27 research outputs found
The impact of adjuvant aripiprazole on olanzapine- induced metabolic adverse effects in schizophrenic patients: a Systematic Review
No full textAbstract
Background: Olanzapine is a second-generation atypical antipsychotic drug which is commonly used in the treatment of psychotic disorders such as schizophrenia. It has been associated with metabolic adverse effects such as, weight gain, hyperglycaemia, dyslipidemia and this has been shown to contribute to the reduction of life expectancy of schizophrenic patients. It has been suggested that adjunctive aripiprazole (another atypical antipsychotic) reduces some of the metabolic adverse effects caused by olanzapine. This systematic review aimed to assess whether adjunctive aripiprazole is effective at reducing metabolic adverse effects induced by olanzapine.
Methods: A systematic review was conducted and due to heterogeneity in the data, a narrative synthesis was completed. A systematic search strategy was developed, recorded, and applied to multiple academic search engines. Using the PRISMA flow diagram, the literature search found a total of 853 results with final inclusion of 7 research articles. Based on a specific inclusion and exclusion criteria, a wide range of study designs were included in the review such as randomised control trials (RCTs), open label trials and case series. Key outcomes were identified which included: glucose levels, lipid profile (which included triglycerides as well as HDL, LDL, and total cholesterol), body weight, BMI and waist circumference. The results were recorded and analysed using narrative synthesis, and conclusions were drawn based on the results reported.
Results: Statistically significant decreases in fasting triglycerides were consistent across multiple studies, supporting the hypothesis that aripiprazole may counteract some of the metabolic adverse effects of olanzapine. Adjunctive aripiprazole shows potential weight loss benefits, with some studies reporting significant reductions in weight and BMI, while one other found no meaningful change. However, this may be a dose dependent outcome, as the study that found no significant change in weight used a substantially lower dose of aripiprazole compared to other studies. Effects on cholesterol and fasting glucose showed non statistically significant reductions and others showed minimal or no impact. Psychiatric symptom control remained stable in most studies, suggesting that aripiprazole does not negatively affect schizophrenia symptoms while potentially providing metabolic advantages.
Conclusions: Adjunctive aripiprazole had variable effects on metabolic parameters in patients on olanzapine therapy, however reductions in triglycerides appeared consistent among the majority of the data and some studies reported significant weight loss. This highlighted that aripiprazole does have some effect in reducing metabolic adverse effects caused by olanzapine. However, there are many possible factors that could influence the metabolic changes shown. This highlights a need for further research and investigations, investigations that will address the gaps in the current research, such as longer randomised control trials (RCTs) with more participants and more information regarding effective dose response.
Keywords: Adjunctive aripiprazole | Olanzapine | Schizophrenia | Metabolic adverse effects
a Stephen Simmons, 4th Year Medical Student, Kent and Medway Medical School, Canterbury, United Kingdom
bDr Soban Sadiq, Senior lecturer, Kent and Medway Medical School, Canterbury, United Kingdom
Main contact email: [email protected]
 
Fingolimod (FTY720) preserves high energy phosphates and improves cardiac function in heterotopic heart transplantation model
No full textDuring heart transplantation, donor heart leads to reduced oxygen supply resulting in low level of high energy phosphate (HEP) reserves in cardiomyocyte. Lower HEP is one of the underlying reasons of cell death due to ischemia. In this study we investigated the role of Fingolimod (FTY720) in heart transplantation ischemia. Eight groups of Sprague-Dawley rats (n = 5 for each subgroup) were made, A1 and C1 were given FTY720 1 mg/kg while B1 and D1 were given normal saline. The hearts were implanted into another set of similar rats after preservation period of 1 h at 4-8 °C. Significantly higher Left ventricular systolic pressure (LVSP), dP/dT maximum (p \u3c 0.05), dP/dT minimum (p \u3c 0.05) were recorded in the FTY720 treated group after 24 h of reperfusion while after 1 h of reperfusion, there were no significant differences in LVSP, maximum and negative dP/dT, and Left ventricular end diastolic pressure (LVEDP) between the control and the FTY720-treated transplant groups. Coronary blood flow (CBF) was enhanced (p \u3c 0.05) in the FTY720 treated group after 1 and 24 h. ATP p \u3c 0.001, p \u3c 0.05 at 1 and 24 h, ADP p \u3c 0.001, p \u3e 0.05 at 1 and 24 h, and phosphocreatine p \u3c 0.05, p \u3e 0.05 at 1 and 24 h were better preserved by FTY720 treatment as compared to control group. The study concluded that pretreatment of grafted hearts with FTY720 improved hemodynamics, CBF, high energy phosphate reserves, reduces the peroxynitrite level and poly (ADP ribose) polymerase (PARP) inhibition that prevents ischemia-reperfusion injury
