Effect Of Diet Control And Physical Activity On Obesity In Clozapine-treated Schizophrenia Patients: A Randomized Controlled Study

Study Design, Study Population and Main Findings

The main purpose of the study by Wu et al., (2017) was to evaluate the effect of diet control and physical activity among obese patients with schizophrenia being treated with Clozapine. Investigation in this area is a novel idea because schizophrenia patients often need to take antipsychotic drugs like Clozapine during their treatment, however it increases the risk of weight gain in patients (Gressier et al., 2016). Hence, in patients who require long term treatment with Clozapine, managing weight gain has become a priority. The research by Wu et al., (2017) is important as it tries to find a solution to address weight gain issues and complication in patients taking Clozapine by determining the effect of diet control and physical activity regimen in such patients. The significance of this research is also realized because past studies of Weight Management Programs gave inconsistent results. Hence, the main exposure or intervention studied in the research article was six months of continuous dietary control and regular physical activity and the outcome expected was weight loss.

Wu et al., (2017) used randomized controlled study design to investigate about the topic and selection of this research design is appropriate for this research as it mainly aims to evaluate an intervention. RCT is the best study design for clinical trials where main aim is to study the effect of a new treatment and use of this study design is likely to reduce bias during research too (McCambridge, Kypri & Elbourne, 2014). The participants include in the study included patients with DSM-IV diagnosis of  schizophrenia and the main inclusion criteria was they must be taking at least 300 mg of Clozapine per day for at least a year and they must be obese. The participants were divided into study group who were placed on diet and physical activity regimen, whereas the control group received no intervention. The final outcome of the study was that decrease in body weight, body mass index and waist circumference was found in study group compared to control group. Despite this outcome, the author reported about the challenges and future work in accordance with the study result which is indicative of high quality and high validity research article. The researcher emphasized that real effect of this intervention cannot be seen unless long term adherence to the diet control and physical exercise regimen is not followed. Hence, by this statement the author suggested about new areas of research such as to find out appropriate strategy to promote long term adherence to diet control and physical activity programs.

Future Direction of the Study

 The future implication from the study is also evidenced which is lifestyle modification interventions must be regularly implemented in schizophrenia patients to avoid obesity related complication. This fact is also supported by Correll et al., (2014) as they explained that considering the impact of psychotropic medication is necessary to implement management strategies to improve physical and mental health outcomes in schizophrenia patients.

Although outcome and intervention in epidemiological studies depend on causal association, however certain non-causal association also alters the outcome of the study. The presence of non-causal association affects the internal validity and transferability of the study results (Elwood, 2017). . In the study by Wu et al., (2017), non-causal association between intervention and outcome needs to be analyzed to find out any error in study design or other variables that affects the desired outcome for an intervention. The results of the study mainly proved that diet control and physical activity intervention is effective in reducing weight in obese schizophrenia patients taking Clozapine. The internal validity of the study was found to be high because all consideration was made by the research to take the appropriate sample for the study. The inclusiveness in the sample was maintained by taking appropriate inclusion and exclusion criteria. The decision of not taking patients who were taking any other medications apart from Clozapine reduces biasness in results. Considering this point was useful because in the presence of other medications, specific effect of Clozapine could not be investigated. Evidence shows that there are various drugs whose common side effect is body weight (Domecq et al., 2015). Hence, including patients taking combination of other medications would have affected the purpose of the study and its outcome.

Although appropriate sample was taken for the study, however one limitation in the research article was that no specific sampling strategy was taken to recruit the participants. Wu et al., (2017) mentioned taking participants from 753 hospitalized patient, however it is not clear what strategy was applied to select only 56 patients.  Secondly, the small sample size also affected the validity of the study result as only 56 samples cannot give a clear idea about the effect of an intervention that needs to applied in real setting. No step was taken to ensure that the correct sample size has been taken for the study.  In addition, as the study results were mainly evaluated on the basis of BMI data too, the author defined specific BMI in the inclusion criteria only for Asian individual. Hence, it is not clear whether only Asian participants were included in the study or other groups too. These factors may have an impact on the final outcome and the transferability of the research. Therefore, both information bias and sampling bias distort the true association between the intervention and outcome and influences the credibility of the study (Skelly, Dettori, & Brodt, 2012).

Appraising the Internal Validity

The potential for confounding in research can also be accessed by analyzing the statistical precision of the study. The baseline data for both control and intervention group was kept same and this is reflective of a high quality RCT study. The body fat percentage was also a confounding variable in the study because no changes in fat percentage were seen both in men and women after three months and six months. Body fat percentage was also a part of anthropometric measurement for the study, however no changes in body fat percentage apart from other variables like waist circumference, hip circumference, body weight and waist circumference is questionable (Wu et al., 2017). No explanation was given by the research for this anomaly. Hence, body fat percentage is the confounding variable in the research. The review of another study investigating body composition after a programmed physical activity also showed no change in body fat percentage and it mainly explained about the effect of puberty in changing this variable (Farias et al., 2009). Therefore, similar type of explanation by Wu et al., (2017) could have enhanced the internal validity of the study. This might also contribute to chance error, however appropriate statistical data for this has not been presented in the research study.

