Olanzapine Is Faster than Haloperidol in Inducing Metabolic Abnormalities in Schizophrenic and Bipolar Patients

Fabrazzo, Michele; Monteleone, Palmiero; Prisco, Vincenzo; Perris, Francesco; Catapano, Francesco; Tortorella, Alfonso; Monteleone, Alessio Maria; Steardo, Luca; Maj, Mario

doi:10.1159/000437430

Cited by 16 publications

(11 citation statements)

References 40 publications

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“…HTRF-based measurement of secreted insulin in INS-1E cells in response to 20 mM glucose stimulation (90 min, 37 ° C). (a) Increasing concentrations of L-DOPA caused dose-dependent inhibition of GSIS, which was best fit to a sigmoidal curve (in black; IC 50 =38.3 μM, R 2 2 =0.84). AADC inhibition by benserazide (10 μM) abolished L-DOPA’s inhibition of GSIS (in red).…”

Section: Figurementioning

confidence: 99%

“…AADC inhibition by benserazide (10 μM) abolished L-DOPA’s inhibition of GSIS (in red). (b) Treatment with the D2R/D3R agonist quinpirole produced a dose-dependent inhibition of GSIS (in black; IC 50 =10.3 μM, R 2 2 =0.90) (c) Concurrent blockade of D2R and D3R by increasing concentrations of raclopride in the presence of 100 μM L-DOPA attenuated L-DOPA’s inhibitory effects on GSIS. Dotted lines indicate the minimum and maximum values constituting the dynamic range of the dose response curve.…”

Section: Figurementioning

confidence: 99%

“…Antipsychotic drugs (APDs) are some of the most widely used psychotropic medications today. Yet, these drugs can also produce profound metabolic disturbances 1, 2 . A key feature of this metabolic dysregulation is impaired glycemic control, which ultimately contributes to the development of systemic insulin resistance and type II diabetes (T2D) 3 .…”

Section: Introductionmentioning

confidence: 99%

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New roles for dopamine D2 and D3 receptors in pancreatic beta cell insulin secretion

et al. 2019

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Although long-studied in the central nervous system, there is increasing evidence that dopamine (DA) plays important roles in the periphery including in metabolic regulation. Insulin-secreting pancreatic β-cells express the machinery for DA synthesis and catabolism, as well as all five DA receptors. In these cells, DA functions as a negative regulator of glucose-stimulated insulin secretion (GSIS), which is mediated by DA D 2 -like receptors including D 2 (D2R) and D 3 (D3R) receptors. However, the fundamental mechanisms of DA synthesis, storage, release, and signaling in pancreatic β-cells and their functional relevance in vivo remain poorly understood. Here, we assessed the roles of the DA precursor L-DOPA in β-cell DA synthesis and release in conjunction with the signaling mechanisms underlying DA’s inhibition of GSIS. Our results show that uptake of L-DOPA is essential for establishing intracellular DA stores in β-cells. Glucose stimulation significantly enhances L-DOPA uptake, leading to increased DA release and GSIS reduction in an autocrine/paracrine manner. Furthermore, D2R and D3R act in combination to mediate dopaminergic inhibition of GSIS. Transgenic knockout mice in which β-cell D2R or D3R expression is eliminated exhibit diminished DA secretion during glucose stimulation, suggesting a new mechanism where D 2 -like receptors modify DA release to modulate GSIS. Lastly, β-cell-selective D2R knockout mice exhibit marked postprandial hyperinsulinemia in vivo . These results reveal that peripheral D2R and D3R receptors play important roles in metabolism through their inhibitory effects on GSIS. This opens the possibility that blockade of peripheral D 2 -like receptors by drugs including antipsychotic medications may significantly contribute to the metabolic disturbances observed clinically.