The reno-protective effect of aqueous extract of <i>Carum carvi</i> (black zeera) seeds in streptozotocin induced diabetic nephropathy in rodents
No full textTo assess the effect of aqueous extract of Carum carvi seeds in experimentally induced diabetic nephropathy (DN) in rodents, we studied 48 adult male Wistar rats divided into 4 groups: normal controls (group A), diabetes positive control (group B), and experimental (groups C and D). They received Carum carvi extract as a renoprotective agent. Rats having fasting blood glucose levels over 280 mg/dL were included in this study. Group C rats received STZ (60 mg/kg) and aqueous extract of Carum carvi at 30 mg/kg of body weights. On the other hand group D rats received STZ (60 mg/kg) and aqueous extract of Carum carvi at 60 mg/kg of body weight. Blood samples were collected on the 60 th day, and kidneys were also extracted for examination. The diabetic group rats showed a variable increase in the serum levels of glucose, urea, creatinine, total urinary protein and microalbuminuric levels. Body weight decreased and urine volume increased in the diabetic groups. 30 mg/kg body weight of Carum carvi dose decreased the levels of these parameters in rats. On the other hand, 60 mg/kg body weight of Carum carvi dose significantly decreased the levels of the biochemical parameters. The morphological examination of group C rats showed no changes whereas the rats in group D showed moderate changes. Carum carvi constituents, especially flavonoids and carvone have strong anti-oxidant activity, which provides reno-protection against diabetes and its complications. In conclusion, high dose of Carum carvi aqueous seeds extract (60 mg/kg) showed reno-protection against STZ induced dia-betic nephropathy in rats
Cardioprotective effects of sphingosine-1-phosphate receptor immunomodulator fty720 in a clinically relevant model of cardioplegic arrest and cardiopulmonary bypass
No full textObjective: FTY720, an immunomodulator derived from sphingosine-1-phosphate, has recently demonstrated its immunomodulatory, anti-inflammatory, anti-oxidant, anti-apoptotic and anti-inflammatory properties. Furthermore, FTY720 might be a key pharmacological target for preconditioning. In this preclinical model, we have investigated the effects of FTY720 on myocardium during reperfusion in an experimental model of cardioplegic arrest (CPA) and cardiopulmonary bypass. Methods: 30 Sprague-Dawley rats (300-350 g) were randomized into two groups: Group-A, treated with FTY720 1 mg/kg via intravenous cannulation, and Group-B, as control. After 15 min of treatment, rats underwent CPA for 30 min followed by initiation of extracorporeal life support for 2 h. Support weaning was done, and blood and myocardial tissues were collected for analysis. Hemodynamic parameters, inflammatory mediators, nitro-oxidative stress, neutrophil infiltration, immunoblotting analysis, and immunohistochemical staining were analyzed and compared between groups. Results: FTY720 treatment activated the Akt/Erk1/2 signaling pathways, reduced the level of inflammatory mediators, activated antiapoptotic proteins, and inhibited proapoptotic proteins, leading to reduced nitro-oxidative stress and cardiomyocyte apoptosis. Moreover, significant preservation of high-energy phosphates were observed in the FTY720-treated group. This resulted in improved recovery of left ventricular systolic and diastolic functions. Conclusion: The cardioprotective mechanism in CPA is associated with activation of prosurvival cell signaling pathways that prevents myocardial damage. FTY720 preserves high-energy phosphates attenuates myocardial inflammation and oxidative stress, and improves cardiac function
The impact of adjunctive aripiprazole on olanzapine‐induced metabolic adverse effects in patients with schizophrenia: a systematic review
