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Meta-analysis of ghrelin alterations in schizophrenia: Effects of olanzapine.
Goetz, RL, Miller, BJ
Schizophrenia research. 2019;:21-26
Abstract
OBJECTIVE Schizophrenia is associated with an increased prevalence of the metabolic syndrome. Patients receiving antipsychotic medications, including olanzapine, are at further risk. Ghrelin is an appetite-stimulating peptide hormone, although whether blood levels are altered by antipsychotic treatment, remains unclear. We performed a systematic review and meta-analysis comparing blood ghrelin levels in patients with schizophrenia before and after treatment with olanzapine. METHOD Two authors independently searched major electronic databases from inception until February 2018 for studies measuring blood ghrelin levels among patients with schizophrenia before and after olanzapine therapy. Random effects meta-analysis calculating standardized mean difference (SMD) and 95% confidence intervals (CI) and meta-regression analyses were performed. RESULTS Six studies met the inclusion criteria. Across these studies, there were 111 patients with schizophrenia (mean age 40, 85% male, baseline BMI 22, and endpoint BMI 23). Olanzapine treatment (mean [standard deviation] duration = 12.3 [7.6] weeks) was associated with a significant decrease in blood ghrelin levels with a medium effect size (SMD = -0.48, 95% CI -0.88 to -0.08, p = 0.018). Age, sex, baseline BMI, geography, olanzapine dose and duration, year of publication, study quality, inpatient status, and antipsychotic washout did not moderate this association. CONCLUSION Our results suggest that in patients with schizophrenia, olanzapine therapy is associated with decreased blood ghrelin levels, a paradoxical phenomenon known to occur in obesity. Future studies should investigate the contribution of dietary factors (e.g., caloric intake) and physical activity to this association, as well as the effects of other antipsychotics on ghrelin levels.
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2.
[Effects of Topiramate for atypical antipsychotic-induced body weight gain and metabolic adversities: a systematic review and meta-analysis].
Liang, H, Li, H, Hu, Y, Li, S, Lü, L, Song, X
Zhonghua yi xue za zhi. 2016;(3):216-23
Abstract
OBJECTIVE To systematically determine the effectiveness of Topiramate to counteract atypical antipsychotic-induced body weight gain and metabolic adversities in patients with psychiatric disorders. METHODS A literature search using MEDLINE, EMBASE, PsycINFO, The Cochrane Library, CNKI, CBM and WanFang Data for randomized, open and double-blind, placebo-controlled trials of Topiramate targeting atypical antipsychotic-induced weight gain was performed.Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality of included studies.Then meta-analysis was performed using RevMan 5.2 software. RESULTS A total of 10 RCTs was included, consisting of 453 subjects. The results of meta-analysis showed that: compared with placebo, Topiramate was moderate effective in reducing antipsychotics-related weight gain (WMD=-1.82 kg (95%CI: -2.65--0.99), P<0.000 1), BMI increase (WMD=-1.31 kg/m(2) (95%CI: -1.69--0.93), P<0.000 01) and fasting glucose increase (SMD=-1.15 (95%CI: -1.50--0.79), P<0.000 01); but can not regulate the lipid metabolic disorders (Cholesterol: SMD=-0.23 (95%CI: -0.81-0.35), P=0.44); Triglycerides: SMD=-0.28 (95%CI: -0.75-0.19), P=0.24; HDL: SMD= 0.01 (95%CI: -0.52-0.53), P=0.98); LDL: SMD=-0.39 (95%CI: -0.89-0.11), P=0.13). Meanwhile, when compared with placebo, Positive and Negative Syndrome Scale (PANSS) in patients with schizophrenia did not show obviously clinical improvement in concomitant Topiramate group. CONCLUSION Topiramate can prevent and/or treat atypical antipsychotic induced weight gain and glucose disorder, but current evidence does not support the effect of Topiramate in lipid metabolic regulation and the clinical symptoms improvement assessed by PANSS.
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3.
Adverse effects of second-generation antipsychotics in children and adolescents: a Bayesian meta-analysis.