The main purpose of epidemiology study is to analyze the cause of any disease or effect of any intervention on specific outcome. The causal association between exposure and outcome is understood from the association between risk factors and outcome. The stronger causal association is evident from the stronger association between the risk factor and the outcome (Szklo & Nieto, 2014). Hence, the success of the Wu et al., (2017) study is understood if specific causal relationship between cause and outcome is clearly defined. The desired outcome in the study was reducing obesity and the main risk factor or cause for it was identified by the use of Clozapine, an antidepressant. This causal association between obesity and Clozapine is also understood from a research study by Mayfield et al., (2015) as it explained that antipsychotic medication like Clozapine is associated with weight gain in patients with schizophrenia and managing this metabolic side effect is clinical challenge in psychiatry. As increase in body weight and risk of type 2 diabetes mellitus increases the cardiovascular morbidity and premature death, evaluating effect of a lifestyle modification intervention became necessary.

The validity of Wu et al., (2017) work can be understood if the causal association is consistent in the study result and the special mechanism for it is clearly illustrated. The link between the use of Clozapine and obesity related outcome is understood from the difference in outcome between the study group and the control group. After three and six months, difference in BMI, body weight, waist circumference was found between the control and study group. Decrease in anthropometric measures was seen for the study group after three months and six months, however waist circumference was reduced only after six months. In the area of metabolic analysis like that of triglyceride level to, reduction in level was seen in treatment group compared to control group. Improvements were also found in triglyceride, insulin and IGF-BP3 levels. In contrast, the control group showed no improvement in anthropometric variables. This proves the causal association between exposure and outcome was established.

Causal Association Between Exposure and Outcome

The credibility of an epidemiology study is also understood when the researcher gives proper explanation regarding the mechanism influencing the exposure and outcome of the study. Wu et al., (2017) also explained the rational for taking both physical activity and diet intervention for schizophrenia patients by stating that focusing on diet only can lead to mental and emotional issues in patient who take lower calories. In addition, the selection of 30 minutes brisk walking was beneficial because it was the most risk free exercise which can be easily accepted and done by patients with severe mental illness. The benefits of brisk walking for individuals with schizophrenia is also proved by Browne et al., (2016) as the study explained that walking as a physical activity intervention resulted in improvement in indicators of physical health, mental health, program satisfaction and activity level. The success rate and adherence to the intervention was also explained by Wu et al., (2017) with the discussion that selection of inpatient instead of outpatients promoted high success rate and better interpretation of the result.

Wu et al., (2017) was successful in proving and explaining that exposure to physical activity and diet programs reduced Clozapine related weight gain among patients with schizophrenia. The study result was also compared with other studies which gave different outcome. Although past studies did not gave favorable outcome in reducing Clozapine related weight gain all participants, however the success of the study is clearly understood. Wu et al., (2017) understood the risk associated with only diet control strategies and took the most effective physical activity intervention for schizophrenia patient. Combination of both diet control and brisk walking contributed to desired outcome in treatment group.

The external validity and overall quality of research study is clearly understood by reviewing the discussion section as it give all information related to study finding, reason for specific strategy, consistency with other studies, usefulness of the research and implications for future research. The external validity of the research is high because the reason for success of the intervention in achieving the desired outcome was explicitly explained by the researcher. Firstly, the rational for taking both diet control and physical activity was justified by the researcher due to the risk of emotional issues in patients taking low calories. Combination of both the intervention was beneficial in achieving the purpose of research. The advantage of diet control intervention is that it had positive impact on weight loss, physical activity and quality of life of schizophrenia patient. Some studies had shown calorie restriction did not reduced weight in patient. Positive outcome was found only when behavioral strategies were combined with diet control (Papanastasiou, 2012). Hence, the Wu et al., (2017) move to combine diet control and physical activity program is commendable as it minimized any risk of alternating outcome. 

The credibility of the research work is also understood by the selection of brisk walking as the physical activity intervention. This was the most appropriate and beneficial intervention considering high drop-out rate and poor adherence to other physical activity interventions. For example, the study by Vancampfort et al., (2016) presented the issue of high drop rate in implementing physical activity interventions for people with schizophrenia. The main physical activity interventions investigated in the research study were yoga, 60 minutes brisk walking for 5 weeks, ergometer cycling, aerobic exercise, resistance training and many others (Wu et al., 2017). The high rate of drop-out pointed out to the need for addition resource to promote adherence. It proposed taking strategies like motivational interviewing or rewards to improve drop-out rate. Similarly, Strohacker, Galarraga & Williams, (2014) also focused on improving adherence to the intervention and this was done by using the rewards as a strategy to maintain regular physical exercise routine in participants. Rewards like toilet paper, soap and other things motivated participants to continue with intervention on a regular basis. Research also proves that rewards can improve exercise behavior of patients. The high success rate can also be attributed to selection of inpatient from hospital instead of outpatient. As in patients were taken, all consideration was done to design a physical activity program suitable for the hospital setting.

