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1.
CNS Drugs ; 36(6): 605-616, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35644903

RESUMO

Olanzapine is a second-generation antipsychotic with established efficacy in several psychiatric disease states, but its use is limited because of weight gain and metabolic side effects. Samidorphan is a novel opioid antagonist that binds to mu-opioid, kappa-opioid, and delta-opioid receptors and is hypothesized to reduce cravings for high-calorie foods thus attenuating antipsychotic-induced weight gain. The combination product olanzapine/samidorphan was approved by the US Food and Drug Administration in June 2021 for the treatment of schizophrenia and bipolar I disorder; this article reviews the pharmacological properties of oral olanzapine/samidorphan and its clinical efficacy and tolerability with a focus on mitigation of olanzapine-induced weight gain in these patient populations. In clinical trials, the combination of olanzapine/samidorphan was associated with significantly less weight gain and smaller increases in waist circumference as compared with olanzapine monotherapy. Olanzapine/samidorphan demonstrated similar efficacy as olanzapine monotherapy and was well tolerated. Weight gain and metabolic side effects associated with olanzapine monotherapy can result in tolerability issues and potentially medication nonadherence. Olanzapine/samidorphan is an effective treatment for schizophrenia and bipolar I disorder with less weight gain than olanzapine monotherapy.


Assuntos
Antipsicóticos , Transtorno Bipolar , Esquizofrenia , Analgésicos Opioides/uso terapêutico , Antipsicóticos/efeitos adversos , Benzodiazepinas/efeitos adversos , Transtorno Bipolar/tratamento farmacológico , Humanos , Naltrexona/análogos & derivados , Olanzapina/efeitos adversos , Esquizofrenia/tratamento farmacológico , Ganho de Peso
2.
J Psychopharmacol ; 36(5): 637-644, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35510655

RESUMO

BACKGROUND: Pediatric bipolar disorder (BP) is frequently comorbid with conduct disorder (CD) and its presence adds to the morbidity of BP. While there are no known pharmacological treatments for CD, pediatric BP is responsive to treatment with medications initially indicated for the treatment of psychosis, several of which have Food and Drug Administration (FDA) approval for the treatment of pediatric mania. AIMS: The main aim of this secondary analysis was to examine whether pediatric BP comorbid with CD responds similarly to treatment with such selected medications. Considering the well-documented morbidity of CD, this finding could have important clinical and public health significance. METHODS: We conducted a secondary analysis of six prospective 8-week open-label trials of selected medications (risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole) using identical methodology in youth with BP with and without comorbid CD. Results: Of 165 youths with BP, 54% (N = 89) met criteria for comorbid CD. The antimanic effects observed did not significantly differ between BP youths with and without comorbid CD, as measured either by a reduction in Young Mania Rating Scale (YMRS) ⩾ 30% or Clinical Global Impression (CGI)-Improvement ⩽ 2 (p = 0.23), or by the more stringent definition of a reduction in YMRS ⩾ 50% (p = 0.61). CONCLUSION: Pediatric BP can be effectively treated with the abovementioned medications in the context of comorbid CD. Based on previous research showing that remission of BP is associated with remission of CD, if confirmed, these findings raise the possibility that antimanic treatment of youth with BP comorbid with CD could have secondary benefits in mitigating the morbidity associated with CD. This is a pilot scale finding, the results of which are promising and should be confirmed by larger and long-term follow-up studies.


Assuntos
Antipsicóticos , Transtorno Bipolar , Transtorno da Conduta , Adolescente , Antimaníacos/uso terapêutico , Antipsicóticos/uso terapêutico , Aripiprazol/uso terapêutico , Benzodiazepinas/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/epidemiologia , Criança , Ensaios Clínicos como Assunto , Transtorno da Conduta/tratamento farmacológico , Transtorno da Conduta/epidemiologia , Humanos , Mania , Olanzapina/uso terapêutico , Piperazinas , Estudos Prospectivos , Fumarato de Quetiapina/uso terapêutico , Risperidona/uso terapêutico , Tiazóis
3.
Clin Med (Lond) ; 22(3): 285-286, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35584835

RESUMO

INTRODUCTION: We describe a case of olanzapine-induced hypothermia and hand oedema in an older adult with behavioural and psychological symptoms of dementia (BPSD). CASE PRESENTATION: An 82-year-old woman with hypothyroidism and dementia was reviewed by the geriatric team at a nursing home in view of lethargy and an unrecordable oral temperature. She was noted to have a bilateral hand oedema and right basal crackles. Investigations revealed high white cell count and inflammatory markers. She was treated as per hypothermia and communityacquired pneumonia protocols. The patient did not have the expected response to treatment. Olanzapine was tailed down and stopped with good effect as it was suspected to be a contributory cause to both the hypothermia and oedema. DISCUSSION AND CONCLUSION: Potentially inappropriate polypharmacy can be specifically targeted with effective deprescribing. Treatment review should be encouraged on a regular basis, especially in frail older adults with polypharmacy.


