T200. METABOLIC SIDE EFFECTS OF ANTIPSYCHOTIC DRUGS – PROTOCOL OF A SYSTEMATIC REVIEW AND NETWORK- METAANALYSIS

Abstract Background Antipsychotic drugs are the mainstay of the pharmacological treatment of schizophrenia, used in the acute episode of the disorder and for prevention of relapses. Unfortunately, antipsychotics cause side effects. Weight gain is one of the most prominent side effects. In line with weight gain, also alterations of lipid- and glucose homeostasis can occur and increase the risk for cardiovascular disorders. So far, the differences between the multiple antipsychotics in propensity to cause these alterations have not been examined based on data from randomized controlled trial. Therefore, we are conducting a systematic review and network-metaanalysis on metabolic side effects of antipsychotic drugs. Methods Systematic review and network-metaanalysis. Population Patients with schizophrenia. Interventions Antipsychotic drugs and placebo. Comparator In network-metaanalysis all interventions are compared with each other. For presentation of Results:, placebo will be used as reference. Outcomes The primary outcomes will be continuous change of body weight. Additional outcomes will be continuous change of blood glucose, triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol as well as dichotomous values of these outcomes (i.e. number of patients with a clinically relevant increase over pathological thresholds). Study design Randomized controlled trials. Statistical analysis Network-metaanalysis. Planned network-metaregression-, subgroup- and sensitivity-analyses will address the role of the potential effect modifiers baseline weight, study duration, age, gender, ethnicity, previous antipsychotic exposure, antipsychotic dose, sponsorship, and use of enriched-design. Results Funding for this project has been received from the German Ministry of Education and Research. At the time of abstract submission, the project has just started and is currently in the stage of protocol development. Discussion At the time of the conference the protocol of the study will be developed further and the literature search will have started. Thus, on the poster, details of the analytic approach can be presented and challenges discussed. Moreover, results of the search process can be presented.

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A Randomized Controlled Trial of a Patient-Centered Approach to Improve Screening for the Metabolic Side Effects of Antipsychotic Medications

Community Mental Health Journal ◽

10.1007/s10597-016-0007-5 ◽

2016 ◽

Vol 53 (2) ◽

pp. 163-175 ◽

Cited By ~ 7

Author(s):

Julie Kreyenbuhl ◽

Lisa B. Dixon ◽

Clayton H. Brown ◽

Deborah R. Medoff ◽

Elizabeth A. Klingaman ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Side Effects ◽

Controlled Trial ◽

Patient Centered ◽

Antipsychotic Medications ◽

Randomized Controlled ◽

Metabolic Side Effects

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P.3.d.001 Development of novel antipsychotic drugs based on olanzapine that display reduced weight gain and metabolic side effects

European Neuropsychopharmacology ◽

10.1016/s0924-977x(11)70823-9 ◽

2011 ◽

Vol 21 ◽

pp. S506-S507

Author(s):

S. Jafari ◽

F. Fernandez ◽

X.F. Huang

Keyword(s):

Weight Gain ◽

Side Effects ◽

Antipsychotic Drugs ◽

Metabolic Side Effects ◽

Novel Antipsychotic

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Does Melatonin and Melatonin Agonists Improve the Metabolic Side Effects of Atypical Antipsychotics?: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Clinical Psychopharmacology and Neuroscience ◽

10.9758/cpn.2018.16.3.235 ◽

2018 ◽

Vol 16 (3) ◽

pp. 235-245 ◽

Cited By ~ 4

Author(s):

Stanley C. Igwe ◽

Francesco Brigo

Keyword(s):

Systematic Review ◽

Side Effects ◽

Randomized Controlled Trials ◽

Atypical Antipsychotics ◽

Meta Analysis ◽

Controlled Trials ◽

Randomized Controlled ◽

Metabolic Side Effects

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Weight gain and metabolic side effects with antipsychotic drugs in children

Middle East Current Psychiatry ◽

10.1097/01.xme.0000418805.27224.cc ◽

2012 ◽

Vol 19 (4) ◽

pp. 237-244

Author(s):

Ghada A.M. Hassan

Keyword(s):

Weight Gain ◽

Side Effects ◽

Antipsychotic Drugs ◽

Metabolic Side Effects

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Metabolic side effects of antipsychotic drugs in individuals with schizophrenia during medium- to long-term treatment: protocol for a systematic review and network meta-analysis of randomized controlled trials

Systematic Reviews ◽

10.1186/s13643-021-01760-z ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Johannes Schneider-Thoma ◽

Angelika Kapfhammer ◽

Dongfang Wang ◽

Irene Bighelli ◽

Spyridon Siafis ◽

...

Keyword(s):