No full textBackground: Olanzapine is a second‐generation atypical antipsychotic drug which is commonly used in the treatment of schizophrenia. It has been associated with metabolic adverse effects such as weight gain, hyperglycaemia, dyslipidaemia, and this has been shown to contribute to the reduction of life expectancy of patients with schizophrenia. This systematic review aimed to assess whether adjunctive aripiprazole is effective at reducing metabolic adverse effects caused by olanzapine. Methods: A systematic review was conducted for this study. A systematic search strategy was developed, recorded, and applied to multiple databases. The literature search found a total of 853 results with the final inclusion of 7 research articles. Based on specific inclusion and exclusion criteria, a wide range of study designs were included in the review, such as randomized control trials (RCTs), open label trials, and case series. Key outcomes were identified, which included glucose levels, lipid profile, body weight, BMI, and waist circumference. The results were recorded and analyzed using narrative synthesis. Results: Statistically significant decreases in fasting triglycerides were consistent across multiple studies. Adjunctive aripiprazole shows potential weight loss benefits, with some studies reporting significant reductions in weight and BMI. Effects on cholesterol and fasting glucose showed reductions, and others showed minimal or no impact. Psychiatric symptom control remained stable in most studies, suggesting that aripiprazole does not negatively affect schizophrenia symptoms while potentially providing metabolic advantages. Conclusion: Adjunctive aripiprazole had variable effects on metabolic parameters in patients on olanzapine therapy; however, reductions in triglycerides appeared consistent among most of the data, and some studies reported significant weight loss. This highlighted that aripiprazole does have some effect in reducing metabolic adverse effects caused by olanzapine
Does Adjuvant Metformin Reduce Olanzapine‐Induced Metabolic Adverse Effects in Patients Diagnosed With Schizophrenia
No full textBackground: Olanzapine is an atypical antipsychotic used in the treatment of schizophrenia, bipolar disorder, and major depressive disorder. In comparison to conventional antipsychotics, it demonstrates superiority in binding to serotonin 5HT-2A than to dopamine D2 receptors, thus presenting as an alternative in having lower extrapyramidal side effects. However, over time, it has become clear that olanzapine carries other prominent adverse effects associated with its use. These relate to the endocrine system and include body weight gain, increased adiposity, insulin resistance, and dyslipidaemia, all of which contribute to metabolic syndrome. Several studies included in this review involved patients with these broader psychiatric diagnoses, not only schizophrenia. This systematic review, therefore, assesses the evidence for the effectiveness of utilizing adjuvant metformin to reduce olanzapine-induced metabolic adverse effects across these populations.
Methods: Due to the heterogeneity in available data, this systematic review was conducted via a narrative synthesis method. Initially, the search question was formulated utilizing the PICO tool, then a rigorous search strategy was applied to four search engines. Utilizing the PRISMA flow diagram for visualization of the flow of articles, the initial search revealed a total of 71 articles, whereby strict inclusion and exclusion criteria were applied, revealing the final six articles included in the review. Detailed analysis of the articles allowed key themes and outcomes to be drawn upon, including body weight/BMI, waist circumference, glucose/insulin level changes, and lipid profile. This allowed key data to be grouped and narratively analyzed, resulting in the confident formulation of conclusions regarding the ability of metformin to reduce the metabolic adverse effects of olanzapine.
Results: Through this review, adjunctive metformin was shown to play a role in reducing metabolic adverse effects associated with olanzapine. Most notably, its positive effect in reducing weight gain/BMI, triglycerides, liver fat content, and insulin resistance—all of which contribute to metabolic syndrome. Furthermore, the addition of metformin was shown to have no impact on waist circumference and certain lipid parameters such as LDL and total cholesterol, warranting further research. However, employing this evidence in the production of guidelines to benefit patients with schizophrenia remains a challenge due to the lack of evidence in the form of randomized controlled trials surrounding the dose-dependent effects, as well as age and gender differences of metformin on olanzapine therapy.
