Overdose of Quetiapine—A Case Report with QT Prolongation

Quetiapine is an atypical antipsychotic drug used to treat bipolar disorder, schizophrenia, and major depressive disorder. Although several studies describe the adverse effects of intoxication with Quetiapine, only a few report an extreme overdose without comedications that lead to a life threat. We present a case of a 75-year-old male who tried to attempt suicide by ingesting 28 g of Quetiapine. During the management in the emergency department, both serum and urine samples were collected, allowing a complete pharmacokinetic analysis to be conducted, from the admission to the discharge.

Assessment of the Effects of Dietary Vitamin D Levels on Olanzapine-Induced Metabolic Side Effects: Focus on the Endocannabinoidome-Gut Microbiome Axis

Vitamin D deficiency is associated with poor mental health and dysmetabolism. Several metabolic abnormalities are associated with psychotic diseases, which can be compounded by atypical antipsychotics that induce weight gain and insulin resistance. These side-effects may be affected by vitamin D levels. The gut microbiota and endocannabinoidome (eCBome) are significant regulators of both metabolism and mental health, but their role in the development of atypical antipsychotic drug metabolic side-effects and their interaction with vitamin D status is unknown. We studied the effects of different combinations of vitamin D levels and atypical antipsychotic drug (olanzapine) exposure on whole-body metabolism and the eCBome-gut microbiota axis in female C57BL/6J mice under a high fat/high sucrose (HFHS) diet in an attempt to identify a link between the latter and the different metabolic outputs induced by the treatments. Olanzapine exerted a protective effect against diet-induced obesity and insulin resistance, largely independent of dietary vitamin D status. These changes were concomitant with olanzapine-mediated decreases in Trpv1 expression and increases in the levels of its agonists, including various N-acylethanolamines and 2-monoacylglycerols, which are consistent with the observed improvement in adiposity and metabolic status. Furthermore, while global gut bacteria community architecture was not altered by olanzapine, we identified changes in the relative abundances of various commensal bacterial families. Taken together, changes of eCBome and gut microbiota families under our experimental conditions might contribute to olanzapine and vitamin D-mediated inhibition of weight gain in mice on a HFHS diet.

Protective effects of Cyathula prostrata leaf extract on olanzapine-induced obese rats

Olanzapine, an atypical antipsychotic drug often induces excessive weight resulting in obesity. The adverse effect hinder adherence to drug regimens and therefore relapse into psychosis. Traditionally in Nigeria, leaf broth from Cyathula prostrata leaf is consumed to achieve weight loss. Rats were first administered 50-200 mg/kg bw CPLE and orlistat (5 mg/kg bw), used as reference. Rats were then administered 8 mg/kg bw of olanzapine one hour after the administration of the CPLE and orlistat, all the administration were done for 28 days. Those with body mass index (BMI) ˃ 0.5 g/cm2 were considered obese. The influence of the extract at varying doses on BMI, lipid profiles, oxidative and enzyme markers in the heart and liver of the obese rats were evaluated. Anthropometric data showed that CPLE significantly (p < 0.05) induced weight loss and attenuated BMI increase when compared to untreated olanzapine-induced obese rats. Biochemical analyses also revealed reduction in the serum level of LDL-c, total cholesterol, triglycerides, lipase and creatine kinase activities in CPLE-treated groups. Concentration of malondialdehyde was decreased, while the activities of antioxidant enzymes as well as that of alkaline phosphatase, alanine and aspartate aminotransferase were increased following administration of CPLE to the obese rats. Findings from this study supported the indigenous use of extracts from C. prostrata leaf in the management of obesity. The study concluded that CPLE can protect against weight gain, obesity, dyslipidaemia, oxidative stress and alteration in the heart and liver function parameters induced by olanzapine co-administration in rats.

Risperidone induced tardive dyskinesia

Risperidone is an atypical antipsychotic drug which has been less likely to produce extrapyramidal symptoms. The aim of this case report is to illustrate that low dose risperidone may cause tardive dyskinesia. A 29 year old male patient with 9 year history of paranoid schizophrenia, developed tardive dyskinesia after receiving risperidone 2 mg for 7 years. He had received small dosages of Haloperidol before the therapy of risperidone for short periods.

