scholarly journals A comparison of the metabolic side-effects of the second-generation antipsychotic drugs risperidone and paliperidone in animal models

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0246211
Author(s):  
Heidi N. Boyda ◽  
Ric M. Procyshyn ◽  
Lurdes Tse ◽  
Jessica W. Y. Yuen ◽  
William G. Honer ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Side Effects ◽  
Glucose Tolerance ◽  
Antipsychotic Drugs ◽  
Second Generation ◽  
Fasting Glucose ◽  
Metabolic Effects ◽  
Metabolic Side Effects ◽  
Second Generation Antipsychotic ◽  
Dose Dependent

Background The second generation antipsychotic drugs represent the most common form of pharmacotherapy for schizophrenia disorders. It is now well established that most of the second generation drugs cause metabolic side-effects. Risperidone and its active metabolite paliperidone (9-hydroxyrisperidone) are two commonly used antipsychotic drugs with moderate metabolic liability. However, there is a dearth of preclinical data that directly compares the metabolic effects of these two drugs, using sophisticated experimental procedures. The goal of the present study was to compare metabolic effects for each drug versus control animals. Methods Adult female rats were acutely treated with either risperidone (0.1, 0.5, 1, 2, 6 mg/kg), paliperidone (0.1, 0.5, 1, 2, 6 mg/kg) or vehicle and subjected to the glucose tolerance test; plasma was collected to measure insulin levels to measure insulin resistance with HOMA-IR. Separate groups of rats were treated with either risperidone (1, 6 mg/kg), paliperidone (1, 6 mg/kg) or vehicle, and subjected to the hyperinsulinemic euglycemic clamp. Results Fasting glucose levels were increased by all but the lowest dose of risperidone, but only with the highest dose of paliperidone. HOMA-IR increased for both drugs with all but the lowest dose, while the three highest doses decreased glucose tolerance for both drugs. Risperidone and paliperidone both exhibited dose-dependent decreases in the glucose infusion rate in the clamp, reflecting pronounced insulin resistance. Conclusions In preclinical models, both risperidone and paliperidone exhibited notable metabolic side-effects that were dose-dependent. Differences between the two were modest, and most notable as effects on fasting glucose.

scholarly journals Metabolic Side-Effects of the Novel Second-Generation Antipsychotic Drugs Asenapine and Iloperidone: A Comparison with Olanzapine

PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e53459 ◽  
Author(s):  
Heidi N. Boyda ◽  
Ric M. Procyshyn ◽  
Catherine C. Y. Pang ◽  
Erin Hawkes ◽  
Daniel Wong ◽  
...  
Keyword(s):  
Side Effects ◽  
Antipsychotic Drugs ◽  
Second Generation ◽  
The Novel ◽  
Metabolic Side Effects ◽  
Second Generation Antipsychotic

Metabolic side effects of second generation antipsychotic drugs in adolescents

2013 ◽  
Author(s):  
Iuliana Dobrescu ◽  
Florina Rad ◽  
Gianina Cristina Anghel ◽  
Cristina Petrescu-Ghenea ◽  
Carmen Trutescu
Keyword(s):  
Side Effects ◽  
Antipsychotic Drugs ◽  
Second Generation ◽  
Metabolic Side Effects ◽  
Second Generation Antipsychotic

scholarly journals Differential Effects of Acute Treatment With Antipsychotic Drugs on Peripheral Catecholamines

2020 ◽  
Vol 11 ◽  
Author(s):  
Heidi N. Boyda ◽  
Amanzo A. Ho ◽  
Lurdes Tse ◽  
Ric M. Procyshyn ◽  
Jessica W. Y. Yuen ◽  
...  
Keyword(s):  
Side Effects ◽  
Acute Treatment ◽  
First Generation ◽  
Antipsychotic Drugs ◽  
Second Generation ◽  
Psychotic Disorders ◽  
Female Rats ◽  
Maximum Increase ◽  
Sympathetic Nervous ◽  
Dose Dependent