Cohen, D, Bonnot, O, Bodeau, N, Consoli, A, Laurent, C
Journal of clinical psychopharmacology. 2012;(3):309-16
Abstract
In adults, second-generation antipsychotics (SGAs) have a low frequency of extrapyramidal syndrome (EPS) and a moderate frequency of metabolic adverse effects. Here we aimed to assess short-term adverse effects of SGAs in children and adolescents. We searched for relevant studies in MEDLINE and EMBASE (1996-2010), Food and Drug Administration and European Medicines Agency clinical trial registries, and reference lists of review articles. We found 41 were short-term (3-12 weeks) controlled studies that evaluated SGA adverse effects in youths. Using Bayesian meta-analysis, we analyzed odds ratios (ORs) or mean average effects. Numbers of arms (subjects) in the 41 trials were aripiprazole, 10 (n = 671); olanzapine, 14 (n = 413); quetiapine, 10 (n = 446); risperidone, 25 (n = 1040); ziprasidone, 4 (n = 228); clozapine, 5 (n = 79); and placebo/untreated, 23 (n = 1138), totaling 93 arms (4015 patients). Clozapine was assessed only for weight gain and somnolence. Compared with placebo, significant treatment-related increases were observed for weight gain with olanzapine (mean ± SD = 3.99 ± 0.42 kg; 95% credible interval, 3.17-4.84 kg), clozapine (2.38 ± 1.13 kg; 95% credible interval, 0.19-4.62 kg), risperidone (2.02 ± 0.32 kg; 95% credible interval, 1.39-2.66 kg), quetiapine (1.74 ± 0.38 kg; 95% credible interval, 0.99-2.5 kg), and aripiprazole (0.89 ± 0.32 kg; 95% credible interval, 0.26-1.51 kg); glucose levels with risperidone (3.7 ± 1.36 mg/dL; 95% credible interval, 1.08-6.42 mg/dL) and olanzapine (2.09 ± 1.08 mg/dL; 95% credible interval, 0.13-4.32 mg/dL); cholesterol levels with quetiapine (10.77 ± 2.14 mg/dL; 95% credible interval, 6.6-14.95 mg/dL) and olanzapine (4.46 ± 1.65 mg/dL; 95% credible interval, 1.24-7.73 mg/dL); triglyceride levels with olanzapine (20.18 ± 5.26 mg/dL; 95% credible interval, 9.85-30.53 mg/dL) and quetiapine (19.5 ± 3.92 mg/dL; 95% credible interval, 11.84-27.17 mg/dL); hyperprolactinemia with risperidone (OR, 38.63; 95% credible interval, 8.62-125.6), olanzapine (OR, 15.6; 95% credible interval, 4.39-41.1), and ziprasidone (OR, 9.35; 95% credible interval, 1.24-37.03); and EPS with ziprasidone (OR, 20.56; 95% credible interval, 3.53-68.94), olanzapine (OR, 6.36; 95% credible interval, 2.43-13.84), aripiprazole (OR, 3.79; 95% credible interval, 2.17-6.17), and risperidone (OR, 3.71; 95% credible interval, 2.18-6.02). All SGAs increased the risk of somnolence/sedation. We conclude that short-term metabolic effects and EPS are frequent in children treated with SGAs. Second-generation antipsychotics have distinct profiles of secondary effects, which should be considered in making treatment decisions.
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4.
Comparing tolerability of olanzapine in schizophrenia and affective disorders: a meta-analysis.
Moteshafi, H, Zhornitsky, S, Brunelle, S, Stip, E
Drug safety. 2012;(10):819-36
Abstract
BACKGROUND Olanzapine is prescribed for a number of psychiatric disorders, including schizophrenia, bipolar mania, and unipolar and bipolar depression. Olanzapine treatment is associated with tolerability issues such as metabolic adverse effects (e.g. weight gain, increase in blood glucose, triglycerides and total cholesterol levels), extrapyramidal symptoms [EPS] (e.g. parkinsonism, akathisia, tardive dyskinesia) and sedative adverse effects. Metabolic issues lead to some long-term consequences, which include cardiovascular diseases (CVD) and type 2 diabetes mellitus, and these complications cause high rates of mortality and morbidity among patients with severe mental illnesses. The expanded indications of olanzapine in psychiatry suggest a need to investigate whether there is a difference in the incidence and severity of adverse effects related to category diagnosis. Are the adverse effects expressed differently according to phenotype? Unfortunately, there are no reported studies that investigated these differences in adverse effects associated with olanzapine treatment in psychiatric patients with different phenotypes. OBJECTIVE The aim of the present meta-analysis is to separately examine olanzapine-induced cardiometabolic adverse effects and EPS in patients with schizophrenia and affective disorders. DATA SOURCES A search of computerized literature databases PsycINFO (1967-2010), PubMed (MEDLINE), EMBASE (1980-2010) and the clinicaltrials.gov website for randomized clinical trials was conducted. A manual search of reference lists of published review articles was carried out to gather further data. STUDY SELECTION Randomized controlled trials were included in our study if (i) they assessed olanzapine adverse effects (metabolic or extrapyramidal) in adult patients with schizophrenia or affective disorders; and (ii) they administered oral olanzapine as monotherapy during study. DATA EXTRACTION Two reviewers independently screened abstracts for choosing articles and one reviewer extracted relevant data on the basis of predetermined exclusion and inclusion criteria. It should be mentioned that for the affective disorders group we could only find articles related to bipolar disorder. DATA SYNTHESIS Thirty-three studies (4831 patients) that address olanzapine monotherapy treatment of adults with schizophrenia or bipolar disorder were included in the analysis. The primary outcomes were metabolic adverse effects (changes in weight, blood glucose, low-density lipoprotein, total cholesterol and triglyceride levels). The secondary outcomes of our study were assessing the incidence of some EPS (parkinsonism, akathisia and use of antiparkinson medication). The tolerability outcomes were calculated separately for the schizophrenia and bipolar disorder groups and were combined in a meta-analysis. Tolerability outcomes show that olanzapine contributes to weight gain and elevates blood triglycerides, glucose and total cholesterol levels in both schizophrenia and bipolar disorder patients. However, olanzapine treatment produced significantly more weight gain in schizophrenia patients than in bipolar disorder patients. In addition, increases in blood glucose, total cholesterol and triglyceride levels were higher in the schizophrenia group compared with the bipolar disorder group, even though these differences were not statistically significant. Based on our results, the incidence of parkinsonism was significantly higher in the schizophrenia group than in the bipolar disorder group. Subgroup analysis and logistic regression were used to assess the influence of treatment duration, dose, industry sponsorship, age and sex ratio on tolerability outcome. CONCLUSIONS Our results suggest that schizophrenia patients may be more vulnerable to olanzapine-induced weight gain. The findings may be explained by considering the fact that in addition to genetic disposition for metabolic syndrome in schizophrenia patients, they have an especially high incidence of lifestyle risk factors for CVD, such as poor diet, lack of exercise, stress and smoking. It might be that an antipsychotic induces severity of adverse effect according to the phenotype.