Conclusion: Metformin addition to olanzapine therapy showed variable effects on some metabolic parameters such as waist circumference and certain lipid parameters. However, it did show consistent effects in managing body weight/BMI, insulin resistance, triglycerides, and liver fat content. This conforms to previous but limited evidence surrounding the use of metformin in reducing metabolic adverse effects of olanzapine therapy. Based on evidence gaps, this review also proposes areas of additional research and offers recommendations, including the use of longer RCTs, larger demographics to determine if the data can be extrapolated to a wider population, and the use of varying doses to ascertain the dose-dependent effects of metformin in alleviating metabolic adverse effects associated with olanzapine therapy
Association of atypical antipsychotics with Lipid abnormalities in adult patients With schizophrenia: A scoping review
No full textBackground: Atypical antipsychotics (AAs) are commonly used in the treatment of schizophrenia and are often preferred as first‐line therapy over typical antipsychotics (TAs) due to their lower risk of extrapyramidal side effects. Both groups are efficacious in treating symptoms of schizophrenia, but increasing research has highlighted AAs as being associated with a risk of developing dyslipidaemia. Existing research has pointed to the need for more data focusing on the effects of individual AAs on dyslipidaemia in this population. Methods: The scoping review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses extension for Scoping reviews (PRISMA‐ScR) checklist. The thematic analysis was used to synthesize data from 12 studies selected through structured searches across six databases. Inclusion criteria focused on primary studies between 2015 and 2025 involving adult patients with schizophrenia (18–65 years) treated with AAs and reporting on lipid abnormalities. The themes were identified via Braun and Clarke's six‐step framework. Results: Clozapine and olanzapine were most strongly associated with increased LDL, total cholesterol, and triglycerides, and reduced HDL. Aripiprazole and lurasidone showed minimal impact. Identified biomarkers included asprosin, IGFBP‐2, MIF, and white blood cell counts. Pharmacogenetic markers such as APOA1 gene polymorphisms and specific SNPs were also linked to lipid profile variability. Anthropometric indicators like waist‐to‐hip ratio were correlated with dyslipidaemic risk. Conclusion: The review shows significant associations between specific AAs and lipid abnormalities, particularly with clozapine and olanzapine. Biomarkers and genetic polymorphisms offer promising avenues for monitoring and personalized treatment. Evidence for certain AAs, such as amisulpride, paliperidone, and ziprasidone, remains sparse, highlighting the need for further targeted research. These findings support informed prescribing and the development of predictive tools to mitigate metabolic risks in the treatment of schizophrenia
Is Aripiprazole an effective adjunct to reduce metabolic adverse effects cause by Clozapine in Schizophrenic Patients: A Systematic Review
No full textBackground: Clozapine is an atypical antipsychotic drug which is used in the treatment of psychotic disorders such as schizophrenia. It has been associated with adverse effects such as, hyperglycaemia, hypercholesterolaemia and weight gain. It has been suggested that Aripiprazole (a newer atypical antipsychotic) reduces some of the metabolic adverse effects caused by Clozapine. This systematic review aims to assess the evidence regarding the effectiveness of adjunctive Aripiprazole (to Clozapine) to reduce these adverse effects
Methods: A systematic review was conducted with a narrative synthesis (due to heterogeneity in the data) by one individual. A comprehensive search strategy was developed and applied to five academic search engines. Using the PRISMA flow diagram, the search had a total of 52 results with final inclusion of 8 research articles. Based on specific inclusion and exclusion criteria, a broad range of study designs were included in the review to investigate the effect of adjunctive Aripiprazole on Clozapine induced metabolic adverse effects. Key outcomes were identified which included: glucose levels, lipid profile, body weight and waist circumference. The results were narratively synthesised, and conclusions were drawn based on the information found.
Results: Adjunctive Aripiprazole may have a role in improving LDL and total cholesterol levels in addition to body weight in those receiving treatment with Clozapine. Fasting glucose levels and waist circumference showed some improvement, but overall evidence is currently limited. Since there is limited research in the form of randomised control trials, further research is required in order to provide accurate evidence-based guidelines for clinical practice.
