out of the side-effects of medication in
Schizophrenic patient is associated with non-compliance (Das, Mendez, Jagasia&Labbate,
2012). Non-compliance is associated with sudden discontinuation of the psychotic treatment
leading to return of psychotic symptoms (Das, Mendez, Jagasia&Labbate, 2012). Therefore,
it is important to strictly regulate weight among the patients who are under long-term
treatment with Clozapine. The aim of this study is to regulate the weight gain among the
Schizophrenic patients who are under long-term treatment with Clozapine. In the process of
execution of control of weight gain, Mei-Kuei et al., observed dietary regulation and physical
activity among the obese inpatients of Schizophrenia. The issue addressed in this paper is
important because patients who are suffering from Schizophrenia are at an increase for
getting affected with metabolic syndromes due to their uncommon lifestyle, suspected genetic
predisposition and long-term exposure to antipsychotic drugs (Hasnain, Fredrickson,
Vieweg&Pandurangi, 2010). Obesity and decrease in IGF-1 is associated with serious health
threats. IGF1 and other growth hormones are important regulatory agents in maintaining
effective functioning of the cardiovascular system. Free IGF-1 has anabolic, autocrine and

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CRITICAL ANALYSIS
endocrine functions so decrease in IGF-1 arising out of antipsychotic medication obesity can
impose threats on the Schizophrenic patient.
Outcome of the research
The research showed that the management program of dietary control and physical
activity is successful in reducing obesity among the Schizophrenic patients who are on oral
medication of Clozarine. The regulated and physical activity was found to reduce the obesity
related complications of these patients.
The study showed that the an intervention program involving dietary control and mild
physical exercise for about six months significantly decrease the body weight, waist and hip
circumference and BMI index of the obese schizophrenic patient of the control group. It also
helped in increasing the blood concentration of the IGFBP-3 levels along with increase in the
molar ratio of IGF-1 to ICFBP-3. Increase in the ration of the IGF-1 is important in
maintaining the balance of the healthy cardiac system (D'amario et al., 2011). The importance
of the findings lies in the fact that it indentified that importance of monitoring weight among
the obese patients who are suffering from Schizophrenia and are under the mediction of
Clozapine for the past one year.
Study Design
A randomized controlled study was observed in this research paper in order to
elucidate the outcome of six months of non-stop dietary control and regulation of physical
activity upon the weight gain of the obese patient suffering from Schizophrenia and is on
Clozapine medication. The study critically analysed the biochemical and anthropometric
parameters in an interval of three and six months. The major factors which were analysed
under the banner of the anthropometric and biochemical parameters are triglyceride, serum
glucose, cholesterol, cortisol, insulin, prolactin, growth hormones, IGF-1 and insulin-like
growth factor–binding protein-3 (IGFBP-3). The dietary intervention was implemented on
the target group via a professional dietician.
Men Women
1600 to 1800 per day 1300 to 1500 per day
Table: Permissible kilo- calorie-intake

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CRITICAL ANALYSIS
The physical activity was observed for six months at a stretch with a plan of three days per
week. The physical activities were selectively chosen in order to effectively fit within the
hospital environment and include walking and warm. The study was performed in accordance
with the Declaration of Helsinki and was simultaneously approved by the veterans of the Yu-
Li Hospital’s Ethic review committee. The results thus obtained wasanalyzed via variance
and covariance analysis (ANCOVA) and the effectiveness of the data obtained was accessed
via SPSS statistical software (version 10.0) on general linear model.
Study population
The randomized control trial consisted of 753 hospitalized inpatients. The patients
who were hospitalised during the tenure of 2003 September to 2004 February are considered
for this randomized control trial. All the patients who were included under the focus group
has tested positive for Diagnostic and Statistical Manual of Mental Disorders fourth edition
(DSM-IV) test. DSM-IV is diagnostic criteria for schizophrenia and associated disorders.
Theage brackets of the patients were broad and lie in between 18 to 65 years. The
main inclusion criteria taken for this study was- patients who are taking oral Clozapine
dosage of 300mg for the past one year with a body mass index (BMI) greater than 27kg/m2
are considered appropriate for the focus group. Here the importance of the BMI lies in the
fact that Asian originals who have BMI greater than the above mentioned value (27kg/m2)
are considered to be obese (Huxley, Mendis, Zheleznyakov, Reddy & Chan, 2010).
Exclusion Criteria
Patients who are using lipid lowering medication
Suffering from abnormal ambulatory complications or organ failure
Suffering from chronic mental illness
Pregnant or lactating
Disability in locomotion
Unwilling to participate in the study
After apply this inclusion and exclusion criteria, only 56 patients were screened out and used
for the final study of them 25 patients was referred as placebo.
Main findings

