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ABSTRACT: OBJECTIVE: The objective of the study was to compare metabolic effects of ziprasidone versus olanzapine treatment in patients with first-episode schizophrenia. METHODS: In this 6-week, multicenter, open-label trial, 260 patients were randomly assigned to receive ziprasidone or olanzapine treatment (130 per group). Primary metabolic measures were changes in weight and body mass index (BMI). Secondary metabolic measures were changes in glucose, insulin, lipids, and blood pressure. Efficacy and safety were also measured additionally. RESULTS: A total number of 230 patients completed the study. The mean daily dosages were 138.2(28.6) mg for ziprasidone and 19.0(2.3) mg for olanzapine. After 6-week treatment, there were significant between-group differences in change scores on weight [4.22(3.49) kg versus -0.84(2.04) kg, p < 0.001] and BMI [1.59(1.37) versus -0.30(0.74), p < 0.001]. In addition, there were significant between-group differences in change scores on fasting plasma glucose, insulin, homeostasis model assessment 2-insulin resistance, low-density lipoprotein, total cholesterol, and triglycerides (p < 0.001); all the changes were clinically in favor of ziprasidone treatment. Both medications were effective in improving schizophrenia symptoms, but the decreases in Positive and Negative Syndrome Scale total scores of the olanzapine group were significantly greater than that of the ziprasidone group (p < 0.05). Compared with olanzapine, ziprasidone also induced more prolonging of corrected QT interval and extrapyramidal side effects (p < 0.05). Both medications were well tolerated, and no serious adverse events were observed in either group. CONCLUSIONS: Compared with olanzapine, ziprasidone treatment was associated with less adverse effects on glucose and lipid metabolism in patients with first-episode schizophrenia.
Psychopharmacologia 08/2012; · 4.08 Impact Factor
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Wen-bin Guo,
Feng Liu,
Jin-dong Chen,
Keming Gao,
Zhi-min Xue,
Xi-jia Xu, Ren-rong Wu,
Chang-lian Tan,
Xue-li Sun,
Zhe-ning Liu,
Hua-fu Chen,
Jing-ping Zhao
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ABSTRACT: Patients with treatment-resistant depression (TRD) and those with treatment-sensitive depression (TSD) responded to antidepressants differently. Previous studies have commonly shown that patients with TRD or TSD had abnormal neural activity in different brain regions. In the present study, we used a coherence-based ReHo (Cohe-ReHo) approach to test the hypothesis that patients with TRD or TSD had abnormal neural activity in different brain regions.
Twenty-three patients with TRD, 22 with TSD, and 19 healthy subjects (HS) matched with gender, age, and education level participated in the study.
ANOVA analysis revealed widespread differences in Cohe-ReHo values among the three groups in different brain regions which included bilateral superior frontal gyrus, bilateral cerebellum, left inferior temporal gyrus, left occipital cortex, and both sides of fusiform gyrus. Compared to HS, lower Cohe-ReHo values were observed in TRD group in bilateral superior frontal gyrus and left cerebellum; in contrast, in TSD group, lower Cohe-ReHo values were mainly found in bilateral superior frontal gyrus. Compared to TSD group, TRD group had lower Cohe-ReHo in bilateral cerebellum and higher Cohe-ReHo in left fusiform gyrus. There was a negative correlation between Cohe-ReHo values of the left fusiform gyrus and illness duration in the pooled patients (r = 0.480, p = 0.001). The sensitivity and specificity of cerebellar Cohe-ReHo values differentiating TRD from TSD were 83% and 86%, respectively.
Compared to healthy controls, both TRD and TSD patients shared the majority of brain regions with abnormal neural activity. However, the lower Cohe-ReHo values in the cerebellum might be as a marker to differentiate TRD from TSD with high sensitivity and specificity.
Journal of psychiatric research 07/2012; 46(10):1366-73. · 3.72 Impact Factor
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ABSTRACT: Abnormalities of the white matter (WM) tracts integrity in brain areas involved in emotional regulation have been postulated in major depressive disorder (MDD). However, there is no diffusion tensor imaging (DTI) study in patients with treatment-responsive MDD at present. DTI scans were performed on 22 patients with treatment-responsive MDD and 19 well-matched healthy subjects. Tract-based spatial statistics (TBSS) approach was employed to analyze the scans. Voxel-wise statistics revealed four brain WM tracts with lower fractional anisotropy (FA) in patients compared to healthy subjects: the bilateral internal capsule, the genu of corpus callosum, the bilateral anterior corona radiata, and the right external capsule. FA values were nowhere higher in patients compared to healthy subjects. Our findings demonstrate that the abnormalities of the WM tracts, major in the projection fibers and corpus callosum, may contribute to the pathogenesis of treatment-responsive MDD.