Assuntos
Demência , Desprescrições , Hipotermia Induzida , Hipotermia , Idoso , Idoso de 80 Anos ou mais , Demência/tratamento farmacológico , Edema , Feminino , Humanos , Hipotermia/induzido quimicamente , Olanzapina , Polimedicação
4.
Pharmacotherapy ; 42(6): 504-513, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35508603

RESUMO

Antipsychotic medications demonstrate a variable range of efficacy and side effects in patients with mental illness. Research has attempted to identify biomarkers associated with antipsychotic effects in various populations. Research designs utilizing healthy volunteers may have the added benefit of measuring the effect of antipsychotics on a given biomarker (s) independent of the varied environmental and clinical factors that often accompany patient populations. The aim of this systematic review and meta-analysis was to synthesize the current evidence of hormonal, inflammatory, and metabolic biomarker studies of antipsychotic treatment in study designs using healthy volunteers. The systematic review was performed according to established guidelines and a random effects meta-analysis of biomarkers appearing in at least three studies was performed while biomarkers in two or less studies were qualitatively summarized. A total of 28 studies including 28 biomarkers were identified. Meta-analyses were carried out for 14 biomarkers, showing significant effects within six biomarkers (cortisol, C-peptide, free fatty acids, leptin, thyroid-stimulating hormone, and prolactin). Many of these effects were associated with olanzapine, the most used antipsychotic amongst the trials, observed on sub-analyses. When combining biomarkers into categories, some additional effects were observed, for example, when grouping inflammatory biomarkers. These findings suggest that antipsychotics exert potentially strong effects on several biomarkers of interest independent of psychiatric disease which could be used to spur future investigations, however, replication work is needed for many biomarkers included in this review.


Assuntos
Antipsicóticos , Antipsicóticos/efeitos adversos , Humanos , Olanzapina
5.
Psychiatry Res ; 313: 114590, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35567853

RESUMO

To guide care for patients with schizophrenia, the Veterans Health Administration (VHA) evaluated the associations between current or recent use of clozapine and all-cause mortality and explored associations for other antipsychotic medications. Using a case-control design, patients with schizophrenia who died in fiscal years 2014-2018 were matched on age, sex, race, and VHA facility to up to 10 controls who were alive on the case's date of death (index date). Medication coverage during the 91 days before the index date was classified as none, partial (1-44 days), and consistent (45-91 days). Medication coverage patterns during the index period were compared to coverage patterns during the period of 92-182 days prior to index date with each medication coverage classified as no change, no coverage, increased, or decreased. Conditional logistic regression analyses controlling for patient characteristics identified no associations of consistent or increasing clozapine coverage with mortality; partial and decreasing coverage were associated with greater mortality and these effects did not differ from those of other the medications considered. Exploratory analyses considering non-clozapine antipsychotic agents suggest that consistent coverage by olanzapine may be associated with increased mortality, that mortality associated with olanzapine may be greater than aripiprazole, and that this effect can be attributed primarily to patients with diabetes. Further study of this topic is needed.


Assuntos
Antipsicóticos , Clozapina , Esquizofrenia , Veteranos , Antipsicóticos/uso terapêutico , Benzodiazepinas/uso terapêutico , Clozapina/uso terapêutico , Humanos , Olanzapina/uso terapêutico , Esquizofrenia/tratamento farmacológico
6.
J Physiol ; 600(11): 2713-2728, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35507699

