Metabolic syndrome and serum homocysteine in patients with bipolar disorder and schizophrenia treated with second generation antipsychotics

Vuksan-Ćusa, Bjanka; Jakovljević, Miro; Šagud, Marina; Peleš, Alma Mihaljević; Marčinko, Darko; Topić, Radmila; Mihaljević, Sanea; Sertić, Jadranka

doi:10.1016/j.psychres.2010.11.021

Cited by 36 publications

(32 citation statements)

References 37 publications

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“…The mean homocysteine level for the currently recruited patients with schizophrenia was very similar to the results of two previous studies [15], [45]. Glucose and insulin seem to influence the metabolism of homocysteine, possibly through affecting the activity of key enzymes in homocysteine metabolism, including methylenetetrahydrofolate reductase and cystathionine-β-synthase [46].…”

Section: Discussionsupporting

confidence: 85%

“…For example: weight change correlated inversely with the plasma concentration level of DMO [8] and levels of the other metabolic parameters such as insulin correlated positively with the ratio of OLZ to DMO concentration [14] in OLZ-treated patients. An earlier study also revealed a strong association between metabolic syndrome and hyperhomocysteinemic patients with bipolar disorder and schizophrenia treated with second generation antipsychotics [15]. In order to clarify the role of DMO in OLZ-related metabolic changes, the steady-state trough concentrations of OLZ and its metabolite DMO were determined by a validated high performance liquid chromatography with electrochemical detection (HPLC-ECD) system which analyzed OLZ and DMO simultaneously in non-smoking patients with schizophrenia or schizoaffective disorder and who were treated with oral OLZ as the only antipsychotic drug.…”

Section: Introductionmentioning

confidence: 91%

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Determination of Olanzapine and N-desmethyl-olanzapine in Plasma Using a Reversed-Phase HPLC Coupled with Coulochemical Detection: Correlation of Olanzapine or N-desmethyl-olanzapine Concentration with Metabolic Parameters

Lin

Chen

et al. 2013

PLoS ONE

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BackgroundOlanzapine (OLZ) is one of the most prescribed atypical antipsychotic drugs but its use is associated with unfavorable metabolic abnormalities. N-desmethyl-olanzapine (DMO), one of the OLZ metabolites by CYP1A2, has been reported to have a normalizing action on metabolic abnormalities, but this remains unclear. Our aim was to explore the correlation between the concentrations of OLZ or DMO with various metabolic parameters in schizophrenic patients.MethodsThe chromatographic analysis was carried out with a solvent delivery system coupled to a Coulochem III coulometric detector to determine OLZ and DMO simultaneously in OLZ-treated patients. The correlation between the concentration of OLZ or DMO and the metabolic parameters was analyzed by the Spearman rank order correlation method (r s).Principal FindingsThe established analytical method met proper standards for accuracy and reliability and the lower limitation of quantification for each injection of DMO or OLZ was 0.02 ng. The method was successfully used for the analysis of samples from nonsmoking patients (n = 48) treated with OLZ in the dosage range of 5–20 mg per day. There was no correlation between OLZ concentrations and tested metabolic parameters. DMO concentrations were negatively correlated with glucose (r s = –0.45) and DMO concentrations normalized by doses were also negatively correlated with insulin levels (r s = –0.39); however, there was a marginally positive correlation between DMO and homocysteine levels (r s = +0.38).ConclusionsThe observed negative correlations between levels of DMO and glucose or insulin suggest a metabolic normalization role for DMO regardless of its positive correlation with a known cardiovascular risk factor, homocysteine. Additional studies of the mechanisms underlying DMO’s metabolic effects are warranted.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 91%

Determination of Olanzapine and N-desmethyl-olanzapine in Plasma Using a Reversed-Phase HPLC Coupled with Coulochemical Detection: Correlation of Olanzapine or N-desmethyl-olanzapine Concentration with Metabolic Parameters

Lin

Chen

et al. 2013

PLoS ONE

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“…There are also studies showing that the presence of MetS is associated with higher Hcy levels in schizophrenia patients as well as in the general population [30, 31]. However, it remains controversial as to whether MetS related to the use of some SGA increases mortality rate in schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