Neuroscience Letters 06/2012; 522(2):139-44. · 2.11 Impact Factor
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Ren-Rong Wu,
Hua Jin,
Keming Gao,
Elizabeth W Twamley,
Jian-Jun Ou,
Ping Shao,
Juan Wang,
Xiao-Feng Guo,
John M Davis,
Philip K Chan,
Jing-Ping Zhao
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ABSTRACT: Data on the treatment of antipsychotic-induced amenorrhea, particularly when occurring with weight gain, are limited. The authors investigated the efficacy and safety of metformin in the treatment of antipsychotic-induced amenorrhea and weight gain in women with first-episode schizophrenia.
Eighty-four women (ages 18-40 years) with first-episode schizophrenia who suffered from amenorrhea during antipsychotic treatment were randomly assigned, in a double-blind study design, to receive 1000 mg/day of metformin or placebo in addition to their antipsychotic treatment for 6 months. The primary outcome measures were restoration of menstruation and change in body weight and body mass index (BMI). Secondary outcome measures were changes in levels of prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, and testosterone; in fasting levels of insulin and glucose; in LH/FSH ratio; and in insulin resistance index. Repeated mixed models with repeated-measures regression analyses and binary logistic regression were used in the analysis.
A total of 76 patients completed the 6-month trial. Significantly more patients in the metformin group (N=28, 66.7%) than in placebo group (N=2, 4.8%) resumed their menstruation. Among patients treated with metformin, BMI decreased by a mean of 0.93 and the insulin resistance index by 2.04. In contrast, patients who received placebo had a mean increase in BMI of 0.85. The prolactin, LH, and testosterone levels and LH/FSH ratio decreased significantly in the metformin group at months 2, 4, and 6, but these levels did not change in the placebo group.
Metformin was effective in reversing antipsychotic-induced adverse events, including restoration of menstruation, promotion of weight loss, and improvement in insulin resistance in female patients with schizophrenia.
American Journal of Psychiatry 06/2012; 169(8):813-21. · 12.54 Impact Factor
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Wen-bin Guo,
Feng Liu,
Zhi-min Xue,
Xi-jia Xu, Ren-rong Wu,
Chao-qiong Ma,
Sarah C Wooderson,
Chang-lian Tan,
Xue-li Sun,
Jin-dong Chen,
Zhe-ning Liu,
Chang-qing Xiao,
Hua-fu Chen,
Jing-ping Zhao
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ABSTRACT: Patients with treatment-resistant depression (TRD) and those with treatment-response depression (TSD) respond to antidepressants differently and previous studies have commonly reported different brain networks in resistant and nonresistant patients. Using the amplitude of low-frequency fluctuations (ALFF) approach, we explored ALFF values of the brain regions in TRD and TSD patients at resting state to test the hypothesis of the different brain networks in TRD and TSD patients.
Eighteen TRD patients, 17 TSD patients and 17 gender-, age-, and education-matched healthy subjects participated in the resting-state fMRI scans.
There are widespread differences in ALFF values among TRD patients, TSD patients and healthy subjects throughout the cerebellum, the visual recognition circuit (middle temporal gyrus, middle/inferior occipital gyrus and fusiform), the hate circuit (putamen), the default circuit (ACC and medial frontal gyrus) and the risk/action circuit (inferior frontal gyrus). The differences in brain circuits between the TRD and TSD patients are mainly in the cerebellum, the visual recognition circuit and the default circuit.
The affected brain circuits of TRD patients might be partly different from those of TSD patients.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 04/2012; 37(1):153-60. · 3.25 Impact Factor
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Wen-bin Guo,
Feng Liu,
Jin-dong Chen,
Xi-jia Xu, Ren-rong Wu,
Chao-qiong Ma,
Keming Gao,
Chang-lian Tan,
Xue-li Sun,
Chang-qing Xiao,
Hua-fu Chen,
Jing-ping Zhao
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ABSTRACT: The association between alterations of the white matter (WM) integrity in brain regions and mood dysregulation has been reported in major depressive disorder (MDD). However, there has never been a neuroimaging study in patients who have treatment-resistant depression (TRD) and are in a current treatment-resistant state. In the present study, we used diffusion tensor imaging (DTI) with tract-based spatial statistics (TBSS) method to investigate the WM integrity of different brain regions in patients who had TRD and were in a current treatment-resistant state.