RESUMO

Antipsychotic (AP) medications, such as olanzapine (OLZ), are used in the treatment of schizophrenia and a growing number of 'off-label' conditions. A single dose of OLZ causes robust increases in blood glucose within minutes of treatment. The purpose of the current study was to investigate whether interventions that increase circulating ketone bodies (fasting, ß-hydroxybutyrate (ßHB), ketone esters or a ketogenic diet (KD)) would be sufficient to protect against the acute metabolic side effects of OLZ. We demonstrate that fasting or the short-term consumption of a KD protects against OLZ-induced hyperglycaemia, independent of alterations in whole-body insulin action, and in parallel with a blunted rise in serum glucagon. Interestingly, the effects of fasting and KDs were not recapitulated by acutely increasing circulating concentrations of ketone bodies through treatment with ßHB or oral ketone esters, approaches which increase ketone bodies to physiological or supra-physiological levels, respectively. Collectively, our findings demonstrate that fasting and the short-term consumption of a KD can protect against acute AP-induced perturbations in glucose homeostasis, whereas manipulations which acutely increase circulating ketone bodies do not elicit the same beneficial effects. KEY POINTS: Antipsychotic medications cause rapid and robust increases in blood glucose. Co-treatment approaches to offset these harmful metabolic side effects have not been identified. We demonstrate that fasting or the consumption of a short-term ketogenic diet, but not treatment with ß-hydroxybutyrate or oral ketone esters, protects against acute antipsychotic-induced hyperglycaemia. The protective effects of fasting and ketogenic diets were paralleled by reductions in serum glucagon, but not improvements in whole-body insulin action.


Assuntos
Antipsicóticos , Dieta Cetogênica , Hiperglicemia , Ácido 3-Hidroxibutírico/efeitos adversos , Ácido 3-Hidroxibutírico/metabolismo , Animais , Antipsicóticos/efeitos adversos , Glicemia , Ésteres , Jejum , Glucagon , Hiperglicemia/induzido quimicamente , Hiperglicemia/prevenção & controle , Insulina , Corpos Cetônicos/metabolismo , Cetonas , Camundongos , Olanzapina/efeitos adversos
7.
J Affect Disord ; 311: 69-77, 2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-35545157

RESUMO

OBJECTIVES: Rapid cycling is a phase of bipolar disorder with increased episode frequencies. It is a severe and disabling condition that often poses a major challenge to the clinician. The aim of this paper is to give an overview of the evidence-based treatment options for rapid cycling. METHODS: A systematic search on Pubmed, Embase and Cochrane databases from inception until December 2021 was conducted according to the PRISMA guidelines. An additional search on clinicaltrials.gov was done. References of retrieved papers and key reviews were hand-searched. Randomized controlled trials including at least 10 patients with bipolar disorder, rapid cycling, reporting an objective outcome measure were selected. RESULTS: Our search, initially revealing 1330 articles, resulted in 16 papers about treatment of an acute mood episode, relapse prevention or both. Lithium, anticonvulsants, second generation antipsychotics, antidepressants and thyroid hormone were assessed as treatment options in the presented data. Evidence supporting the use of aripiprazole, olanzapine, quetiapine, valproate and lamotrigine for treatment of rapid cycling bipolar disorder was found. LIMITATIONS: Small sample sizes, different index episodes and variety of outcome measures. CONCLUSION: Evidence regarding treatment of rapid cycling remains scarce. Evidence supports the use of aripiprazole, olanzapine, and valproate for acute manic or mixed episodes, quetiapine for acute depressive episodes and aripiprazole and lamotrigine for relapse prevention. Given the paucity of available evidence, and the burden that accompanies rapid cycling, future research is warranted.


Assuntos
Antipsicóticos , Transtorno Bipolar , Anticonvulsivantes/uso terapêutico , Antipsicóticos/uso terapêutico , Aripiprazol/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/prevenção & controle , Humanos , Lamotrigina/uso terapêutico , Olanzapina/uso terapêutico , Fumarato de Quetiapina/uso terapêutico , Ácido Valproico/uso terapêutico
8.
Xenobiotica ; 52(4): 413-425, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35582917

RESUMO

1. Olanzapine is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. An intronic single nucleotide polymorphism (SNP) that highly significantly predicts increased olanzapine clearance (rs472660) was previously identified in the CYP3A43 gene, which encodes a cytochrome P450 enzyme. But until now there was no experimental evidence for the metabolism of olanzapine by the CYP3A43 enzyme.2. In the present study we provide this evidence, together with a thorough analysis of olanzapine metabolism by all human CYP3A enzymes. We also rationalise our findings by molecular docking experiments. Moreover, we describe the activities of several CYP3A43 mutants and present the first enzymatic activity data for the CYP3A43.3 variant; with respect to prostate cancer, this polymorphic variant is associated with both increased risk and increased mortality. The catalytic properties of the wild type enzyme and the tumour mutant were analysed by molecular dynamics simulations, which fit very well with the observed experimental results.3. Our findings suggest that the SNP rs472660 likely causes an increased CYP3A43 expression level and demonstrate that, depending on the substrate under study, the tumour mutant CYP3A43.3 can have increased activity in comparison to the wild type enzyme CYP3A43.1.


