Effect of liraglutide on neural and peripheral markers of metabolic function during antipsychotic treatment in rats

Background: Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that prevents metabolic side effects of the antipsychotic drugs (APDs) olanzapine and clozapine through unknown mechanisms. Aim: This study aimed to investigate the effect of chronic APD and liraglutide co-treatment on key neural and peripheral metabolic signals, and acute liraglutide co-treatment on clozapine-induced hyperglycaemia. Methods: In study 1, rats were administered olanzapine (2 mg/kg), clozapine (12 mg/kg), liraglutide (0.2 mg/kg), olanzapine + liraglutide co-treatment, clozapine + liraglutide co-treatment or vehicle for six weeks. Feeding efficiency was examined weekly. Examination of brain tissue (dorsal vagal complex (DVC) and mediobasal hypothalamus (MBH)), plasma metabolic hormones and peripheral (liver and kidney) cellular metabolism and oxidative stress was conducted. In study 2, rats were administered a single dose of clozapine (12 mg/kg), liraglutide (0.4 mg/kg), clozapine + liraglutide co-treatment or vehicle. Glucose tolerance and plasma hormone levels were assessed. Results: Liraglutide co-treatment prevented the time-dependent increase in feeding efficiency caused by olanzapine, which plateaued by six weeks. There was no effect of chronic treatment on melanocortinergic, GABAergic, glutamatergic or endocannabionoid markers in the MBH or DVC. Peripheral hormones and cellular metabolic markers were unaltered by chronic APD treatment. Acute liraglutide co-treatment was unable to prevent clozapine-induced hyperglycaemia, but it did alter catecholamine levels. Conclusion: The unexpected lack of change to central and peripheral markers following chronic treatment, despite the presence of weight gain, may reflect adaptive mechanisms. Further studies examining alterations across different time points are required to continue to elucidate the mechanisms underlying the benefits of liraglutide on APD-induced metabolic side effects.

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Liraglutide prevents metabolic side-effects and improves recognition and working memory during antipsychotic treatment in rats

Journal of Psychopharmacology ◽

10.1177/0269881118756061 ◽

2018 ◽

Vol 32 (5) ◽

pp. 578-590 ◽

Cited By ~ 10

Author(s):

Ilijana Babic ◽

Ashleigh Gorak ◽

Martin Engel ◽

Dominic Sellers ◽

Paul Else ◽

...

Keyword(s):

Working Memory ◽

Weight Gain ◽

Locomotor Activity ◽

Side Effects ◽

Antipsychotic Treatment ◽

Clozapine Treatment ◽

Metabolic Side Effects ◽

Glucagon Like Peptide ◽

Test Discrimination ◽

Glucagon Like Peptide 1

Background: Antipsychotic drugs (APDs), olanzapine and clozapine, do not effectively address the cognitive symptoms of schizophrenia and can cause serious metabolic side-effects. Liraglutide is a synthetic glucagon-like peptide-1 (GLP-1) receptor agonist with anti-obesity and neuroprotective properties. The aim of this study was to examine whether liraglutide prevents weight gain/hyperglycaemia side-effects and cognitive deficits when co-administered from the commencement of olanzapine and clozapine treatment. Methods: Rats were administered olanzapine (2 mg/kg, three times daily (t.i.d.)), clozapine (12 mg/kg, t.i.d.), liraglutide (0.2 mg/kg, twice daily (b.i.d.)), olanzapine + liraglutide co-treatment, clozapine + liraglutide co-treatment or vehicle (Control) ( n = 12/group, 6 weeks). Recognition and working memory were examined using Novel Object Recognition (NOR) and T-Maze tests. Body weight, food intake, adiposity, locomotor activity and glucose tolerance were examined. Results: Liraglutide co-treatment prevented olanzapine- and clozapine-induced reductions in the NOR test discrimination ratio ( p < 0.001). Olanzapine, but not clozapine, reduced correct entries in the T-Maze test ( p < 0.05 versus Control) while liraglutide prevented this deficit. Liraglutide reduced olanzapine-induced weight gain and adiposity. Olanzapine significantly decreased voluntary locomotor activity and liraglutide co-treatment partially reversed this effect. Liraglutide improved clozapine-induced glucose intolerance. Conclusion: Liraglutide co-treatment improved aspects of cognition, prevented obesity side-effects of olanzapine, and the hyperglycaemia caused by clozapine, when administered from the start of APD treatment. The results demonstrate a potential treatment for individuals at a high risk of experiencing adverse effects of APDs.