Twenty-three patients with TRD and Hamilton Rating Scale total score of ≥18 and 19 healthy controls matched with age, gender, and education level to patients were scanned with DTI. Thirty 4 mm thick, no gap, contiguous axial slices were acquired and fractional anisotropy (FA) images were generated for each participant. An automated TBSS approach was used to analyze the data.
Voxel-wise statistics revealed that patients with TRD had lower FA values in the right anterior limb of internal capsule, the body of corpus callosum, and bilateral external capsule compared to healthy subjects. Patients with TRD did not have increased FA values in any brain regions compared to healthy subjects. There was no correlation between the FA values in any brain region and patients' demographics and the severity of illness.
Our findings suggest the abnormalities of the WM integrity of neuronal tracts connecting cortical and subcortical nuclei and two brain hemispheres may play a key role in the pathogenesis of TRD.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 04/2012; 38(2):201-6. · 3.25 Impact Factor
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ABSTRACT: Using a newly developed regional homogeneity (ReHo) approach, we were to explore the features of brain activity in patients with treatment-resistant depression (TRD) in resting state, and further to examine the relationship between abnormal brain activity in TRD patients and specific symptom factors derived from ratings on the Hamilton Rating Scale for Depression (HRSD).
24 patients with TRD and 19 gender-, age-, and education-matched healthy subjects participated in the fMRI scans.
1. Compared with healthy controls, decreased ReHo were found in TRD patients in the left insula, superior temporal gyrus, inferior frontal gyrus, lingual gyrus and cerebellumanterior lobe (culmen) (p<0.05, corrected). 2. Compared with healthy controls, increased ReHo were found in the left superior temporal gyrus, cerebellum posterior lobe (tuber), cerebellum anterior lobe (culmen), the right cerebellar tonsil and bilateral fusiform gyrus (p<0.05, corrected). 3. There was no correlation between the ReHo values in any brain region detected in our study and the patients' age, years of education, illness duration, HRSD total score and its symptom factors.
The influence of antidepressants to the brain activity in TRD patients was not fully eliminated.
The pathogenesis of TRD may be attributed to abnormal neural activity in multiple brain regions.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 02/2011; 35(5):1297-302. · 3.25 Impact Factor
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Jian-Jun Ou,
Guang-Lei Xun, Ren-Rong Wu,
Le-Hua Li,
Mao-Sheng Fang,
Hong-Geng Zhang,
Shi-Ping Xie,
Jian-Guo Shi,
Bo Du,
Xue-Qin Yuan,
Jing-Ping Zhao
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ABSTRACT: S-citalopram (escitalopram) is the very active moiety of citalopram. It has been shown in many studies to be an effective and safe antidepressant for treating major depressive disorder (MDD).
The aim of our study was to compare the efficacy and safety of escitalopram vs citalopram in Chinese MDD patients.
In the double-blind study, 240 MDD patients were randomly assigned to treatment for 6 weeks either with escitalopram (10-20 mg/d) or citalopram (20-40 mg/d). The primary efficacy measurement was the change of 17-item Hamilton Depression Rating Scale (HAMD-17) total score from baseline to the end of study. The secondary efficacy measurements were response and remission rates. The adverse events (AEs) were recorded by the investigator.
Two hundred and three (85%) patients completed the trial. The average dose was 13.9 mg/d in the escitalopram group and 27.6 mg/d in the citalopram group. No significant differences were found between the two groups in the change in HAMD-17 total score, response, and remission rate. These results were similar in severe MDD patients. No significant differences were found between the two groups in AEs. No serious AEs were observed in this study.
The study suggests that escitalopram 10-20 mg/d are as effective and safe as citalopram 20-40 mg/d in the short-term treatment for Chinese MDD patients.
Psychopharmacologia 03/2010; 213(2-3):639-46. · 4.08 Impact Factor
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ABSTRACT: To determine whether antipsychotic agent-induced weight gain was associated with 5-hydroxytryptamine 2C receptor (HTR2C) gene-759C/T and -697G/C polymorphisms.
A case-matching controlled study was done. Eighty-five patients who had gained more than 7% of their pre-drug body weight served as a study group, and 85 patients who had gained less than 7% of their pre-drug body weight served as a control group. The control group were matched with the study group in the kinds of antipsychotic agents and the course of antipsychotic treatment. The ligation diction reaction technique was used to analyse the frequencies of HTR2C gene-759C/T and -697G/C polymorphisms.