Assuntos
Antipsicóticos , Antipsicóticos/uso terapêutico , Benzodiazepinas , Citocromo P-450 CYP3A/genética , Sistema Enzimático do Citocromo P-450/genética , Humanos , Masculino , Simulação de Acoplamento Molecular , Olanzapina
9.
Curr Psychiatry Rep ; 24(7): 345-351, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35576089

RESUMO

PURPOSE OF REVIEW: Identifying medications that may be used as therapeutic agents for eating disorders is a longstanding focus of research, with varying degrees of success. The present review consolidates the most recent findings on pharmacological treatment of three eating disorders, including anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). RECENT FINDINGS: Recent research suggests that olanzapine demonstrates positive effects on weight gain among outpatients with AN. There are fewer recent advances in psychopharmacological treatment for BN and BED, likely due to the relative success of prior medication trials. Olanzapine is the first medication to safely promote weight gain among individuals with AN. Fluoxetine is FDA-approved for BN treatment, and lisdexamfetamine is FDA-approved for BED treatment. BN and BED also generally respond well to SSRIs prescribed off-label. Research on psychopharmacological treatments for other eating disorders, such as avoidant-restrictive food intake disorder and other specified feeding and eating disorders, are sorely needed.


Assuntos
Anorexia Nervosa , Transtorno da Compulsão Alimentar , Bulimia Nervosa , Transtornos da Alimentação e da Ingestão de Alimentos , Anorexia Nervosa/tratamento farmacológico , Transtorno da Compulsão Alimentar/tratamento farmacológico , Bulimia Nervosa/tratamento farmacológico , Transtornos da Alimentação e da Ingestão de Alimentos/tratamento farmacológico , Humanos , Olanzapina/uso terapêutico , Ganho de Peso
10.
J Child Adolesc Psychopharmacol ; 32(5): 304-310, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35612433

RESUMO

Background: Although recent articles have investigated the use of low-dose olanzapine in different psychiatric conditions, only one study so far has assessed this treatment in 13 girls with anorexia nervosa (AN). Methods: Observational naturalistic case-control study aimed at reporting the use and tolerability of low-dose olanzapine in the context of a multidisciplinary hospital intervention for adolescents with AN. Three groups with AN were compared: group 1 was treated with low-dose olanzapine (≤5 mg/day), group 2 with full-dose olanzapine (>5 mg/day), and group 3 (control group) was treated without antipsychotics. Psychopathology was assessed at admission (T0) and discharge (T1) with Eating Disorders Inventory-3 Eating Disorders Risk, Body Uneasiness Test Global Severity Index (BUT-GSI), Beck's Depression Inventory-II (BDI-II), and Self-administered Psychiatric Scales for Children and Adolescents, Depression subtest (SAFA-D). Possible differences among the three groups, concerning clinical and treatment variables, were screened. Then, potential differences of T0-T1 modifications in psychopathological variables among the three treatment groups were assessed with analyses of covariance, corrected for baseline psychopathology and potential confounders, including possible concurrent antidepressants. Results: A total of 118 patients were enrolled (F = 94.1%; mean age = 15.4 ± 1.7 years), including 52 controls, 37 treated with low-dose olanzapine, and 29 with full-dose olanzapine. Low-dose olanzapine was well tolerated and used for a mean of 132.1 (±98.6) days, starting with a dosage of 3.4 (±1.2) mg/day and increasing to a maximum dose of 4.4 (±1.1) mg/day. The multidisciplinary intervention resulted in an improvement of BUT-GSI (p < 0.001), BDI-II (p < 0.001), and SAFA-D (p < 0.001) for the entire sample. Individuals treated with full-dose olanzapine experienced a significantly lower improvement in depressive measures: BDI-II (F[2,61] = 12.653, p < 0.001, η2 = 0.269) and SAFA-D (F[2,57] = 7.413, p = 0.001, η2 = 0.170), than the other groups. Discussion: This naturalistic controlled study expands the existing evidence on the use and tolerability of low-dose olanzapine in adolescents with AN. These results should be assessed in wider and prospective samples.