Atypical Antipsychotic Drug Ziprasidone Protects against Rotenone-Induced Neurotoxicity: An In Vitro Study

Schizophrenia is a severe, chronic mental illness characterized by delusions, hallucinations, negative symptoms, and cognitive dysfunction. Recently, several studies have demonstrated that the pathogenesis of schizophrenia involves mitochondrial dysfunction and oxidative stress. However, the effect of antipsychotic drugs for these events has been poorly investigated. In the present study, we evaluated the neuroprotective effect of an atypical antipsychotic drug, ziprasidone (ZPD), on rotenone (ROT)-induced neurotoxicity involving oxidative stress in PC12 cells. Our data showed that ZPD treatment promoted the translocation of NF-E2-related factor-2 (Nrf2) from cytoplasm to nucleus and activated the expression of its target genes NAD(P)H quinone oxidoreductase (NQO-1), catalase (CAT), and heme oxygenase (HO-1). Additionally, ZPD prevented ROT-induced cell death and intracellular reactive oxygen species production. Interestingly, the use of serotonin 5-HT1A receptor antagonist 1-(2-methoxyphenyl)-4 (4-(2-phtalimido) butyl) piperazine (NAN-190) completely blocked the protective effect of ZPD against ROT-induced cell death. Our results demonstrate the neuroprotective effect of ZPD against ROT-induced neurotoxicity and suggest that ZPD may be a potential candidate for the prevention of mitochondrial dysfunction and oxidative stress in schizophrenia.

Use of sodium tetraphenyl boron for fabrication of potentiometric membrane sensor for the assay of olanzapine in pharmaceuticals and human urine

Olanzapine (OLP), chemically known as 2-Methyl-10-(4-methyl-piperazin-1-yl)-4H-3-thia-4, 9-diaza-benzo[f]azulene, is an atypical antipsychotic drug. It is used for the treatment of schizophrenia and bipolar disorder. A new simple and selective membrane based potentiometric sensor was developed for potentiometric determination of olanzapine. The membrane was constructed using an ion-pair of OLP and sodium tetraphenyl boron in dioctyl phthalate and PVC. The membrane provides good linear Nernstian response covering relatively wide concentration range of 4 × 10-6 - 1 × 10-2 M OLP over pH range of 2.6 - 7.8. The detection limit for the developed sensor was founded as 2.02 × 10-6 M. The response time of developed sensor is <10 s for the range of determination. The sensor showed good selectivity for OLP in the presence of various cations, anions and other organic molecules. The membrane was successfully applied in direct potentiometric determination of OLP in tablets. The percentage recovery of OLP, ranged from 96.2 to 99.68% with a mean standard deviation <5%, indicates the adoptability of sensor for the direct estimation of OLP in pharmaceuticals. The developed sensor was used to determine OLP in spiked human urine sample and the satisfactory results were obtained.

Aripiprazole: An FDA Approved Bioactive Compound to Treat Schizophrenia- A Mini Review

Objective: Aripiprazole, a synthetic compound, obtained by chemical modification of the structure of quinolinone is considered as an atypical antipsychotic drug. The present review is an attempt to summarize the updated information related to reported chemistry and pharmacology of Aripiprazole. Development: Aripiprazole, under development by Otsuka Pharmaceutical, was approved by the U.S. Food and Drug Administration (USFDA) by the end of 2002 with an aim to treat patients with schizophrenia. This drug got approved by European Commission in February 2013 to treat the patients having severe manic episodes in bipolar I disorder Additionally, it got approval in Japan in January 2006 and in Canada in 2014. Pharmacology: Aripiprazole shows high specificity for dopamine receptor especially D2 and D3, serotonin 5-HT1A and serotonin 5-HT2A receptors, reasonable specificity for dopamine D4, serotonin 5- HT2C and 5-HT7, alpha1-adrenergic and histamine H1 receptors. It also shows moderate specificity for the serotonin reuptake. The major side effects include headache, agitation, akithesia, anxiety, tachycardia, insomnia, postural hypotension, constipation, vomiting, dizziness, nervousness and somnolence. Conclusion: The present article embarks the available information on Aripiprazole with emphasis on its clinical pharmacology, mechanism of action, pharmacokinetics, pharmacodynamics, metabolism and clinical trials.