The study group were more likely to be hemizygous for the -759C (for male) and the -759CC genotype (for female) than the control group. The study group were more likely to be hemizygous for the -697G (for male) and the -697CG/GG genotype (for female) (all P<0.05) than the control group.
The -759C/T and -697G/C polymorphisms of the promoter region of HTR2C gene may be associated with antipsychotic agent-induced weight gain.
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 04/2008; 33(4):312-5.
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ABSTRACT: The purpose of this study was to assess the efficacy of metformin in preventing olanzapine-induced weight gain.
Forty patients with schizophrenia were randomly assigned to treatment for 12 weeks with olanzapine, 15 mg/day, plus metformin, 750 mg/day (N=20), or olanzapine, 15 mg/day, plus placebo (N=20). This investigation was conducted in a double-blind fashion. Planned assessments included body weight, body mass index, proportion of patients who gained more than 7% of their baseline weight at the end of the 12-week treatment, waist circumference, waist-to-hip ratio, fasting glucose and insulin, insulin resistance index, and scores on the Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS).
Of the 40 patients who were randomly assigned, 37 (92.5%) completed treatments. The weight, body mass index, waist circumference, and waist-to-hip ratio levels increased less in the olanzapine plus metformin group relative to the olanzapine plus placebo group during the 12-week follow-up period. The insulin and insulin resistance index values of the olanzapine plus placebo group increased significantly at weeks 8 and 12. In contrast, the insulin and insulin resistance index levels of the olanzapine plus metformin group remained unchanged. Significantly fewer patients in the olanzapine plus metformin group relative to patients in the olanzapine plus placebo group increased their baseline weight by more than 7%, which was the cutoff for clinically meaningful weight gain. There was a significant decrease in SAPS and SANS scores within each group from baseline to week 12, with no between-group differences. Metformin was tolerated well by all patients.
Metformin was effective and safe in attenuating olanzapine-induced weight gain and insulin resistance in drug-naive first-episode schizophrenia patients. Patients displayed good adherence to this type of preventive intervention.
American Journal of Psychiatry 04/2008; 165(3):352-8. · 12.54 Impact Factor
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ABSTRACT: Weight gain, a common adverse effect of antipsychotic medications, is associated with medical comorbidities in psychiatric patients.
To test the efficacy of lifestyle intervention and metformin alone and in combination for antipsychotic-induced weight gain and abnormalities in insulin sensitivity.
A randomized controlled trial (October 2004-December 2006) involving 128 adult patients with schizophrenia in the Mental Health Institute of the Second Xiangya Hospital, Central South University, China. Participants who gained more than 10% of their predrug weight were assigned to 1 of 4 treatment groups.
Patients continued their antipsychotic medication and were randomly assigned to 12 weeks of placebo, 750 mg/d of metformin alone, 750 mg/d of metformin and lifestyle intervention, or lifestyle intervention only.
Body mass index, waist circumference, insulin levels, and insulin resistance index.
All 128 first-episode schizophrenia patients maintained relatively stable psychiatric improvement. The lifestyle-plus-metformin group had mean decreases in body mass index (BMI) of 1.8 (95% confidence interval [CI], 1.3-2.3), insulin resistance index of 3.6 (95% CI, 2.7-4.5), and waist circumference of 2.0 cm (95% CI, 1.5-2.4 cm). The metformin-alone group had mean decreases in BMI of 1.2 (95% CI, 0.9-1.5), insulin resistance index of 3.5 (95% CI, 2.7-4.4), and waist circumference of 1.3 cm (95% CI, 1.1-1.5 cm). The lifestyle-plus-placebo group had mean decreases in BMI of 0.5 (95% CI, 0.3-0.8) and insulin resistance index of 1.0 (95% CI, 0.5-1.5). However, the placebo group had mean increases in BMI of 1.2 (95% CI, 0.9-1.5), insulin resistance index of 0.4 (95% CI, 0.1-0.7), and waist circumference of 2.2 cm (95% CI, 1.7-2.8 cm). The lifestyle-plus-metformin treatment was significantly superior to metformin alone and to lifestyle plus placebo for weight, BMI, and waist circumference reduction.
Lifestyle intervention and metformin alone and in combination demonstrated efficacy for antipsychotic-induced weight gain. Lifestyle intervention plus metformin showed the best effect on weight loss. Metformin alone was more effective in weight loss and improving insulin sensitivity than lifestyle intervention alone. Trial Registration clinicaltrials.gov Identifier: NCT00451399.