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Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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New roles for dopamine D2 and D3 receptors in pancreatic beta cell insulin secretion

et al. 2019

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“…Cross-sensitivity reactions may pertain to medications of the same class or of different classes. Therefore, it seems essential to accurately monitor the administration of the psychotropic drug to early detect and manage the adverse cutaneous reactions, especially during the initial months of treatment [ 52 , 53 ].…”

Section: Antipsychotics As Potential Inducers Of Bpmentioning

confidence: 99%

“…Nevertheless, cutaneous adverse drug eruptions are less frequent when administering second-generation antipsychotics (SGAs) [ 52 ]. Adjunctive therapy with atypical antipsychotics is widely used to treat acute bipolar depressive or manic episodes to foster treatment adherence and control psychotic symptoms typical of the manic phases [ 53 ]. In addition, atypical antipsychotics may also inhibit the monoaminergic reuptake transporter, contributing to stabilizing further the mood episodes [ 55 , 56 , 57 ].…”

Section: Antipsychotics As Potential Inducers Of Bpmentioning

confidence: 99%

Bipolar Patients and Bullous Pemphigoid after Risperidone Long-Acting Injectable: A Case Report and a Review of the Literature

et al. 2021

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Neuropsychiatric disorders are found to be associated with bullous pemphigoid (BP), an autoimmune subepidermal blistering disease. Antipsychotics have emerged as possible inducing factors of BP. However, large sample studies concerning BP associated with antipsychotics, as well as with specific mental disorders, are still lacking. Our review retrieved a few clinical studies and case reports on the topic, producing controversial results. We report for the first time a bipolar patient case presenting BP following five-month therapy with risperidone long-acting injectable (LAI). We hypothesize that the dermatological event is associated with the medication administered. The issue emerged during psychiatric consultation and was confirmed by histological examination, direct and indirect immunofluorescence studies, plus positive plasma and cutaneous BP180 and BP230 IgG. Neurodegeneration or neuroinflammation might represent a primary process leading to a cross-reactive immune response between neural and cutaneous antigens and contributing to self-tolerance failure. Furthermore, the time sequence of the shared biological mechanisms leading to clinical manifestations of the neuropsychiatric disorder and BP remains undefined. BP comorbid with bipolar disorder might occasionally represent a serious health risk and affect patients’ physical and psychosocial quality of life. Thus, clinicians treating psychiatric patients should consider BP as a possible adverse effect of psychotropic medications.

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Second-Generation Antipsychotic Drugs for Patients with Schizophrenia: Systematic Literature Review and Meta-analysis of Metabolic and Cardiovascular Side Effects

2021

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Background and Objectives Second-generation antipsychotics (SGAs) for schizophrenia show different risk profiles, whose evidence has been evaluated through comparative reviews on randomized controlled trials (RCTs) and observational studies. Methods We performed a systematic review and meta-analysis of weight gains, metabolic and cardiovascular side effects of SGAs, relying on both RCTs and observational studies, by comparing variations between the start of treatment and the end of follow-up. The systematic review refers to papers published from June 2009 to November 2020. PRISMA criteria were followed. No restrictions on heterogeneity level have been considered for meta-analysis. A test for the summary effect measure and heterogeneity (I 2 metric) was used. Results Seventy-nine papers were selected from 3076 studies (61% RCTs, 39% observational studies). Olanzapine and risperidone reported the greatest weight gain and olanzapine the largest BMI increase. Paliperidone showed the highest increase in total cholesterol, but is the only drug reporting an increase in the HDL cholesterol. Quetiapine XR showed the highest decrease in fasting glucose. Lurasidone showed the lowest increase in body weight and a reduction in BMI and was also the only treatment reporting a decrease in total cholesterol and triglycerides. The highest increase in systolic and diastolic blood pressure was reported by quetiapine XR. Conclusions Despite some limitations (differences in the mean dosages per patient and other side effects not included) this paper provides the first complete meta-analysis on SGAs in variations on metabolic risk profile between start of treatment and end of follow-up, with useful results for clinical practice and possibly for future economic evaluation studies.

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Olanzapine Is Faster than Haloperidol in Inducing Metabolic Abnormalities in Schizophrenic and Bipolar Patients

Cited by 16 publications

References 40 publications

New roles for dopamine D2 and D3 receptors in pancreatic beta cell insulin secretion

New roles for dopamine D2 and D3 receptors in pancreatic beta cell insulin secretion

Bipolar Patients and Bullous Pemphigoid after Risperidone Long-Acting Injectable: A Case Report and a Review of the Literature

Second-Generation Antipsychotic Drugs for Patients with Schizophrenia: Systematic Literature Review and Meta-analysis of Metabolic and Cardiovascular Side Effects

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