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CRITICAL ANALYSIS
Under the anthropometric measurements, there was no significant different between
the BMI, waist circumference, waist-to-hip ratio among the control and the study group.
Moreover, when the data was separately tallied between the male and the female participants
on the basis of the fat percentage of free fat mass, no significant change was observed.
However, BMI, weight of the body and hip circumference experienced significant changes
within the first three months and the change in the circumference of the hip was observed
after the six months.
In the domain of the metabolic analysis and enzyme immunoassay, no significant
difference was observed at the baseline when the obtained results were compared with the
control and the trial groups. Cholesterol, serum glucose, prolactin, cortisol and insulin did not
changed significantly upon the intervention. However, at the end of six months, there was a
significant change in the blood concentration level of the triglycerides and cortisol between
the control and focused group was observed. Triglyceride level was found increasing among
the control group during the transition between three to six months. Decrease in the insulin
level was only observed after six months in comparison to that with the three month
assay.vNo significant difference in the assay of IGF-1 was observed during the entire stretch
of six months however, concentration of IGFBP-3 was found significantly lower in the
placebo group.
Thus, the findings of the study can be summarized as follows: There lies a significant
benefit of six-month weight control intervention upon the obese schizophrenic patients who
are under clozapine medication for the past one year. The benefits are reflected via integrated
dietary control and regular physical activity. The study showed a significant decrease in BMI,
percentage of body fat and hip to wait circumference. The study also showed that restricted
calorie intake along with period physical exercise also improve the metabolic profiles of
insulin, IGFBP3 and IGF-1 to IGFBP-3 molar ratio and triglycerides. This improvement of
the in insulin like growth factor level promotes health cardiac functioning thereby reducing
fatal threats on the obese Schizophrenia patients (Henderson, Vincenzi, Andrea, Ulloa&
Copeland, 2015).
Future research scope
The study did not able to show the significant variance in the concentration of IGF-1
in blood in six months and hence future studies are required to be undertaken in order to
ascertain the affect on the concentration of IGF blood upon the observance of the physical

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CRITICAL ANALYSIS
activity and calorie restricted diet. Moreover, several benefits of the metabolites of the diet
were not realised and hence long term adherence of such programs is necessary to study their
effects. The future research also needs to ascertain the affect of the other lifestyle changes on
the obesity of the schizophrenic patients so that they can successfully avoid the obesity
related abnormalities.
In the exclusion criteria, patients who are using lipid lowering medication were
excluded from the focus group. Future research studies are needed to be undertaken if the
lifestyle changes could aggravate the overall weight loss regime of the obese schizophrenic
patients when observed alongside with the lipid lowering medication.
Internal Validity
Confounding
The result obtained in this study is not that confounding. It is already known that the
management of weight via restricted calorie diet cumulated with regular physical activity
helps in weight loss and thus preventing the chances of morbidity among the obese
individuals. However, previous studies, which were conducted in regards to weight
management regime for the schizophrenic patients with clozapine medication showed
contradictory results. Nevertheless, the study is indeed significant as it gave a clear light
towards successful weight loss regime among the obese Schizophrenic patients who are under
oral clozapine. It also showed that such weight loss is not associated with any negative side
effects or require any administration of other extra drugs. Though weight loss is previously
initiated via the application of number of pharmacological interventions like metformin,
aripiprazole, fluvoxamine, and topiramate appear to be beneficial but are associated with
negative side effects (Whitney, Procyshyn, Fredrikson& Barr, 2015).
Chance Variation
The results are conducted via taking a large age group encompassing 18 to 65 years
old and hence there must be a chance of getting affected via chance variation. Moreover,
effectiveness of the subsequent treatment was analyzed via applying variance and covariance
analysis (ANCOVA) method with the help of SPSS statistical software (version 10.0). The
entire analysis is based on the general linear model. Chance variance or chance error is an
inherent error in any predictive statistical model and this model is not an exception (Busk
&Marascuilo, 2015).

