As we known , this is the first study to investigated the effects of risperidone on glucose-regulating , lipid metabolism and weight-gain in a large sample size of FEDN patients with schizophrenia. All patients were hospitalized and on a regular diet. This study minimized the impact of course of illness, the history of antipsychotic medication and the impact of an individual's diet. We found that after 10 weeks of risperidone treatment, patients' mean body weight, waist-hip ratio, BMI and waist circumference all increased significantly. This finding in our study was support by Chen et al11 and Ader et al14.By prospective design and OGTT,Chen's study showed that risperidone is associated with increased BMI. However, anotherstudy had shown that risperidone has a relatively small effect on weight among antipsychotic drugs.. Wu et al10 found that among first-episode schizophrenia inpatients in China, clozapine, olanzapine and sulpiride (rather than risperidone) treatment at 8 weeks significantly increased average BMI and WHR . This discrepancy in the two independent study may be that difference of drug treatment duration. Duration of antipsychotic treatment in Wu et al reports was only 8 weeks ,where our study was 10 weeks. We also found weight gain after treatment independently associated with weight in baseline and triglycerides levels at the endpoint, suggest that pre-treatment weight play a key role in weight gain causing by risperidone . The pathophysiological mechanism weight gain is almost completely unknown. Possible receptor related mechanism of weight gain has been attributed to antagonists at histamine H1 receptors15 and 5-HT2C receptors since the genetic variation of 5-HT2C receptor may be related to weight gain16.Our study shows that increase in insulin and HOMA-IR levels reached statistical significance compared with baseline. This is consistent with Wu et al study10,who reported on 29 Chinese inpatients experiencing 8 weeks treatments of risperidone, suggest that inducing abnormalities in the sensitivity of insulin by risperidone. Our finding is partial consistent with that reported by Chen et al .They found that insulin levels was significant higher excepting HOMA-IR level after treatment.
Dyslipidemia is a major side effect of antipsychotics17.In our study, total cholesterol and triglycerides significant increase after 10 week treatment of risperidone. This was consistent with a study conducted by Saddichha S et al18 . They found a statistically increase in triglycerides levels in 6 weeks the risperidone-treated patients with first episode schizophrenia. However, our results was inconsistent with Wu et al report, They did not find statistical significance increasing in total cholesterol and triglycerides levels in first-episode schizophrenia receiving 8 weeks treatments of risperidone. We believe that our study is most consistent with the real situation, because we used a larger sample size and longer duration of drug treatment to observe this effect.
In our study, in the glucose tolerance test after oral risperidone, we did not find significant increases in fasting mean and 2-hour glucose levels.Meanwhile, we also did not find significant difference in the proportion of patients with IGT and IFG pre-treatment and post-treatment. Our results was support by other study. Chen et al report11 showed that the proportion of patients with abnormal blood glucose did not increased as detected by either IGT or IFG after risperidone treatment compared with baseline.Wu et al10 did not find a significant increases in mean fasting glucose levels before and after risperidone treatment. Our current study suggests that risperidone did not affect glucose metabolism or risk factors for diabetes, such as dyslipidemia or decreased physical activity following drug sedation.
Over the past decade, gender differences in antipsychotic responses and adverse reactions have been widely reported19-21. Wang CC et al22 showed that male patients receiving antipsychotic treatment had more newly developed diabetes than female patients. Attux C et al17 reported that but only women patients with first-episode psychosis presented significant waist abnormalities after six-month follow-up. In this study, we found that weight gain, waist-hip ratio and waist circumference elevated higher in male first-episode schizophrenia patients than in female patients after 10-weeks of risperidone treatment, suggesting that risperidone might have more effects on weight gain and abdominal obesity in male schizophrenia patients than in female schizophrenia patients. However, result of our was not consistent with Wu et al study. They did not found significant gender-related difference in all assessment in the risperidone group23. This discrepancy in the two independent study may be that difference of drug treatment duration. Clearly further studies need to be took. Consistent with other studies11,23,no significant gender differences in glucose and lipid metabolic parameters were found in our samples .
Our study has some limitations. First of all, the current study was lifestyle was not evaluate the patient's lifestyle during the experiment period , which is an important factor in the development of glucose and lipid metabolism diseases. Second , we did not rated diet and exercise associated with the reported changes in all subjects. Finally, the 10-week study period is relatively short and may not produce more changes in blood sugar and lipids.
In summary, current research suggests that risperidone is associated with increased insulin, total cholesterol,triglycerides and HOMA-IR levels, increasing in weight, BMI, waist circumference and waist-hip ratio in FEDN Chinese Han patients with schizophrenia. Weight gain, waist-to-hip ratio and waist circumference among patients treated with risperidone had significant gender differences.