Treatment Of Antipsychotic-induced Weight Gain Research Articles

The Optimal Dosage and Duration of Metformin for Prevention and Treatment of Antipsychotic-Induced Weight Gain: An Updated Systematic Review and Meta-Analysis.

Weight gain and metabolic complications are substantial adverse effects associated with second-generation antipsychotics. However, comprehensive guidelines for managing antipsychotic-induced weight gain are lacking. This review included all double-blind, placebo-controlled studies investigating metformin's effectiveness in addressing antipsychotic-related weight gain. We systematically searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, Google Scholar, and ClinicalTrials.gov for relevant studies from the inception to 2024. A random-effects model was used for the meta-analysis. This meta-analysis, including 20 studies with 1070 patients, revealed that metformin significantly surpassed placebo in attenuating weight gain in patients receiving antipsychotics. The mean weight change with metformin was -3.32kg [95% confidence interval (CI): -4.57 to -2.07]. Additionally, metformin use resulted in a marked decrease in body mass index [-1.24kg/m2 (95% CI: -1.70 to -0.77)]. Metformin could maintain the effects from 12 to 24 weeks. This updated meta-analysis investigated the durations and dosages of metformin use in patients with schizophrenia experiencing antipsychotic-induced weight gain. The findings highlight the need for additional large-scale research to validate our findings.

Orlistat for the treatment of antipsychotic-induced weight gain: an eight-week multicenter, randomized, placebo-controlled, double-blind trial

BackgroundWeight gain and metabolic disorders are commonly induced by antipsychotics. Orlistat is a lipase inhibitor used for weight control. The effect of orlistat on weight gain and metabolic disturbances in people (especially women) treated with antipsychotics has not been sufficiently studied. This study aimed to investigate the efficacy of orlistat in mitigating antipsychotic-induced weight gain and abnormal glycolipid metabolism.MethodsPatients with schizophrenia or bipolar disorder with a weight gain ≥ 7% after taking antipsychotics were recruited. Participants were randomly allocated to two groups: one received eight weeks of orlistat (360 mg/day) and the other received a placebo. Anthropometric and fasting serum biochemical parameters were measured at baseline, week 4 and week 8.ResultsSixty individuals (orlistat:placebo = 32:28) participated in the study. After controlling for the study center, the eight-week changes in body mass index (BMI), cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-CH) and low-density lipoprotein cholesterol (LDL-CH) were significantly different between the groups. According to the mixed linear models, CHOL and LDL-CH were significantly lower in the orlistat group than in the control group at week 8. The week 0-to-8 slopes of BMI, CHOL and LDL-CH were also significantly lower in the orlistat group.ConclusionsThese findings suggested that orlistat is an effective intervention for attenuating weight gain and serum lipid disturbances in antipsychotic-treated patients.Trial registrationClinicalTrials.gov NCT03451734.

Brief Report: Metformin for Antipsychotic-Induced Weight Gain in Youth with Autism Spectrum Disorder.

Antipsychotic treatment in youth with autism spectrum disorder (ASD) is becoming increasingly common, placing individuals at risk for antipsychotic-induced weight gain and associated complications. Metformin hydrochloride, a biguanide medication FDA-approved for treatment of type-2 diabetes in youth, may hold promise for treatment of antipsychotic-induced weight gain in youth with ASD. In this report we assess the long-term impact of metformin on antipsychotic-associated weight gain in a naturalistic sample of 53 youth with ASD. Results indicate that treatment with metformin stabilized BMI z-score over a nearly 2year mean treatment period. Further work is indicated to determine the safety and efficacy of metformin treatment in youth with ASD, as well as predictors of response as a treatment for antipsychotic-induced weight gain.

Metformin for treatment of antipsychotic-induced weight gain in a South Asian population with schizophrenia or schizoaffective disorder: A double blind, randomized, placebo controlled study.

Antipsychotic-induced weight gain causes serious health problems. We investigated the efficacy and safety of metformin in treating antipsychotic-induced weight gain in South Asian patients. Sixty six adult patients with schizophrenia or schizoaffective disorder treated, with atypical antipsychotics, and who had increased by more than 10% their pre treatment body weight, were randomly assigned to receive metformin or placebo in a double-blind study. Patients received usual treatment and metformin 500 mg or placebo twice daily for 24 weeks. The primary outcome measure was change in body weight from baseline to week 24. Linear mixed models were used in the analysis. Mean change in body weight in the metformin group was -1.56 kg (95% CI=-3.06 to -0.05) and 1.0 kg (95% CI=0.03-1.97) in the placebo group. Between-group difference was 2.56 kg. At 24 weeks the between-group difference showed significant time-by-treatment interaction (F=3.23, p=0.004). Between-group difference in BMI showed significant time-by-treatment interaction (F=3.41 p=0.03). There was no significant difference in waist-hip ratio or fasting blood sugar. Metformin is effective in reducing weight in South Asian patients with schizophrenia or schizoaffective disorder who had increased their body by more than 10% after treatment with atypical antipsychotics.

