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Adjunctive metformin for antipsychotic-induced dyslipidemia: a meta-analysis of randomized, double-blind, placebo-controlled trials.

ABSTRACT: Antipsychotic-induced dyslipidemia could increase the risk of cardiovascular diseases. This is a meta-analysis of randomized double-blind placebo-controlled trials to examine the efficacy and safety of adjunctive metformin for dyslipidemia induced by antipsychotics in schizophrenia. The standardized mean differences (SMDs) and risk ratios (RRs) with their 95% confidence intervals (CIs) were calculated using the random-effects model with the RevMan 5.3 version software. The primary outcome was the change of serum lipid level. Twelve studies with 1215 schizophrenia patients (592 in metformin group and 623 in placebo group) were included and analyzed. Adjunctive metformin was significantly superior to placebo with regards to low density lipoprotein cholesterol (LDL-C) [SMD: -0.37 (95%CI:-0.69, -0.05), P?=?0.02; I²?=?78%], total cholesterol [SMD: -0.47 (95%CI:-0.66, -0.29), P?2?=?49%], triglyceride [SMD: -0.33 (95%CI:-0.45, -0.20), P?2?=?0%], and high density lipoprotein cholesterol [SMD: 0.29 (95%CI:0.02, 0.57), P?=?0.03; I²?=?69%]. The superiority of metformin in improving LDL-C level disappeared in a sensitivity analysis and 80% (8/10) of subgroup analyses. Metformin was significantly superior to placebo with regards to decrease in body weight, body mass index, glycated hemoglobin A1c, fasting insulin, and homeostasis model assessment-insulin resistance (P?=?0.002-0.01), but not regarding changes in waist circumference, waist-to-hip rate, leptin, fasting glucose, and blood pressure (P?=?0.07-0.33). The rates of discontinuation due to any reason [RR: 0.97 (95%CI: 0.66, 1.43), P?=?0.89; I²?=?0%] was similar between the two groups. Adjunctive metformin could be useful to improve total cholesterol and triglyceride levels, but it was not effective in improving LDL-C level in schizophrenia.

SUBMITTER: Jiang WL

PROVIDER: S-EPMC7181777 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Adjunctive metformin for antipsychotic-induced dyslipidemia: a meta-analysis of randomized, double-blind, placebo-controlled trials.

Jiang Wen-Long WL Cai Dong-Bin DB Yin Fei F Zhang Ling L Zhao Xi-Wu XW He Jie J Ng Chee H CH Ungvari Gabor S GS Sim Kang K Hu Mei-Ling ML Zheng Wei W Xiang Yu-Tao YT

Translational psychiatry 20200423 1

Antipsychotic-induced dyslipidemia could increase the risk of cardiovascular diseases. This is a meta-analysis of randomized double-blind placebo-controlled trials to examine the efficacy and safety of adjunctive metformin for dyslipidemia induced by antipsychotics in schizophrenia. The standardized mean differences (SMDs) and risk ratios (RRs) with their 95% confidence intervals (CIs) were calculated using the random-effects model with the RevMan 5.3 version software. The primary outcome was th ...[more]