Systematic Review ◽

Side Effects ◽

Antipsychotic Drugs ◽

Meta Analysis ◽

Density Lipoprotein ◽

Term Treatment ◽

Controlled Trials ◽

Metabolic Side Effects ◽

Long Term Treatment

Abstract Background Antipsychotic drugs and especially the newer compounds are known to cause metabolic side effects. However, a comprehensive comparison of the different substances regarding their propensity to cause metabolic side effects in medium- to long-term treatment of schizophrenia is lacking. Methods We will conduct a systematic review and network meta-analysis (NMA). We will include randomized controlled trials (RCTs) in which participants received either placebo or an antipsychotic (i.e. placebo-controlled trials and head-to-head comparisons of drugs). We will include studies in individuals with schizophrenia or related disorders (such as schizophreniform or schizoaffective disorders) at any stage of the disease (acute episode; maintenance phase). We will include studies with a duration of more than 3 months (medium- to long-term treatment). The primary outcome will be the change in body weight. Secondary outcomes will be the further metabolic parameters: fastening glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides. We will search for eligible studies (independent of the publication status) in Cochrane Schizophrenia Group’s Study-Based Register of Trials, which is compiled by regular searches in trial registries and multiple electronic databases from their inception onwards including MEDLINE, EMBASE and PsycINFO. Additionally, we will search previously published systematic reviews and websites of pharmaceutical companies for eligible studies. At least two reviewers will independently conduct the process of study selection and data extraction. We will use the Cochrane Risk of Bias 2 tool to evaluate the risk of bias in studies. We will conduct random-effects NMA within a Bayesian framework to synthesize all evidence for each outcome. We will conduct sensitivity and subgroup analyses to assess the robustness of the findings and to explore heterogeneity. The confidence in the results will be evaluated using the Confidence in Network Meta-Analysis (CINeMA) framework. Discussion This systematic review and network meta-analysis will provide a synthesis of the existing evidence from RCTs how antipsychotic drugs differ in terms of metabolic side effects during medium- to long-term treatment. The findings have the potential to influence the choice of antipsychotic medication made by individuals with schizophrenia and their physicians. Systematic review registration PROSPERO CRD42020175414

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A systematic review of metabolic side effects related to the use of antipsychotic drugs in dementia

International Psychogeriatrics ◽

10.1017/s1041610213001658 ◽

2013 ◽

Vol 26 (1) ◽

pp. 19-37 ◽

Cited By ~ 11

Author(s):

A.R. Atti ◽

B. Ferrari Gozzi ◽

G. Zuliani ◽

V. Bernabei ◽

P. Scudellari ◽

...

Keyword(s):

Lipid Metabolism ◽

Weight Gain ◽

Side Effects ◽

Glucose Homeostasis ◽

Older Patients ◽

Antipsychotic Drugs ◽

Old Patients ◽

Metabolic Side Effects ◽

Moderate Dementia ◽

Increased Risk

ABSTRACTBackground:In clinical practice, Second Generation Antipsychotics (SGAs) are often used as first-line treatment for the Behavioral and Psychological Symptoms of Dementia (BPSD) in older adults due to their fewer neurological adverse events and similar effectiveness compared with First Generation Antipsychotics (FGAs). SGAs, however, are associated with more severe metabolic side effects (weight gain, hyperglycemia, diabetes risk, and hyperlipidemia) than FGAs are. In general, older patients, especially those affected by dementia, are at increased risk for malnutrition, and tend to have lower basal metabolism and reduced liver and kidney function. However, little is known about the metabolic side effects of antipsychotic drugs in this population.Methods:A comprehensive review of the literature published between January 1996 and December 2012 investigating the metabolic side effects related to FGAs and SGAs use in old patients affected by dementia.Results:Antipsychotic drugs currently used to treat BPSD in subjects with mild to moderate dementia are associated with weight gain. Currently, there are insufficient data to support a causal relationship between the use of FGAs and SGAs and changes in glucose homeostasis or lipid metabolism in older persons affected by severe dementia (MMSE <14).Conclusion:A possible association between antipsychotic drugs use and weight gain might exist, in particular in subjects with mild to moderate dementia whereas no significant effects are demonstrated regarding glucose homeostasis and lipid metabolism. The antipsychotic drugs potential for causing metabolic abnormalities in older patients requires further specifically designed studies. Clinicians must be aware of this possibility even if the shorter periods of treatment administered in late-life might not be as harmful as it is in younger individuals.

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Metabolomic profiles associated with a mouse model of antipsychotic-induced food intake and weight gain

Scientific Reports ◽

10.1038/s41598-020-75624-2 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Rizaldy C. Zapata ◽

Sara Brin Rosenthal ◽

Kathleen Fisch ◽

Khoi Dao ◽

Mohit Jain ◽

...

Keyword(s):

Weight Gain ◽

Side Effects ◽

Food Intake ◽

Palmitoleic Acid ◽

Antipsychotic Drugs ◽

Plasma Metabolites ◽

Plasma Citrulline ◽

Metabolic Side Effects ◽

Psychiatric Conditions ◽

Underlying Mechanisms

Abstract Antipsychotic drugs (AP) are used to treat a multitude of psychiatric conditions including schizophrenia and bipolar disorder. However, APs also have metabolic side effects including increased food intake and body weight, but the underlying mechanisms remain unknown. We previously reported that minocycline (MINO) co-treatment abrogates olanzapine (OLZ)-induced hyperphagia and weight gain in mice. Using this model, we investigated the changes in the pharmacometabolome in the plasma and hypothalamus associated with OLZ-induced hyperphagia and weight gain. Female C57BL/6 mice were divided into groups and fed either i) control, CON (45% fat diet) ii) CON + MINO, iii) OLZ (45% fat diet with OLZ), iv) OLZ + MINO. We identified one hypothalamic metabolite indoxylsulfuric acid and 389 plasma metabolites (including 19 known metabolites) that were specifically associated with AP-induced hyperphagia and weight gain in mice. We found that plasma citrulline, tricosenoic acid, docosadienoic acid and palmitoleic acid were increased while serine, asparagine and arachidonic acid and its derivatives were decreased in response to OLZ. These changes were specifically blocked by co-treatment with MINO. These pharmacometabolomic profiles associated with AP-induced hyperphagia and weight gain provide candidate biomarkers and mechanistic insights related to the metabolic side effects of these widely used drugs.

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