Assuntos
Anorexia Nervosa , Antipsicóticos , Adolescente , Anorexia Nervosa/tratamento farmacológico , Antipsicóticos/efeitos adversos , Benzodiazepinas/efeitos adversos , Estudos de Casos e Controles , Criança , Feminino , Humanos , Olanzapina/uso terapêutico , Estudos Prospectivos
11.
Curr Opin Psychiatry ; 35(3): 171-176, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35579871

RESUMO

PURPOSE OF REVIEW: To provide updated guidance for the medication treatment of acute agitation in the setting of psychosis or mania on inpatient psychiatric units. RECENT FINDINGS: This topic presented challenges: studies are sparse, tend to be under-powered, and are difficult to compare. Though there have been few recent studies, there have been several recent meta-analyses, Cochrane reviews, and published guidelines that sift through the primarily older evidence as well as more recent trials. The reviewers often do not agree on what seems to have the best evidence for efficacy and safety. SUMMARY: We conclude that the best approach is to summarize in some detail the evidence for each possible treatment and the interpretations published recently on each of those treatments, and then present recommendations for medication management in tiered rankings, based on the authors' qualitative review of the data and opinions. For oral treatment, the first-tier options are (alphabetically) haloperidol with lorazepam, lorazepam alone, and olanzapine. The second tier includes haloperidol with promethazine, loxapine inhaler, and risperidone alone. Tier 3 includes asenapine and quetiapine. For intramuscular treatment, the first-tier includes haloperidol plus promethazine, and olanzapine alone, and the second-tier includes haloperidol with lorazepam, and lorazepam alone.


Assuntos
Antipsicóticos , Psicofarmacologia , Transtornos Psicóticos , Antipsicóticos/uso terapêutico , Benzodiazepinas/uso terapêutico , Quimioterapia Combinada , Haloperidol/uso terapêutico , Humanos , Lorazepam/uso terapêutico , Mania , Olanzapina/uso terapêutico , Prometazina/uso terapêutico , Agitação Psicomotora/tratamento farmacológico , Agitação Psicomotora/etiologia , Transtornos Psicóticos/complicações , Transtornos Psicóticos/tratamento farmacológico
12.
J Psychopharmacol ; 36(4): 479-488, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35475374

RESUMO

BACKGROUND: Although numerous studies reported some changes of cortical silent period (CSP), an indicator of gamma-aminobutyric acid (GABA) function in central nervous system, in schizophrenia patients, it has been unknown how the disease stage and antipsychotic medication affect CSP values. METHODS: The present study conducted a systematic review of previous literature comparing CSP between schizophrenia patients and healthy subjects, and then performed meta-analysis on the effects of (1) the disease stage and (2) antipsychotics on CSP. RESULTS: (1) In the comparison of the disease stage comprising a total of 17 reports, there was no significant difference in CSP between patients under drug-naïve first-episode psychoses and healthy controls, or between patients with antipsychotic medication and healthy controls. (2) In the comparison of the antipsychotic class, patients treated with clozapine were longer in CSP compared to healthy controls. Patients treated with olanzapine/quetiapine or with other type of antipsychotics were not different from healthy controls. Regarding other type of antipsychotics, the iteration analysis after leaving out one literature showed that patients were shorter in CSP than healthy controls. CONCLUSION: The results showed that clozapine seems to surely prolong CSP, indicating the enhancement of GABA transmission via GABAB receptors, suggesting the possible relationship between the CSP prolongation by clozapine and its high efficacy in psychopathology. The finding of shorter CSP in patients with other type of antipsychotics was distinct from clozapine/olanzapine/quetiapine, but was difficult to interpret since this group included a variety of transcranial magnetic stimulation (TMS) methodologies and patients' background.