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CRITICAL ANALYSIS
Clear representation of the data
The conclusion derived from the study is clearly represented via citing relevant
statistical data obtained from the six months old study. The data generated after metabolic,
anthropometric and hormonal study from the focus group were thoroughly tallied with the
data generated from the placebo group. This comparison of the data was done during the
onset of the scientific assessment and after the completion of three months and six months of
the trial respectively. The data obtained towards the onset of the study, baseline data or initial
data were cited as covariate. The comparative analysis was done with repeated application of
ANCOVA which helped in the critical adjustment of the baseline values. In this study, the
researchers have employed a two-way mixed design of ANCOVA to correct the confounding
variables and to analyse the relation between the variables. In all the cases taken for statistical
analysis, 0.5 was considered as o value in order to make the data free from chance error and
statistically significant.
The sampling of the focus group undertaken for the randomized control trial was done
based on the approach stated by the CONSORT 2010 checklist(Moher et al., 2010).
Source: CONSORT, 2010
Causal Association between Exposure and Outcome

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CRITICAL ANALYSIS
The principal aim of the epidemiology is associated with the assessment of the cause
of the disease. However, the majority of the epidemiological studies are observational than
experimental and so is this study carried out by Mei-Kuei Wu et al. Thus an observed
statistical association between the risk factor and the disease does not lead to a causal
relationship between the two entities. However, in this study, there lies a stronger strength of
association between the risk and the outcome for example here the risk is the increase in the
obesity and the outcome shows decrease in the hip and waist circumference thus, showing a
significant degree of association. Moreover, there also lies a consistency of findings among
the different population. Here the population bracket that have been selected for the study is
large encompassing 18 to 65 years, both male and females and hence making the population
large. There is also a specificity of the association that is one to one relationship between the
cause and the outcome that is maintenance of the calorie restricted diet and physical exercise
helps in weight loss. There is also a temporal sequence of association along with biological
gradient. Moreover, there also lies a coherence that is the relationship agrees with the present
knowledge of the natural history. Here the relationship is, restricted diet and regular physical
exercise promotes weight loss. Moreover, the removal of the exposure alters the frequency of
the desired outcome as shown by the placebo group. So there is no plausible causal
association between the exposure and the outcome (Von Elm et al., 2014).
The findings of the study are consistent. The majority of the factors, which are
undertaken for the analysis of the weight loss regime showed significant results by the end of
six months trial. However, no special interaction or mechanism was illustrated in this study.
This is due to the fact that it is an epidemiological study and is based on observation and not
on experiments(Von Elm et al., 2014).
External Validity
Application to source population
The findings can be effectively applied to the source population. Here the source
population means the population from which the focus group of the study population was
derived. The study was carried with the inpatients who are under the clozapine medication for
the past one year and are suffering from Schizophrenia. So the source population that is the
population who are suffering from the Schizophrenia and are under antipsychotic medication
of clozapine will be effective in applications of the interventions elucidated from the studies.

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CRITICAL ANALYSIS
However, the main criterion is, the individual must be suffering from obesity and that obesity
has been generated as an after affect of long term clozapine treatment.
Study here has taken certain exclusion criteria and one significant one Schizophrenic
patient who are using lipid lowering medication are excluded from the study. So the
relevancy of the results obtained in this study may get affect if studies over an obese
population who are under both clozapine and lipid lowering medication.
Application to relevant population
The study results can also be applied to other population who are suffering from the
obesity arising out of the antipsychotic medication of the mental disorder. Moreover, since
the experimental plan undertaken in this study is restricted calorie diet along with regular
physical activity, the results can also be applied to general population who are suffering from
obesity due to lifestyle related problems.

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CRITICAL ANALYSIS
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