PMID: 32327628

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Project description:Insulin resistance has been proposed as one of the causes of poor glycemic control in overweight/obese youth with type 1 diabetes (T1D). However, the role of adjunctive metformin, an insulin sensitizer, on glycemic control in these patients is unclear.To compare the effect of metformin vs. placebo on hemoglobin A1c (HbA1c), total daily dose (TDD) of insulin, and other parameters in overweight/obese youth with T1D.Adjunctive metformin therapy will improve glycemic control in overweight/obese youth with T1D.A 9-mo randomized, double-blind, placebo controlled trial of metformin and placebo in 28 subjects (13m/15f) of ages 10-20years (y), with HbA1c >8% (64 mmol/mol), BMI >85%, and T1D > 12 months was conducted at a university outpatient facility. The metformin group consisted of 15 subjects (8 m/ 7f), of age 15.0 ± 2.5 y; while the control group was made up of 13 subjects (5m/ 8f), of age 14.5 ± 3.1y. All participants employed a self-directed treat-to-target insulin regimen based on a titration algorithm of (-2)-0-(+2) units to adjust their long-acting insulin dose every 3rd day from -3 mo through +9 mo to maintain fasting plasma glucose (FPG) between 90-120 mg/dL (5.0-6.7 mmol/L). Pubertal maturation was determined by Tanner stage.Over the course of the 9 months of observation, the between-treatment differences in HbA1c of 0.4% (9.85% [8.82 to 10.88] for placebo versus 9.46% [8.47 to 10.46] for metformin) was not significant (p = 0.903). There were non-significant reduction in fasting plasma glucose (189.4 mg/dL [133.2 to 245.6] for placebo versus 170.5 mg/dL [114.3 to 226.7] for metformin), (p = 0.927); total daily dose (TDD) of short-acting insulin per kg body weight/day(p = 0.936); and the TDD of long-acting insulin per kg body weight per day (1.15 units/kg/day [0.89 to 1.41] for placebo versus 0.90 units/kg/day [0.64 to 1.16] for metformin) (p = 0.221). There was no difference in the occurrence of hypoglycemia between the groups.This 9-month RCT of adjunctive metformin therapy in overweight and obese youth with T1D resulted in a 0.4% lower HbA1c value in the metformin group compared to the placebo group.ClinicalTrial.gov NCT01334125.

Project description:BackgroundMany patients with obsessive-compulsive disorder do not respond adequately to serotonin reuptake inhibitors. Augmentation with antipsychotic drugs can be beneficial in this regard. However, since new relevant randomized controlled trials evaluating new antipsychotics were conducted, a recalculation of the effect sizes appears necessary.MethodsWe meta-analyzed all double-blind, randomized, placebo-controlled trials comparing augmentation of serotonin reuptake inhibitors with antipsychotics to placebo supplementation in treatment-resistant obsessive-compulsive disorder. The primary outcome was mean change in the Yale-Brown Obsessive-Compulsive Scale total score. Secondary outcomes were obsessions, compulsions, response rates, and attrition rates. The data collection process was conducted independently by 2 authors. Hedges's g and risks ratios were calculated as effect sizes. In preplanned meta-regressions, subgroup analyses, and sensitivity analyses, we examined the robustness of the results and explored reasons for potential heterogeneity.ResultsAltogether, 14 double-blind, randomized, placebo-controlled trials (n=491) investigating quetiapine (N=4, n=142), risperidone (N=4, n=132), aripiprazole (N=2, n=79), olanzapine (N=2, n=70), paliperidone (N=1, n=34), and haloperidol (N=1, n=34) were incorporated. Augmentation with antipsychotics was significantly more efficacious than placebo in Yale-Brown Obsessive-Compulsive Scale total reduction (N=14, n=478; Hedges's g=-0.64, 95% CI: -0.87 to -0.41; P=<.01). Aripiprazole (Hedges's g=-1.35), haloperidol (Hedges's g=-0.82), and risperidone (Hedges's g=-0.59) significantly outperformed placebo. Antipsychotics were superior to placebo in treating obsessions, compulsions, and achieving response. There was no between-group difference concerning all-cause discontinuation. The nonsignificant meta-regressions suggest no influence of the antipsychotic dose or baseline symptom severity on the meta-analytic results.ConclusionsAccording to our findings, antipsychotic augmentation of serotonin reuptake inhibitors can be regarded as an evidence-based measure in treatment-resistant obsessive-compulsive disorder.

