Comparative cardiovascular safety of risperidone and olanzapine, based on electrocardiographic parameters and blood pressure: A prospective open label observational study

Choure, Balwant K.; Gosavi, Devesh D; Nanotkar, Sanjay

doi:10.4103/0253-7613.140579

Cited by 10 publications

(9 citation statements)

References 19 publications

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“…Our anatomical analysis shows that olanzapine activates the parasympathetic branch of the ANS, with melatonin vastly mitigating this effect. To evaluate the functional significance of this finding, we measured the acute effects of olanzapine and melatonin on blood pressure and heart rate; two variables influenced by autonomic function and modified by olanzapine. In agreement with the observed increase in activity of DMV neurons, olanzapine also induced a significant decrease in systolic, diastolic and mean arterial blood pressure (MAP), as well as in heart rate.…”

Section: Resultsmentioning

confidence: 62%

“…Parasympathetic activity plays a key role in blood pressure regulation, adiposity and metabolic activity.Acutely, olanzapine induces a potent increase of parasympathetic tone translated into a decrease in blood pressure and heart rate in rats and postural hypotension in humans. Parasympathetic hyperactivation may contribute to the development of metabolic syndrome, obesity or other SGA‐induced adverse metabolic effects.…”

Section: Resultsmentioning

confidence: 99%

“…Olanzapine is a SGA effectively used to treat patients with mental disorders, but unfortunately induces adverse cardiometabolic effects including weight gain, fat mass, glucose, insulin, and lipid increases. Interestingly, in rats and humans, acute SGA treatment may induce hypotension, while long‐term SGA treatment is associated with increased blood pressure. In consequence, they have become an enormous health problem in a population in which the risk of metabolic abnormalities is two to threetimes greater than that of the general population.…”

Section: Introductionmentioning

confidence: 99%

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Olanzapine‐induced early cardiovascular effects are mediated by the biological clock and prevented by melatonin

Romo‐Nava

Buijs

Valdés-Tovar

et al. 2017

Journal of Pineal Research

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Second generation antipsychotics (SGA) are associated with adverse cardiometabolic side effects contributing to premature mortality in patients. While mechanisms mediating these cardiometabolic side effects remain poorly understood, three independent studies recently demonstrated that melatonin was protective against cardiometabolic risk in SGA-treated patients. As one of the main target areas of circulating melatonin in the brain is the suprachiasmatic nucleus (SCN), we hypothesized that the SCN is involved in SGA-induced early cardiovascular effects in Wistar rats. We evaluated the acute effects of olanzapine and melatonin in the biological clock, paraventricular nucleus and autonomic nervous system using immunohistochemistry, invasive cardiovascular measurements, and Western blot. Olanzapine induced c-Fos immunoreactivity in the SCN followed by the paraventricular nucleus and dorsal motor nucleus of the vagus indicating a potent induction of parasympathetic tone.The involvement of a SCN-parasympathetic neuronal pathway after olanzapine administration was further documented using cholera toxin-B retrograde tracing and vasoactive intestinal peptide immunohistochemistry. Olanzapine-induced decrease in blood pressure and heart rate confirmed this. Melatonin abolished olanzapineinduced SCN c-Fos immunoreactivity, including the parasympathetic pathway and cardiovascular effects while brain areas associated with olanzapine beneficial effects including the striatum, ventral tegmental area, and nucleus accumbens remained activated. In the SCN, olanzapine phosphorylated the GSK-3β, a regulator of clock activity, which melatonin prevented. Bilateral lesions of the SCN prevented the effects of olanzapine on parasympathetic activity. Collectively, results demonstrate the SCN as a key region mediating the early effects of olanzapine on cardiovascular function and show melatonin has opposing and potentially protective effects warranting additional investigation. K E Y W O R D Sblood pressure, cardiovascular, melatonin, olanzapine, suprachiasmatic nucleus

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Section: Resultsmentioning

confidence: 62%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Olanzapine‐induced early cardiovascular effects are mediated by the biological clock and prevented by melatonin

Romo‐Nava

Buijs

Valdés-Tovar

et al. 2017

Journal of Pineal Research

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“…AAP-induced metabolic syndrome consists of excessive weight gain, type II diabetes mellitus, hyperglycemia, dyslipidemia, insulin resistance and cardiovascular disease 3 – 7 , 9 , 10 . Of note, the incidence of cardiovascular mortality in the schizophrenic population is over twice that of the general population 5 , 11 , which may also be related to AAP treatment. Consequently, it is important to monitor the metabolic function of patients with schizophrenia, who have a higher risk of metabolic disorders due to the use of AAPs.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of Insig-2 inhibits atypical antipsychotic-induced adipogenic differentiation and lipid biosynthesis in adipose-derived stem cells