Sibutramine in the treatment of antipsychotic-induced weight gain

Weight gain represents a frequent side effect of antipsychotic drug treatment. The current trial investigated the effect of add-on treatment with sibutramine in schizophrenia outpatients who had gained more than 7% of weight during the course of treatment. This 24-week placebo-controlled study evaluated the effects of sibutramine added to ongoing antipsychotic treatment. Weight, waist-hip ratio, BMI, blood pressure/pulse and ECG were monitored regularly. In addition, several laboratory tests were performed. Psychopathological symptoms and side effects were assessed frequently. Fifteen patients were assigned randomly to add-on treatment with sibutramine 10 mg or placebo. The two groups did not differ in weight, sociodemographic, or clinical data. Eleven patients were considered for statistical analysis. Significant weight loss was observed in the sibutramine group (mean = -6.1 kg), whereas patients on placebo experienced a mean weight gain of 1.9 kg. A reduction in HbA1c was apparent in the sibutramine but not in the placebo group. No significant between-group differences were found in changes in psychopathology or drug safety. This pilot trial suggests that adjunctive treatment with sibutramine may be safe and effective in schizophrenic patients with antipsychotic-induced weight gain.

Metformin: Prevention and Treatment of Antipsychotic-Induced Weight Gain

This Hospital Pharmacy feature is extracted from Off-Label Drug Facts, a publication available from Wolters Kluwer Health. Off-Label Drug Facts is a practitioner-oriented resource for information about specific drug uses that are unapproved by the US Food and Drug Administration. This new guide to the literature enables the health care professional or clinician to quickly identify published studies on off-label uses and determine if a specific use is rational in a patient care scenario. References direct the reader to the full literature for more comprehensive information before patient care decisions are made. Direct questions or comments regarding Off-Label Drug Uses to jgeneral@ku.edu.

Metformin for treatment of antipsychotic-induced weight gain: A randomized, placebo-controlled study

ObjectivesTo evaluate the efficacy of metformin for treatment of antipsychotic-induced weight gain. MethodsSeventy-two patients with first-episode schizophrenia who gained more than 7% of their predrug weight were randomly assigned to receive 1000mg/d of metformin or placebo in addition to their ongoing treatment for 12weeks using a double-blind study design. The primary outcome was change in body weight. The secondary outcomes included changes in body mass index, fasting glucose and insulin, and insulin resistance index. ResultsOf the 72 patients who were randomly assigned, 66 (91.6%) completed treatments. The body weight, body mass index, fasting insulin and insulin resistance index decreased significantly in the metformin group, but increased in the placebo group during the 12-week follow-up period. Significantly more patients in the metformin group lost their baseline weight by more than 7%, which was the cutoff for clinically meaningful weight loss. Metformin was tolerated well by majority patients. ConclusionMetformin was effective and safe in attenuating antipsychotic-induced weight gain and insulin resistance in first-episode schizophrenia patients. Patients displayed good adherence to metformin.

Contingency Management for the Treatment of Antipsychotic-Induced Weight Gain: A Randomized Controlled Pilot Study

Objective: Weight gain is common for individuals with serious mental illness (SMI) receiving antipsychotic drug therapy. Contingency management (CM) is a behavioral intervention that rewards positive performance and has demonstrated effectiveness in reducing drug use in SMI populations. This study evaluated the feasibility of using CM to promote weight loss in individuals with SMI over 8 weeks. Method: 30 individuals (BMI ≥ 28 kg/m²) were randomized to one of three conditions: i) The combination of a standardized lifestyle modification (LM) program for individuals with SMI and payment for group attendance (CM_attendance), ii) The combination of LM and payment for weight loss (CM_weight), and iii) waitlist control (CON). After the waitlist period, those participants joined a LM group and received payment for behavioral change (CM_behavior). Results: Subjects in the CM_attendance and in the CM_weight group lost a mean of 1.16 kg and 1.23 kg, respectively, while subjects in the CON gained a mean of 0.68 kg. Subjects receiving CM_behavior, lost a mean of 2.54 kg, which was a significant weight loss compared to the control period. Conclusion: LM supplemented with CM may facilitate weight loss in patients taking antipsychotic medications; financial reimbursement for behavioral change may be particularly effective in this population.

Ask the Expert: Schizophrenia

Ask the Expert: Schizophrenia

Efficacy of Metformin and Topiramate in Prevention and Treatment of Second-Generation Antipsychotic–Induced Weight Gain