Project description:Aripiprazole, metformin, and paeoniae-glycyrrhiza decoction (PGD) have been widely used as adjunctive treatments to reduce antipsychotic (AP)-induced hyperprolactinemia in patients with schizophrenia. However, the comparative efficacy and safety of these medications have not been previously studied. A network meta-analysis of randomized controlled trials (RCTs) was conducted to compare the efficacy and safety between aripiprazole, metformin, and PGD as adjunctive medications in reducing AP-induced hyperprolactinemia in schizophrenia. Both international (PubMed, PsycINFO, EMBASE, and Cochrane Library databases) and Chinese (WanFang, Chinese Biomedical, and Chinese National Knowledge infrastructure) databases were searched from their inception until January 3, 2019. Data were analyzed using the Bayesian Markov Chain Monte Carlo simulations with the WinBUGS software. A total of 62 RCTs with 5,550 participants were included in the meta-analysis. Of the nine groups of treatments included, adjunctive aripiprazole (<5 mg/day) was associated with the most significant reduction in prolactin levels compared to placebo (posterior MD = -65.52, 95% CI = -104.91, -24.08) and the other eight treatment groups. Moreover, adjunctive PGD (>1:1) was associated with the lowest rate of all-cause discontinuation compared to placebo (posterior odds ratio = 0.45, 95% CI = 0.10, 3.13) and adjunctive aripiprazole (>10 mg/day) was associated with fewer total adverse drug events than placebo (posterior OR = 0.93, 95% CI = 0.65, 1.77) and other eight treatment groups. In addition, when risperidone, amisulpride, and olanzapine were the primary AP medications, adjunctive paeoniae/glycyrrhiza = 1:1, aripiprazole <5 mg/day, and aripiprazole >10 mg/day were the most effective treatments in reducing the prolactin levels, respectively. Adjunctive aripiprazole, metformin, and PGD showed beneficial effects in reducing AP-induced hyperprolactinemia in schizophrenia, with aripiprazole (<5 mg/day) being the most effective one.

Project description:Background: Parkinson's disease (PD) is a debitlitating, chronic, progressive neurodegenerative disorder without modifying therapy. Here, we aimed to evaluate the available evidence of herbal medicine (HM) formulas for patients with PD according to randomized double-blind placebo-controlled clinical trials. Methods: HM formulas for PD were searched in eight main databases from their inception to February 2018. The methodological quality was assessed using Cochrane Collaboration risk of bias tool. Meta-analysis was performed using RevMan 5.3 software. Results: Fourteen trials with Seventeen comparisons comprising 1,311 patients were identified. Compared with placebo groups, HM paratherapy (n = 16 comparisons) showed significant better effects in the assessments of total Unified Parkinson's Disease Rating Scale (UPDRS) (WMD: -5.43, 95% CI:-8.01 to -2.86; P < 0.0001), UPDRS I (WMD: -0.30, 95% CI: -0.54 to -0.06; P = 0.02), UPDRS II (WMD: -2.21, 95% CI: -3.19 to -1.22; P < 0.0001), UPDRS III (WMD: -3.26, 95% CI:-4.36 to -2.16; P < 0.00001), Parkinson's Disease Quality of Life Questionnaire (p < 0.01) and Parkinson's Disease Questionnaire-39 (WMD: -7.65, 95% CI: -11.46 to -3.83; p < 0.0001), Non-motor Symptoms Questionnaire (p < 0.01) and Non-Motor Symptoms Scale (WMD: -9.19, 95% CI: -13.11 to -5.28; P < 0.00001), Parkinson's Disease Sleep Scale (WMD: 10.69, 95% CI: 8.86 to 12.53; P < 0.00001), and Hamilton depression rating scale (WMD: -5.87, 95% CI: -7.06 to -4.68; P < 0.00001). The efficiency of HM monotherapy (n = 1 comparison) was not superior to the placebo according to UPDRS II, UPDRS III and total UPDRS score in PD patients who never received levodopa treatment, all P > 0.05. HM formulas paratherapy were generally safe and well tolerated for PD patients (RR: 0.41, 95% CI: 0.21 to 0.80; P = 0.009). Conclusion: The findings of present study supported the complementary use of HM paratherapy for PD patients, whereas the question on the efficacy of HM monotherapy in alleviating PD symptoms is still open.

Dataset Information

Adjunctive metformin for antipsychotic-induced dyslipidemia: a meta-analysis of randomized, double-blind, placebo-controlled trials.

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Adjunctive metformin for antipsychotic-induced dyslipidemia: a meta-analysis of randomized, double-blind, placebo-controlled trials.

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