JAMA The Journal of the American Medical Association 02/2008; 299(2):185-93. · 30.03 Impact Factor
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ABSTRACT: The present study was to investigate the sex difference in effects of clozapine, olanzapine, risperidone, and sulpiride on glucose and lipid metabolism in first-episode schizophrenia.
One hundred twelve patients with schizophrenia were assigned randomly to receive clozapine, olanzapine, risperidone, or sulpiride for 8 weeks. Planned assessments included body mass index, waist-hip ratio, fasting glucose, insulin, C-peptide, insulin resistance index (IRI), cholesterol and triglyceride levels. All measures were collected at baseline and at the end of the 8-week treatment.
After treatment, waist-hip ratio and triglyceride and IRI levels of men were increased higher than that of women in clozapine and olanzapine groups. In sulpiride group, body mass index and triglyceride, insulin, and IRI levels of women increased higher than those of men. There was no significant sex difference for all assessments in risperidone group. Insulin, C-peptide, and IRI, but not fasting glucose levels, were significantly increased in the 4 groups. Cholesterol and triglyceride levels were significantly increased in the clozapine and olanzapine groups. Patients treated with clozapine and olanzapine had higher fasting insulin, C-peptide, and IRI levels than those treated with risperidone and sulpiride.
These results suggest that clozapine, olanzapine, and sulpiride had effects on glucose and lipid metabolism in first-episode schizophrenia with sex difference. Clozapine and olanzapine seem to have the greatest potential to induce glucose and lipid metabolism abnormalities, and risperidone has the least.
Journal of Clinical Psychopharmacology 09/2007; 27(4):374-9. · 4.10 Impact Factor
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ABSTRACT: Glucose and lipid metabolism dysfunction is a significant side effect associated with antipsychotics. Although there are many studies about the linkages between drugs and metabolic dysfunction, most of these studies have compared the effects of two antipsychotics on only one metabolic measure: either glucose or lipid metabolism.
The present study aimed to investigate the effects of clozapine, olanzapine, risperidone, and sulpiride on glucose and lipid metabolism in first-episode schizophrenia.
One hundred twelve schizophrenics were assigned randomly to receive clozapine, olanzapine, risperidone, or sulpiride for 8 weeks. Planned assessments included body mass index (BMI), waist-to-hip ratio, fasting glucose, insulin, C-peptide, insulin resistance index (IRI), cholesterol, and triglyceride. All measures were collected at baseline and at the end of the 8-week treatment.
After treatment, insulin, C-peptide, and IRI were significantly increased in the four groups, but not fasting glucose levels. Cholesterol and triglyceride levels were significantly increased in the clozapine and olanzapine groups. Patients treated with clozapine and olanzapine had higher fasting insulin, C-peptide, and IRI levels than those treated with risperidone and sulpiride. Among the four antipsychotics, the increases of mean BMI from high to low were as follows: clozapine, olanzapine, sulpiride, and risperidone.
This study confirmed that the four antipsychotic drugs were associated with an increase of insulin, C-peptide, and IRI. It was found that clozapine and olanzapine were associated with an increase in cholesterol and triglyceride levels. The effects of clozapine and olanzapine on the glucose and lipid metabolism outweighed those of risperidone and sulpiride.
Psychopharmacologia 08/2006; 186(4):572-8. · 4.08 Impact Factor
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ABSTRACT: Context
Weight gain, a common adverse effect of antipsychotic medications,
is associated with medical comorbidities in psychiatric patients.Objective
To test the efficacy of lifestyle intervention and metformin alone and in combination for antipsychotic-induced weight gain and abnormalities in insulin sensitivity.Design, Setting, and Patients
A randomized controlled trial (October 2004-December 2006) involving 128 adult patients with schizophrenia in the Mental Health Institute of the Second Xiangya Hospital, Central South University, China. Participants who gained more than 10% of their predrug weight were assigned to 1 of 4 treatment groups.Interventions
Patients continued their antipsychotic medication and were randomly assigned to 12 weeks of placebo, 750 mg/d of metformin alone, 750
mg/d of metformin and lifestyle intervention, or lifestyle intervention only.Main Outcome Measures
Body mass index, waist circumference, insulin levels, and insulin resistance index.Results
All 128 first-episode schizophrenia patients maintained relatively stable psychiatric improvement. The lifestyle-plus-metformin group had mean decreases in body mass index (BMI) of 1.8 (95% confidence interval [CI], 1.3-2.3), insulin resistance index of 3.6 (95% CI,
2.7-4.5), and waist circumference of 2.0 cm (95% CI, 1.5-2.4 cm).