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Long-term metabolic effect of second-generation antipsychotics in first episode of psychosis

European Psychiatry ◽

10.1016/j.eurpsy.2017.02.431 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S388-S388

Author(s):

J. Vázquez Bourgon ◽

R. Pérez-Iglesias ◽

V. Ortiz-García de la Foz ◽

B. Crespo-Facorro

Keyword(s):

Side Effects ◽

Second Generation ◽

Resistance Index ◽

Metabolic Parameters ◽

First Episode ◽

Antipsychotic Treatment ◽

Metabolic Side Effects ◽

Long Term Follow Up ◽

Competing Interest

IntroductionThere is growing evidence indicating that the use of second-generation antipsychotic (SGA) treatments in psychosis is related to potential metabolic side effects. Previous studies have shown clear metabolic side effects at short-term (12 weeks). However, to detect clinically-relevant impairment in metabolic parameters a long-term follow-up is preferred.ObjectivesThe aim of this study was to investigate the effect of aripiprazole, ziprasidone and quetiapine on metabolic measures in medication-naïve first episode psychosis patients after 1 year of treatment.MethodsOne hundred and sixty-eight, drug-naïve patients, suffering from a non-affective first episode of psychosis, were included in the present study. Patients were randomly assigned to quetiapine, ziprasidone or aripiprazole treatment lines. Weight and glucemic/lipid parameters were recorded at baseline and after 1 year of treatment. Other clinical and socio-demographic variables were recorded to eliminate potential confounding effects.ResultsWeight (t = −10.85; P < 0.001), BMI (t = −11.38; P < 0.001), total cholesterol (t = −5.37; P < 0.001), LDL-cholesterol (t = −5.21; P < 0.001), triglycerides (t = −5.18; P < 0.001) and the triglyceride/HDL insulin resistance index (t = −4.09; P < 0.001), showed statistically significant increments after 1 year of treatment.Moreover, on comparing the percentage of patients with pathological levels before and 1 year after the antipsychotic treatment, we detected higher percentages of patients with obesity (5.1% vs. 15.3%; P < 0.001), hypercholesterolemia (23.2% vs. 39.6%; P < 0.001) and hypertriglyceridemia (5.8% vs. 14.2%; P = 0.021) after 1 year of treatment.ConclusionsThe primary exposure to SGAs during the first year of psychosis was associated with significant increments in weight and metabolic parameters leading to a significant increment in the proportion of obesity, hypertriglyceridemia and hypercholesterolemia in our sample.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Chronic treatment with olanzapine increases adiposity by changing fuel substrate and causes desensitization of the acute metabolic side effects

Naunyn-Schmiedeberg s Archives of Pharmacology ◽

10.1007/s00210-013-0933-5 ◽

2013 ◽

Vol 387 (2) ◽

pp. 185-195 ◽

Cited By ~ 8

Author(s):

Elodie M. Girault ◽

Bruno Guigas ◽

Anneke Alkemade ◽

Ewout Foppen ◽

Mariëtte T. Ackermans ◽

...