Assuntos
Antipsicóticos , Clozapina , Esquizofrenia , Antipsicóticos/farmacologia , Antipsicóticos/uso terapêutico , Clozapina/farmacologia , Clozapina/uso terapêutico , Humanos , Inibição Neural , Olanzapina/farmacologia , Fumarato de Quetiapina/uso terapêutico , Receptores de GABA , Esquizofrenia/tratamento farmacológico , Ácido gama-Aminobutírico/uso terapêutico
13.
Neurosci Lett ; 781: 136657, 2022 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-35483503

RESUMO

Haloperidol and olanzapine are first and second-generation antipsychotic (neuroleptic) medications approved to treat schizophrenia. Glutamate signaling is known to play an important role in the manifestation of schizophrenia symptoms, as phencyclidine, a non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist, replicates and exasperates these symptoms. While initial reports show that neuroleptic treatments can impact aspects of NMDAR expression, there is little attention on the interaction between neuroleptics and dietary conditions. Thus, we examined the impact of chronic haloperidol and olanzapine treatment under both normal and high-fat dietary conditions on NMDAR expression. Adult male rats were treated for 28-days with either oral vehicle, haloperidol (1.5 mg/kg), or olanzapine (10 mg/kg), and fed either a standard control diet or a high-fat diet. In-vitro receptor autoradiography binding was performed using [3H] MK-801 as a measure of NMDAR expression. Results showed that olanzapine, irrespective of the diet, significantly decreased [3H] MK-801 binding within the cingulate cortex, substantia nigra, insular cortex, piriform cortex, ectorhinal cortex and perirhinal cortex, the forelimb region of the somatosensory cortex, and all quadrants of the caudate-putamen. In contrast, haloperidol treatment did not impact [3H] MK-801 binding, and we also report no effect of diet on [3H] MK-801 binding. These data suggest that the effects seen in olanzapine treatment are not mediated by diet, nor does a 28-day chronic high-fat diet alter [3H] MK-801 binding. Furthermore, these data also importantly support that combined consumption of a high-fat diet and pharmacological treatments are not immediately detrimental to NMDARs and contribute to the expansive literature of precision medicine.


Assuntos
Antipsicóticos , Haloperidol , Animais , Antipsicóticos/uso terapêutico , Benzodiazepinas/farmacologia , Dieta , Maleato de Dizocilpina/farmacologia , Haloperidol/farmacologia , Masculino , Olanzapina , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato , Substância Negra
14.
Chemosphere ; 301: 134710, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35487358

RESUMO

The present work focuses on the development of a new electrochemical platform based on CoMn2O4-rGO/1-ethyl-3-methylimidazolium chloride modified carbon paste electrode (CoMn2O4-rGO/IL/CPE) for electrochemical determination of pethidine in the presence of biological species. For the first time, the electrooxidation mechanism of pethidine in presences of morphine and olanzapine is investigated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) technologies. The as-synthesized CoMn2O4-rGO nanocomposites are characterized by physicochemical measurements such as X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX), Field emission scanning electron microscopy (FE-SEM), and Fourier transform infrared (FT-IR). The obtained results illustrated synergistic interactions between rGO and CoMn2O4 structures. Also, to investigate the electrode charge-transfer resistances, electrochemical features of the resulting nanocomposites are studied via electrochemical impedance spectroscopy (EIS) analysis. Based on the result, three segmented linear ranges are observed over the range 0.08-900 µM and detection limit of 0.024 µM. Over the 10.0-40.0 µM ranges of pethidine in phosphate buffer solution (PBS-pH 7.0), suitable diffusion coefficient of 5.67 × 10-7 cm2 s-1 is evaluated by chronoamperometry technique (CHA). Finally, the CoMn2O4-rGO/IL/CPE with high sensitivity, selectivity and repeatability is successfully used for determination of pethidine in real sample and drug formulation.


Assuntos
Carbono , Cloreto de Etil , Carbono/química , Cloretos , Técnicas Eletroquímicas/métodos , Eletrodos , Grafite , Imidazóis , Meperidina , Morfina , Olanzapina , Espectroscopia de Infravermelho com Transformada de Fourier
15.
Molecules ; 27(8)2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35458749