The metformin-alone group had mean decreases in BMI of 1.2 (95% CI,
0.9-1.5), insulin resistance index of 3.5 (95% CI, 2.7-4.4), and waist circumference of 1.3 cm (95% CI, 1.1-1.5 cm). The lifestyle-plus-placebo group had mean decreases in BMI of 0.5 (95% CI, 0.3-0.8) and insulin resistance index of 1.0 (95% CI, 0.5-1.5). However, the placebo group had mean increases in BMI of 1.2 (95% CI, 0.9-1.5), insulin resistance index of 0.4 (95% CI, 0.1-0.7), and waist circumference of 2.2 cm (95% CI, 1.7-2.8 cm). The lifestyle-plus-metformin treatment was significantly superior to metformin alone and to lifestyle plus placebo for weight,
BMI, and waist circumference reduction.Conclusions
Lifestyle intervention and metformin alone and in combination demonstrated efficacy for antipsychotic-induced weight gain. Lifestyle intervention plus metformin showed the best effect on weight loss.
Metformin alone was more effective in weight loss and improving insulin sensitivity than lifestyle intervention alone.Trial Registration
clinicaltrials.gov Identifier: NCT00451399
Since their introduction, atypical antipsychotic (AAP) medications have been used increasingly for the management of patients with a variety of psychotic disorders and severe behavioral disturbances.
In the past decade, there has been a growing concern among clinicians and researchers that use of AAP medications may be related to potentially serious adverse metabolic effects, including weight gain, hyperlipidemia,
and glucose intolerance.1- 5
The induction of obesity by antipsychotic agents has been documented since the introduction of chlorpromazine in the mid-1950s.6 According to a recent study, 78.8% of patients receiving antipsychotic agents increased their baseline weight by more than 7%.7 Clinical studies indicate that AAP medications may have a greater potential for inducing weight gain than conventional antipsychotic medications and vary in their propensity to induce weight gain. Clozapine and olanzapine produce the most weight gain, quetiapine and risperidone produce intermediate weight gain, and ziprasidone and aripiprazole produce the least weight gain.8- 12
This antipsychotic-related adverse effect has lately become a major concern in the treatment of psychosis because weight gain not only influences adherence with drug treatment but also is associated with substantial medical morbidity and mortality.13 Recent studies14- 15 suggest that people with severe mental illness die up to 3 decades earlier than the general population. Heart disease is a leading cause of death in these patients.
One of the major risk factors for heart disease and early death in these patients is weight gain.
The mechanism underlying weight gain resulting from antipsychotic drugs has not been fully understood, although it might be associated with central histamine H1 antagonism and increased appetite or with direct impairment of metabolic regulation and alteration of insulin sensitivity.16- 17 A combination of genetic, environmental, and lifestyle factors could likely play a role in the high rate of weight gain and metabolic dysregulation in patients taking antipsychotics.
Lifestyle intervention has demonstrated efficacy for weight loss in obese persons and has been shown to prevent or delay the development of type 2 diabetes by 40% to 60% in different populations in controlled studies.18- 19 In patients with schizophrenia, several lifestyle interventions have been used to reduce obesity or to prevent weight gain induced by AAP medications.20- 23 Preliminary evidence has suggested that behavioral interventions are effective in weight gain control for patients who had weight gain induced by antipsychotics.7,24
Metformin, which inhibits hepatic glucose production, is well tolerated and prevents continual weight gain while it decreases measures of insulin resistance. Some studies find that metformin can reduce body weight in patients with type 2 diabetes and in obese individuals who do not have diabetes.25- 26 Metformin can also reduce weight gain induced by antipsychotic agents.27- 28 However, Baptista et al29 reported that metformin did not improve weight gain induced by antipsychotic agents.
To our knowledge, no double-blind, placebo-controlled studies have directly compared lifestyle intervention and metformin alone or in combination for weight gain induced by antipsychotic medications among patients with schizophrenia. In this article, we report on a 12-week randomized, double-blind, placebo-controlled trial that tested the efficacy of lifestyle intervention and metformin alone and in combination to reduce weight gain and abnormalities of insulin sensitivity induced by antipsychotic medications in patients with schizophrenia.
JAMA The Journal of the American Medical Association 299(2):185-193. · 30.03 Impact Factor