Conclusions: Adjunctive Aripiprazole showed variable effects on metabolic parameters with Clozapine use, however reductions in LDL, total cholesterol and bodyweight appeared consistent among the majority of the data. This showed that Aripiprazole does have some effect in reducing metabolic adverse effects caused by Clozapine however, the complex nature of possible factors that could determine metabolic changes highlights a need for further investigation and consideration of individual subject factors. In addition, gaps in the current research such as longer RCTs, boarder demographics and limited research regarding effective dose response, prompt the need for further investigation
Exploring the metabolic adverse effects induced by Nilotinib in adult patients diagnosed with Chronic Myeloid Leukaemia – A Scoping Review
No full textBackground: Chronic myeloid leukaemia (CML), characterised by the BCR-ABL1 gene mutation, is a myeloproliferative condition primarily managed with tyrosine kinase inhibitors (TKIs), such as 2nd generation Nilotinib. However, the wide range of therapies available, alongside the generally favourable outcomes, may lead to the misconception that CML is a straightforward disease to manage. This attitude can expose high-risk patients to delayed treatment responses, insufficient attention to toxicity concerns and poor outcomes. Thus, a scoping review was conducted to address these concerns, particularly the metabolic safety profile of Nilotinib.
Methods: This review utilised the PRISMA Extension for Scoping Review (PRISMA-ScR) checklist as a foundation for research. A systematic literature search was conducted across multiple databases, and these studies were inputted into Rayyan software. Fifteen studies met the inclusion criteria following a comprehensive review process and data were synthesised through thematic analysis. The papers consisted primarily of observational cohort studies, however there was also 1 randomised controlled trial (RCT) and 1 case report.
Results: All the studies observed adverse Nilotinib-induced metabolic changes, and most commented on the long-term cardiovascular implications of these adverse effects. One of the most prevalent adverse effects was hyperglycaemia; according to several studies, up to 11% of patients experienced grade 3/4 hyperglycaemic episodes and elevated fasting glucose levels. Significant rises in HbA1c, however, were rare. Within three to six months of starting medication, lipid abnormalities such as increased LDL, HDL, and total cholesterol were noted, indicating the necessity of proactive lipid monitoring. Although no clear connection to pancreatitis was found, elevated pancreatic enzymes were also reported. Cardiovascular implications, including increased risk of diabetes, dyslipidaemia, and peripheral arterial disease, were evident, with higher cumulative CV events in patients on prolonged Nilotinib therapy, particularly at higher doses.
Conclusions: Findings highlight the need for robust cardiovascular risk assessment and careful monitoring of Nilotinib's metabolic effects to reduce long-term risks
Antihyperglycaemic and antihyperlipidemic effects of ethanolic extract of syzygium aromaticum(clove)/in streptozotocin induced diabetic rats
No full textObjective: The purpose of the present study was to assess the effect of ethanolic extract of Syzygium aromaticum buds in streptozotocin(STZ) induced diabetes in rats. Study Design: Randomized controlled trial Place and Duration of Study: This study was conducted at the Department of Pharmacology, Islamic International Medical College, Rawalpindi from 1 st Jan 2011 to 30 st June 2011. Materials and Methods: Single injection of STZ was given intraperitoneally to rats and rats showed fasting glucose level over 280mg/dl were included in the study. After induction of diabetes all rats were divided into, normal control group (A), diabetes positive control group (B), and the two groups (C and D) served as experimental groups while group E served as standard as it received glibenclamide. Group C and D diabetic experimental rats received ethanolic extract of Syzygium aromaticum at 250 mg/kg and 500mg/kg of body weight orally for eight weeks on daily basis. On the other hand group E rats received glibenclamide at 0.5 mg/kg body weight orally for eight weeks. Blood samples were collected after eight weeks. Results: The diabetic positive group rats showed variable increase in serum levels of glucose, triglycerides, low density lipoprotein (LDL) and total cholesterol levels. Serum high density lipoprotein (HDL) levels decreased in diabetic positive group. Syzygium aromaticum 250mg/kg and 500mg/kg dose and glibenclamide significantly decreased the levels of these parameters in rats. On comparison Syzygium aromaticum 500mg/kg dose reduced glucose and lipid levels more, effectively than the 250mg/kg dose of Syzygium aromaticum and glibenclamide. Syzygium aromaticum constituents, especially polyphenols and flavonoids have strong anti-oxidant activity which might be involved in glucose and lipid lowering effect. Conclusion: Syzygium aromaticum ethanolic extract decrease glucose and lipid levels in experimentally induced diabetic rats.</p