Chen

Hsu

Huang

et al. 2017

Sci Rep

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Atypical antipsychotics (AAPs) are considered to possess superior efficacy for treating both the positive and negative symptoms of schizophrenia; however, AAP use often causes excessive weight gain and metabolic abnormalities. Recently, several reports have demonstrated that AAPs activate sterol regulatory element-binding protein (SREBP). SREBP, SREBP cleavage-activating protein (SCAP) and insulin-induced gene (Insig) regulate downstream cholesterol and fatty acid biosynthesis. In this study, we explored the effects of clozapine, olanzapine and risperidone on SREBP signaling and downstream lipid biosynthesis genes in the early events of adipogenic differentiation in adipose-derived stem cells (ASCs). After the induction of adipogenic differentiation for 2 days, all AAPs, notably clozapine treatment for 3 and 7 days, enhanced the expression of SREBP-1 and its downstream lipid biosynthesis genes without dexamethasone and insulin supplementation. Simultaneously, protein level of SREBP-1 was significantly enhanced via inhibition of Insig-2 expression. By contrast, SREBP-1 activation was suppressed when Insig-2 expression was upregulated by transfection with Insig-2 plasmid DNA. In summary, our results indicate that AAP treatment, notably clozapine treatment, induces early-stage lipid biosynthesis in ASCs. Such abnormal lipogenesis can be reversed when Insig-2 expression was increased, suggesting that Insig/SCAP/SREBP signaling may be a therapeutic target for AAP-induced weight gain and metabolic abnormalities.

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“…The studies by Hempel et al and Choure et al, found that risperidone did not cause significant changes in blood pressure while the present study found a decrease in initial two months followed by regaining normal range. 13,14 This may be due to risperidone significant action at alpha-2 adrenergic receptors. Metabolic syndrome developed in 18.86% of the patients in the present study, with 4 patients in haloperidol group (16.6%) and 6 patients in risperidone group (20.6%).…”

Section: Discussionmentioning

confidence: 99%

A comparative study between first generation and second generation antipsychotics over the development of metabolic syndrome in persons with first episode drug naive schizophrenia

Pakkiyalakshmi¹,

Suriyamoorthi²,

Ravishankar³

2018

Int J Res Med Sci

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Background: Antipsychotic treatment for schizophrenia is prone for drug side effects. Both typical and atypical antipsychotics are prone for metabolic derangements. The aim of this study was to compare the emergence of metabolic syndrome with haloperidol and risperidone in drug naïve first episode schizophrenics.Methods: This was a prospective observational study conducted at the Institute of Mental health, Chennai, India from April 1, 2011 to November 15, 2011. 24 patients received haloperidol and 29 patients received risperidone and followed up for 6 months, after obtaining informed consent. PANSS score, AHA criteria for metabolic syndrome, plasma glucose, waist-hip ratio, body mass index and lipid profile were recorded at every two months interval.Results: PANSS score showed a decrease in both groups, systolic blood pressure showed an increase with Haloperidol and an initial decrease with risperidone while diastolic blood pressure increased with haloperidol. Weight gain, increase in waist circumference and hip circumference, rise in triglyceride levels and fall in HDL cholesterol were equally observed in both groups. Increase in plasma glucose was seen more with risperidone (93.1%). 18.86% (n = 10) developed metabolic syndrome at the end of 6months with no difference in emergence between both groups.Conclusions: Risperidone may be considered equivalent to haloperidol in efficacy and with minimal changes in metabolic profile. Blood pressure lowering effect of risperidone is more marked in earlier months warranting patient education. Stringent guidelines are needed during antipsychotic treatment to prevent cardiovascular and cerebrovascular morbidity and mortality.

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Comparative cardiovascular safety of risperidone and olanzapine, based on electrocardiographic parameters and blood pressure: A prospective open label observational study

Cited by 10 publications

References 19 publications

Olanzapine‐induced early cardiovascular effects are mediated by the biological clock and prevented by melatonin

Olanzapine‐induced early cardiovascular effects are mediated by the biological clock and prevented by melatonin

Overexpression of Insig-2 inhibits atypical antipsychotic-induced adipogenic differentiation and lipid biosynthesis in adipose-derived stem cells

A comparative study between first generation and second generation antipsychotics over the development of metabolic syndrome in persons with first episode drug naive schizophrenia

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