Wu et al., (2017) mainly focused on analyzing the effect of diet control and physical activity on managing obesity related complication in schizophrenia patient. The success and transferability of the research can be understood if the findings can be easily applied in local and relevant population group. The study was mainly done in Taiwan and the main population of interest was obese schizophrenia patient taking Clozapine. Taiwan is an Asian country and the researcher focused on BMI definition for Asian population. However, no demographic detail of participants was provided like the presence of participants only from Taiwan or other foreign countries. Giving this specification would have given a clear idea regarding the difference in uptake rate of intervention in participating group according to country of origin. However, this limitation can be ignored because the intervention was planned mainly in inpatient setting where following all the intervention was easier in front of supervision staff. Hence, the diet control and physical activity can be applied for both the local and relevant target population group. However, the only consideration for the success of the intervention was that long-term adherence to such program is necessary to improve health of schizophrenia patients. Therefore, to implement this intervention specifically for obese schizophrenia patient taking Clozapine, there is a need to employ strategies to promote adherence to the intervention. This would guarantee success rate in improving health of the target population.

Conclusion

The main purpose of the report was to evaluate the results of the study by Wu et al., (2017) to decide the usefulness of the intervention for application in real setting. The choice of intervention and research design was effective as most appropriate design was chosen to closely evaluate the performance of the intervention. The external validity of the research is also observed by the focus on explaining the causal association between exposure and outcome and considering all the factors that can affect the outcome of the study. Due to this consideration, inpatient participants were taken and program was designed in hospital setting. The only factor that limited the wider application of the study was the presence of certain internal bias such as taking no sampling strategy to determine the correct sample size and presence of certain confounding variable. Despite this, the study outcome is significant and main implication is to plan appropriate strategies to maximize long-term adherence to diet and physical activity intervention to provide benefit to relevant population group in real setting. 

Reference

Browne, J., Penn, D. L., Battaglini, C. L., & Ludwig, K. (2016). Work out by Walking: A Pilot Exercise Program for Individuals With Schizophrenia Spectrum Disorders. The Journal of nervous and mental disease, 204(9), 651-657.

Correll, C. U., Detraux, J., De Lepeleire, J., & De Hert, M. (2015). Effects of antipsychotics, antidepressants and mood stabilizers on risk for physical diseases in people with schizophrenia, depression and bipolar disorder. World Psychiatry, 14(2), 119-136.

Domecq, J. P., Prutsky, G., Leppin, A., Sonbol, M. B., Altayar, O., Undavalli, C., … & Lababidi, M. H. (2015). Drugs commonly associated with weight change: a systematic review and meta-analysis. The Journal of Clinical Endocrinology & Metabolism, 100(2), 363-370.

Elwood, M. (2017). Critical appraisal of epidemiological studies and clinical trials. Oxford University Press.

Farias, E. S., Paula, F., Carvalho, W. R., Gonçalves, E. M., Baldin, A. D., & Guerra-Júnior, G. (2009). Influence of programmed physical activity on body composition among adolescent students. Jornal de Pediatria, 85(1), 28-34.

Gressier, F., Porcelli, S., Calati, R., & Serretti, A. (2016). Pharmacogenetics of clozapine response and induced weight gain: a comprehensive review and meta-analysis. European Neuropsychopharmacology, 26(2), 163-185.

Mayfield, K., Siskind, D., Winckel, K., Hollingworth, S., Kisely, S., & Russell, A. W. (2015). Treatment of clozapine-associated obesity and diabetes with exenatide (CODEX) in adults with schizophrenia: study protocol for a pilot randomised controlled trial. British Journal of Psychiatry Open, 1(1), 67-73.

McCambridge, J., Kypri, K., & Elbourne, D. (2014). In randomization we trust? There are overlooked problems in experimenting with people in behavioral intervention trials. Journal of clinical epidemiology, 67(3), 247-253.

Papanastasiou, E. (2012). Interventions for the metabolic syndrome in schizophrenia: a review. Therapeutic advances in endocrinology and metabolism, 3(5), 141-162.

Skelly, A. C., Dettori, J. R., & Brodt, E. D. (2012). Assessing bias: the importance of considering confounding. Evidence-based spine-care journal, 3(01), 9-12.

Strohacker, K., Galarraga, O., & Williams, D. M. (2014). The impact of incentives on exercise behavior: a systematic review of randomized controlled trials. Annals of Behavioral Medicine, 48(1), 92-99.

Szklo, M., & Nieto, J. (2014). Epidemiology. Jones & Bartlett Publishers.

Vancampfort, D., Rosenbaum, S., Schuch, F. B., Ward, P. B., Probst, M., & Stubbs, B. (2016). Prevalence and predictors of treatment dropout from physical activity interventions in schizophrenia: a meta-analysis. General hospital psychiatry, 39, 15-23.

Wu, M. K., Wang, C. K., Bai, Y. M., Huang, C. Y., & Lee, S. D. (2007). Outcomes of obese, clozapine-treated inpatients with schizophrenia placed on a six-month diet and physical activity program. Psychiatric services, 58(4), 544-550.