Keyword(s):

Side Effects ◽

Chronic Treatment ◽

Metabolic Side Effects

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GLP1 receptor agonism protects against acute olanzapine-induced hyperglycemia

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00309.2020 ◽

2020 ◽

Vol 319 (6) ◽

pp. E1101-E1111 ◽

Cited By ~ 1

Author(s):

Kyle D. Medak ◽

Hesham Shamshoum ◽

Willem T. Peppler ◽

David C. Wright

Keyword(s):

Lipid Metabolism ◽

Side Effects ◽

Antipsychotic Drug ◽

Antipsychotic Drugs ◽

Glucose And Lipid Metabolism ◽

Metabolic Dysregulation ◽

Metabolic Side Effects ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Effective Adjunct

Antipsychotic drugs cause rapid perturbations in glucose and lipid metabolism. In the present study we have demonstrated that cotreatment with glucagon-like peptide 1 (GLP1) receptor agonists, such as liraglutide, protects against metabolic dysregulation caused by the antipsychotic drug olanzapine. These findings suggest that pharmacological targeting of the GLP1 receptor could be an effective adjunct approach to mitigate the harmful acute metabolic side effects of antipsychotic drugs.

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Strategies for prevention and management of second generation antipsychotic-induced metabolic side effects

Mental Health Clinician ◽

10.9740/mhc.n166832 ◽

2013 ◽

Vol 3 (3) ◽

pp. 154-161

Author(s):

Marketa Marvanova

Keyword(s):

Metabolic Syndrome ◽

Side Effects ◽

Second Generation ◽

Treatment Modalities ◽

Atherogenic Dyslipidemia ◽

Antipsychotic Treatment ◽

Metabolic Abnormalities ◽

Metabolism Regulation ◽

Metabolic Side Effects ◽

Second Generation Antipsychotic

Preventing, minimizing and managing risks associated with second generation antipsychotic (SGA) use in patients with schizophrenia and other psychotic disorders is a priority for clinicians working with this population. Among these risks is metabolic syndrome. As this population exhibits increased rates of obesity, diabetes and atherogenic dyslipidemia compared to the general population, metabolic syndrome deserves serious consideration in patient care planning for managing risks. This article comprehensively reviews different strategies and recommendations for prevention and/or management of metabolic abnormalities associated with the use of SGAs. Baseline screening and follow-up metabolic monitoring as well as education and counseling on risk for SGA-induced weight gain and other metabolic abnormalities, physical activity and healthy diet for weight maintenance/loss should be promoted shortly after initiation of SGAs. In select patients, the clinician can consider simplifying the antipsychotic treatment regimen by switching to an agent with a lower propensity of metabolic side effects or possibly adding metformin for weight loss and glucose metabolism regulation in those experiencing a first episode of schizophrenia. Future research should focus on combinations of interventions and treatment modalities and exploration of novel interventions.

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The effect of spinach-derived thylakoids on anthropometric parameters and metabolic profile in antipsychotic treatment: A case report

Medical Research Archives ◽

10.18103/mra.v9i8.2498 ◽

2021 ◽

Vol 9 (8) ◽

Author(s):

Kajsa Lycken ◽

Charlotte Albertsson

Keyword(s):

Body Weight ◽

Case Report ◽

Side Effects ◽

Adverse Effects ◽

Psychotic Disorders ◽

Lifestyle Changes ◽

Antipsychotic Treatment ◽

Safe Treatment ◽

Metabolic Side Effects ◽

History Of

Background: Antipsychotics is the first line, evidence-based treatment of schizophrenia and other primary psychotic disorders. Metabolic adverse effects are common, including body weight gain, hypertension and metabolic syndrome. There is still no safe treatment for these adverse effects, except from lifestyle changes. Studies of thylakoids have shown body weight loss and improved metabolic parameters in overweight women. Case report: A 53-year old female with a history of unspecified nonorganic psychosis, treated with Quetiapin and Topimax (Topiramat), was given a supplement of 5g thylakoids daily for 12 weeks. She reported a rapid decrease of sweet craving and loss of body weight was observed. Conclusion: We report a successful treatment with thylakoid supplements of the metabolic side effects of antipsychotics in a female adult with a history of body weight problems and sweet craving. Further investigation and larger studies are needed. A safe treatment of metabolic side effects could increase quality of life for patients in need of antipsychotic treatment.

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