Effects of second-generation antipsychotics on selected markers of one-carbon metabolism and metabolic syndrome components in first-episode schizophrenia patients

Misiak

Frydecka

Łaczmański

et al. 2014

Eur J Clin Pharmacol

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PurposeAlterations in one-carbon metabolism (OCM) have been repeatedly reported in schizophrenia. However, there is a scarcity of studies addressing the effects of antipsychotics on selected OCM markers in schizophrenia and provided results are inconsistent.MethodsWe recruited 39 first-episode schizophrenia (FES) patients and determined serum profile of total homocysteine (tHcy), folate, vitamin B12, lipoproteins and glucose at baseline and after 12 weeks of treatment with second-generation antipsychotics (SGA) including olanzapine and risperidone in monotherapy.ResultsAfter 12 weeks of treatment, all patients had significantly higher body mass index (BMI), serum levels of total cholesterol (TC), low-density lipoproteins (LDL), triglycerides (TG) and tHcy together with significantly lower levels of folate and vitamin B12. The analysis of differences between SGA revealed the same biochemical alterations in patients treated with olanzapine as in the whole group, while those receiving risperidone had no statistically significant changes in serum folate, vitamin B12 and TG. There was a significantly higher increase in BMI and TC in patients treated with olanzapine in comparison with those treated with risperidone. Patients receiving olanzapine had a higher decrease in vitamin B12 than those assigned to the treatment with risperidone. Changes in folate, vitamin B12, tHcy and TC levels were significant only in males, even after Bonferroni correction. Multiple regression analysis revealed that changes in tHcy levels are associated with gender and baseline metabolic parameters (BMI, glucose, TC, LDL and HDL) but not with selected SGA.ConclusionsThese results indicate that SGA may influence OCM, especially in first-episode schizophrenia (FES) males.Electronic supplementary materialThe online version of this article (doi:10.1007/s00228-014-1762-2) contains supplementary material, which is available to authorized users.

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“…[68] An investigation which evaluated the relationship of MetS with IL-6 in BPAD patients demonstrated that IL-6 levels correlated significantly with a number of criteria of MetS and suggested that it may be a diagnostic marker of MetS. [82]…”

Section: Prevalence Of Components Of Metsmentioning

confidence: 99%

Metabolic Syndrome in Bipolar Disorders

Grover

Malhotra

Chakrabarti

et al. 2012

Indian Journal of Psychological Medicine

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To review the data with respect to prevalence and risk factors of metabolic syndrome (MetS) in bipolar disorder patients. Electronic searches were done in PUBMED, Google Scholar and Science direct. From 2004 to June 2011, 34 articles were found which reported on the prevalence of MetS. The sample size of these studies varied from 15 to 822 patients, and the rates of MetS vary widely from 16.7% to 67% across different studies. None of the sociodemographic variable has emerged as a consistent risk factor for MetS. Among the clinical variables longer duration of illness, bipolar disorder- I, with greater number of lifetime depressive and manic episodes, and with more severe and difficult-to-treat index affective episode, with depression at onset and during acute episodes, lower in severity of mania during the index episode, later age of onset at first manic episode, later age at first treatment for the first treatment for both phases, less healthy diet as rated by patients themselves, absence of physical activity and family history of diabetes mellitus have been reported as clinical risk factors of MetS. Data suggests that metabolic syndrome is fairly prevalent in bipolar disorder patients.

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Metabolic syndrome and serum homocysteine in patients with bipolar disorder and schizophrenia treated with second generation antipsychotics

Cited by 36 publications

References 37 publications

Determination of Olanzapine and N-desmethyl-olanzapine in Plasma Using a Reversed-Phase HPLC Coupled with Coulochemical Detection: Correlation of Olanzapine or N-desmethyl-olanzapine Concentration with Metabolic Parameters

Determination of Olanzapine and N-desmethyl-olanzapine in Plasma Using a Reversed-Phase HPLC Coupled with Coulochemical Detection: Correlation of Olanzapine or N-desmethyl-olanzapine Concentration with Metabolic Parameters

Effects of second-generation antipsychotics on selected markers of one-carbon metabolism and metabolic syndrome components in first-episode schizophrenia patients

Metabolic Syndrome in Bipolar Disorders

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