RESUMO

Olanzapine is a commonly used drug in the treatment of schizophrenia, but its clinical application has been restricted by metabolic-related side effects. In order to mitigate the weight gain side effects caused by olanzapine, other drugs with different targets were selected for combined use and evaluated in animal models of schizophrenia. SEP-363856 is a novel psychotropic agent which is under phase III clinical trials for schizophrenia treatment. The aim of the research was to evaluate whether co-administration of olanzapine and SEP-363856 exerts synergistic anti-schizophrenic effects in the apomorphine (APO)-induced climbing test, the MK-801-induced hyperactivity test, and the Morris water maze test, and therefore reduces the weight gain side effects induced by olanzapine. Through isobolographic analysis, the results showed a synergistic interaction in the climbing test; the experimental ED30 (3 mg/kg) was significantly smaller (p < 0.05) than the theoretical ED30 (5 mg/kg). Additionally, such potentiating effects appeared additive in the MK-801 challenge experiment. Co-treatment with an effective dose of olanzapine and a low dose of SEP-363856 reversed MK-801-induced cognitive impairment symptoms in mice. Moreover, combination treatment with olanzapine and SEP-363856 controls sustained weight gain in mice with chronic exposure to olanzapine. These results support further clinical trials to test the effectiveness of co-treatment of olanzapine and SEP-363856 for controlling symptoms and weight gain in patients with schizophrenia during antipsychotic treatments.


Assuntos
Antipsicóticos , Esquizofrenia , Animais , Antipsicóticos/efeitos adversos , Benzodiazepinas/efeitos adversos , Maleato de Dizocilpina/farmacologia , Humanos , Camundongos , Olanzapina , Piranos , Esquizofrenia/induzido quimicamente , Esquizofrenia/tratamento farmacológico , Ganho de Peso
16.
Sci Rep ; 12(1): 5502, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35365730

RESUMO

Obesity induced by antipsychotics have plagued more than 20 million people worldwide. However, no drug is available to eliminate the obesity induced by antipsychotics. Here we examined the effect and potential mechanisms of a gold nanoclusters (AuNCs) modified by N-isobutyryl-L-cysteine on the obesity induced by olanzapine, the most prescribed but obesogenic antipsychotics, in a rat model. Our results showed that AuNCs completely prevented and reversed the obesity induced by olanzapine and improved glucose metabolism profile in rats. Further mechanism investigations revealed that AuNCs exert its anti-obesity function through inhibition of olanzapine-induced dysfunction of histamine H1 receptor and proopiomelanocortin signaling therefore reducing hyperphagia, and reversing olanzapine-induced inhibition of uncoupling-protein-1 signaling which increases thermogenesis. Together with AuNCs' good biocompatibility, these findings not only provide AuNCs as a promising nanodrug candidate for treating obesity induced by antipsychotics, but also open an avenue for the potential application of AuNCs-based nanodrugs in treating general obesity.


Assuntos
Antipsicóticos , Nanopartículas Metálicas , Animais , Antipsicóticos/farmacologia , Ouro , Humanos , Obesidade/induzido quimicamente , Obesidade/tratamento farmacológico , Olanzapina , Ratos
17.
Trials ; 23(1): 311, 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35422053

RESUMO

BACKGROUND: The phenomenon of restlessness, agitation, or cognitive disturbances experienced by dying patients is well-known in palliative care; more than half of these patients will experience delirium symptoms at end-of-life. When not identified early and effectively managed, delirium symptoms could lead to caregiver and patient distress and harm. METHODS: Eighty patients with a prognosis of 7 days or less will be recruited for an open-label randomised control trial. The two arms compare oral-transmucosal haloperidol 2.5 mg vs olanzapine 5 mg over 72 h. The severity of agitation, delirium and toxicities of treatments will be compared at the 24th, 48th and 72nd hour after drug administration. DISCUSSION: This trial is the first to compare anti-psychotics in the management of delirium at the dying stage in the home hospice setting using the oral transmucosal route. Ethical considerations, as well as recruitment procedures, are discussed. TRIAL REGISTRATION: This study was registered in ClinicalTrials.gov - identifier NCT04750395.


Assuntos
Antipsicóticos , Delírio , Antipsicóticos/efeitos adversos , Delírio/diagnóstico , Delírio/tratamento farmacológico , Haloperidol/efeitos adversos , Humanos , Olanzapina/efeitos adversos , Agitação Psicomotora/tratamento farmacológico
18.
Sci Rep ; 12(1): 5639, 2022 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-35379885