To review the literature describing the efficacy of metformin and topiramate for the treatment of second-generation antipsychotic-induced weight gain. Articles were identified by searching the MEDLINE database (from 1949 through January 2010) using the key words metformin, topiramate, antipsychotic, weight, weight gain, and obesity. All randomized, placebo-controlled trials of metformin and topiramate were selected for review. Weight gain due to second-generation antipsychotic use is a concern due to the risk of long-term metabolic and cardiovascular effects with these agents. These effects include obesity, hyperglycemia, and insulin resistance, all of which may contribute to diabetes and cardiovascular disease. Second-generation antipsychotics vary in the degree to which they cause weight gain, and dietary and lifestyle changes may not be feasible or sufficient in counter-acting this weight gain. Although other pharmacologic agents may be beneficial to prevent and treat antipsychotic-induced weight gain, metformin and topiramate have been the most extensively studied in this setting. Metformin acts peripherally to cause weight loss, while topiramate acts centrally. Review of 11 randomized, controlled trials demonstrates beneficial effects of metformin and topiramate in prevention and treatment of weight gain. Metformin is generally well tolerated and has been studied in pediatric patients, while topiramate is associated with more drug interactions and may possibly interfere with control of schizophrenia. Data for the use of metformin and topiramate in the treatment and prevention of second-generation antipsychotic-induced weight gain are limited. Both may be effective in helping patients lose weight via mechanisms that have yet to be clearly defined. The use of metformin results in greater weight loss than topiramate, and topiramate is associated with more risks and may compromise the treatment of schizophrenia. Treatment of antipsychotic-induced weight gain with metformin may be an option after lifestyle and dietary changes have failed.

Metformin plus a lifestyle intervention was more effective than either alone for antipsychotic-induced weight gain

ACP Journal Club19 August 2008Metformin plus a lifestyle intervention was more effective than either alone for antipsychotic-induced weight gainFrancisco J. Vaz-Leal, MD, PhDFrancisco J. Vaz-Leal, MD, PhDUniversity of Extremadura Medical School and, University Hospital Network, Badajoz, Spain (F.J.V.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-149-4-200808190-02005 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationWu RR, Zhao JP, Jin H, et al. Lifestyle intervention and metformin for treatment of antipsychotic-induced weight gain: a randomized controlled trial. JAMA. 2008;299:185-93. https://pubmed.ncbi.nlm.nih.gov/18182600Clinical Impact RatingsGIM/FP/GP: Mental Health: Endocrinology: Reference1 Shiloh R, Weizman A, Stryjer R, Nutt D. Atlas of Psychiatric Pharmacotherapy. 2nd edition. Abingdon, UK: Taylor & Francis; 2006. Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Extremadura Medical School and, University Hospital Network, Badajoz, Spain (F.J.V.)This article was published at Annals.org on 5 August 2008. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 August 2008Volume 149, Issue 4Page: JC2-5KeywordsAntipsychoticsBody mass indexExerciseInsulinInsulin resistancePatientsSafetySchizophreniaSubstance abuseWeight gain ePublished: 19 August 2008 Issue Published: 19 August 2008 Copyright & PermissionsCopyright © 2008 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...

Lifestyle Intervention and Metformin for Treatment of Antipsychotic-Induced Weight Gain

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.

Lifestyle Intervention and Metformin for Treatment of Antipsychotic-Induced Weight Gain: A Randomized Controlled Trial

Lifestyle Intervention and Metformin for Treatment of Antipsychotic-Induced Weight Gain: A Randomized Controlled Trial

Atypical antipsychotics and weight gain.

This article reviews what is known about weight gain associated with the use of atypical antipsychotics and focuses on relative liability for weight gain with the different agents, correlates of weight gain, putative mechanisms, and management strategies. Data on weight gain from short- and long-term studies with the different atypical antipsychotics are presented. A number of sociodemographic variables--including patient age, ethnicity, and baseline weight--that may have a correlation with weight gain with atypical antipsychotics are considered. Mechanisms that may be involved in antipsychotic-induced weight gain are discussed, including the role of monoamine activity, histamine antagonism, muscarinic receptors, reproductive hormones, other neurotransmitters, insulin, neuropeptides, cytokines, uncoupling proteins, the peroxisome proliferator-activated receptor, and genetic factors. Treatment of antipsychotic-induced weight gain involves the use of exercise and nutritional counseling as well as pharmacological strategies.

Weight gain with risperidone among patients with mental retardation: effect of calorie restriction.

The atypical antipsychotics cause weight gain, which is poorly understood in terms of its mechanism and treatment. A usual recommendation for treatment of antipsychotic-induced weight gain includes calorie restriction and exercise. The authors describe their recent clinical experience with calorie restriction in adults with mental retardation treated with risperidone. A retrospective chart review was performed on the records of 50 adult patients with mental retardation treated with risperidone while residing at a habilitation center. We assessed dose and duration of risperidone treatment, weight, changes in calorie intake, and frequency of aggressive behavior. Of the 50 patients, 39 had adequate data for analysis. Thirty-seven of the 39 patients gained weight with a mean of 18.8 lb (8.3 kg) over about 2 years. Twenty of the 37 patients were calorie restricted. Three of the 20 calorie-restricted patients lost weight at a rate of 0.2 lb (0.1 kg) per month. The other 17 calorie-restricted patients and the 17 patients who were not calorie restricted continued to gain weight at a rate of 0.8 lb (0.4 kg) per month over about another 2 years of treatment. The amount of weight gain was not dose related. Calorie restriction led to no deterioration in behavior. The current investigation lends support to data that note weight gain with risperidone in adults with mental retardation. It suggests that calorie restriction does not lead to weight loss or behavioral deterioration and that weight gain is not dose related.