Antipsychotic drugs represent the most effective treatment for chronic psychotic disorders. The newer second generation drugs offer the advantage of fewer neurological side-effects compared to prior drugs, but many cause serious metabolic side-effects. The underlying physiology of these side-effects is not well-understood, but evidence exists to indicate that the sympathetic nervous system may play an important role. In order to examine this possibility further, we treated separate groups of adult female rats acutely with either the first generation antipsychotic drug haloperidol (0.1 or 1 mg/kg) or the second generation drugs risperidone (0.25 or 2.5 mg/kg), clozapine (2 or 20 mg/kg), olanzapine (3 or 15 mg/kg) or vehicle by intraperitoneal injection. Blood samples were collected prior to drug and then 30, 60, 120, and 180 mins after treatment. Plasma samples were assayed by HPLC-ED for levels of norepinephrine, epinephrine, and dopamine. Results confirmed that all antipsychotics increased peripheral catecholamines, although this was drug and dose dependent. For norepinephrine, haloperidol caused the smallest maximum increase (+158%], followed by risperidone (+793%), olanzapine (+952%) and clozapine (+1,684%). A similar pattern was observed for increases in epinephrine levels by haloperidol (+143%], olanzapine (+529%), risperidone (+617%) then clozapine (+806%). Dopamine levels increased moderately with olanzapine [+174%], risperidone [+271%], and clozapine [+430%]. Interestingly, levels of the catecholamines did not correlate strongly with each other prior to treatment at baseline, but were increasingly correlated after treatment as time proceeded. The results demonstrate antipsychotics can potently regulate peripheral catecholamines, in a manner consistent with their metabolic liability.

scholarly journals Second-Generation Antipsychotic Drugs and Extrapyramidal Side Effects: A Systematic Review and Meta-analysis of Head-to-Head Comparisons

2010 ◽  
Vol 38 (1) ◽  
pp. 167-177 ◽  
Author(s):  
Christine Rummel-Kluge ◽  
Katja Komossa ◽  
Sandra Schwarz ◽  
Heike Hunger ◽  
Franziska Schmid ◽  
...  
Keyword(s):  
Systematic Review ◽  
Side Effects ◽  
Antipsychotic Drugs ◽  
Second Generation ◽  
Meta Analysis ◽  
Extrapyramidal Side Effects ◽  
Second Generation Antipsychotic

scholarly journals Pathophysiology of drug induced weight and metabolic effects: findings from an RCT in healthy volunteers treated with olanzapine, iloperidone, or placebo

2018 ◽  
Vol 32 (5) ◽  
pp. 533-540 ◽  
Author(s):  
Jacob S Ballon ◽  
Utpal B Pajvani ◽  
Laurel ES Mayer ◽  
Zachary Freyberg ◽  
Robin Freyberg ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Energy Expenditure ◽  
Glucose Tolerance ◽  
Healthy Volunteers ◽  
Second Generation ◽  
Metabolic Effects ◽  
Insulin Metabolism

Second generation antipsychotics are prescribed for an increasing number of psychiatric conditions, despite variable associations with weight gain, dyslipidemia, and impaired glucose tolerance. The mechanism(s) of the apparent causal relationships between these medications and metabolic effects have been inadequately defined and are potentially confounded by genetic risk of mental illness, attendant lifestyle, and concomitant medications. Therefore, we conducted a study in which 24 healthy volunteers were randomized to olanzapine (highly weight-gain liability), iloperidone (less weight-gain liability), or placebo treatment for 28 days under double-blind conditions. We hypothesized that antipsychotics induce weight gain primarily through increased caloric intake, which causes secondary dyslipidemia and insulin resistance. Subjects were phenotyped pre- and post-treatment for body weight, adiposity by dual energy X-ray absorptiometry, energy expenditure by indirect calorimetry, food intake, oral glucose tolerance, plasma lipids, glucose, insulin, and other hormones. We found significantly increased food intake and body weight but no change in energy expenditure in olanzapine-treated subjects, with associated trends towards lipid abnormalities and insulin resistance the extent of which were presumably limited by the duration of treatment. Iloperidone treatment led to modest non-significant and placebo no weightgain, lipid increases and alterations in insulin metabolism. We conclude that second generation antipsychotic drugs, as represented by olanzapine, produce their weight and metabolic effects, predominantly, by increasing food intake which leads to weight gain that in turn induces metabolic consequences, but also through other direct effects on lipid and glucose metabolism independant of food intake and weight gain.

Metabolic side effects of second generation antipsychotic agents in antipsychotic-naïve patients: One-month prospective evaluation

2008 ◽  
Vol 157 (1-3) ◽  
pp. 269-271 ◽  
Author(s):  
Ilaria Tarricone ◽  
Alessandro Serretti ◽  
Beatrice Ferrari Gozzi ◽  
Laura Mandelli ◽  
Daniela Grieco ◽  
...  
Keyword(s):  
Side Effects ◽  
Second Generation ◽  
Antipsychotic Agents ◽  
Prospective Evaluation ◽  
Metabolic Side Effects ◽  
Second Generation Antipsychotic

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

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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