RESUMO

Studies have confirmed that olanzapine, the mainstay treatment for schizophrenia, triggers metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). However, the etiology of olanzapine-induced NAFLD is poorly understood. Proprotein convertase subtilisin kexin type 9 (PCSK9) is involved in NAFLD pathogenesis, and metformin can significantly decrease circulating PCSK9. The purpose of this study was to investigate the role of PCSK9 and explore the therapeutic effect of metformin for olanzapine-associated NAFLD. Olanzapine significantly upregulated PCSK9 and promoted lipid accumulation in mouse livers and HepG2 and AML12 cells. Metformin ameliorated these pathological alterations. PCSK9 upstream regulator liver X receptor α (LXRα) was significantly upregulated in olanzapine-induced NAFLD. LXRα antagonist treatment and LXRα overexpression resulted in a decrease and increase of PCSK9, respectively. Hepatic lipogenesis-associated genes FAS and SCD1 were significantly upregulated in olanzapine-induced NAFLD mice and HepG2 cells overexpressing PCSK9, and genes related to lipid ß-oxidation (SCAD and PPARα) were downregulated, while metformin reversed these changes. In addition, we found that LXRα overexpression compromised the effect of metformin on PCSK9 levels and intracellular lipid droplet formation. Taken together, our findings suggest that olanzapine enhances hepatic PCSK9 expression by upregulating LXRα, thereby increasing FAS and SCD1 expression as well as decreasing SCAD and PPARα, and promoting lipid accumulation, and, subsequently, NAFLD, which is ameliorated by metformin.


Assuntos
Metformina , Hepatopatia Gordurosa não Alcoólica , Animais , Receptores X do Fígado/genética , Metformina/farmacologia , Camundongos , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Olanzapina , Pró-Proteína Convertase 9/genética , Pró-Proteína Convertase 9/metabolismo
19.
Support Care Cancer ; 30(7): 6225-6232, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35449368

RESUMO

OBJECTIVE: A prospective randomized controlled trial was conducted to compare 5 mg olanzapine plus standard triple antiemetic therapy for the prevention of nausea and vomiting induced by multiple-day cisplatin chemotherapy. METHODS: Patients who received a 3-day cisplatin-based chemotherapy (25 mg/m2/d) were given either 5 mg olanzapine plus triple therapy with aprepitant, tropisetron, and dexamethasone (quadruple group) or 5 mg olanzapine plus tropisetron and dexamethasone, omitting aprepitant (triplet group). The primary endpoint was the complete response (CR) in the overall phase (OP) (0-120 h) between quadruple group and triplet group. The secondary endpoints were the CR in the acute phase (AP) (0-24 h) and delayed phase (DP) (25-120 h) between two groups. The first time of vomiting was also compared by Kaplan-Meier curves. The impact of chemotherapy-induced nausea and vomiting (CINV) on the quality of life was assessed by the Functional Living Index-Emesis (FLIE). Aprepitant-related adverse effects (AEs) were also recorded. RESULTS: (1) The primary endpoint CR during OP was 76.0% (45/59) vs 67.0% (41/61) between the quadruple group and triplet group (P = 0.271). The secondary endpoint CR during the AP was significantly higher in the quadruple group than in the triplet group, which was 100.0% (59/59) vs 93.0% (57/61) (P = 0.045). The difference of CR during delayed phase between the groups was especially higher in the quadruple group compared to the triplet group (76.0% (45/59) vs 67.0% (41/61) (P = 0.271)). The rate of patients who achieved total protection in the overall phase was also higher in the quadruple group than the triplet group (28.8% (17/59) vs 23.0% (14/61) (P = 0.463)). During the OP, the incidence of no vomiting in the quadruple group and the triplet group was 93.2% (55/59) vs 80.3% (49/61) (P = 0.038), respectively. (2) Kaplan-Meier curves of time to first emesis were obviously longer in the quadruple group compared with the triplet group (P = 0.031). According to FLIE, no impact of CINV on daily life was defined as total score of questionnaire > 108; this study exhibited identical life quality between two groups. (3) The most common aprepitant- or olanzapine-related AEs included sedation, fatigue, and constipation. The occurrences between two groups were identical. CONCLUSION: It may been recommended that 5 mg olanzapine plus tropisetron and dexamethasone, omitting aprepitant triplet regimen as an alternative therapy in prevention CINV induced by multiple-day cisplatin chemotherapy due to the excellent CINV control rate and safety.


Assuntos
Antieméticos , Antineoplásicos , Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Aprepitanto/uso terapêutico , Cisplatino/efeitos adversos , Dexametasona/uso terapêutico , Humanos , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Náusea/prevenção & controle , Olanzapina/uso terapêutico , Estudos Prospectivos , Qualidade de Vida , Tropizetrona/uso terapêutico , Vômito/induzido quimicamente , Vômito/tratamento farmacológico , Vômito/prevenção & controle
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